PT2014285E - Antagonistas de y5 de npy - Google Patents

Antagonistas de y5 de npy Download PDF

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Publication number
PT2014285E
PT2014285E PT08014713T PT08014713T PT2014285E PT 2014285 E PT2014285 E PT 2014285E PT 08014713 T PT08014713 T PT 08014713T PT 08014713 T PT08014713 T PT 08014713T PT 2014285 E PT2014285 E PT 2014285E
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Portugal
Prior art keywords
nmr
δppm
dmso
ppm
cdcl3
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PT08014713T
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English (en)
Inventor
Yasuyuki Kawanishi
Hideyuki Takenaka
Kohji Hanasaki
Tetsuo Okada
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Shionogi & Co
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Publication of PT2014285E publication Critical patent/PT2014285E/pt

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    • A61K31/4965—Non-condensed pyrazines
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    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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Description

1
DESCRIÇÃO "ANTAGONISTAS DE Y5 de NPY"
Domínio Técnico A invenção presente diz respeito a uma composição farmacêutica para utilização a titulo de antagonista de receptores Y5 de NPY, especificamente a titulo de agente contra a obesidade e novos compostos com actividade anti-obesidade.
Estado da Técnica à Data da Invenção 0 neuropéptido Y (doravante referido neste documento como NPY) é um péptido constituído por 36 residuos de aminoácidos que foi isolado a partir do cérebro porcino em 1982. 0 NPY encontra-se largamente distribuído no sistema nervosa central e nos tecidos periféricos dos seres humanos e dos animais.
Foi descrito que o NPY possui uma actividade de estimulação do consumo de alimentos, uma actividade contra as convulsões, uma actividade de promoção da aprendizagem, uma actividade contra a ansiedade, uma actividade contra o stress, etc. no sistema nervoso central, e pode estar envolvido de forma fulcral nas doenças do sistema nervoso 2 central tais como a depressão, a doença de Alzheimer e a doença de Parkinson. Pensa-se que o NPY se encontra associado com as doenças cardiovasculares, uma vez que induz uma contracção dos músculos lisos tais como os dos vasos sanguíneos ou os músculos cardíacos nos tecidos periféricos. Para além disto, também se sabe que o NPY se encontra envolvido em doenças metabólicas tais como a obesidade, a diabetes, e as anormalidades hormonais (Trends in Pharmacological Sciences, Vol. 15, 153 (1994)). Espera-se portanto que um antagonista de receptores de NPY seja um remédio para impedir ou para tratar diversas doenças envolvendo o receptor de NPY.
Os subtipos Yl, Y2, Y3, Y4, Y5, e Y6 já foram identificados a título de receptores de NPY (Trends in Pharmacological Sciences, Vol. 18, e 372 (1997)). Foi sugerido que o receptor Y5 esteja pelo menos envolvido no comportamento de consumo alimentar e espera-se que o seu antagonista seja um agente contra a obesidade (Peptides, Vol. 18, e 445 (1997)). São descritos compostos de quinazolina com estruturas semelhantes às dos compostos da invenção presente e que exibem actividade antagonística em relação ao receptor de NPY nos WO 97/20.820, WO 97/20.821, WO 97/20.823 e outros semelhantes. Para além disto, está descrito que os derivados de ureia com um grupo sulfonamida e os derivados amida com um grupo sulfonilo no WO 99/64.349 3 bem como os derivados de benzilsulfonamida na EP 1010691-A, possuem uma actividade antagonista face ao NPY.
Estão descritos compostos com estruturas semelhantes às dos compostos da invenção presente noa JP59-16871-1-A e no WO 97/15567. As suas actividades são bastante diferentes das dos compostos da invenção presente e aqueles documentos não sugerem a invenção presente.
Descrição da Invenção 0 objecto da invenção presente é proporcionar uma composição farmacêutica melhor para utilização a titulo de antagonista dos receptores Y5 de NPY e novos compostos possuindo essa actividade. A invenção presente proporciona de um composto com a fórmula:
~ \ H
00 G.JL um seu sal aceitável do ponto de vista farmacêutico ou um solvato destes.
Uma composição farmacêutica que inclua um composto com a fórmula: 4 4
cf3 . um seu sal aceitável do ponto de vista farmacêutico ou um solvato destes
Um composto com 3 fórmula;
um seu sal aceitável do ponto de vista farmacêutico ou um solvato destes para utilização no tratamento da obesidade.
Melhor Mnelra de Levar a Cabo a Invenção
Os compostos da invenção presente incluem também quaisquer dos seus sais capazes de serem formados e aceitáveis do ponto de vista farmacêutico. São exemplos de um "sal aceitável do ponto de vista farmacêutico" os sais com ácidos inorgânicos tais como ácido clorídrico, ácido sulfúrico, ácido azótico e ácido fosfórico; sais com ácidos orgânicos tais como ácido para-toluenossulfónico, ácido metanossulfónico, ácido oxálico e ácido cítrico; sais com 5 bases orgânicas tais como os de amónio, trimetilamónio e trietilamónio; sais com metais alcalinos tais como sódio e potássio; e sais com metais alcalino-terrosos tais como o cálcio e o magnésio.
Os compostos da invenção presente incluem solvatos. Hidrato é preferível e pode coordenar-se com o composto da invenção presente um número arbitrário de moléculas de água.
Quando o composto (I) da invenção presente possui um átomo de carbono assimétrico, ele inclui os próprios racematos, todos os enantiómeros e todos os estereoisómeros, tais como os seus diastereómeros, epímeros e enantiómeros.
Quando o composto (I) da invenção presente contendo uma ou mais ligações duplas forma um isómero E ou um isómero Z, o composto (I) inclui ambos os isómeros. Quando X é cicloalquileno, o composto (I) inclui tanto o isómero cis como o isómero trans.
Por exemplo, o composto (I) da invenção presente pode ser sintetizado pelo método seguinte. (Compostos nos quais Y=CONR7) 6 R^JN-X-COaH 1
em que Hal seja halogéneo, Q seja um grupo protector de amino e os outros símbolos são tais como acima.
Passo A
Faz-se reagir o composto 1 com o Composto Amino 2 possuindo os substituintes pretendidos Z e R7, num solvente apropriado, a entre 0°C e 50°C durante entre diversos minutos e diversas horas. A titulo de solvente, pode utilizar-se tetrahidrofurano, dimetilformamida, éter dietilico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, pentano, heptano, dioxano, acetona, acetonitrilo, água, uma mistura de todos estes, etc.. Pode utilizar-se um activador tal como cloreto de tionilo, um halogeneto de acilo, um anidrido de ácido e um éster activado, caso seja necessário.
Passo B
Desprotege-se o composto 3 pelo método habitual e faz-se reagir com o Halogeneto de Sulfonilo 4 que tinha o 7 substituinte R1 pretendido num solvente adequado, a entre 0°C e 50°C durante entre diversos minutos e diversas horas para se obter o composto (I-A) no qual n é 2. Pode utilizar-se a titulo de solvente tetrahidrofurano, dimetilformamida, éter dietilico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, pentano, heptano, dioxano, acetona, acetonitrilo, água e misturas de todos estes, etc. .
Passo C
Pode sintetizar-se o Composto (I-B) no qual n é 1 fazendo reagir o Composto 3 com o Halogeneto de Sulfinilo 5 contendo o substituinte R1. As condições reaccionais para a reacção são as mesmas que se utilizaram no Passo B.
Passo D
Oxida-se o Composto (I-B) obtido no Passo C pelo método habitual para se obter o Composto (I-A) no qual n é 2. Pode utilizar-se como oxidante ácido m-cloroperbenzóico, ácido peracético, peróxido de hidrogénio, ácido trifluoroperacético, periodato de sódio, hipoclorito de sódio, permanganato de potássio, etc., e pode levar-se a cabo a entre 0°C e 50°C. São exemplos de solventes, tetrahidrofurano, dimetilformamida, éter dietilico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, 8 pentano, heptano, dioxano, acetona, acetonitrilo, água, metanol, etanol, isopropanol e uma mistura de todos estes.
Quando X é heterociclo-di-ilo contendo pelo menos um átomo de N e o átomo de N liga-se a CONR7-Z no composto (I), pode empregar-se a reacção seguinte para se obter o Composto (I-A') ou (I-B'). Pode levar-se a cabo o Passo D logo após o Passo C ou o Passo E.
o,A N'2 9
Passo F í? R2 R2 PassoT* YUCOOR ^ V N^H Passo E O v ° 7 8 R1· N' o ^ (I-B1)
Passo D xXy*6% ^ (i-A·) no qual R é alquilo inferior ou arilo e L é um grupo de saida.
Passo C
Faz-se reagir o Composto 5 com o Composto 6 de um modo semelhante ao Passo C acima, para se obter o Composto 7.
Passo E 0 Composto 7 obtido desta forma é tratado com uma base num solvente adequado, para se obter o Composto 8. Por 9 exemplo, o hidróxido de bário, hidróxido de sódio, hidróxido de potássio, hidrazina ou propanotiolato de litio como base. A titulo de solvente, pode aprovar-se o tetrahidrofurano, a dimetilformamida, o dioxano, a acetona, o acetonitrilo, o metanol, o etanol, o propanol, a água, qualquer mistura destes ou outros semelhantes. Pode levar-se a cabo a reacção a entre 0°C e 100°C durante entre diversos minutos e várias dezenas de horas.
Passo F
Faz-se reagir o composto 8 com o Composto 9 contendo um grupo rejeitado e o substituinte pretendido, num solvente adequado, na presença ou na ausência de uma base, a entre 0°C e 100°C durante entre diversos minutos e diversos dias, para se obter o Composto (I-B'). São exemplos de grupo rejeitado fenoxilo, cloro e triclorometilo. São exemplos da base trietilamina, piridina, di- isopropiletilamina, hidróxido de sódio, carbonato de potássio e hidrogenocarbonato de sódio. São exemplos do solvente tetrahidrofurano, dimetilformamida, éter dietilico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, pentano, heptano, dioxano, acetona, acetonitrilo, metanol, etanol e as misturas destes.
Passo D 10
Faz-se reagir o Composto (I—B') de uma maneira semelhante à do Passo D acima, para se obter o Composto (ΙΑ') . (Composto no qual Y=NR7CO) 0 7 H Λ 11 ?7 Hal Z _2.... „.N Z R1-S02-Hal 4 nV .n-v.-·1 A x Jf R HN-X-NHR -10 -FrHN-X^Y^ Passo B o o Passo G 12 0 Passo C (l-C) II R'*SHal 5 Passo D q2 r'
R,vVV o 0 (l-D) em que todos os símbolos sejam tais como acima.
Passo G e Passo B
Faz-se reagir o Composto 10 com o Composto 11 nas mesmas condições reaccionais que no Passo B. Faz-se reagir o Composto 12 que desta forma se obtém de um modo semelhante ao do Passo B acima para se obter o Composto (ΙΟ no qual n=2.
Passo C e Passo D
Para se sintetizar o Composto (I-D), pode fazer-se reagir o Composto 12 obtido no Passo G de um modo semelhante aos do Passo C e do Passo D acima. 11 (Composto no qual Y=OCONR7) - · ·· R7 2 ' OCN—2 14 R2HNn o n
Passo H R2HN-X-OH--► * Y 2 13 0 15
RV 1 .Hal
.N P
R t N
->* \vv v s Passo C S a g Z
II O
Passo D
<5' //Λ o O 16 R? O (l-E) em que todos os símbolos são tal como acima.
Passo H
Faz-se reagir o Composto 13 com o Isocianato, Composto 14, contendo um substituinte Z, num solvente adequado e na presença de um catalisador apropriado, a entre 0°C e 100°C durante entre diversos minutos e diversos dias, para se obter o Composto 15. São exemplos do solvente, tetrahidrofurano, dimetilformamida, éter dietílico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, pentano, heptano, dioxano, acetona, acetonitrilo e as misturas destes.
Passo C e Passo D 12
Faz-se reagir o Composto 15 que desta forma se obteve de modos semelhantes aos do Passo C e do Passo D para se obter o Composto (I-E) da invenção presente. (Composto no qual Y=CSNR7 ou NR7CS)
Pode sintetizar-se o Composto (I) no qual Y seja CSNR7 ou NR7CS fazendo reagir o composto (I) no qual Y seja CONR7 ou NR7CO, sintetizado por qualquer um dos métodos acima, com o reagente de Lawesson ou com pentassulfureto de fósforo num solvente adequado a entre 30°C e 100°C durante entre diversos minutos e várias horas. São exemplos do solvente tetrahidrofurano, dimetilformamida, éter dietilico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, pentano, heptano, dioxano, acetona, acetonitrilo e misturas de todos estes.
Podem proteger-se os grupos amino com um grupo protector adequado da forma habitual num passo apropriado.
Por exemplo, pode utilizar-se como grupo protector a ftalimida, um alcoxicarbonilo inferior, um alceniloxicarbonilo inferior, um halogenoalcoxicarbonilo inferior, um aril-alcoxil(inferior)carbonilo, um trialquilsililo, um alquilsulfonilo inferior, um halogenoalquilsulfonilo inferior, um arilsulfonilo, um alquilcarbonilo inferior e um arilcarbonilo. 13
Depois da protecção do grupo amino, submete-se o composto às reacções mencionadas acima e desprotege-se o composto obtido por um tratamento com um ácido ou com uma base num solvente adequado, numa altura apropriada. São exemplos de um solvente, tetrahidrofurano, dimetilformamida, éter dietilico, diclorometano, tolueno, benzeno, xileno, ciclohexano, hexano, clorofórmio, acetato de etilo, acetato de butilo, pentano, heptano, dioxano, acetona, acetonitrilo e as misturas destes. São exemplos de bases a hidrazina, a piridina, o hidróxido de sódio e o hidróxido de potássio e são exemplos de um ácido o ácido clorídrico, o ácido trifluoroacético e o ácido fluorídrico. 0 composto da invenção presente tem uma actividade antagonista do Y5 de NPY. 0 antagonista de receptores Y5 de NPY da invenção presente é eficaz para todas as doenças nas quais esteja envolvido ο Y5 de NPY, e é especialmente útil para impedir e/ou tratar a obesidade e para suprimir o consumo de alimentos. Para além disto, o antagonista é eficaz para impedir e/ou tratar doenças nas quais a obesidade actua como factor de risco, por exemplo, a diabetes, a hipertensão, a hiperlipidémia, a aterosclerose e a síndrome aguda de coronárias.
Para além disto, o antagonista de receptor Y5 de NPY da invenção presente tem pequena afinidade para os receptores Y1 e Y2 de NPY Yl, e é altamente selectivo para 14 o receptor Υ5 de ΝΡΥ. A ΝΡΥ provoca uma acção vasoconstritora prolongada na periferia, e esta acção é sobretudo através do receptor Y1. Uma vez que o receptor Y5 não está de todo envolvido nesta acção, o antagonista do receptor Y5 de NPY apresenta um pequeno risco de induzir efeitos colaterais baseados na vasoconstrição periférica, e espera-se que seja utilizado adequadamente como um medicamento seguro. 0 antagonista de receptor Y5 de NPY evidencia um efeito contra a obesidade por suprimir o consumo de alimentos. Esta é uma das caracteristicas deste antagonista para não apresentar efeitos colaterais, por exemplo uma indigestão provocada por um agente contra a obesidade que iniba a digestão e a absorção, e um efeito colateral central tal como efeito anti-depressivo provocado pela inibição de um transportador de serotonina que tenha um efeito contra a obesidade. 0 composto da invenção presente pode ser administrado por via oral ou parentérica como agente contra a obesidade ou anoréxico. No caso da administração por via oral, ele pode assumir qualquer uma das formas habituais tais como comprimidos, grânulos, pós, cápsulas, pílulas, soluções, xaropes, tabletes bucais e tabletes sublinguais. Quando o composto é administrado por via parentérica, qualquer uma das formas habituais é preferível, tais como, por exemplo, injecções (por exemplo, endovenosas, intramusculares), supositórios, agentes endérmicos e 15 vapores. É especialmente preferida a administração por via oral porque os compostos da invenção presente apresentam uma elevada capacidade de sofrer absorção quando administrados pela via oral.
Uma composição farmacêutica pode ser fabricada misturando uma quantidade eficaz de um composto da invenção presente com diversos aditivos farmacêuticos adequados para a forma de administração, tais como excipientes, aglomerantes, agentes humidificantes, desintegrantes, lubrificantes e diluentes. Quando se tratar da composição para uma injecção, pode esterilizar-se um ingrediente activo em conjunto com um veiculo adequado para se obter a composição farmacêutica.
Incluem-se nos exemplos dos excipientes a lactose, a sacarose, a glucose, o amido, o carbonato de cálcio e a celulose cristalina. Incluem-se nos exemplos dos aglomerantes a metilcelulose, a carboximetilcelulose, a hidroxipropilcelulose, a gelatina e a polivinilpirrolidona. Incluem-se nos exemplos de agentes desintegrantes a carboximetilcelulose, a carboximetilcelulose sódica, o amido, o alginato de sódio, o agar e o laurilsulf ato de sódio. Incluem-se nos exemplos dos lubrificantes o talco, o estearato de magnésio e o macrogol. Podem utilizar-se a titulo de materiais de base para os supositórios a manteiga de cacau, o macrogol, a metilcelulose, etc.. Quando a composição for fabricada sob a forma de soluções, injecções emulsionadas ou injecções de suspensões, podem adicionar-se 16 aceleradores da dissolução, agentes de suspensão, emulsionantes, estabilizadores, conservantes, agentes isotónicos e outros semelhantes. Para administração por via oral, podem adicionar-se agentes edulcorantes, sabores e outros semelhantes.
Embora a dosagem de um composto da invenção presente a titulo de agente contra a obesidade ou de agente anoréxico deva ser determinada levando em consideração a idade e o peso do paciente, o tipo e o grau das suas doenças, a via de administração, etc., uma dosagem habitual por via oral para um adulto é de entre 0,05 e 100 mg/kg/dia, e é preferível uma dosagem de entre 0,1 e 10 mg/kg/dia. Para administração parentérica, embora a dosagem varie pronunciadamente com as vias de administração, uma dosagem habitual é de entre 0,005 e 10 mg/kg/dia, preferivelmente de entre 0,01 e 1 mg/kg/dia. Pode administrar-se a dosagem de uma vez, ou em diversas parte ao longo do dia. A invenção presente é explicada em mais pormenor pelos Exemplos e Experiências seguintes, que não se pretende seja limitativos do âmbito da invenção presente.
Exemplos de Referência (não incluídos na invenção presente excepto o Composto Ia-178)
Exemplo 1 Síntese do Composto (1-7) 17
Passo 1 17
O OEt
NagCOe
COjH co2h
Dissolveu-se carbonato de sódio (995 mg, 9,38 mmol) em 30 mL de água e adicionaram-se à solução o aminoácido utilizado como matéria-prima (1,0 g, 8,53 mmol) e N-carbetoxiftalimida (2,49 g, 11,4 mmol). Agitou-se a mistura à temperatura ambiente de um dia para o outro. Ajustou-se o pH da mistura a 1 adicionando-lhe ácido clorídrico concentrado. Lavaram-se com água os cristais precipitados e secaram-se para se obter o composto pretendido (1,72 g, rendimento de 82 %) . RMN de ΧΗ (CD3OD) δ ppm: 1,59-1,77 (m, 4H) , 2,34 (t, 2H, J = 6,3 Hz), 3,69 (t, 2H, J = 6,6 Hz), 7,78-7,87 (m, 4H).
Passo 2
Dissolveu-se o composto obtido no Passo 1 (1,0 g, 4,0 mmol) em 5 mL de diclorometano, a temperatura ambiente. 18
Adicionaram-se à mistura cloreto de oxalilo (0,459 mL, 5,2 mmol) e uma quantidade vestigial de DMF, arrefecendo sobre gelo, e deixou-se reagir arrefecendo sobre gelo e à temperatura ambiente, 30 minutos para cada uma destas condições. Depois de se remover o solvente sob pressão reduzida, adicionou-se 5 mL de diclorometano. Arrefecendo sobre gelo, adicionaram-se á mistura 4-butilanilina (664 mg, 4,4 mmol) e trietilamina (0,564 mL, 4,4 mmol), e deixou-se a mistura reagir durante 30 minutos à temperatura ambiente. Verteu-se a mistura reaccional sobre água e extraiu-se com clorofórmio. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de sílica para se obter o composto pretendido (1,49 g, rendimento de 97 %). RMN de (CDCls) δ ppm: 0, 91 (t, 3H, J = 7,5 Hz) , 1, 27-1, 39 (m , 2H), 1, 51-1,62 (m, 2H) , 1,72 -1, 84 (m, 4H) , 2, 40-2, 46 (m, 2H) , 2,5 6 (t, 2H , J = 7,5 Hz) , 3,76 (t, 1H, J = = 5,7 Hz) , 7,12 (d, 2H, J = 7,8 Hz) , 7,33 (s, 1H) , 7,42 (d , 2H, J = 8 , 1 Hz), Ί, r 71-7,73 (m, 2H) , 7,83- 7,86 (m,
Passo 3
248.36 19
Depois de se dissolver o composto obtido no Passo 2 (1,49 g, 3,9 mmol) em 30 mL de etanol, adicionou-se-lhe monohidrato de hidrazina (0,591 mg, 11,8 mmol) e deixou-se reagir a 50°C durante 3 horas. Removeu-se o solvente, adicionou-se uma solução aquosa de NaOH a 1 mol/L e extraiu-se a solução com acetato de etilo. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o residuo por cromatografia sobre gel de silica para se obter o composto pretendido (808 mg, rendimento de 83 %). RMN de λΗ (CD3OD) δ ; ppm: 0,93 (t, 3H, J = 7,2 Hz) , 1,28 -1,4 0 (m, 2H), 1, 50-1 , 62 (m, 4H) , 1,67-1, 77 (m, 2H) , 2,37 (t, 2H, J = 7,5 Hz) , 2,56 (t, 2H, J = 7, 8 Hz) , 2, 68 (t, 2H, J = 7, 2 Hz) , 7,11 (d, 2H, J = 8,1 Hz) r 7,42 (d, 2H, J = 8,4 Hz) .
Suspendeu-se 0 composto obtido no Passo 3 (808 mg, 3,25 mmol) em 5 mL de diclorometano arrefecendo a mistura sobre gelo, e adicionaram-se-lhe cloreto de isopropilsulfonilo (696 mg, 4,9 mmol) e trietilamina (494 mg, 4,9 mmol). Depois de se deixar a mistura reagir arrefecendo-a sobre gelo durante uma hora, verteu-se a mistura reaccional sobre água e extraiu-se com clorofórmio. 20
Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de sílica para se obter o composto pretendido quantitativamente. RMN de XH (CDC13) δ ppm: 0,91 (t, 3H, J = 7,2
Hz), 1,27-1,40 (m, 2H) , 1,36 (d, 6H, J = 6,6 Hz), 1,51-1,69 (m, 4H) , 1,77-1, 86 (m, 2H) , 2,38 (t, 2H, J = 7,2 Hz), 2,56 (t, 2H, J = 7,5 Hz), 3,12-3,21 (m, 3H) , 4,38 (t, 1H, J = 5,7 Hz), 7,11 (d, 2H, J = 8,4 Hz), 7,36-7,41 (m, 3H).
Exemplo 2 Síntese do Composto (1-10)
C15H24N0O Mol.Wt.: 248.36
o II >fsa
\ HN-K
Cl gHggNpOjS Moí. WtT: 852.54
Sintetizou-se o composto pretendido de uma forma semelhante à do Passo 4 do Exemplo 1, excepto que se adicionaram cloreto de terc-butilsulfinilo (689 mg, 4,9 mmol) e trietilamina (494 mg, 4,9 mmol) ao composto obtido no Passo 3 do Exemplo 1. RMN de XH (CDC13) δ ppm: 0,91 (t, 3H, J = 7,5 Hz), 1,22 (s, 9H) , 1,30-1,37 (m, 2H) , 1,51-1,68 (m, 4H) , 1,76-1,86 (m, 2H) , 2,31-2,40 (m, 2H) , 2,56 (t, 2H, J = 7,5 Hz), 21
3,15-3,26 (m, 3H), 7,11 (t, 2H, J = 8,7 Hz), 7,42 (d, 2H, J 8,1 Hz) , 7,54 (s, 1H) .
Exemplo 3 Síntese do Composto (1-11)
mCPBA Moí. WtT: 352.54 CjoHojNoOoS
^19^32^2^30 Mol. Wt.: 368.54 CigHaaNaOgS
Dissolveu-se o composto obtido no Exemplo 2 (352 mg, 1,0 mmol) em 5 mL de diclorometano arrefecendo sobre gelo e adicionou-se mCPBA (259 mg, 1,5 mmol) à solução. Deixou-se a solução reagir à temperatura ambiente durante uma hora e separou-se o material insolúvel por filtração. Lavou-se o filtrado sucessivamente com uma solução de naOH a 1 mol/L, com solução de Na2S20s e com água, e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de sílica para se obter o composto pretendido (338 mg, rendimento de 92 %) . RMN de H (CDC13) δ ppm: 0,91 (t, 3H, J = 7,5
Hz), 1,29-1,39 (m, 2H) , 1,39 (s, 9H) , 1,51-1,68 (m, 4H) , 1,76-1,84 (m, 2H) , 2,37 (t, 2H, J = 7,5 Hz), 2,56 (t, 2H, J = 7,8 Hz), 3,19-3,26 (m, 2H) , 4,20 (t, 1H, J = 5,7 Hz), 7,11 (t, 2H, J = 8,1 Hz), 7,42 (d, 2H, J = 8,7 Hz), 7,46 (s, 1H).
Exemplo 4. Síntese do Composto (1-72) 22
Passo 1
HaN
COzH SOCI2 MeOH1
HjN HCI
COzMe C7H13N02 Mol. Wt.: 143.18 0βΗ16αΝ02 Mol. Wt.: 193.67
Dissolveu-se o aminoácido utilizado como matéria-prima (uma mistura dos isómeros cis e trans) (1,0 g, 8,53 mmol) em 7,5 mL de metanol. Adicionou-se à mistura cloreto de tionilo (1,0 mL, 13,7 mmol) arrefecendo sobre gelo e agitou-se a mistura à temperatura ambiente de um dia para o outro. Em seguida concentrou-se a mistura sob pressão reduzida, adicionou-se-lhe éter dietilico e separaram-se por filtração os cristais que haviam precipitado. Lavaram-se os cristais com éter dietilico e secaram-se para se obter o composto pretendido (1,25 g, rendimento de 93 %). RMN de XH (CDC13) δ ppm: 1,50-2, 60 (m, 9H) , 3,08-3,36 (m, 1H), 3,67 (s, 3H, C02Me do isómero cis), 3,71 (s, 3H, C02Me do isómero trans), 8,15-8,55 (m, 3H).
Passo 2
HQ kA COgMe
mCP8A b3n COjMe c8h16cino2 Mol. Wt.: 193.67 C, 2^23 NOaS Mol. Wt.: 277.38 23
Sintetizou-se a sulfonamida pretendida (uma mistura do seu isómero cis com o seu isómero trans) a partir do éster metilico utilizado como matéria-prima de modos semelhantes aos utilizados no Passo 3 do Exemplo 1 e do Exemplo 2. isómero cis: RMN de (CDCI3) δ ppm: 1,39 (s, 9H) , 1,52-1, 99 (m, 8H) , 2,43-2,53 (m, 1H) , 3, 42-3, 55 (m, 1H), 3,69 (s, 3H) , 3,85 (d, 1H, J = 9,0 Hz).
Passo 3 >yi 00
NaOMe ν'ΓΓα/ο MeOH COjMe C12H23NO4S Mol. WÍ.: 277.38 COjMe
C12H23NO4S 277.38
Dissolveu-se a sulfonamida utilizada como matéria-prima (19,4 g, 70,0 mmol, uma mistura do isómero cis com o isómero trans) em 30 mL de metanol. Adicionou-se à mistura metóxido de sódio a 28 % (284 mL, 140,0 mmol) e aqueceu-se ao refluxo sob agitação arrefecendo sobre gelo?. Depois de se remover o solvente, diluiu-se o resíduo com clorofórmio, e adicionou-se-lhe HC1 a 1 mol/L sob arrefecimento até o pH da fase aquosa atingir 3. Extraiu-se a fase aquosa com clorofórmio, lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Recristalizaram-se os cristais obtidos em bruto a partir de 24 hexano-acetato de etilo para se obter a sulfonamida pretendida (isómero trans, 7,75 g, rendimento de 40 %). isómero trans RMN de ΧΗ (CD3OD) δ ppm: 1,16-1,32 (m, 2H) , 1,39 (s, 9H) , 1,44-1,52 (m, 2H) , 1, 98-2 ,09 (m 2H) , 2,14 -2,29 (m, 3H) , 3,18-3,37 (m, 1H), 3,63 (d, 1H, J : 9,0 Hz) , 3, 67 (s, 3H) .
Passo 4 C02Me
NaOH aquoso H . * - S MeOH OÒ oo
Ci o do3 N04S Mol. Wt.: 277.3Θ co2h CnH^NC^S Mol. Wt.: 263.35
Dissolveu-se o éster metilico utilizado como matéria-prima (4,77 g, 17,2 mmol) em 95 mL de metanol e adicionou-se NaOH a 1 mol/L (43 mL, 43,0 mmol) sob agitação e arrefecendo sobre gelo. Agitou-se a mistura à temperatura ambiente de um dia para o outro e concentrou-se sob pressão reduzida. Em seguida adicionou-se HC1 a 1 mol/L sob agitação até o pH da mistura atingir o valor de 3, sempre sobre arrefecimento com gelo, recolheram-se os cristais precipitados por filtração, lavaram-se com água e secaram-se. Recristalizaram-se os cristais obtidos em bruto a partir de hexano-acetato de etilo para se obter o ácido carboxilico pretendido (4,20 g, rendimento de 93 %) . 25 25 RMN de ΧΗ (CDC13) δ ppm: 1 1 00 \—1 -1,35 (m, 2H) , 1,39 (s, 9H) , 1,46-1, 63 (m, 2H) , 2,01-2, 14 (m, 2H) , 2,14 -2,32 (m, 3H) , 3,18-3,35 (m, 1H) , 3,80 (d, 1H, J = 9, 6 Hz) .
Passo 5 1) (COa)2, DMF/ 2) HjNhQ-n^Jo B3N \ CH2az
'co2h
CuH,,N04S Mol. wf.: 263.3S
Dissolveu-se o ácido carboxilico utilizado como matéria-prima (5,86 g, 22,3 mmol) em 88 mL de diclorometano à temperatura ambiente. Adicionou-se à mistura cloreto de oxalilo (2,34 mL, 26,7 mmol) e uma quantidade catalitica de DMF enquanto se arrefecia sobre gelo e agitou-se à temperatura ambiente durante uma hora. Depois de se remover o solvente sob pressão reduzida, adicionaram-se diclorometano (115 mL) , anilina substituída (5,05 g, 24,5 mmol) e trietilamina (4,65 mL, 33,4 mmol). Agitou-se a mistura à temperatura ambiente durante 2,5 horas, verteu-se sobre ela a água gelada de arrefecimento, e extraiu-se a mistura com clorofórmio. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e adicionaram-se ao resíduo acetato de etilo e hexano. Separaram-se os cristais precipitados por filtração para se obter a amida pretendida (7,00 g, rendimento de 70 %). 26 RMN de (CDCI3) δ ppm: 1,25 (d, 6H, J = 6,3
Hz), 1,17-1,42 (m, 2H) , 1,40 (s , 9H), 1,60-1,78 (m, 2H) , 1,98-2,43 (m, 7H), 3,20-3,43 (m, 3H) , 3,67 (d, 1H, J = 9, 6 Hz), 3,74-3,86 (m, 2H) , 6,86 (d, 2H, J = 9, 0 Hz) , 7,04 (s, 1H), 7,38 (d, 2H, J = 9,0 Hz) .
Exemplo 5 Síntese do Composto (1-2)
Passo 1
C6H10CI2N2 C17H2oN20
Mol.Wt.: 181.06 Mol. Wt.: 268.35
Depois de se suspender a matéria-prima, uma diamina, (461 mg, 2,5 mmol) em diclorometano arrefecendo sobre gelo, adicionou-se-lhe um cloreto de acilo (500 mg, 2,5 mmol) e trietilamina (773 mg, 7,5 mmol) e deixou-se a mistura reagir durante 30 minutos. Adicionaram-se-lhe água e diclorometano e separaram-se materiais insolúveis por filtração. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida para se obter o composto pretendido como residuo (100 mg, rendimento de 15 %). RMN de XH (CDCI3) δ ppm: 0, 93 (t, 3H, J = 7,2 Hz), 1,30-1,42 (m, 2H) , 1,57-1, 67 (m, 2H) , 2,66 (t, 2H, J = 7,8 Hz), 3,50 (s lg, 1H) , 6,57 (s, 1H) , 6, 68 (d, 2H, J = 27 co Hz) , 7,26 (d, 2H, J = 8,4 Hz), 7,39 (d, 2H, Hz) , 7, 68 (s, 1H), 7,75 (d, 2H, J = 8,1 Hz) . J =
Passo 2
HjN
C17H20N5® Mol.Wt.: 268.35
EtgN
Sintetizou-se o composto pretendido de maneira semelhante à utilizada no Passo 4 do Exemplo 1. uma RMN de 1H-NMR (CDC13) δ ppm: 0,94 (t, 3H, J = Hz) , 1,34 \—1 1 (m, 2H), 1,40 (d, 6H, J = 6, 6 Hz) , 1 σι LO \—1 (m, 2H) , 2, 69 (t, 2H, J = 7, 8 Hz), 3 ,24- -3, 35 (m, 1H) , (s, 1H) , 7,23- 7,32 (m, 4H) , 7,6 (d, 2H, J = 8,7 Hz) , (d, 2H, J = 8,1 Hz), 7,85 (s, 1H) . 7,5 1, 68 6,49 7,79
Exemplo 6 Síntese do Composto (1-31)
Passo 1
BocNH <3 "NH2 CiiH22N202 Mol.Wf. :214.30 /—\ Boc20 h2n-<^--nh2 -—
CrH14N2 Mol.Wt.: 114.19
Dissolveu-se a diamina utilizada como matéria-prima (8,37 g, 73,3 mmol) em 30 mL de dioxano à temperatura 28 ambiente e adicionou-se-lhe uma solução de Boc20 (2 g, 9,2 mmol) em dioxano (30 mL). Fez-se reagir a mistura à temperatura ambiente durante 3 dias e removeu-se o solvente. Adicionou-se água ao residuo e extraiu-se a mistura com clorofórmio. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida para se obter o composto sob a forma de um residuo (1,8 g, rendimento de 92 % com base no Boc20). RMN de 1H-NMR (CDC13) δ ppm: 1,07-1,26 (m, 6H) , 1,44 (s, 9H), 1,84-2,00 (m, 4H), 2,58-2,67 (m, 1H), 3,37 (s lg, 1H), 4,43 (s lg, 1H).
Passo 2 -KD,"nh* C11H22N002 Mol. Wt : 274.30
BocNH·
BocNH, Ό. C22H34N2O3 Moirwf! 374.52
Sintetizou-se o composto pretendido de uma maneira semelhante à utilizada no Passo 1 do Exemplo 5. RMN de 1 H (CDCI3) δ ppm: 0,92 (t, 3H, J = 7, Hz) , 1, 26-1,42 (m, 6H) , 1,45 (s, 9H) , 1 ,54- -1,68 (m, 2H) 1, 99' -2, 12 (m, 4H) , 2,64 (t, 2H, J = 7, 8 Hz) , 3,43 (s ig 1H) , 3, 90-4,00 (m, 1H), 4,48 (d, 1H, J = 5,7 Hz) , 5,95 (d 29 1Η, J = 8,4 Hz), 7,21 (d, 2H, J = 8,4 Hz), 7,65 (d, 2H, J = 8,4 Hz).
Passo 3
C22H34N0O3
Moi: Wt 1374.52 Mo1· Wt.: 310.86
Dissolveu-se o composto de Boc utilizado como matéria-prima (2,08 g, 5,55 mmol) em 20 mL de acetato de etilo enquanto se arrefecia sobre gelo e adicionou-se 20 mL de HCl/AcOEt a 4 mol/L. Fez-se reagir a mistura à temperatura ambiente durante uma hora e removeu-se o solvente sob pressão reduzida para se obter o composto pretendido sob a forma de um residuo (1,7 g, rendimento de 98 %) . RMN de 1 H (CD3OD) δ ppm: 0,93 (t, 3H, J= 7,2 Hz), 1,29- 1,41 (m, 2H) r 1,50-1, 66 (m, 6H) , 2,02-2,18 (m, 4H) , 2, 66 (t, 2H, J = 7 ,8 Hz) , 3,13 (s lg, 1H) , 3, 82-3, 94 (m, 1H) , 7,26 (d, 2H, j =8,7 Hz), 7,72 (d, 2H, J = 8,4 Hz).
Passo 4 30
C17H27CIN20 Mol.Wt.: 310.86
H
C21H34N202S Mol. Wt: 378.57
Sintetizou-se o composto pretendido de uma maneira semelhante à do Passo 4 no Exemplo 1. RMN de LH (CDCI3) δ ppm : 0 , 92 (t, 3H, J = 7,5 Hz) , 1, 21 (s, 9H) r 1,28-1, 62 (m, 8H) , 2 , 07-2 ,14 (m, 4H) , 2, 64 (t , 2H, J = 7 ,8 Hz), 3, ,11 (d, 1H, J = = 5,1 Hz) , 3,20 (s ig, 1H) , 3,90- 4,04 (] m, 1H), 6, 06-6, 14 (m, 1H) , 7,21 (t, 2H, J = 8,1 Hz) , 7 , 67 (t , 2H, J = 8,4 H tz) .
Exemplo 7 Síntese do Composto (1-32)
H
C2i h34n2o2s Mol. Wt.: 378.57
mCPBA '00 C2i h34n2o3s
Mol. Wt:394.57
Sintetizou-se o composto pretendido a partir do composto obtido no Exemplo, de uma maneira semelhante à utilizada no Exemplo 3. RMN de ΧΗ (CDCI3) δ ppm: 0,92 (t, 3H, J = 7,2 Hz) , 1,27-1,65 (m, 8H) , 1,40 (s, 9H) , 2,10-2,23 (m, 4H) , 2,65 (t, 2H, J = 7, 5 Hz) , 3,23-3,35 (m, 1H), 3,49 (s, 1H), 3,88- 31 4,02 (m, 1H) , 5, 84-5, 92 (m, 1H) , 7,13 (t, 2H, J = 8,4 Hz), 7,65 (d, 2H, J = 8, 1 Hz) .
Exemplo 8 Síntese do Composto (1-5)
Passo 1 o2n
c5h3no4s Mol.Wt.: 173.15 1. (COCl)2. DMF-/CH2CI2
2. anilina
KJ
Sintetizou-se o composto pretendido de uma maneira semelhante à do Passo 2 do Exemplo 1. RMN de XH (CDC13) δ ppm: 0, 94 (t, 3H, J = 7,5 1,30-1,42 (m, 2H) , 1,50- -í- , 65 (m, 2H) , 2, 61 (t, 2H, J = z), 7,20 (d, 2H, J = 7, 2 Hz) , 7 ,48-7, , 51 (m, 3H) , 7,72 (s, 1H), 7,88-7,90 (m, 1H).
Passo 2
Sn
H2NiH
Moí. Wt.: 304.37 HH~\j C.sH^N.OS Mol.Wt.: 274.38
Adicionou-se a uma mistura do composto nitro utilizado como matéria-prima (593 mg, 1,95 mmol) com estanho (358 mg, 3,0 mmol), 30 mL de uma solução de HC1 6 32 mol/L e 6 mL de THF, e a reacção prosseguiu a 50°C durante 3 horas. Depois de arrefecer, removeu-se o solvente e neutralizou-se o resíduo com NaOH, extraindo-se com clorofórmio. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de sílica para se obter o composto pretendido (110 mg, rendimento de 21 %) . RMN de 1 H-NMR (CDC1 3) δ PPm : 0, 91 (t, 3H, J = 7,2 Hz) , . 1,26 -1,39 (m, 2H) , 1,49- 1,59 (m, 2H) , 2,50 (t, 2H, J = 7,8 Hz) , 4,37 (s, 1H) , 6, 65 (d, 2H, J = 8 ,4 Hz), 6, 97 (d, 2H, J = 8 , 4 Hz ), 7 ,14 (d ., 1H, J = 8,4 Hz) , 7,43 (d, 1H, J = 8,7 Hz).
Passo 3
ci5Hi8N2os C18H24N203S2
Mol. Wt.: 274.38 Mo1· 380.53
Sintetizou-se o composto pretendido de uma maneira semelhante à do Passo 4 do Exemplo 1. RMN de XH (CDC13) δ ppm: 0,92 (t, 3H, J = CM Hz) , 1,28-1,41 (m, 2H) , 1,46 (d, 6H, J = 6, 9 Hz) , 1,53- 1, 63 (m, 2H), 2,59 (t, 2H, J = 7, 8 Hz), 3,35-3,44 (m, 1H) , 7,15 33 (d, 2H, J = 8,7 Hz), 7,38 (s, 1H) , 7,45 (d, 2H, J = 8,7
Hz), 7,57 (s, 1H).
Exemplo 9 Síntese do Composto (1-4) Passo 1 Cl Vs' H H2n^o ó 0 |Q>-C02Me-* \ Nv--0 O ' /^οΪ/Λμ. C6H7N03 CgH-j 3NO5S Mol. Wt.: 141.12 Mol. Wt.: 247.27 Sintetizou-se 0 composto pretendido de uma maneira semelhante à do Passo 4 do Exemplo 1. RMN de XH (CDC13) δ ppm: 1,44 (d, 6H, J = 6, 9 Hz), 3,33-3,43 (m, 1H) , 3,88 (s, 9H) , 6, 24-6, 26 (m, 1H) , 7,11-7,14 (m, 2H).
Passo 2
NaOH
CgHi 3NO5SMol. Wt..· 247.27
CeH^NOgS Mol. Wt.: 233.24
Sintetizou-se o composto pretendido de uma maneira semelhante à utilizada no Passo 4 do Exemplo 4. 34 RMN de (CDC13) δ ppm: 1,44 (d, 6H, J =
Hz), 3,33-3,45 (m, 1H) , 6, 25-6, 28 (m, 1H) , 7,27-7,28 1H), 7,51 (s, 1H).
Passo 3 6, 3 (m,
CgHjiNOsS Mol. Wt.: 233.24 1. (COCI)2. OMF /CH2CIz 2. anilina
\ N^o ohoU-L-Q
Mol. wt.: 364.46
Sintetizou-se o composto pretendido de maneira semelhante à do Passo 2 no Exemplo 1. RMN de (CD3OD) δ ppm: 0,92 (t, 3H, J =
Hz) , 1,28 -1,41 (m, 2H), 1,46 (d, 6H, J = 6,3 Hz), 1,53- (m, 2H) , 2,58 (t, 2H, J = 7,8 Hz) , 3,33-3,43 (m, 1H), 6 6,29 (m, 1H) , 7,14-7,16 (m, 3H) , 7,50 (d, 2H , J = 8,4 7, 90 (s, 1H) .
Exemplo 10 Síntese do Composto (1-28)
Passo 1 uma 6, 9 1, 63 ,27-Hz) ,
HaN-^)"OH Η·αCaH14CINO ΜοΐΛΛ/t: 151.63
N-4 OEt
NaOMe
O
•OH O C14H15N03 Mol. Wt.: 245.27 35
Sintetizou-se o composto pretendido de uma maneira semelhante à utilizada no Passo 1 do Exemplo 1. RMN de ΧΗ (CDC1 3) δ ppm: 1,37-1,52 (m, 3H) , 1, 74- 1,79 (m, 2H) , 2,07-2,13 (m, 2H) , 2,28-2,42 (m, 2H) , 3, 72- 3, 81 (m, 1H) , 4,09-4,20 (m, 1H) , 7,68-7,73 (m, 2H) , 7, 81- 7,85 (m, 2H) .
Passo 2
Dissolveu-se isocianato de 4-butilfenilo (2,85 g, 16,3 mmol) em 30 mL de THF, e adicionou-se o álcool utilizado como matéria-prima (1,0 g, 4,08 mmol) e óxido de bis (tributilestanho) (972 mg, 1,63 mmol). Em seguida agitou-se a mistura de um dia para o outro, removeu-se o solvente, adicionou-se água e extraiu-se a mistura com clorofórmio. Lavou-se a fase orgânica com água e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de sílica para se obter o composto pretendido (332 mg, rendimento de 19 %) . RMN de ΧΗ (CDCI3) δ ppm: 0,92 (t, 3H, J = 6,9
Hz), 1,30-1,40 (m, 2H) , 1,48-1, 62 (m, 4H) , 1,79-1, 83 (m 36 2H) , 2,21- -2,25 (m, 2H), 2,37-2,50 (m, 2H) , 2,57 (t, 2H, J 7,8 Hz) , 4,11-4,22 (m, 1H), 4,77-4, 87 (m, 1H) , 6, 49 (s 1H) , 7,11 (d, 2H, J = 8,7 Hz), 7,28 (d, 2H, J = 8,7 Hz) 7, 69 -7,73 (m, 2H), 7,80-7,84 (m, 2H).
Passo 3 ο
ό-4 ο
HjNN^-HaO
HN“VJ
HjN -0-0^° N-/ HN—3 ^25^28^2^4 Mol. Wt.: 420.50 ^17*^26^2^2 Mol. Wt.: 290.40 -4 .ci
EtaN
-oO
,0 o-^ /=> HN-W C21H34N203S Mol. Wt.: 394.57
Sintetizou-se o composto pretendido de maneira semelhante às utilizadas no Passo 3 do Exemplo 1 e no Exemplo 2. RMN de 1 H (CDCI3) δ ppm: 0 , 91 (t, 3H, J = 7,2 Hz) , 1,21 (s, 9H) , 1,30-1,62 (m, 8H), 2,08 (d , 4H, J = 11, 1 Hz) , 2,56 (t, 2H, J = 7,8 Hz) , 3,04 (d, 1H, J = 4, 8 Hz) , 3,20 -3,30 (m, 1H) , 4, 65-4,76 (m, 1H) , 6, 57 (s, 1H) , 7,10 (d, 2H, J = 8, 7 Hz) , 7,26 (d, 2H, J = 8,1 Hz) .
Exemplo 11 Síntese do Composto (1-29) 37 37
mCPBA
HN C21H34N0O4S Moí. VW. :410.57
Sintetizou-se o composto pretendido de uma maneira semelhante à utilizada no Exemplo 3. RMN de XH (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7,2 Hz) , 1,23- -1, 62 (m, 8H), 1,40 (s, 9H), 2,12 (d, 4H, J = 14,4 Hz) , 2,56 (t, 2H, J = 7,8 Hz ), 3,28-3,40 (m, 1H), 3, 90 (s, 1H) , 4, 60· -4,73 (m, 1H) , 6,57 (s, 1H), 7,10 (d, 2H, J = 8,4 Hz) , 7,25 (d, 2H, J = 8,4 Hz)
Exemplo 12 Síntese do Composto (1-114) Η H1 o'o 0 Η H Y^S."N N Y^iÒÒ s
Adicionou-se reagente de Lawesson, 2,4-dissulfureto de [2,4-bis (4-metoxifenil) 3-ditia-2,4-difosfetano] (132 mg) a uma solução de 100 mg do Composto (I — 110) sintetizado de uma maneira equivalente à utilizada no Exemplo 1, em tolueno (2,7 ml) e agitou-se a mistura a 80°C durante 3 horas. Concentrou-se a mistura reaccional sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de silica (acetato de etilo:n-hexano a 1:1) para se obterem cristais amarelo claros (82,3 38 mg, 79 %) . Recristalizaram-se os cristais a partir de cloreto de metileno-éter di-isopropilico para se obter o composto pretendido sob a forma de agulhas incolores (50,5 mg, 48 %).
Exemplo 13 Síntese do Composto (1-120)
Passo 1
Dissolveram-se 4-amino-l-piperidinacarboxilato de etilo (300 mg) e trietilamina (258 mg) em 5 mL de diclorometano. Adicionou-se à mistura 2 mL de uma solução de cloreto de t-butilsulfinilo (222 mg) em diclorometano, e agitou-se a mistura à temperatura ambiente durante 4 horas, tratou-se esta mistura com uma solução aquosa de hidrogenossulfato de potássio e com acetato de etilo. Lavou-se a fase orgânica com salmoura e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de silica para se obterem 378 mg de 4-t-butylsulfinilamino-1-etoxicarbonilpiperidina.
Passo 2 39Λ-Β II Ο
Ba(OH)2
PhO^N
Cu.
Suspendeu-se numa mistura de 5 mL de 2-propanol e 5 mL de água, 378 mg de 4-t-butylsulf inilamino-1-etoxicarbonilpiperidina e adicionou-se-lhe 1,77 g de hidróxido de bário. Aqueceu-se a mistura ao refluxo com agitação e aquecimento durante 4 horas.
Diluiu-se a mistura com metanol e separou-se por filtração o material insolúvel. Removeu-se o solvente sob pressão reduzida para se obter 4-t-butilsulfinilaminopiperidina. Sem purificação adicional dissolveu-se o material obtido em 5 mL de THF, e adicionou-se-lhe 984 mg de N-fenoxicarbonil-4-butil-anilina e 236 mg de di-isopropil-etilamina, agitando-se em seguida à temperatura ambiente de um dia para o outro. Adicionou-se à mistura uma solução aquosa de hidrogenossulfato de potássio e extraiu-se a mistura com acetato de etilo. Lavou-se a fase orgânica com salmoura e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o resíduo por cromatografia sobre gel de sílica para se obterem 291 mg de (4-t-butilfenil)amida do ácido 4-t-butilsulfinilaminopiperidina-l-carboxílico. RMN de XH (CDC13) δ ppm: 0,89(t, 3H, J = 7,3 Hz), 1,19 (s, 9H) , 1,25-1,38 (m, 4H) , l,40-l,60(m, 4H) , 1,89-2,03 (m, 3H) , 2,52(t, 2H, J = 7,7 Hz), 2,89-3, 04(m, 2H) , 40 3,14 (d, 1H, J = 5,2 Hz), 3,37(m, 1H) , 3,96(m, 2H) , 6, 67 (s, 1H) , 7,05 (d, 2H, J = 8,5 Hz), 7,22(d, 2H, J = 8,5 Hz).
Passo 3
II o
MMPP
Numa mistura de 2 mL de metanol com 2 mL de cloreto de metileno, dissolveu-se 291 mg de (4-t-butilfenil)amida do ácido 4-t-butilsulfinilaminopiperidina-1-carboxílico. Adicionou-se à mistura 570 mg de MMPP (hexahidrato de monoperoxiftalato de magnésio) a 80 %, e agitou-se a mistura à temperatura ambiente durante 2 horas. Diluiu-se a solução com água e extraiu-se com acetato de etilo. Lavou-se a fase orgânica com salmoura e secou-se sobre sulfato de magnésio anidro. Removeu-se o solvente sob pressão reduzida e purificou-se o residuo por cromatografia sobre gel de silica para se obterem 130 mg de (4-butilfenil)amida do ácido 4-t-butilsulfonilaminopiperidina-1-carboxilico (1-120).
Sintetizam-se outros Compostos (I) por métodos semelhantes. Ilustram-se adiante as estruturas e as propriedades fisicas deles. 41
42
42 1-23 9 - H u"s O_' 1-34 ^α, 1 1-24 QP 1-35 xJLO δ 1-25 / ^ co°'5nO— 1-36 >ς3ΧΤ 1-26 *\~~íNXX^ 1-37 XjLO 0¾ 1-27 >γ^·^ϊνΟ—- 1-38 1-28 VnO.-0?njCT^ 1-39 1-29 H ^%"0.·ΛΡ~~ 1-40 H H O VsAN-s. I H 1-30 N" <X> >Ά'ν*ΤΊ h óAoU-TMrt o κ,ο
I H 1-31 Vcc 1-32 ^O·»
H 1-41
43
1-55 . 44
45 1-91 1-103 1 H AffN^ív Me ^°5νΌ_ 1-92 1-104 8 ^Vcu. 1-93 ^"Cu 1-105 ^ΟγΜ^ 0 lA^v 1-94 I Μθ 0 o CX^ 1-106 1-95 do MJSrNr^t o vA>^ 1-107 r 1 Cl H a^°Ax. 1-96 Λ^/ί3 ãn*Vcl~ 1-108 1-97 <5o n»Aj.n_^s o 1-109 . Η H /;>ΧΝ'^γΝΓΐ do o IA^ 1-98 ^iOvU o —--- 1-110 Ύ3ε"—sMa~ 1-99 1-111 ^_Ag~N^--- do O 1-100 1-112 1 Η H fí^OMe do o 1-101 1 H Α«Νγ^ H S o lAv- 1-113 . Η H ci V-~lNtÍLa 1-102 1-114 1-115 do o 1-116 . H H do o lV1-0'-v-^ 1-117 dt) O 1^-oMe 1-118 1 H H ob 0 1-119 ---- 1-120 1 H ^usncl~ 1-121 %Ou 1-122 1-123 O 1-124 1 H H · do 1>_Λ.-Ν,γ^ϊ. 1-125 1 H ^0SNa!rSH 1-126 1 H do Ιν^'.,^-Ν^^γΟΟΡ2ΟΗ?2 o 1-127 1-128 1-129 1-130 1-131 1-132 1-133 1-134 1-135 1-136 1-137 1-138
47 47
1-139 1-140 1-141 η
^U'5nÇO &n°?h“oq H S rNA{ O V-QMe dbNC. i n >SN, USNT^l H o
1-142 db kArN« o N 1-154 ο I n τ ιλ-i >^<5ΝΥ^ h COzMe 1-143 (¾ Lj-.-j-N^VcOíMe 0 *-s
i H FÍTF ι-ΐ55 4&"o.àVn
OH S-N
I H 1-156 0¾ C1yn o b 1-145 AU-g"jQí 1-157 ^N0.gN^ 0
1-146 ^O^n^vSJ
o N^NH
1 H >ο·Νγ^Ί H 1-158 dbUfN Λ i n 1-147 0¾ O ^OMe ' I H >sN-n H M59 o° s' o 1-148 ο 1-149 ^LnO ó < I H _ — >C.N^ H Cl 1-150 (¾ ΤΟ'-,-Ν-^ε'^ι^
1-160. H 1-161 QS0 O-yN
Tu
1-162 ^"Oi O .O^OMe 48 48 X u r T ^^NMe2 1 H VNrNr°~^ 0 N^J Me 1-179 H ° N^J O Me 1-180 nJ°2 % 1-181 VOvíÍ^.
vj H 1-163 h
A OvN^OH O 1-164 ti ’
O J-165
vj H 1-166 ^V, H
°° ^VNrvOH o M67 4¾ H o M68 ^oví; o 1 ... >ua. ΙΊ73 4¾..^ O X^T^CQsMe 1-174
O £PC02H M75' M7B ^vW^v.
o H 1-177 ΪΠ ”
^'vNrv°-coaH 1-178 ^O!
M72 ÍXL -J £ 1-182 d^O n 49 1-183 ^OyJ-x? ο 1-184 ^OvnJíÍ? 0 1-185 η Ον ο 1-186 0 1-187 ^0.,5,0-0^ ο 1-188 , Η OMe >SNT0 Η {Ζγ°Μ* db LArNj*J^oMa Ο 1-189 ο 1-190 ο 1-191 1 Η ^0SN7—1 Η db 0J"yNO'^Q'°---- 1-192 ^fO&Cr°~ 0 Η Μ93 ^ο.,ίΐα“* 1-194 1-195 1-196 1-197 1-198 1-199 1-200 1-201 1-202 ο Η ^•SNr"> Η ο ΥΝγ3. Ο N^C02Me I Η db L9-vN^^OEt ΌΒ I " Η ο Ôb U'VNt ο 11 I Η Η do k>vN. Ν—ΟΗ ο I Η >1„-Μ etxa
CN Ν-Υ'Vo I Η >03^ Η Ο Ο Ο 50 1-203 1-204 1-205 1-206 1-207 ° ^ . ΗΗ 1-110 Λ>ί-γ.0Λ oAoWV^0 Η 1-211^o.svoNH< 0 ^ , Η I Η 1-212 Η ° o0fO-cF,^Ον5^ W08
1-215
51 1-216 1-217 1-218 1-219 1-220 1-221 1-222 1-223 1-224 1-225 Η Ο ΗCÃV,9
1-227 ^-s-nΛ>Η vj H 1-228 °b^H ό >UJ ο% •N-\ «s.
Λ·ν d-Ò^H Λ-ν <A>^\ h Ν'"»
’Ν'Ν V-NH
ο^λα >ij* 'Λ,·? o 0 Λ\; Ό 1-229 o'o" >^sN 1-230 db nJ h 1-231 H rN o o ò 1-232 >ij N0 Λ 'v-N.
Ν'"-·, J'233 V H ^0o\nH 1-234 1-235 >*53·ν 0¾ Λ- ^ !U α ‘{Tb 1-226
N 1-236 ^g-N db Ν·> ^irvOMí 'OMe oÃo\JJrcx 1-237 ^;Nw . H °°^N. •OEt ‘ν,Ν. Ό 52 1-238 1-239 1-240 1-241 1-242 1-243 1-244 1-245 1-246 1-247 1-248 Ό I Η >L.N ó% oAo
CO
I H >U-N Λ Ό
N^N CI^CI
Br
1-249 1-250 1-251 1-252 1-253 1-254 1-25 1-256 1-257 1-258 1-259
53 1-260 1-261 1-262 1-263 1-264 1-265 1-271 J H0¾
Ο ο 1-273 γΝ-Ο' ^ 1- 272 ι Η α 1-274 ~Ι Η Η:X~y o'b ίΛ Ν'Ν <5ν£γΜθ ί-275 V-Vb. Ο ο ΌΜβ u η >sN 1-276 όο^\ η ΟΗ 1-266 ^0¾ 1-267 >L.n 5¾ 1-268
>L.£d-V ηχ^ 1-277 ι Η >ί»Ν \ ι •CQjMe V Ο -COaH 1-278 1 Η >-ο·Ν (Λ) "Λ Η rt I Tis Η ι Η Xg-N (Λ'-Λ Η ίλ Ο
Vn^,ocf2chf2 N>o>,f 1-279 1-269 Λ·ν ο ο O-ΟΗ 1-280 I Η Χ-Ν (Λ)'"Λ Η 1-270 I Μθ Ò ΗÍCU. 1-281 ι Η >L.N CÃ-Λ Η SMq
54
1-287 db''^-VN o
1-299 %o-^N o ,OMe OWe 1-288
H 1-300
:JJLh C? db^~yN-- O 1-289
CH 1-301 . π „ 'jLç.N_ H 1-290 &^YNT0^ , Γ1 1-291 oo
O N 1-302 1-303 ο α OO^yH-^S 1 o p α 1-292 H oso^ - ‘· Ò 55 1-304 >L. Η SN cfoS H VN-s ÇF, 1-315 >Ln db 1-305 >L.N <Ã
i H (Λ'-λ h 1-316
>L 1-306 O h S-fOH SMe
1-317 H OH rVS M07 ^18
o H SN a:
OH 1-308 <?b^A H YN- 1-319
>Ln <&-Λ_ H
H
No'''-'*'- 1-309
S.P 1-320
i H >-sN 1-310
>U3 KlS H
NO' í-321 «â-V^V O 1-311 1-312 1-313 >Un*^-.κ
Me cft SS H o KX 1-322 0%S H 4 Me S H 1-323 >U5 >03 1-314 h λΝΪ^Γ°^ΟΜθ ^'325
1-324 , H V Η NH, íNtX- 56 56 1-326 1-327 1-38 1-329 1-330 1-331 1-332 1-333 1-334 1-335 1-336
ι Η do
1-337. 1-338 1-339 1-340 1-341 1-342 1-343 1-344 1-345 1-346 1-347
57 1-348 1-349 1-350 1-351 1-352 1-353 1-354 1-355 1-356 1 Η >ίς·Ν ίΓθ"Λ_ Η ΥΝ^γΟΕΙ 0 ^oet 1-357 1 Η >L.n 0'1^_ 1 Η >ο·Ν 1-358 d'V ι Η >^Ν Ι*·ΟΗ 1-359 I Π >*S.N 0¾ •CONH-<. , Η >Lsn ο'ο I Η >SsN Ο Ο >Ls-n oò t! ι"Ό 1-360 ο Η
CN 1-361 1-362
I Η Ν·ν
ι Η >1·3·ν Λ' 1-363 1-364 1-365
I Η>U ,-Λ.' ΗirNrVOCH3 0 tOCH3 och3 ο ο CF, Ο ο Η N-<V\ >-F Ο Ν-Ν 58 1-366 1-367 1-368 1-369 1-370 1-371 1-372 1-373 1-374 1-375 1-376
1-377 1-378 1-379 1-380 1-381 1-382 1-383 1-384 1-385 1-386 1-387
>s-N X' Ο Ο
F Λ3·ν ο%
59 , Η Η 1.388 λ*"—τΝ Η Η Α«-··Ά—.—„.Νγ^γΟγ.Ο Ν~Ί ^ΝγΝ Ν^1 1-399 dÃo''^Uy 1-389 Ar .. „ , ο ο Ο ΙΑΑΝ·^ ^Ν^ν-ΟΜθ 1-400 ΌΜΘ Η Η 1-390 Λ^ν^^,ν ΟΌ Ο Ον 0£t 1-401 Ο Α. Η Η 1-391 Λ^ν-jN-ς, Ό
Η Η 1-402 ^C-Ν^-γΝ^Ν cfo ο U 1-392 Ό . Η Η Ας·Νν^γΝ. 1-393 ο ο ο , Η Η 1-394 Asn~^-vn * ΟΟ ο 1-395 AgjN. ο* ο Ν αΜα Η Η 1-403 Ag--N^->.— 1-404 ~Ίί 0ΝΗ2 Μ* 1.406 ο° Ο ^ 4"Q ° Λ" Η Η 1-396 ι Η As-N. Το . Η -ν_Ν 1-407 Ά"-ΪΝ0 2Η-α
Br Ό"·νη2 1-397 Η Η ΑΝ—«“οφ . Η Η 1-408 ο ο ò L-* Η Η 1-398 Acr-N^-vN 0¾ Ο ι Η As-n. 1-409 ο 60 1-410 H |Ί Ν“ 1-421 ι Η As-n^>. /,s' 0 ο ^ XX^COjH 1-411 cv^ 1-422 , Η Η ο'° ο νη2 1-412 Η Η V^Ttx- 1QS 1-423 1 Η Λ5-ν^ oð Η Η -----~ , Me Η 1-413 Λτ d'ο 1-424 Õ Ο 1-414 Η . Η Me Μ25 _ Η Η 1-415
OTBS
^jOTBS Η Η ^OMe 1-426 1-416 ι Η ΛτΝ~ d'o ΗνΝ Ο J Η .η η α 1-427 σ 1-417 Ν=Ν I Η Η 1-428 ^Ν~^ΥΝ 1-418 . Η Η γΝ Me Ο Ο Ο S-* Μ29 1-419 , Η Η 1-430 yleNv^S^j-Νγ^ όο ο 'U^q'- 1-420 I Η As-N. d ο Η Η ^O-N^-^yN. 1-431 οο ο OMe COzMe 61 1-432 1-433 1-434 1-435 1-436 1-437 1-438 1-439 1-440 1-441 1-442
jsN 'i&N'~1SN0^YoJ^ M54
H O- 1-443
&'OSN0aO 1-455
O N-NH 62 1-456 OMe OMe I H H rO j-457do o , Η H 1-467 1-468 I H 1-458 H Vn^N O k Μ59 , Η H Cl 1-460 1-469 1-470
I H Λ
H
H *N-~-~SNOc Η H N^^O-JDMe M71 1-461 X n db ÇF3 H -N, 1-472 .- H J-eN- Cft> 1-462 OH SMe 1-473 I H^N·
H OH
O 1-463db c r ,ΠΛ , Η H 1-474 ,λdb Ô U,
Nr^yOH , Η Η o , 1-464 .1-475
, H H 1-465 db^o X , H Hf-j—5nOTn 1-466 1-476 1-477 I H4N- Xn.. db i Hdb 0 NO’ v_-N^N O N '
Me 63 1-478 1-479 1-480 1-481 1-482 1-483 1-484 1-485 1-486 1-487 1-488 Η Η
.. τί Ο N
Me , Η H N024Ν-~Ί5Νΐ\- I H 4n' Η NH, ' *· ^N^^N^pC02Me I H ΛςΝ I H -ASNL Cfò
H
1 •NH 0^C02Me Η H cíb c
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Ic-176 104 Ic-177 Ic-178 Ic-179 Ic-180 Ic-181 Ic-182 Ic-183 Ic-184 Ic-185 Ic-186 Ic-187
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105 Ic-199 Ic-200 Ic-201 Ic-202 Ic-203 Ic-204 Ic-205 Ic-206 Ic-207 Ic-208 Ic-209 Ic-210 Ic-211
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nXXn-€Yf3 RMN de 1H-NMR (CDC13) δ ppm: 0,94 (t, 3H, J = 7,5
Hz), 1,34-1,44 (m, 2H) , 1,40 (d, 6H, J = 6,6 Hz), 1,59-1,68 (m, 2H) , 2,69 (t, 2H, J = 7,8 Hz), 3,24-3,35 (m, 1H) , 6,49 156 (s, 1H) , 7,23-7,32 (m, 4H) , 7,6 (d, 2H, J = 8,7 Hz), 7,79 (d, 2H, J = 8,1 Hz), 7,85 (s, 1H) . 1-3 RMN de XH (CDC13) δ ppm: 0,92 (t, 3H, J = 7,2 Hz), 1,30- -1,39 (m, 2H) , 1, 37 (d, 6H, J = 6 , 9 Hz) , 1,57 (quinteto, 2H, J = 7,5 Hz) , 1,96 (quinteto, 2H, J = 6,6 Hz), 2,49 (t, 2H, J = 6,6 Hz) , 2,57 (t, 2H, J = 7,8 Hz) , 3,16-3,26 (m, 3H) , 4,62 (s lg, 1H), 7,12 (d, 2H , J = 8,1
Hz), 7,43 (d, 2H, J = 8,4 Hz), 7,64 (s, 1H). 1-4 RMN de XH (CD3OD) δ ppm: 0,92 (t, 3H, J = 6, 9
Hz), 1,28-1,41 (m, 2H) , 1,46 (d, 6H, J = 6,3 Hz), 1,53-1,63 (m, 2H), 2,58 (t, 2H, J = 7,8 Hz), 3,33-3,43 (m, 1H) , 6,27-6,29 (m, 1H) , 7,14-7,16 (m, 3H) , 7,50 (d, 2H, J = 8,4 Hz), 7, 90 (s, 1H) . 1-5 RMN de ΧΗ (CDCls) δ ppm: 0,92 (t, 3H, J = 7,2 Hz) , , 1,28-1,41 (m , 2H) , 1,46 (d, 6H, J = 6,9 Hz) , 1,53- -1, 63 (m, 2H), 2,59 (t, 2H, J = 7, 8 Hz), 3 ,35-3,44 (m, 1H) , 7,15 (d, 2H, J = 8 ,7 Hz) , 7,38 (s, 1H), 7,45 (d , 2H, . J = : 8,7
Hz), 7,57 (s, 1H). 1-6 157 RMN de1H (CDCls) δ ppm: 0, 91 (t, 3H, J = 7,5 Hz) , 1,29 -1,39 (m, 2H) , 1 ,37 (d, 6H, J = 6, 9 Hz) , 1, 55 (quinteto , 2H, J = 7,5 Hz) , 2,55 (t, 2H, J = 5 ,1 Hz) , 3 ,18- 3,27 (m, 1H) , 3, 92 (d, 2H, J = 6, 0 Hz) , 5,51 (t, 1H, J = 5,7 Hz) , 7,10 (d, 2H, J = 8,4 Hz) , 7,39 (d, 2H, J = 8 ,4 Hz) , 8,23 (s, 1H) . 1-7 RMN de ^ H (CDC13) δ ppm: 0, 91 (t, 3H , J = 7 ,2 Hz) , 1,28 -1,38 (m, 2H) , 1,37 (d, 6H, J = 6 ,9 Hz) , 1,51- 1, 67 (m, 4H) , 1,78- 1,88 (m, 2H) , 2,39 (t, r 2H, J = 7,2 Hz) , 2, 57 (t, 2H, J = 7,5 Hz), 3,12-3,22 (m, 3H), 4,30-4,37 (m, 1H) , 7,12 (d, 2H, J = 8,4 Hz), 7,36-7,42 (m, 3H). 1-8 RMN de 1 R (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7 ,5 Hz) , 1, 21-1,47 (m, 4H) , 1,35 (d, 6H, J = 6,6 Hz), 1,51- -1, 63 (m, 4H) , 1,67- 1,77 (m, 2H) , 2,34 (t, 2H, J = 7 ,5 Hz) , 2, 55 (t, 2H, J = 7 ,8 Hz), 3,08-3 ,17 (m, 3H) , 4,71 (t, , 1H, J = 6, 0 Hz) , 7,09 (d, 2H, J = 8,1 Hz), 7,43 (d, 2H, J = = 8 ,4 Hz) , 7, 74 (s, 1H) . 1-9 RMN de XH (CDC13) δ ppm: 0,91 (t, 3H, J = 7,2
Hz), 1,29-1,39 (m, 2H) , 1,35 (d, 6H, J = 6,9 Hz), 1,50-1,60 158 158 (m, 2H) , 2, 54 (t, 2H, J = 7,8 Hz), 2, 64 (t, 2H, J = 5, 7 Hz) , 3,14 -3, r 23 (m, 1H) , 3, ,41-3,47 (m, 2H) , 5,29 (t, 1H, J = 6, 3 Hz) , 7, 10 (d, 2H, J = 8,4 Hz), 7,39 (d, 2H, J = 8, 4
Hz) , 7, 91 (s, 1H) . 1-10
RMN de XH (CDCI3) δ ppm: 0, ,91 (t, 3H, J Hz) , 1,22 (s, 9H) , 1,30-1,37 (m, 2H) , 1,51-1,68 (m, 1,76- -1,86 (m, 2H) , 2 ,31-2,40 (m, 2H) , 2,56 (t, 2H, J
Hz), 3,15-3,26 (m, 3H), 7,11 (t, 2H, J = 8,7 Hz), 7,42 (d, 2H, J = 8,1 Hz), 7,54 (s, 1H). 1-11
pf: 128-129°C ppm: 0,91 (t; 3H, J = 7,5 (s, 9H) , 00 ^0 \—1 1 \—1 LO \—1 (m, 4H) , J II ^1 ΟΊ Hz), 2,56 (t, 2H, J 4, 20 (t, 1—> C-i II 5,7 Hz) , (d, 2H, J = 8,7 Hz) , 7,46 RMN de XH (CDC13) δ Hz), 1,29-1,39 (m, 2H) , 1,39 1,76-1,84 (m, 2H), 2,37 (t, 2H, = 7,8 Hz), 3,19-3,26 (m, 2H) , 7,11 (d, 2H, J = 8,1 Hz), 7,42 (s, 1H). 1-12 RMN de XH (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7,5 Hz) , . 1,28-1,37 (m, 2H) , 1,47- -i. r68 (m, 6H) , 2,23 (t, 2H, J = 7,2 Hz), 2,56 (t, 2H, J = 7, 5 Hz) , 2 ,90-2, , 97 (m, 2H) , 5, 10 159 (s lg, 1H) , 7,11 (d, 2H, J = 8,4 Hz), 7,36 (d, 2H, J = 8,1
Hz), 7,50-7, 68 (m, 3H) , 7,93 (d, 1H, J = 8,1 Hz), 8,06 (d, 1H, J = 8,4 Hz), 8,24 (d, 1H, J = 7,5 Hz), 8,66 (d, 1H, J = 8,7 Hz). 1-13 RMN de XH (CDC13) δ ppm: 0, 91 (t, . 3H, J = 7,5 Hz) , • 1, 28 -1,40 (m , 2H) , 1,45-1 ,73 (m, 6H) , 2, 23 (t ., 2H, J = 7,5 Hz) r 2,56 (t, 2H, J = 7, 8 Hz) , 2 ,88 (s, 6H) , 2,88- -2, 95 (m, 2H) r 5, 04 (s ig, 1H) , 7,10 (d, 2H, J = 8,1 Hz) , 7, 17 (d, 1H, J = 7 ,2 Hz) , 7,37 (d, , 2H, J = 8, 4 Hz) , 7,48- -7,54 (m, 2H) r 8,23 (d , 1H, J = 7, 2 Hz) , 8,30 (d , 1H, J = : 8,7 Hz) , • 8, 53 (d, 1H, J = 8,4 Hz). 1-14 RMN de XH (CDCI3) δ ppm: 0,91 (t , 3H, J = = 7,2 Hz) , 1,30-1,43 (m, 6H), 1,36 (d, 6H, J = 6,6 Hz) , 1,51- -1, 62 (m, 4H) , 1,67- 1,78 (m, 2H), 2,34 (t, 2H, J = = 7,5 Hz) , 2,56 (t, 2H, J = 7 ,8 Hz), 3,09-3,20 (m, 3H), 4, 34 (s ig, 1H) , 7,10 (d, 2H, J =8,4 Hz), 7,41-7, 44 (m, 3H) . 1-15 RMN de XH (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7,5 Hz) , 1,23 (s, 9H) , 1 , 27-1,80 (m, 12H), 2, 30-2,38 (m, 2H) , 2,56 (t, 2H, J = 7,5 Hz), 3,15 (s ig, 2H) , 7,11 (d, 2H, J = co Hz), 7,43 (d, 2H, J = 7, 8 Hz) , 7, 59 (s, , 1H) . 160 1-16 RMN de ΧΗ (CDC13) δ ppm: 0,91 (t, 3H, J = 7,5 Hz), 1,29-1,44 (m, 6H) , 1,39 (s, 9H) , 1,51-1,61 (m, 4H) , I, 68-1,78 (m, 2H) , 2,35 (t, 2H, J = 7,5 Hz), 2,56 (t, 2H, J, = 8,1 Hz), 3,15-3,21 (m, 2H) , 4,14-4,23 (m, 1H) , 7,11 (d, 2H, J = 7,8 Hz), 7,36-7,44 (m, 3H). 1-19
RMN de XH (CDCls) δ ppm: 0,92 (t, 3H, J = 7,5 Hz) , 1,21 (s, 9H) , 1,30-1, 40 (m, 2H) , 1,55- -1,72 (m , 6H) , 2, 64 (t, 2H, J = 7, 8 Hz) , 3 , 08 -3,33 (m, 3H), 3,42 -3, 50 (m, 2H) , 6,39 (s, 1H), 7, ,22 (d, 2H, J = 8,4 Hz), 7, 69 (d, 2H, J = 8,1 Hz) . 1-20 RMN de 1R (CDC13) δ ppm: 0, 92 (t, 3H, J = 7,2 Hz) , 1,31-1,39 (m, 2H) , 1, 39 (s, 9H), 1, 55-1 ,72 (m, 6H) , 2, 64 (t, 2H, J = 7, 8 Hz), 3 ,24 (quarteto, 2H, J = 6, 6 Hz) , 3, 48 (quarteto, , 2H, J = 6,6 Hz) , 4,21 (t, 1H, J = 6, 3 Hz) , 6, 29 (s, 1H), 7,22 (d, 2H, J = = 7,8 Hz) , 7, 67 (d, 2H, J = 8, 1 Hz) . 1-21 161 Hz) , 2,30 1H) , 2H, RMN de ΧΗ (CDC13) δ ppm: 0,91 (t, 3H, J = 7,2 1,23 (s, 9H) , 1,30-1,42 (m, 2H) , 1, 50-2 ,02 (m, 1 OH) , -2,42 (m, 1H) , 2,57 (t, 2H, J = 8,1 Hz) , 3,10 (s ig, 3,57 (s ig, 1H), 7,12 (d, 2H, J = 8,4 Hz), 7,41 (d, J = 7,8 Hz) . 1-22
pf: 7 8-7 9 °C RMN de XH (CDC13) δ ppm: 0,91 (t, 3H, J = 7,2
Hz) , 1,70 Hz) , (m, 1,30-1,40 (m, 2H) , 1,40 (s, 9H) , 1,50-1, 65 (m, 4H) , -1,98 (m, 8H) , 2,30-2,40 (m, 1H) , 2,57 (t, 2H, J = 7,5 3,58-3,70 (m, 1H) , 4,16 (d, 1H, J = 9,3 Hz), 7,11-7,15 3H), 7,40 (d, 2H, J = 8,1 Hz). 1-23
Hz) , 1,86 Hz) , 1H) , 2H, RMN de 1 H (CDC13) δ ppm: 0, 91 (t, 3H, J = 1- r 2 1 (s, 9H) , 1,21-1,41 (m, 4H) , 1,51- 1, 64 (m, 2, 01 (m, 4H) , 2,12-2,25 (m, 1H) , : 2,56 (t ·, 2H, J = 2, r 87- -2, 96 (m, 1H) , 3,00 -3, 12 (m, 1H) , 3,23- 3, 34 3, 67- -3,75 (m, 1H), 7,11 (d, 2H, J = 8,1 Hz) , 7,40 7,2 4H) , 7,5 (m, (d, J = 8,4 Hz). 1-24 RMN de XH (CDC13) δ ppm: 0,91 (t, 3H, J = 7,2
Hz), 1,25-1,37 (m, 2H) , 1,40 (s, 9H) , 1,48-1, 65 (m, 6H) 162 1, 90 (d, 2H, J = 11 ,7 Hz), 2,02 (d, 2H, J = 11, 7 Hz), 2, , 12- 2,24 (m, 1H) , 2,56 (t , 2H, J = 7,5 Hz) r 3, 04 (t, 2H, J = 6, 3 Hz) , 4,31 (t, 1H, J = 5,7 Hz) , 7, 11 (d, 2H, J = 8,1 Hz) , 7,42 (d, 2H, J = 8,4 Hz). 1-25
pf: 232-233 °C RMN de 1 H (CDC13) δ ppm : 0 , 91 (t, 3H, J = 7,5 Hz) , 1, 23- -1,40 (m, 4H), 1, 40 (s, 9H) , 1, 51- -1,76 (m , 4H) , 1 \—1 o CM 2, 26 (m, 5H) , 2,56 (t, 2H , J = 7 ,5 Hz) , 3,22 -3, 38 (m, 1H) , 3, 79 (d, 1H, J = 9, 3 Hz) , 7, 11 (d, 2H, J = 8, 7 Hz) , 7,17 (s , 1H), 7,40 (d, 2H, , J = 8,4 Hz) • 1-26 RMN de 1 H (CDCI3) δ ppm : 0 , 91 (t, 3H, J = 7,2 Hz) , 1, 22 (s, 9H) , 1,28-1, 40 (m, 2H) , 1, 52- -1, 62 (m , 2H) , 1 LO 00 \—1 1, 96 (m, 1H) , 2,00-2, 14 (m, 1H) , 2, 38- 2,53 (m , 2H) , 2,56 (t , 2H, J = 7, 5 Hz), 3 , 22- 3,37 ' (m 3H), 7, 11 (d, 2H, J = 8,4 Hz) , 7,45 (d, 2H, J = 8,4 : Hz) , 8 ,19 (s, 1H) . 1-27 RMN de XH (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7, Hz) , 1,30-1,40 (m, 2H) , 1,40 (s, 9H) , 1, 52-1,61 (m, 2H) LO σι \—1 (quinteto, 2H, J = 6,3 Hz) , 2,50 (t, 2H, J = 6, 9 Hz) 2,56 (t, 2H, J = 7,8 Hz), 3,31 (quarteto, 2H, J = 6,0 Hz) 163
4,30-4,36 (m, 1H), 7,12 (d, 2H, J = 8,4 Hz), 7,43 (d, 2H, J = 8,4 Hz), 7,65 (s, 1H) . 1-28 RMN de 1 H (CDC13) δ ppm: 0 , 91 (t, 3H, J = 7,2 Hz) , 1,21 (s, 9H) , 1,30-1,62 (m, 8H), 2,08 (d , 4H, J = 11, 1 Hz) , 2,56 (t, 2H, J = 7,8 Hz) , 3,04 (d, 1H, J = 4, 8 Hz) , 3,20 -3,30 (m, 1H) , 4, 65-4,76 (m, 1H) , 6, 57 (s, 1H) , 7,10 (d, 2H, J = 8, 7 Hz) , 7,26 (d, 2H, J = 8,1 Hz) . 1-29 RMN de ΧΗ (CDC13) δ ppm: 0,91 (t, 3H, J = 7,2 Hz), 1,23-1, 62 (m, 8H), 1,40 (s, 9H) , 2,12 (d, 4H, J = 14,4 Hz), 2,56 (t, 2H, J = 7,8 Hz), 3,28-3,40 (m, 1H) , 3,90 (s, 1H) , 4, 60-4,73 (m, 1H) , 6,57 (s, 1H) , 7,10 (d, 2H, J = 8,4 Hz), 7,25 (d, 2H, J = 8,4 Hz). 1-30 RMN de 1 H (CDCI3) δ ppm : 0 ,91 (t, 3H, J = 7,5 Hz) , 1, 26 -1,39 (m, 2H) , 1, 51- 1, 64 (m r 4H) , 1,72- 1, 81 (m, 2H) , 2, 34 (t, 2H, J = 6 , 9 Hz) , 2, 56 (t , 2H, J = 7, 8 Hz) , 2, 95- 3, 01 (m, 2H) , 4,84 (t, 1H , J = 5 ,7 Hz) , 6, 99- -7, 12 (m, 6H) , 7, 19. -7,24 (m, 1H) , 7, 30 (s, 1H) r 7,38- 7,43 (m r 4H) , 7,79 (d , 2H, J = 8, 7 Hz) 1-31 164 RMN de lH (CDCI3) δ ppm : 0 , 92 (t, 3H, J = 7,5 Hz) , 1, 21 (s, 9H) r 1,28-1, 62 (m, 8H) , 2 , 07-2 ,14 (m, 4H) , 2, 64 (t , 2H, J = 7 ,8 Hz), 3, ,11 (d, 1H, J = = 5,1 Hz) , 3,20 (s ig, 1H) , 3,90- 4,04 (m, 1H), 6, 06-6, 14 (m, 1H) , 7,21 (t, 2H, J = 8,1 Hz) , 7 , 67 (t , 2H, J = 8,4 Hz). 1-32 RMN de (CDC13) δ ppm: 0,92 (t, 3H, J = 7,2
Hz), 1,27-1, 65 (m, 8H) , 1,40 (s, 9H) , 2,10-2,23 (m, 4H) , 2,65 (t, 2H, J = 7,5 Hz), 3,23-3,35 (m, 1H), 3,49 (s, 1H), 3, 88-4,02 (m, 1H) , 5, 84-5, 92 (m, 1H) , 7,13 (t, 2H, J = 8,4
Hz) , 7, 65 (d, 2H, J = 8,1 Hz) . 1-33 RMN de XH (CDC13) δ ppm: 0,94 (t, 3H, J = 7,2
Hz), 1,30-1,42 (m, 2H) , 1,32 (s, 9H) , 1,57-1, 66 (m, 2H) , 2,67 (t, 2H, J = 7,8 Hz), 5,61 (s, 1H) , 6,93 (d, 2H, J = 8,7 Hz), 7,25 (d, 2H, J = 8,4 Hz), 7,49 (d, 2H, J = 9,0
Hz), 7,80 (d, 2H, J = 8,1 Hz), 8,22 (s, 1H). 1-34 RMN de XH (CD3OD) δ ppm: : 0, 95 (t, , 3H, J = 7, 5 Hz) , 1,35 (s, 9H) , 1,35-1,44 (m, 2H) , 1,57- -1, 69 (m, 2H) r 2, 69 (t, 2H, J = 7,5 Hz) , 7,28- -7,33 (m, 4H) , 7,56 (d, 2H, j = 9,0 Hz), 7,83 (d, 2H, J = 8,4 Hz). 165 1-36 RMN de ΧΗ (CDC13) δ ppm: 0,92 (t, 3H, J = 7,5
Hz), 1, 31-1, 70 (m, 11H), 1,39 (s , 9H) , 1,75-1,85 (m, 1H) , 2,65 (t , 2H, J = 8,1 Hz) , 3,13 (t, 2H, J = 6,6 Hz) , 3,40 (t, 2H, J = 7,2 Hz) , 4,10 (t, 1H, J = 5, 7 Hz) , 6,21 (t, . 1H, J = 5,7 Hz) , 7,23 (d, 2H, J = 8, 1 Hz) , 7 , 67 (d, 2H, J = = 8,4 Hz) . 1-37 RMN de XH (CDC13) δ ppm: 0,92 (t, 3H, J = 7,5
Hz), 0,95-1,10 (m, 2H) , 1,31-1,40 (m, 2H) , 1,39 (s, 9H) , 1,55-1, 63 (m, 4H) , 1, 80-1, 92 (m, 4H) , 2,65 (t, 2H, J = 7,8
Hz), 3,03 (t, 2H, J = 6,6 Hz), 3,31 (t, 2H, J = 6,6 Hz), 4,06 (t, 1H, J = 6,0 Hz), 6,22 (t, 1H, J = 6,0 Hz), 7,23 (d, 2H, J = 8,4 Hz), 7,67 (d, 2H, J = 8,1 Hz). 1-39 RMN de XH (CDC13) δ ppm: 1,13 (t, 3H, J = 7,2
Hz), 1,39 (s, 9H) , 1, 69-1, 97 (m, 8H) , 2,27-2,38 (m, 1H) , 3,29-3,35 (m, 4H) , 3, 60-3, 70 (m, 1H) , 4,52 (d, 1H, J = 9,3
Hz), 6,64 (d, 2H, J = 8,4 Hz), 7,22 (s, 1H), 7,31 (d, 2H, J = 9,0 Hz) . 1-40 166 RMN de (CDC13) δ ppm: 1,38 (s, 9H) , 1,68-1,96 (m, 8H), 2,30-2,40 (m, 1H), 3,11 (t, 4H, J = 4,8 Hz), 3,60- 3, 72 (m, 1H) , 3,86 (t, 4H, J = 4,8 Hz), 4,51 (s lg, 1H) , 6, 89 (d, 2H, J = 9,0 Hz) , 7,42 (d, 2H, J = 8,7 Hz). 1-41 pf: >27 8 °C (dec.) RMN de XH (CDCI3) δ ppm: 1,18- O \—1 (m, 2H) , 1 ,40 (s, 9H) , 1,62-1,75 (m, 2H) r 2,01-2,27 (m, 5H) , 3, 10 -3 ,13 (m, 4H) , 3,22-3,38 (m, 1H), 3, 72 (d, 1H, J = 9,3 Hz) , 3, 85- 3, 88 (m, 4H) , 6,87 (d, 2H, J = 9,0 Hz) , 7,10 (s, 1H) , 7 ,40 (d, 2H, J = 9,0 Hz) . 1-42 RMN de ΧΗ (CDCls) δ ppm: 1,40 (s, 9H) r 1 \—1 \—1 1, 97 (m, 8H) , 2,16 (s , 3H) , 2, 33-2, 43 (m, 1H) , 3, 60- -3,70 (m, 1H) , 4, 66 (s lg, 1H), 7 ,12 (d, 1H, J = 8,7 Hz) r 7,46- 7,50 (m, 1H) , 7,62 (s, H), 7, 75- 7,78 (m, 1H) , co 1 <1 91 (m, 2H) . 1-43 RMN de 1H (CDCI3) δ ppm: 1,40 (s, 9H), 1, 62- -2,00 (m, 8H) , 1, 87 (s, 3H) , 2,36-2, 47 (m, 1H) , 3,24 (s, 3H) , 3, 64 -3,74 (m, 1H) , 4,87 (s lg, 1H) , 7, 13 (d, 2H, J = = 9, 0 Hz) , 7, 64 (d, 2H, J = 8,4 Hz), 7 ,81 (s, H) . 167
1-44 pf: 235-236°C RMN de XH (CDC13) δ ppm: 1,13 (t , 6H, J = = 6, 9 Hz) , 1,18 :-1,33 1 (m, 2H) , 1,40 (s, 9H) , 1,60 -1,77 (m, 2H) , 2,00 -2,26 (m, 5H) , 3,28-3,35 (m, 4H), 3,73 (d, 1H, J = 9,3 Hz) , 6, 60 -6,70 (m, 2H) , 7,03 (s lg, 1H) , 7, 31 (d, 2H , J = 7,8 Hz) . 1-45 pf: >268 °C (dec.) RMN de XH (CDCls) δ ppm: 1,20-1,34 (m , 2H) , 1,40 (s, 9H) , 1,56- -1,76 (m, 8H) , 2,' 00-2,26 (m, 5H) , 3,06 -3, 14 (m, 4H) , 3,24- 3,36 (m, 1H), 3,72 : (d, 1H, J = = 9, 3 Hz) , 6, 90 (d, 2H, J = 8 ,7 Hz) , 7,09 (s, 1H) , 7,36 (d, 2H, J = = 8,7 Hz) . 1-46 pf: > 272 °C (dec.) RMN de ΧΗ (DMSO-d( 5) δ ppm: 1,28 (s, 9H) , 1,31- 1,59 (m, 7H) , 1,87- -2,00 (m, 4H) , 2,23-2,34 (m, 1H) , 3, 00- 3,16 (m, 1H) , 4,35- 4,45 (m, 2H) , 6,81 (d, 1H, J = 9,0 Hz) , 7,16 (t, 1H, J = 7, ,2 Hz), 7 ,43 (t, 1H, J = 8,4 Hz) , 7,52- 7,58 (m, 3H) , 8,04 (d, 1H, J = 7 ,8 Hz), 8,43 (s, 1H) . 168 1-47 RMN de XH (CDC13) δ ppm: 1 ,20- 1,36 (m, 2H) , 1,40 (s, 9H) , 1, 62 -1, 77 (m, 2H) , 1,98-2, 32 (m, 5H) , 3,31- 3,40 (m, 1H) , 3, 62 (d , 1H, J = 9, 0 Hz), 7,08 (s, 1H) , 7,29 (d, 2H, J = 9 ,0 Hz), 7,61 (d, 2H, J = 9, 0 Hz) \ . 1-48 RMN de XH (CDCI3) δ ppm: 1 , 22- 1,36 (m, 2H) , 1,40 (s, 9H) , 1, 62 -i, 77 (m, 2H) , 2,00-2, 31 (m, 5H) , 3,24- 3,40 (m, 1H) , 3, 62 (d , 1H, J = 1C 1,2 Hz), 7,01 (t, 2H , J = 8,7 Hz) , 7,09 (s, 1H) , 7,42-7,50 (m, 2H). 1-49 pf: 2 7 0 0 C (dec.) RMN de 1R (CDCI3) δ ppm: 1,20 -1,36 (m, 2H) , 1,40 (s, 9H) , 1, 61 -1,77 (m, 2H) , 1, 95- 2,30 (m, 9H) , 3, 17- -3,38 (m, 5H) , 3, 67 (d, 1H, J = 9,3 Hz) , 6, 50 (d, 2H , J = = 9, 0 Hz) , . 6, 97 (s, 1H) , 7,30 (d, 2H, J = 9, 0 Hz) .
1-50 pf: 252-253 C 169 RMN de (CDC13) δ ppm: 1,21-1,37 (m, 2H) , 1,40 (s, 9H) , 1, 62-1,78 (m, 2H) , 1, 98-2,32 (m, 5H) , 3,26-3,40 (m, 1H), 3 , 68 (d, 1H, J = 9,6 (t, 1—> C-i = 7,5 Hz) , 7,13 (s Hz) , . 7,46 (d, 2H, J = 9,0 Hz) .
Hz), 6, 94-7,02 (m, 4H) , 7,08 1H) , 7,31 (t, 2H, J = 7,5
1-51 pf: 278-279°C RMN de XH (CDCI3) δ ppm : 1, 02 (d; 6H, J = 6, Hz) , 1- , 35 (s, 9H) , 1,39-1, 71 (m, 6H) , 1, 90- 2,09 (m, 2H) 3,16- -3, 30 (m, 1H) , 3,46 (d, 1H , J : = 9, 0 Hz) , 4, 92- -5, 01 (m 1H) , 6, , 91- -6, 95 (m , 2H), 7, 00- 7,07 (m, 3H) , 7,13- 7, 16 (m 2H) , 7, 30- 7,36 (m, 2H) .
1-52 pf: 27 6-277 °C
RMN de XH (CDCI3) δ ppm: 1,20-1,36 (m, 2H) O \—1 (s, 9H) , 1, 60 -1,78 (m, 2H) , 1, 98-2,30 (m, 5H) , 2, 36 (s, 3H), 2,58 (t, 4H, J = 4,5 Hz), 3,17 (t, 4H, J = 4, 5 Hz) , 3,21-3,40 (m, 1H), 3 ,64 (d, 1H, J = 9,0 Hz) , 6, 88 (d, 2H, J = 9,0 Hz), 7,01 (s, 1H) , 7,37 (d, 2H, J = 9,0 Hz). 1-53
pf: > 300 °C 170 RMN de 1 H (DMSO- de) δ ppm: 1 .20 -1. 54 (m, 4H) , 1. .27 (s, 9H) , 1. 73 Ei 00 00 \—1 1 , 2H), 1. 89- 2. 01 (m , 2H) , 2.13- 2 . .25 (m, 1H) , 2 . 98 -3.12 (m, , 1H), 3. 15- 3. 31 (m , 8H) , 6.76- 6. . 84 (m, 2H) , 6. 93 (d, 2H, J = 9.0 Hz; ) , 6. 99 (d, 2H , J = 8 . . 1 Hz) , 7.24 (d, 2H, J = 8.1 Hz), 7 . 46 (d, 2H, J = 9.0
Hz) , 9.60 (s, 1H) . 1-54 pf: > 215°C (dec.) RMN de (DMSO-d6) δ ppm: 1.27 (s, 9H) , 1.27- 2.00 (m, 18H), 2.14-2.26 (m, 1H) , 2.53-2.84 (m, 4H), 2.86- 3.30 (m, 2H) , 3.46-3.54 (m, 1H) , 3.62-3.74 (m, 2H) , 6.78 (d, 1H, J = 8.7 Hz), 6.87 (d, 2H, J = 7.8 Hz) , 7 .42 (d, 2H, J = 8.7 Hz), 9.58 (s, 1H). 1-55 pf: > 2 90 °C (dec.) RMN de XH (CDC13) δ ppm: 1, 23-1, 40 (m, 2H) , 1,40 (s, 9H) , 1, 60 -1,76 (m, 2H) , 2,02 -2, 27 (m, 5H) , 3, 20 (t, . 4H, J = 5,4 Hz) , 3,21-3,32 (m, 1H) , 3, 67 (d, 1H, J = = 9,3 Hz) , 3, 98 (t, 4H, J = 4,8 Hz) , 6, 52 (t r 1H, J = 4,8 Hz) , 6, 93 (d, 2H, J = 8,4 Hz), 7,06 (s, 1H) r 7,41 (d, 2H J = : 8,7
Hz), 8,33 (d, 2H, J = 4,8 Hz). 171 1-56 pf: > 232 °C (dec.) RMN de (DMSO-de) δ ppir i: 1,27 (s, 9H), 1, . 27- 1,48 (m, 4H) , l,í 30-1 , 99 (m, 4H) , 2, 14· -2,25 (m, 1H), 3, . 04- 3,24 (m, 8H) , 3, 68 (s, 3H), 3, 76 (s, 3H) , 6, 44-6,47 (m, 1H) , 6,66 (s, 1H) , 6, 03 1 03 co (m, 2H) r 6, 92 (d, 2H, J = 8,4 Hz) , 7,46 (d, 2H, J = = 8,4 Hz) , 9 , 61 (s, 1H) . 1-57 pf: 284-285°C (dec.) RMN < de XH (CDCls) δ ppm: 1,27 (t, 3H, J = 7,2 Hz) , 1, 40 (s, 9H) , 1,61-2,24 (m, 9H) , 2,35- -2,49 (m, 1H) , 2,76 (t , 2H, J = 10,2 Hz), 3, 04 -3, 15 (m, 2H) , 3,20 -3, 36 (m, 1H) , 3, 55-3,59 (m, 2H) , 3,87 (d , 1H, J = 9, 6 Hz) , 4, 12- 4,19 (m, 2H) , 6, 90 (d, 2H, J = 8, 7 Hz) , 2,79 (s, 1H) , 7, 40 (d, 2H, J = 8,7 Hz) 1-58 pf: > 299°C (dec.) RMN de XH (CDC13) δ ppm: 1,26 -1,33 (m, 2H), 1,40 (s, 9H) , 1,56 -2,42 (m, 19H) r 2,73-2,81 (m, 4H), 3,16-3,26 (m, 4H) , 3, 64 (d, 1H, J = 9, 6 Hz) , 6, 87 (d, 2H, J = 8,7 Hz) , 7,04 (s, 1H) , 7,37 (d, 2H , J = 9,0 Hz) . 172 1-59 pf: > 27 0 °C (dec.) (s, (m, J = 9H) 3H) 8,7 RMN de XH (CDC13) δ ppm: 1,26-1,47 (m, 2H), 1,47 O 00 \—1 1 o \—1 (m, 4H) r 2,01-2,32 (m, 5H) , 3,28-3,40 :, 62-3,74 (m, 3H) , 5, 74-5,96 (m, 2H), 6, 92 (d, 2H, Hz), 7,13 (s, 1H) , 7,39 (d, 2H, J = 9,0 Hz). 1-60 pf: 247-250°C (dec.) RMN de XH (CDCI3) δ ppm: 1 ,20 -1,37 (m, 2H) , 1, .40 (s, 9H) , 1,60· -1, 78 (m, 2H) , 1,98-2, 33 (m, 5H) , 2, 93- -3, . 03 (m, 2H) , 3,22- 3,40 (m, 1H), 3,52 (t, 2H , J = 6,0 Hz) , 3, . 62 (d, 1H, J = 8 ,4 Hz), 4,36 (s, 2H) , 6, 93 (d, 2H, J = = Ϊ 3,7 Hz) , 7, 00 (s, 1H) r 7,11-7,22 (m, 4H) , 7 ,39 (d, 2H , J = Ϊ 3,7 Hz) ,
1-61 pf: 280-281°C RMN de XH (CDCI3) δ ppm: 1,21-1,38 (m, 2H), 1,41 (s, 9H) , 1, 64 -1,80 (m, 2H) , 2,02-2,33 (m, 5H) , 3,24-3,40 (m, 1H) , 3, 61 (d, 1H, J = 9,0 Hz), 6,33 (t, 2H , J = 2,1 173
Hz), 7,04 (t, 2H, J = 2,1 Hz), 7,14 (s, 1H), 7,34 (d, 2H, J = 9,0 Hz), 7,56 (d, 2H, J = 9,0 Hz).
1-62 pf: 2 60-2 62 °C RMN de XH (CDCls) δ ppm: 1,22 -1,39 (m, 2H), 1,41 (s, 9H) , 1, 64 -1,82 (m, 2H) , 2,02-2,35 (m, 5H) , 3,24-3,40 (m, 1H) , 3, 62 (d, 1H, J = 9,6 Hz) , 7, 31 (d, 2H , J = 9,0 Hz) , 7,51 (s, 1H) , 7,69 (d, 2H, J = 9, 0 Hz) . 1-63
pf: 2 4 8 ° C RMN de XH (CDC13) δ ppm: 1,2 Ο 1,38 (m, 2H), 1,40 (s, 9H) , 1, 61 -1,78 (m, 2H) , Ι, 98-2,32 (m, 5H) , 3,22-3,45 (m, 1H) , 3, 64 (d, 1H, J = 9,3 Hz), 7,11 (s, 1H) , 7,37-7,46 (m, 4H). 1-64 pf: 272-275°C (dec.) RMN de XH (DMSO-d6) δ ppm: 1,20-1,53 (m, 4H) , 1,27 (s, 9H) , 1,75-1, 88 (m, 2H), 1, 88-2, 00 (m, 2H), 2,11- 2,24 (m
1H) , 2,96-3,12 (m, 1H) , 5,96 (s, 2H) , 6,77 (d, 1H 174 J = 8,7 Hz), 6,82 (d, 1H, J = 8,4 Hz), 6,95 (dd, 1H, J = 1,8, 8,4 Hz), 7,29 (d, 1H, J = 1,8 Hz), 9,70 (s, 1H). 1-65 pf: 293-296°C (dec.) RMN de XH (DMSO-de) δ ppm : 1, 20- 1,70 (m, 1 OH) , 1,27 (s, 9H) , 1,79-: 2,038 (m, 4H) , 2, 18-2 , 33 (m, 1H) , 2, 98- 3,30 (m, 5H) , 6,79 (d, 1H, J = 9, 0 Hz) , 6, 97 (d, 2H , J = 8,1 Hz) , 7,43- 7,57 (m, 4H), 7 , 62 (d, 2H, J = = 8, 1 Hz) , 9, 82 (s, 1H) . 1-66 pf: > 300 c 'C RMN de XH (DMSO-de) δ ppm : 1, 27 (s, 9H) , 1,27- 1,53 (m, 4H) , 1,86- -1, 99 (m, 4H) , 2, 22-2 ,34 (m , 1H) , 2,39 (s, 3H) , 3, 00- 3, 14 (m, 1H) , 6 , 25 (s, 1H) , r 6, , 79 (d, 1H , J = 9, 0 Hz) , 7,47- -7,50 (m, 1H) , 7,69-7, 76 (m, 1H) , 10,27 (s, 1H) . 1-67 pf: 248-249°C RMN de ΧΗ [ (DMSO-de: 1 δ ppm: 1 ,20· -1,54 (m, 4H) , 1,27 (s, 9H) , 1,77- -1,90 (m, 2Η) , 1, 90-2 , 02 (m , 2H) , 2,02 175 (s, 3H) , 2, 17-2,32 (m, 1H) , r 2,96-3,13 (m, 1H) , 6,78 (d, 1H J = 8,7 Hz) , 7,12-7,30 (m, 3H) , 7,89 (s, 1H) , 9,79 (s, 1H) 9, 88 (s, 1H) .
1-68 pf: > 300 °C RMN de ΧΗ (DMSO-d6) δ ppm: 1,20-1,54 (m, 4H) , 1,27 (s, 9H) , 1,77-1, 89 (m, 2H) , 1, 89-2,03 (m, 2H) , 2,00 (s, 3H), 2,14-2,28 (m, 1H), 2,95-3,13 (m, 1H), 6,78 (d, 1H, J = 8,7 Hz), 7,40-7,54 (m, 4H), 9,72 (s, 1H), 9,83 (s, 1H).
1-69 pf: 199-201°C RMN de XH (DMSO-d6) δ ppm: 1,21-1,53 (m, 4H) , 1,27 (s, 9H) , 1 ,76-1,89 (m, 2H) , 1,89-2 , 02 (m, 2H) , 2 ,13 2,30 (m, 1H) , 2 ,85 (s, 6H) , 2, 94-3,14 (m, 1H) , 6, 40 (dd 1H, J = 2,4, 8, 4 Hz), 6 ,78 (d, 1H, J = 8,7 Hz) , 6 , 90 (d 1H, J = 8,4 Hz), 7,05 (t, , 2H, . J = 8,4 Hz) , 9, , 60 (s, 1H) .
1-70 pf: 227-230°C RMN de XH (DMSO-d6) δ ppm: 1,22-1,52 (m, 4H) , 1,27 (s, 9H) , 1,72-1, 87 (m, 2H), 1,87-2,01 (m, 2H), 2,12- 176 2,29 (m, 1H) , 2,96-3,12 (m, 1H) , 5,00 (s, 2H) , 6,22 (d, 1H, J = 7,5 Hz), 6,66 (d, 1H, J = 7,5 Hz), 6,78 (d, 1H, J = 9,0
Hz), 6,86 (d, 1H, J = 7,5 Hz), 6, 89-6, 95 (m, 1H) , 9,46 (s, 1H) . 1-71
pf: 270-272°C RMN de XH (DMSO-d6) δ ppm: 1,22-1,52 (m, 4H) , 1,26 (s, 9H), 1,73-1,86 (m, 2H), 1,88-2,00 (m, 2H), 2,08- 2,22 (m, 1H) , 2,95-3,11 (m, 1H) , 4,80 (s, 2H) , 6,47 (d, 2H, J = 8,4 Hz), 6,77 (d, 1H, J = 8,4 Hz), 7,20 (d, 2H, J = 8,4
Hz) , 9, 35 (s, 1H) . 1-72
pf: 262-263°C RMN de 1 H (CDC13) δ ppm: 1, 25 (d, 6H, J = 6, 3 Hz) , 1, , 17- -1,42 (m, 2H) , 1,4C ) (s, 9H) , 1,60-1,78 (m, 2H) , 00 σι \—1 -2, 43 (m, 7H) , 3,20-3,43 (m, 3H) , 3,67 (d, 1H, . J = 9, 6 Hz) , 3, 74- -3,86 (m, 2H) , 6,86 (d, 2H, J = 9,0 Hz) , 7, 04 (s, 1H) , 7,38 (d, 2H, J = 9,0 Hz) . 1-73
pf: 218-219°C 177 RMN de (CD3OD) δ ppm: 1,36 (s, 9H) , 1,36-1,69 (m, 4H) , 1,45 (s, 9H) , 1,88-2,02 (m, 3H) , 2,06-2,30 (m 4H) , 3, 05' -3,44 (m, 3H) , 3,46-3,56 (m, 1H) , 4,16-4,26 (m 1H) , 6, 51 (d, 2H, J = 9,0 Hz), 7,30 (d, 2H, J = 8,7 Hz). 1-74 pf: 295-296°C (dec.) RMN de XH (CD3OD) δ ppm: 1,36 (s, 9H) , 1, 36-1,67 (m, 4H) , 1,92-2,13 (m, 4H) , 2,26-2,40 (m, 2H) , 2, 62-2,75 (m, 1H) , 3,16-3,25 (m, 1H) , 3,58-3,98 (m, 4H) , 4, 16-4,25 (m, 1H) , 7,20-7,30 (m, 2H), 7,62 (d, 2H, J = 9, 0 Hz) . 1-75
pf: 250-251°C RMN de 1 H (DMSO- -d6) δ ppm: 1 , 23- 1,55 (m f 4H) i, 27 (s, 9H) , 1,78 -i, , 90 (m , 2h; 1, 1,90-2, . 02 (m, 2H) , 2 ,15' 2, 28 (m, 1H) , 2, 98- -3, 14 (m, 1H) , 3,0 6 (t , 2H , J = 8, 4 Hz) 3, 87 (t, 2H, J = 8 ,4 Hz) r 6, 67 (dd, 1H, J = 1,5, 7, 2 Hz) 6, 80 (d, 1H, J = 8 , 4 Hz) , 1 6, 94- 7,05 (m, 2H) , 7,12-7, 19 (m 1H) , 7,16 i (d, 2H, J = 9 ,3 Hz) , 7,57 (d, 2H, J = 9, 3 Hz) 9, 73 (s, 1H) .
1-76 pf: 265-266°C 178 RMN de XH (DMSO-de) δ ppm: 1 , 23 -i, 58 (m, 4H) , i, 28 (s, 9H) , 1,83-2, 04 (m, 4H) , 2,20-2, 36 (m , 1H) , 2 , 97- 3, 16 (m, 1H) , 6,67 (d ., 1H, J = 3 , 0 Hz), 6, 82 (d, 1H, J = 8, 4 Hz) , 7, 07- 7,22 (m, 2H), 7, 47-7 ,53 (m, 1H) , 7,50 (d, 2H, J = 9, 0 Hz) , 7 ,58 (d, 1H, J = 3, 0 Hz), 7, 64 (d, 1H, J = 7,5 Hz) , 7,79 (d, 2H, J = 9,0 Hz), 10, 02 (s, 1H) . 1-77 pf: 2 81 ° C RMN de XH (DMSO-de) δ ppm: 1 ,21-1,56 (m, 4H) 1,27 (s, 9H) , 1,80-2,03 (m, 4H), 2,18-2, 31 (m, 1H) , 2 , 97 3, 14 (m, 1H) , 6, 51 (dd, 1H, J = 2,1, 2,7 Hz), 6, 81 (d, 1H J = 9, 0 Hz) , 7,67-7,78 (m, 5H), 8,41 (d, 1H, J = 2,1 Hz) 9, 96 (s, 1H) . 1-78 pf: > 300 °C (dec.) RMN de XH (DMSO-d e) δ ppm: 1,27 (s, 9H) , 1,27- 1,52 (m, 4H) , 1, 74-2, r 04 (m, 7H), 2,10- 2,25 (m, 2H) , 2, 96- 3,20 (m, 2H) , 3, 48-3 , 58 (m, 1H), 3,75 -3, 84 (m, 1H) , 6,39 (d, 2H, J 8,4 Hz) , 6, ,79 (d, 1H, J : = 8,4 Hz) , 7, 02 (s, 1H) , 7,30 (s, 1H) , 7, 36 (d, 2H, J = 8,1 Hz) , 9,48 (s, 1H) . 1-79 179 pf: 248 i-250 °C (dec.' ) RMN de (DMSO-de) δ ppm : 1, 27 (s, 9H), 1, r 27- 1, 54 (m, 4H) , 1, 85-1 , 99 (m, 4H), 2, 24-2 , 33 (m, 1H) , -3, , 00- 3, 14 (m, 1H) , 6, 82 (d, 1—1 C-I = 8,7 Hz) , 7, 77 (d, 2H, J = 8, 4 Hz) , 8,07 (d, 2H, J = 8,4 Hz) . 1-80 pf: > 300 °C RMN de 1 H (DMSO- d6) δ ppm: 1 , 22- 1,58 (m, 4H) , 1, 27 (s, 9H) , 1,80- -2, 03 (m, , 4H), 2,18-2, 32 (m, 1H) , 2 , 98- 3, 14 (m, 1H) , 6, 80 (d , 1H, J = 8, 7 Hz) , 7,35 -7,50 (m, 2H) , 7, 99 (s, 1H) , 8,11 (s, 1H) , 9,79 (s, 1H), 12, 94 (s, 1H) . 1-81
pf: 2 61-2 62 °C RMN de 1 H (DMSO- d6) δ ppm: 1 ,21- -i, 57 (m, 4H) , 1, 27 (s, 9H) , 1,78 -2, 02 (m , 4H) , 2, 17-2, 30 (m, r 1H), 2 , 96- 3, 16 (m, 1H) , 6, 34 (s, - 1H), 6, 80 (d, 1H, J = 8, 7 Hz), 7 ,14- 7, 32 (m, 3H) , 7,85 (s, - 1H) , 9, 58 (s, 1H) , 10, , 95 (s, 1H) 1-82 180 180 RMN de (CDC13) δ ppm: 0,86 (s, 18H) , 1,24-1,37 (m, 2H) , 1,37 (s, 9H) , 1,56 .-1,74 (m, 2H) , 1,95-2, 19 (m, 5H) , 3,: 18-3,32 (m, 1H), 3 ,44 (t, 4H, J = 6,3 Hz) , 3, . 70 (t, 4H, j = 6, 3 Hz) , 4,39 (d, 1H, J = 9,0 Hz) , 6, 59 (d, 2H, J = 9, 0 Hz) , . 7,31 (d, 2H, J = 8,7 Hz), 7,43 (s, 1H) . 1-83 pf: 264-265 °C RMN de XH (DMSO-d6) δ ppm: 1,27 1 (s, 9H) , 1 ,27- 1,52 (m , 4H) , 1,78-1, , 88 (m, 2H) , 1,90- 2, 00 (m, 2H) , 2 ,14- 2,26 (m , 1H) , 2,96-3 ,14 (m, 1H) , 6,72 -6, 82 (m, 2H) r 6,99 (t, 4H, J = 7, 8 Hz) , 7,18 (t, 2H, J = 7 ,5 Hz) , 7, ,46 (d, 2H, J = 9, 0 Hz) , 8 ,00 (s, 1H) , 9, 65 (s, 1H) . 1-84 pf: 257 °C (dec.) RMN 1,27 (s, 9H) , 3, 15 (m, 1H) , 9, 0 Hz) , 8,34 1H) . de (DMSO-de) δ ppm: 1,23-1,57 (m, 4H) , 1,83-2,03 (m, 4H) , 2,23-2,35 (m, 1H), 2,98- 6,80 (d, 1H, J = 8,1 Hz), 7,87 (d, 2H, J = (d, 2H, J = 9,0 Hz), 9,21 (s, 1H) , 10,20 (s,
1-85 pf: 256-258 °C 181 181 (m, 4H), 2,28-2,42 Hz) , 6,80 RMN de (DMSO-d6) δ ppm: 1,22-1,53 1,26 (s, 9H) , 1,79-2,01 (m, 4H) , 2,25 (s, 3H) , (m, 1H) , 2, 97-3, 02 (m, 1H) , 6,71 (d, 1H, J = 0,9 (d, 1H, J = 8,1 Hz), 11,91 (s, 1H) . 1-86
pf: 228-230 °C (m, (m, J = Hz) RMN de XH (CD3OD) 2H) , 1,55-1,70 (m, 2H) 2H), 2,20-2,32 (m, 1H), 5,7 Hz), 3,69 (t, 4H, J 7,29-7,33 (m, 2H). δ ppm: 1,36 (s, 9H), 1,36-1,48 , 1, 87-1, 98 (m, 2H) , 2,08-2,17 3,15-3,27 (m, 1H), 3,50 (t, 4H, = 5,7 Hz) , 6,72 (d, 2H, J = 9,0
1-87 pf: 183-184°C RMN de XH (DMSO- d6) δ ppm: 1, 27 (s, 9H) , 1,27- 1, 48 (m, 4H) , 1,73- -1,89 (m , 4H) , 1 , 90- -2, r 0 0 (m, 2H) , 2,16- 2, 28 (m, 1H) , 2,28 (t, 2H, J = 7 ,5 Hz) r 2,51-2, 54 (m, 2H) , 2, 97- 3, 13 (m, 1H) , 3,58 (s, 3H) , 6, 79 (d , 1H, J = 8,7 Hz) , 7, 08 (d, 2H, J = 8 ,7 Hz), 7,49 (d, 2H d J = 8, 4 Hz) , 9, 73 (s, 1H). 1-88 182
pf: 217-218°C RMN de ΧΗ (CD3OD) δ ppm: 1,36 (s, 9H), 1,36-1,46 (m, 2H) , 1,55-1,69 (m, 2H) r 1,83-2,00 (m, 4H), 2,07-2,18 (m, 2H) , 2,26-2,36 (m, 3H), 2, 61 (t, 2H, J = 7,5 Hz), 3,14- 3,26 (m, 1H), 7,13 (d, 2H, j = 8,1 Hz) , 7,44 (d, 2H, J = 8,1 Hz) . 1-89 RMN de XH (CDCI3) δ ppm: 0, 08 (d, 6H, J : = 3,3 Hz) , 0, 8 8 (s, 9H) , 1,21-1,36 (m, 2H) , 1, 39 (s, 9H), 1, 61- 1, 74 (m, 2H) , 1, 88-2,23 (m, 6H) , 3 ,06- -3, 11 (m, 1H) , 3,24- 3, 74 (m, 4H) , 3, 92 (d, 1H, J = 9 , 6 Hz) r 4,48-4,56 (m, 1H) , 6, 47 (d, 2H, J = = 9,0 Hz), 7 ,17 (s, 1H) , 7,32 (d, 2H , J = 9, 0 Hz) . 1-90 pf: amorfo RMN de XH (CD3OD) δ ppm: 1,36 (s, 9H) , 1,36-1,47 (m, 2H) , 1,56 -1, 70 (m, 3H) , 1,88-2,30 (m, 6H) , 3,05-3,49 (m, 5H) , 4,50 (s lg , 1H), 6,50 (d, 2H, J = 9, 0 Hz), 7,29 (d, 2H, J = 9,0 Hz) . 1-91
pf: 105-106°C 183 RMN de (CDCls) δ ppm: 0 . 92 (t, 3H, J = 7 . 3 Hz) , 1.25 -1.27 (m, 2H), 1.36 (d , 6H, J = 6. 9 Hz) , 1 .51- 1.59 (m, 2H) , 2.56 (t, 2H, J = 7 . 8 Hz) , 3.: 27 (septeto, 1H, J = 6.9 Hz) , 7.12 (d, 2H, J = 8.6 Hz) , 7 .32 (t, 1H, J = 7 . 8 Hz) , 7.45 (d lg, 1H, J = 7.8 Hz), 7 . 53 (d, 2H, J = 8 . 6 Hz) r 7.58 (d, 1H, J = 7 .8 Hz), 7. 71- 7.72 (m, 2H) , 8.27 (s , 1H) . 1-92
pf: 163-164 °C RMN de XH (CDC13) δ ppm: 0, 93 (t, 3H, J = 7,3 Hz) , 1, 32 -1,39 (m, 2H) , 1, 55-1 , 65 (m, 2H) , 1 ,87 (s, 3H) , LO σι \—1 (s r 3H) , 2,60 (t, 2H, J = : 7,6 Hz) , 7 ,07 (d, 2H, J = 8,4 Hz) r 7,18 (d, 2H, J = 8,5 Hz) , 7 ,54 (d, 2H, J = 8,5 Hz) , 7, 91 (s lg, 1H), 8,18 (d, 2H, J = 8, 4 Hz) , 8,77 (s, 1H) . 1-93
pf: 17 3 ° C RMN de ΧΗ (CDC13) δ ppm: 0, 93 (t, 3H, J = 7, 3 Hz) , 1, 32· -1,40 (m, 2H) , 1,39 (d , 6H, J = 6 ,9 Hz) , 1,55- -1, 62 (m, 2H) r 2, 60 (t, 2H, J = 7, 8 Hz) , 3, 13 (septeto, , 1H, J = 6, 9 Hz) r 4,39 (d, 2H, J = 6,3 Hz) , 4,45 (t, 1H, J = : 6, 3 Hz) , 7, 18 (d, 2H, J = 8,7 Hz), 7,46 (d, 2H, J = 8,7 Hz) r 184 7,54 (d, 2H, J = 8,7 Hz), 7,80 (s, 1H) , 7,85 (d, 2H, J = 8,7 Hz).
1-94 pf: 159-160°C RMN de XH (CDCI3) δ ppm: 0, 93 (t, 3H, J = 7,3 Hz) , 1, 32-1,39 (m, 2H) , 1,54-1, 80 (m, 2H) , 1,79 (s, 3H) , 1,80 (s , 3H) , 2,601 , 2H, J = 7, ,7 Hz), 3 ,18 (s, 3H) , 7,18 (d, 2H, J = 8,5 Hz) , 7,30 (d, 2H , J = 8,8 Hz) , 7,52 (d, 2H, J = 8,5 » Hz), 7,70 (s lg, 1H) , 7,84 l (d, 2H, J = 8, 8 Hz) , 8,77 (s, , 1H) . 1-95 pf: 177-178°C RMN de ΧΗ (CDCI3) δ ppm: 0, 94 (t, 3H, J = 7,2 Hz) , 1, 31-1,48 (m, 8H) , 1,54-1, 66 (m, 2H) , 2,55 (s, 3H) , 2, 62 (t , 2H, J = 7, 6 Hz), 3,92 (septeto, 1H, J = 6, 6 Hz) , 7,20 (d , 2H, J = 8, 45 Hz), 7,74 (d, 2H, J = 8,5 Hz) , 9, 01 (s lg, 1H), 9,17 (s, 1H) .
1-96 pf: 220-223°C 185 RMN de ΧΗ (CDC13) δ ppm: 0, 93 (t, 3H, J = 7 ,3 Hz) , . 1,28 -1,42 (m, 2H) , 1,50 (d , 6H, J = 6 , 8 Hz), 1 ,54- 1, 65 (m, 2H) , 2, 62 (t, 2H, J = 7, , 6 Hz) , 4,08 (septeto, 1H, J = 7,1 Hz) , 7,20 (d, 2H, J = í 3,5 Hz) , 7,48 (d, 2H, J = 8 ,5
Hz), 7,71 (s lg, 1H), 8,51 (s lg, 1H), 8,95 (s, 1H) .
1-97 pf: 195-197 °C RMN de (CDC13) δ ppm: 0,91 (t, 3H, J = 7,6
Hz), 0,94 (t, 3H, J = 7,3 Hz), 1,32-1,44 (m, 6H) , 1,54-1,64 (m, 2H) , 1, 66-1,78 (m, 2H) , 2,62 (t, 2H, J = 7,7 Hz), 2,86 (s lg, 2H), 3,98 (septeto, 1H, J = 7,1 Hz), 7,19 (d, 2H, J = 8,5 Hz), 7,63 (d, 2H, J = 8,4 Hz), 8,72 (s lg, 1H) , 8,81 (s lg, 1H). 1-98
pf: 216-218°C RMN de XH (CDCI3+CD3OD) δ ppm: 0,93 (t, 3H, J = 7,4 Hz) , 1,29- 1,40 (m, 2H) , 1, 43 (d, 2H, J = 6 ,9 Hz) , 1, , 51- 1, 63 (m , 2H), 2, 60 (t. , 2H, , J = = 7, 8 Hz) , 3, 65 (septeto; 1H, J = 6, 9 Hz) , 7 ,18 (d, 2H, J = 8,5 Hz) , 7, 22 (d 1—> c-l II 8,8 Hz) , 7, 55 (d, 2H, J = 8,5 Hz) , 8 ,18 (dd, , 1H, J = 8,8, 2,4 Hz) , 8, 63 (d, 1H, J = 2,4 Hz) . 1-99 186
pf: 201-202 °C RMN de ΧΗ (CDC13) δ ppm: 0, , 93 (t, 3H, J = 7,3 Hz) , 1, 22- -1,40 (m, 2H), 1, 49 (d , 2H, J = 7,1 Hz) , 1,51- -1, 63 (m, 2H) r 2,59 (t, 2H, J = 7, 7 Hz) , 4, 22 (septeto , 1H, J = 7,1 Hz) r 7,16 (d, 2H, J = = 8 ,4 Hz) , 7 ,41 (s lg, 1H) , 7,52 (d, 2H, j = 8, 4 Hz), 8 ,10 (s lg, 1H) , 8,: 13 (d, 1H , J = = 2,2 Hz) , 8, 61 (s lg, 1H). 1-100
pf: 160-162°C RMN de XH (CDCls) δ ppm: 0, , 93 1 (t , 3H, J = 7,3 Hz) , 1, 22-1,42 (m, 2H), 1, 45 (d , 2H, J = 6, 9 Hz) , 1,51- 1, 63 (m, 2H) , 2,61 (t, 2H , J = 7, 8 Hz) , 3, 37 (septeto , 1H, J = 6, 9 Hz) , 6,89 (s ig, 1H) , 7, 19 ' (d, 2H, J = 8,4 Hz) , 7, 65 (d, 2H, J = 8, .4 Hz), 7,80 (dd, 1H, J = 8,4, 2,4 Hz) , 8,27 (d, 1H, J = 8, 4 Hz) , 8,45 (d, . 1H, J = 2, 4 Hz), 9, 75 (s ig, 1H) .
1-101, 1-214 pf: 192-194 °C RMN de (CDC13) δ ppm: 0,93 (t, 3H, J = 7,3
Hz) , 1,27-1, 41 (m, 2H) , 1,35 (s, 9H), 1, \—1 1 o LO 66 (m, 2H) 2, 60 (t, 2H, J = 7, 6 Hz) , OD LO LO (s \—1 ií i—1 7,07 (d, 2H, . J 187 8,5 Hz), 7,17 (d, 2H, J = 8,5 Hz), 7,52 (d, 2H, J = 8,5
Hz), 7,71 (s lg, 1H), 7,79 (d, 2H, J = 8,5 Hz). 1-102
pf: 216-217°C RMN de XH (CDC13) δ ppm: 0,93 (t, 3H, J = 7,3
Hz), 1,26-1,42 (m, 2H) , 1,45 (s, 9H) , 1,70-1,83 (m, 2H) , 2,60 (t, 2H, J = 7,7 Hz), 6,42 (s lg, 1H) , 7,18 (d, 2H, J = 8,5 Hz), 7,35 (d, 2H, J = 8,5 Hz), 7,51 (d, 2H, J = 8,5 Hz), 7,68 (s lg, 1H) , 7,82 (d, 2H, J = 8,5 Hz). 1-103 RMN de ΧΗ (CDCls) δ ppm: 0, 91 (t, 3H, J = 7 ,3 Hz) , 1, 28 -1,36 (m, 2H) , 1,32 (d , 6H, J = 6 , 9 Hz), 1 ,49- 1, 59 (m, 2H) r 2,54 (t, 2H, J = 7, 7 Hz) , 3,23 (septeto, 1H, J = 6, 9 Hz) r 3,46 (s, 3H) , 6,76 (s ig, 1H) , 6,91 (d, 2H, J = 8,2 Hz) r 6, 99 (d, 2H, J = 8 ,8 Hz) , 7,03 (d, 2H, J = 8 ,2 Hz) , 7, 25 (d, 2H, J = 8,8 Hz) . 1-104
pf: 182-183°C RMN de XH (CDC13) δ ppm: 0,93 (t, 3H, J = 7,3
Hz) , 1,28- O \—1 1 (m, 2H) , \—1 1 \—1 LO \—1 63 (m, 2H) , 1, 64- 00 00 \—1 1 (m, 4H) , 1, 90- -2,23 (m, 4H) , 2,60 (t, 2H, J = 7,6 Hz) , 3,39 (m, 188 1H) , 6,16 (s lg, 1H) , 7,07 (d, 2H, J = LO 00 Hz) , 7, 16 (d 2H, J = 8,5 Hz), 7,52 (d, 2H, . J = 8, 5 Hz) , 7, 74 (s ig, 1H) 7,77 (d, 2H, J = 8,5 Hz). 1-105 pf: 190-191°C RMN de ΧΗ (CDC13) δ ppm: 0, 93 (t, 3H, J = 7, Hz) , 1,28-1,41 (m, 2H) , 1,52-1,69 (m, 4H) , 1,75- 1, 90 (m 2H) , 1, 92-2,07 (m, 4H) , 2,58 (t, 2H, r J = 7, 6 Hz) , 3,59 (m 1H) , 6,53 (s lg, 1H) , 7,18 (d, 2H, J = 8,5 Hz) , 7,31 (d 2Η, J = 8,5 Hz), 7,52 (d, 2H, J = 8,5 Hz), 7,67 (s lg, 1H) 7,84 (d, 2H, J = 8,5 Hz). 1-106
pf: 194-197°C RMN de XH (CDC13) δ ppm: 0, 93 (t, 3H, J = 7, Hz) , 1,22-1,41 (m, 2H) , 1, 53-1 , 65 (m, 2H) r 1, 90 (s, 6H) 2, 60 (t, 2H, J = 7,8 Hz), 6 ,86 (s lg , 1H) , 7, 18 (d , 2H, J LO 00 Hz), 7,43 (d, 2H, J = 8,5 Hz) , 7,51 (d , 2H, J = 8,
Hz), 7,71 (s lg, 1H), 7,84 (d, 2H, J = 8,5 Hz). 1-107
pf: 211-212 °C 189 RMN de (CDC13) δ ppm: 0,93 (t, 3H, J = 7,3
Hz), 1,24-1,40 (m, 2H), 1,50-1, 62 (m, 2H) , 2,60 (t, 2H, J = 7,6 Hz), 6,19 (s lg, 1H) , 7,17 (d, 2H, J = 8,5 Hz), 7,18 (d, 2H, J = 8,5 Hz), 7,51 (d, 2H, J = 8,5 Hz), 7,66 (s lg, 1H), 7,86 (d, 2H, J = 8,5 Hz). 1-108 pf: 298- 300 °C RMN de lH (DMSO-d6) δ ppm: 0, 90 (t, 3H, J = 7,3 Hz) , 1,22-1,39 (m, 2H) , 1,48-1, 60 (m, 2H) , 2,54 (t, 2H, J = 7,3 Hz), 7,04 (d, 2H, J = 8,8 Hz), 7, 12 (d, 2H, J = 8,5 Hz) , 7,64 (d, 2H, J = 8,5 Hz) , 7,69 (d, 2H, J = 8, 8 Hz) , 9, 80 (s, 1H). 1-109
pf: 122-123°C RMN de XH (CDCI3) δ ppm: 0, 90 (t, 3H, J = 7,4 Hz) , 0, 97 (t, 3H, J = 7,7 Hz), 1,26- 1,38 (m, 2H) , 1,30 (s, 6H) , 1, 50- -1, 66 i (m, 4H) , 1 ,72-1, 83 (m, . 4H) , 2, 34 (t, , 2H, J = 7,1 Hz) r 2,55 (t, 2H, J = 7,6 Hz) , 3,19 (q , 1H, J = 6, 0 Hz) , 4, 60 (s ig, 1H) , 7, 08 (d, 2H, J = 8 ,5 Hz) , 7,42 (d, 2H, J = 8, ,5 Hz), 7 , 85 (s, 1H) . 1-110 190
pf: 109-110°C RMN de ΧΗ (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7,4 Hz) , 1, 10 (d, 6H, J = 6,7 Hz) , 1,29' -1,38 (m, 2H) , 1,55 (s, 9H) , 1, 60 -1,70 (m, 2H), 1,78-1,89 (m, 2H) , 2,26 (m, 1H) , 2,39 (t r 2H, J = 7, 0 Hz) , 2,57 (t, 2H, J 7,7 Hz) , 2, 90 (d, 2H, j = 6, 6 Hz) , 3,16 (s lg, 1H) , 4,24 (s ig, 1H) , 7, 12 (d, 2H, j = 8, 5 Hz) , 7,40 (d, 2H, J = 8,5 Hz) • 1-111 pf: 64-65° C RMN de 1H, (CDCI3) δ ppm: 0, 91 (t, 3H, J = 7,3 Hz) , 1, 02 (t, 3H, J = 7,5 Hz) , 1,35 (d, 3H, J = 6,7 Hz) , 1,26 -i, 38 (m, 2H) , 1,48-1, 69 (m, 5H) , 1, 76- 1,87 (m, 2H) , 2,04 (m, 1H) , 2,38 (t, 2H, J= 7,3 Hz), 2,56 (t, 2H, J = 7,6
Hz), 2,91 (m, 1H) , 3,16 (s lg, 2H) , 4,42 (s lg, 1H) , 7,11 (d, 2H, J = 8,5 Hz), 7,42 (d, 2H, J = 8,5 Hz), 7,47 (s lg, 1H) . 1-112
pf: 7 9-80 °C RMN de XH (CDC13) δ ppm: 1, ,36 (s, 9H) , 1,52- -1, 62 (m, 2H) , 1, 67-1,76 (m, 2H) , 2,22 (t, 2H, J = 7,4 Hz) , 3,16 (q, 2H, J = 6,3 Hz), 3,78 (s, 3H) , 4,33 (d, 2H, , J = : 5,4 191
Hz) , 4, 62 (s ig, 1H) , 6,20 (s lg, 1H) , 6,85 (d, 2H, J = 8,8 Hz) , 7,19 (d, 2H, J = : 8,8 Hz) . 1-113
pf: 125-126°C RMN de XH, (CDC13) δ ppm: 1,38 (s, 9H) , 1,62-1,70 (m, 2H) , 1,76-1, 88 (m, 2H) , 2,46 (t, 2H, J = 7,4 Hz), 3,22 (q, 2H, J = 6,1 Hz), 4,22 (t, 1H, J = 6,1 Hz), 7,24 (dd, 1H, J = 8,9, 2,3 Hz), 7,36 (d, 1H, J = 2,3 Hz), 7,65 (s lg, 1H), 8,29 (d, 1H, J = 8,9 Hz). 1-114
pf: 8 9-91°C RMN de lH (CDCI3) δ ppm: 0, 92 (t, 3H, J = 7, 0 Hz) , 1, 06 (d, 6H, J = 7,0 Hz) , 1 ,36 (m 1H) , 1,50 -1,72 (m , 5H) , 1 , 94-2,0 6 (m f 2H), 2, 2 6 (m, 1H) , 2, 60 (t , 2H, J = 7, 7 Hz) , 2, 84 (t, 2H, J = 7,7 Hz) , 2 , 93 (d, 2H, J = 6,3 Hz) r 3,20 (t , 2H, J = 6 , 6 Hz) , 4 , 30 (s ig, 1H) , 7,19 (d, 2H, J = LO 00 Hz) , 7,63 (d, 2H , J = 8 ,5 Hz) , 9, 15 (s lg, 1H) .
1-115 pf: 94-95°C 192 RMN de XH (CDC13) δ ppm: 0,92 (t, 3H, J = = 7 ,5 Hz) , 1,03 (t, 3H, J = 7,5 Hz) , 1,23- 1,40 (m ,5H), 1,42 -1, 65 (m, 6H) , 1,75 (m, 1H), 2, 02 (m, 1H) , 2,24 (t, 2H, r J = 7 ,0 Hz) , 2,59 (t, 2H, J = 8, 0 Hz) , 2,90 (m, 1H), 3,14 (q, 2H, J = 6, 6 Hz) , 4,20 (m, 1H), 4,40 (d, 2H, J = 5,4 Hz) , 5, 70 (s ig, 1H) , 7,14 (d, 2H, J = 8 ,1 Hz), 7,18 (d, 2H, J = 8 . 1
Hz) . 1-116
pf: 8 9-91°C RMN de 1 H (CDCI3) δ ppm: 0,97 (t, 3H, J = 7,3 Hz) , 1,02 (t, 3H, J = 7,5 Hz) , 1,35 (d, 3H, J = 7,0 Hz) , 1, 40 -1, 90 (m , 9H) , 2,04 (m , 1H) , 2,37 (t, 2H, J = 7,0 Hz), 2, 90 (m, 1H) , 3, 17 (q, 2H, J = 6,6 Hz) , 3, 93 (t, 2H, J = 6, 6 Hz) , 4,32 (m, 1H) , 6,84 (d , 2H, J = 9, 0 Hz) , 7,31 (s lg, 1H) , 7,40 (d, 2H, J = 9,0 Hz). 1-117
pf: 110-111°C RMN de ΧΗ (CDCI3) δ ppm: 1, 02 (t, 3H, J = 7,5 Hz) , 1,34 (d, 3H, J = 6,6 Hz) , 1,45-1,70 (m , 3H) , 1,75-1,85 (m, 2H) , 2,05 (m ,1H), 2, 36 (t , 2H, J = 7,5 Hz) , 2,90 (m, 1H) , 3,16 (q, 2H, J = 6,6 Hz) , 3,78 (s r 3H) , 4,50 (m, 1H), 6, 84 (d, 2H, J = 6, 8 Hz) , 7,42 (d, 2H, J = 6, 8 Hz) , 7,48 (s lg, 1H). 193 1-118
pf: 113-115°C RMN de XH (CDC13) δ ppm: 0, 92 (t, 3H, J = 7 ,0 Hz) , 1, 20- -1,34 (m , 1H) , 1 ,37 (d , 6H, J = 7, 0 Hz) , 1 00 \—1 -1, 70 (m, 3H) r 2,43 (q, 2H, J = 6 , 6 Hz) , 2 , 58 (t, 2H, j = = 7 ,7 Hz) , 3, 10- -3,31 (m, 3H) , 4 ,75 (m , 1H) , e 5, 04 (d, 1H, j = 15 ,0 Hz) , 6, 77 (dt, 1H, J = 7, 7, : L5, 0 Hz) r 7, 14 (d, 2H , j = = 8 ,4 Hz) , 7, 55 (d, 2H, J = 8 ,4 Hz) r 7,85 (s ig, 1H) . 1-119
pf: 139-140°C
RMN de (CDC13) δ ppm: 1,19 (s, 9H) , 1,47 (m, 2H) , 1,61 (m, 2H) , 2,18 (t, 2H, J = 7,6 Hz), 3,03 (q, 2H, J = 6, 3 Hz) , 4, 09 (t, 1H , J = 5 , 9 Hz) , 6,85 (d ig, 1H, J = 8,0 Hz) , 7,00 (t, 1H, J = 8, 0 Hz), 7,16 (d ig, 1H, J = 8,0) , 7,48 (s lg, 1H), 7,57 (s ig, 1H) . 1-120 pf: 183°C RMN de XH (CDCI3) δ ppm: 0,91 (t, 3H, J = 7,3 Hz) , 1,20 -1,58 (m, 6H) , 1, 40 (s, 9H), 2,07 (dd, 1H, J = 12, 9 , 3,1 Hz) , 2,52 (t, 2H, J = 7 ,7 Hz), 2,95 (dd, 2H, J = 194 11,5, 2,5 Hz), 3,46 (m, 1H) , 3, 88-4, 07 (m, 3H) , 6,47 (s, 1H) , 7,08 (d, 2H, J = 8,5 Hz), 7,22 (d, 2H, J = 8,5 Hz). 1-121
pf: 163-166°C RMN de lH (CDCls) δ ppm : 0, 91 (t, 3H, J = 7,3 Hz) , 1,32-1,62 (m, r 6H), 1, 45 (s, 9H) , 1 , 95-2 ,07 (m, 3H) , 2,20 (m, 1H) , 2, 46 (td, 1H, J = 10, 4, 3, 7 Hz) , 2,37 (t, . 2H, J = 7, 6 Hz) , 3, 43 (d lg, 2H, J = 10,4 Hz) , 4 , 80 (s, 1H) , 7, 12 (d, 2H, J = 8,4 Hz), 7,14 (s , 1H) r 7,39 (d, 2H, J = 8,4 Hz). 1-122
pf: 188-189°C RMN de ΧΗ (CDC13) δ ppm: 0,91 (t, 3H, J = 7,5 Hz), 1,25-1,41 (m ,2H), 1,42 (s, 9H) , 1,50-1, 62 (m , 2H) , 1,78- LO σι \—1 1 (m ,4H), 2,00-2, 20 (m , ,6H), 2,57 (t, 2H, J = 7,5 Hz) , 3, 99 (s lg, 1H), 7,10 (s ig, 1H), 7,12 (d, 2H, J = 6, 5
Hz) , 7,41 (d, 2H, J = 6,5 Hz) .
1-123 pf: 197-198°C 195
RMN de XH (CDC13) δ ppm: : 0 ,91 (t, 3H, J = 7,5 Hz) , 1,24-1,40 (m ,2H) , 1, 39 (s, 9H) , 1,50-1,70 (m ,2H) , 1, 99 (s lg , 12H) , 2,56 (t , 2H, J = 7,5 Hz), 3, 47 (s lg, 1H) , 7,10 (s, 1H), 7,11 (d, 2H, J = 8, 5 Hz), 7,38 (d, 2H, J = 8,5 Hz) . 1-124
pf: 258-260°C RMN de XH (CDCI3) δ ppm: 1,20-1,40 (m, 2H) , 1,41 (s, 9H) , 1, 62 -1, 81 (m, 2H) , 2,03- -2,35 (m, 5H) , 2,37 (s, 3H) , 2,71 (s, 3H) , 3,32 (m, 1H), 3, ,64 (d, 1H, J = 8,4 Hz) , 7,08 (s lg, 1H) , 7,24 (m, 1H) , 7,33 (m, 2H) , 7,60 (d, 1H, J = 8,1 Hz), 7,77 (s, 1H) , 7,80 (d, 1H, J = 8,4 Hz), 8,14 (m, 1H) . 1-125
pf: 297-299°C RMN de XH (DMSO-de) δ ppm: 1,27 (s, 9H) , 1,28- 1,56 (m, 4H) , 1,80-2, 01 (m, 4H) , 2,47 (m, 1H) , 2,76 (s lg, 1H) , 3, 05 (m, 2H) , 6, 78 (d, 1H, J = 9, 0 Hz) , 7, 23 (d, 1H, J = 9,0 Hz) , 7, 46 (dd, 1H, J = 2,0, 9, 0 Hz) , 8,03 (d, 1H, J = 2,0 Hz) . 1-126 196
pf: 198-199°C RMN de (CDC13) δ ppm: 1 ,18- 1,39 (m, 2H) , 1,40 (s, 9H) r 1, 60 -i, 79 (m, 2H), 1,98—2, , 35 (m, 5H) , 3, 30 (m, 1H) , 3, 67 (d, 1H, J = 9,6 Hz) , 5,89 (tt, . 1H, J = 3,0, 50,0 Hz) , 6, 97 (d, 1H, J = 7,8 Hz) , 7,21 (s, 1H) , 7,30 ,7,40 (m, 2H) , 7, 55 (s, 1H) . 1-127
pf: 262-264°C RMN de XH (CDCI3) δ ppm: 1,20-1,39 (m, 2H) , 1,41 (s, 9H) , 1, 60 -1, 80 (m, 2H) , 2,00-2,36 (m, 5H) , 2,57 (s, 3H) , 3,33 (m, 1H) r 3, , 62 (d, 1H, J = 8,7 Hz) , 7,28 (s ig, 1H) , 7, 62 (d, 2H, j = 8,7 Hz), 7,94 (d, 2H, J = 8,7 Hz) . 1-128
pf: 252-254 °C RMN de XH (CDCI3) δ ppm: 1,18-1,39 (m, 2H), 1,40 (s, 9H) , 1,58-1, 7 9 (m, 2H) , 1, 99-2,30 (m, 5H) , 2,46 (s, 3H) , 3,32 (m, 1H) , 3,,64 (m, 1H), 7,11 (s lg, 1H) , 7,23 (d, 2H, J = 9, 0 Hz) , 7,44 (d, 2H, J = 9,0 Hz) .
1-129 pf: > 300 °C 197
RMN de XH (CDC13+CD30D) δ ppm: 1,30 LO \—1 1 (m, 2H) , 1,42 (s, 9H) , 1, 70-1,88 (m, 2H) , 2, 10- 2,37 (m, 4H) , 2,52 (m, 1H) , 3,34 (m, 1H), 7 , 43-7 ,54 (m, 3H), 7, 82 (d , 1H, J = 6,7 Hz) , 7,88 (d, 1H, J = 8,5 Hz) , 7 , 98 -8,07 (m, 2H) , 8,44 (s, 1H) , 8,46 (s, 1H) . 1-130 pf: 123 -124 °C RMN de XH (CDC13) δ ppm : 1, . 18- -1,34 (m, 2H) , 1,40 (s, 9H) , 1, 62 -i, 75 (m, 2H) , 2,00-2, 28 (m, 5H) , 3, 31 (m, 1H) , 3, 61 (d, 1H, J = 9, 5 Hz) , 5, 59 (s, 1H) , 7,17 (s, 1H) , 7,30 -7,37 (m, 6H) , 7,41 (d, 1H, J = 8 ,5 Hz) , 7,84 (d, 1H, J = 2,1 Hz) . 1-131
pf: 202-204 °C RMN de XH (CDC13) δ ppm: 1,27- i, 38 (m, 2H) , 1, 38 (s, 9H) , 1, 62 -1,75 (m, 2H) , 1,97-2,04 (m , 2H) , 2,18- -2, 27 (m, 3H) , 3,26 (m, 1H) , 3,81 (s, 3H), 4, 62 (d , 1H , J = = 7 , 9 Hz) , 7, 12 (d, 1H, J = 7,8 Hz) , 7,40 (t / 1H, J = 7, 8 Hz) , 7,51 (s , 3H) , 7, 61 (d, 1H, J = 7,8 Hz) , 7, 71 (s, 1H) , 8, 21 (s ig, 1H) . 1-132 198
pf: 236-237 °C RMN de 1R (CDC13) δ ppm: 1 ,23-1,43 (m, 2H) , 1,41 (s, 9H) , 1,66· -1,80 (m, 2H) , 2,08-2, 12 (m, 2H) , 2,23- 2,31 (m, 3H) , 3,34 (m, 1H) , 3, 87 (d, 1H, J = 9,5 Hz) , 4,02 (s, 3H) , 7, 30 (td, r 1H, J = = 7,3 , 1,1 Hz), 7,36 (s, 1H) , 7,39 (td, 1H , J = 7,3, 1,5 Hz) , 7,53 (d lg, 1H, J = 7,3 Hz) , 7,84 (d lg, 1H , J = 7,3 Hz) , 8,05 (s, 1H), 8, 73 (s, 1H) φ 1-133
pf: 198-200°C RMN de XH (CDCI3) δ ppm: 0,93 (t, 3H, J = 7,3 Hz) , 0, 97 (t, 3H, J = 6,7 Hz), 1,18-1,81 (m, 7H) , 1, 39 (s, 9H) , 1, 98 -2,05 (m r 2H) , 2 ,21-2,24 (m, 3H) , 3,29 (m r 1H) , 4,00 (dd, 1H, J = 10 ,7, 6, 7 Hz), 4,09 (dd, 1H , J = =10, 7, 6,1 Hz) , 4, 27 (d, 1H, j = 9,8 Hz), 6,37 (d, 1H, J = 15, 9 Hz) , 7,47 (d f 2H, J = 8, 5 Hz) , 7,59 (d, 2H, J = 8,5 Hz) r 7, 62 (d, 1H, J = 15,9 Hz) , 7,83 (s lg, 1H). 1-134
pf: 212-213°C RMN de XH (CDC13) δ ppm: 1,21-1,32 (m, 2H) , 1,39 (s, 9H) , 1,59 -1,73 (m, 2H) , 1, 99-2,04 (m, 2H) , 2,10-2,26 (m, 3H) , 3,26 (m, 1H), 3,72 (d, 1H, J = 9, 6 Hz) , 6, 74 (m, 199 1Η) , 7,02 (d, 2H, J = 7,4 Hz), 7,11 (t, 1H, J = 7,4 Hz), 7,13-7,19 (m, 2H) , 7,22-7,26 (m, 2H) , 7,34 (t, 2H, J = 7,4 Hz) . 1-135
pf: 294-296°C RMN de M (DMSO-d6) δ ppm: 1,27 (s, 9H) , 1,28- 1,55 (m, 4H) , 1,81 LO O CM 1 (m, 4H) , 2,26 (m, 1H) , 2,98-3,20 (m, 2H) , 6,78 (d; 1H, J = 9,0 Hz), 7,31 (t, 1H, J = 7,5 Hz) , 7,54-7,72 (m, 5H) , 7 ,94 (s lg, 1H). 1-136
pf: > 300 °C RMN de (DMSO -d6) δ ppm: 1, 28 (s, 9H) , 1 ,29 1,59 (m, 4H) , 1, 81-2 , 02 (m, 4H) , 2, 27 (m, 1H) , 3, 06 (m 1H) , 6, 81 (d, 1H, , J = 8,7 Hz) , 7,38 (t, 1H, J = 7, 2 Hz) 7,48 (t, 2H, J = 7,2 Hz) , 7,62-7 ',81 (m, 1 OH) , 9, 93 (s lg 1H) . 1-137
pf: 2 91-2 92 °C RMN de M (CDC13) δ ppm: 1,25-1,39 (m, 2H) , 1,41 (s, 9H) , 1,61-1,80 (m, 2H) , 2,01-2,36 (m, 5H) , 3,32 (m, 200 200 1Η) , (m, (m, 3, 15 = 9, 1H, (s, 3H) , = 7, 7, 9 8,86 3,63 (d, 1H, J = 9,3 Hz), 7,20 (s lg, 1H) , 7,53-7,74 8H) . 1-138
pf: 259-262°C RMN de XH (CD3OD) δ ppm: 1,40 (s, 9H) , 1,40-1,80 4H) , 2,00-2,30 (m, 4H) r 2,45 (m, 1H) , 3, 00 (s, 3H), -3,30 (m, 2H) , 7 , 90 (d, 1H , J = 8,4 Hz), 8,12 (d, 1H, J 0 Hz) , 8,39 (d, 1H, J = 9, 0 Hz) , 8,72 (s, 1H) , 8,92 (d, J = 8,4 Hz), 10,4 (s, 1H). 1-139
pf: 2 65-2 68 °C RMN de XH (CDC13) δ ppm: 1,25-1,40 (m, 2H) , 1,40
9H), 168-1,81 (m, 2H), 2,05-2,10 (m, 2H), 2,23-2,37 (m, 3,32 (m, 1H), 4,27 (d, 1H, J = 9,1 Hz), 7,53 (t, 1H, J 9 Hz), 7,63 (td, 1H, J = 7,9, 1,4 Hz), 7,77 (d, 1H, J =
Hz), 8,03 (d, 1H, J = 7,9 Hz), 8,37 (s lg, 1H) , 8,85- (m, 2H).
1-140 pf: 258-260°C 201 RMN de (CDC13) δ ppm: 1,20-1,40 (m, 2H) , 1,41 (s, 9H) r 1,52 -1,85 (m, 2H), 2,03-2,35 (m, 5H) , 3,34 (m, 1H) , 3, 75 (m, 1H), 7 ,35-7,66 (m, 3H) , 8, 05 (d, 1H, J = 9, 0 Hz) , 8, 11 (d, 1H, J = 9,0 Hz) , 8,40 (s lg, 1H) , 8,83 (s, 1Η) . 1-141
pf: 205-206°C RMN de XH (CDC13) δ ppm: 1 ,20 -1,37 (m, 2H) , 1 ,40 (s, 9H) , 1.43 -1, 62 (m, 2H) , 1,90-2, 01 (m, 2H) , 2,02-2 , 23 (m, 3H) , 3,27 (m , 1H) , 3,63 (d, 1H, J = 9,6 Hz) , 3, 70 (s, 3H) , - 6, 64 (d, 1H , J = 8, 8 Hz) , 7,28- -7, 41 (m , 5H) , 7,45 (s ig. 1H) , 8,26 (d, 1H, J = 8,8 Hz) . 1-142
pf: 277-280°C RMN de XH (CDCI3) δ ppm: 0,23- -0,34 (m, 2H) , 1,34 (s, 9H) , 1,34 -1,55 (m, 5H), 1,76- -1,80 (m, 2H) , 2, 97 (m, 1H) , 3,31 (d, 1H, J = 9,6 Hz) , 7,18 (s, 1H) , 7,50 -7,59 (m, 4H) , 7,77 (dd , 1H, J = 7,4, 1,0 Hz) , 7, 91- -7, 98 (m, 2H) , 8,39 (dd, 1H, J = 7, 4, 1,9 Hz)
1-143 pf: 202-203°C 202 202 1,40 2,28 (d, RMN de (CDC13) δ ppm: 1,23-1,40 (m, 2H) , (s, 9H) , 1,57-1,71 (m, 2H) , 2,05-2,10 (m, 2H) , 2,18- (m, 3H) , 3,31 (m, 1H) , 3,91 (s, 3H) , 3,93 (s, 3H) , 4,05 1H, J = 9,5 Hz), 8,15 (s, 1H) , 9,56 (s, 1H) . 1-144
pf: 177-178°C RMN de XH (CDCI3) δ ppm: 1 ,27- -1, 39 (m, 2H) , (s, 9H) , 1, 65 -1, 79 (m, 2H) , 2, 04-2, 07 (m r 2H) , 2,12- (m, 3H) , 3,22 (m, 1H) , 3, 93 (d, 1H, J = 9, 1 Hz) , 1 0 (m, 3H) , 7,25 (m, 1H) , 7,77 (dd, 1H, J = 4, 9 ’ J / 1,7 Hz) , 1,40 2,34 7,03 7,81 (s lg, 1H), 8,72 (dd, 1H, J = 7,8, 1,5 Hz). 1-145
pf: > 300 °C RMN de XH (DMSO· -d6) δ ppm : 1, 30 (s, 9H) , 1 1,70 (m, 4H) , 2,05- 2,19 (m, 4H) , 2, ,73 (m, 1H) , , 3, 18 1H) , 6,86 (d, 1H, J = 8,8 Hz) , 7, 62 (t, . 2H , J = 8,5 7,86 (t, 2H, J = 8, 5 Hz) , 7,89 (d, 2H, J = 8,5 Hz) , (d, 2H, J = 8, 5 Hz). ,44- (m, Hz) , 8,16
1-146 pf: 240-242 °C 203 RMN de XH (DMSO-' Ηβ) δ ppm: 1:26- 1,53 (m, 4H) , 1,27 (s, 9H) , 1, 74-1,83 (m , 2H) , 1, 90- -1, 97 (m, 2H) , 2,26 (m, 1H) , 3, 04 (m, 1H) , 6,59 (s lg, 1H) , 6, 74 -6,79 (m, 3H) , 7,74 (s, 1H) , 10, 32 (s, 1H) , 12,80 (s , 1H) . 1-147 pf: 167 -169°C RMN de ΧΗ (CDC13) δ ppm: 1- r 05 -1,28 (m, 2H) , 1,38 (s, 9H) , 1,47 -i, 70 (m, 2H) , 1,80- 2, 00 (m, 3H) , 2,13- 2,25 (m, 2H) , 2,75 (t, 2H, J ' = 6 ,9 Hz) , 3 ,24 (m, 1H) , 3,49 (dt, 2H, J = 6,3, 6, 9 Hz) , 3,58 (d, 1H r J = = 8,7 Hz) , 3, 87 (s, 6H) , 5,40 (s ig. 1H) , 6,71 (m, 2H) , 6, 82 (d, 1H, , J = 8,7 Hz) . 1-148 pf: 171 -172 °C RMN de ΧΗ (CDCls) δ ppm: 1- ,16· -1,38 (m, 2H) , 1,39 (s, 9H) , 1,50 -1, 79 (m, 4H) , 1,85- 2, 02 (m, 3H) , 2,15- 2,30 (m, 2H) , 2,35- -2,56 (m, 6H) , 3,25 (m, 1H), 3, 33 (q , 2H, J = 6, 0 Hz) , 3, 63 (d , 1H, J = 9,0 Hz) / 3, 72 (t ., 4H, J = 4, 6
Hz) , 6,77 (s lg, 1H). 1-149 204 RMN de (CDC13) δ ppm: 1,20-1,36 (m, 2H) , (t, 3H, J = 7,2 Hz), 1,39 (s, 9H), 1,45-1,70 (m, 2H), 1 2,30 (m, 7H) , 2,43 (s, 3H) , 3, 05-3,42 (m, 3H) , 3,46-(m, 3H) , 7,31 (d, 1H, J = 7,2 Hz), 7,40-7,52 (m, 3H), (s lg, 1H). 1-150
pf: 203-204 °C 1,28 , 85- 3, 80 8,18 RMN de XH (CDC13) δ ppm: 1,15-1,37 (m, 2H) , (s, 9H) , 1,42- -1,70 (m, 2H) , 1,85 -2,29 (m, 5H), 2,76 (t J = 6, 0 Hz) , 3,26 (m, 1H) , 3,49 (q, 2H, J = 6,0 Hz) , (m, 1H) , 4,03 (s, 2H) , 5, 88 (s lg, 1H), 7,15 (dd, 1H, 7,0, . 8,8 Hz) , 7,30- -7,35 (m, 2H) . 1,39 2H, 3, 61 J = 1-151
pf: 181-183°C RMN de XH (CDCI3) δ ppm: LO \—1 \—1 -1,30 (m, 2H) , (s, 9H) , 1,45-1, 64 (m, 2H) , 1,88- 2,05 (m, 3H) , 2,15- (m, 2H) , , 2,69 (t , 2H, J = 6,0 Hz) , 3,28 (m, 1H) , 3, 47 2H, J = 6,0 Hz), 3,58 (d, 1H, . J = 9, 9 Hz) , 3, 87 (s, 5, 83 (s lg, 1H), 7,00 (m, 1H) , 7,20 (m, 2H) . 1,39 2,25 (q, 2H) ,
1-152 pf: 222-224°C 205 RMN de XH (CDCI3) δ ppm: 1 1 \—1 1,37 (m, 2H) , 1,39 (s, 9H) r \—1 1 03 \—1 70 (m, 2H), 1 ,90-2, r 25 (m, 5H) , 3,26 (m, 1H) , 3, 36 (t, 2H, J = 6,4 Hz), 3, 66 (dt , 3H, J = 6, 0, 6, 4 Hz) , 5, 87 (t, 1H, J = 6,0 Hz) , 7,58 (s, 1H) , 7, 68 (dd, 1H, J = 7,0 r 8,5 Hz), 7, 83 (dd, 1H, J = 7,0, 8,5 Hz) , 8, 19 (t, 2H, J = 8 ,5 Hz). 1-153
pf: 207-209°C RMN de (CDC13) δ ppm: 1,05-1,25 (m, 2H) , 1,38 (s, 9H) O \—1 -2,03 (m, 10H) , 2, 05-2, . 25 (m, 2H) , 2,58 (s, 3H) , 2, 76 (m, 1H) , 3 , 05-3,35 (m, 2H) , 3, 97 (d, 1H , J = = 9,5 Hz) , 4, 94 (t, 1H, J = 4,0 Hz), 8,42 (d, , 1H, J = 5, 5 Hz) , 8, 97 (d , 1H, J = 5,5 Hz) . 1-154 pf: 184-185°C RMN de XH (CDCI3) δ ppm: 1, 05- 1,25 (m, 2H) , 1,37 (s, 9H) , 1,50-1, 69 (m, 2H) , 1,85-2,05 (m, 3H) , 2,10-2,21 (m, 2H) , 3,24 (m, 1H) , 3,64 (m, 1H) , 4,87 (s, 1H) , 4,88 (s, 1H) , 5,67 (s lg, 1H) , 7,42 (d, 2H, J = 5,5 Hz), 7,52 (m, 2H) , 7,78 (m, 1H) , 7,82 (m, 1H) , 7,95 (d, 1H, J = 7,0 Hz). 1-155 206 pf: 208 -210 °C RMN de XH (DMSO-de) δ ppm: 1 ,26 ( :s, 9H), 1 ,27- 1,50 (m, 4H) , 1, 75-2 , 0 0 (m, 4H) , 2, 16 (m, 1H) , 2, 81 (s, 3H) , 3, 02 (m, 1H) , 6, 79 (d, 1H , J = 8 ,5 Hz) , 10,00 1 (s, 1H) , 10,66 (s, 1H) . 1-156 pf: 256 -257 °C RMN de XH (CDC13) δ ppm: 1, 20- -1,39 (m, 2H) , 1,41 (s, 9H), 1 ., 60- 1,81 (m , 2H), 2, 01-2, 35 (m, 5H) , 2,69 (t, 2H, J = 6,0 Hz) , 3,11 (t, , 2H, J = 6, 0 Hz) , 3,30 (m, 1H) , 3, 61 (d, 1H, J = 9,3 Hz) , 7,21 (d , 1H, J = 8,0 Hz) , 7,31 (s, 1H) , 7,70 (d, 1H, J = 8,0 Hz) , 7, 99 (s, 1H) . 1-157 pf: 269 -271 °C RMN de XH (CDC13) δ ppm: 1, 20- -1,45 (m, 2H) , 1,41 (s, 9H) , 1,70 -1, 90 (m, 2H) , 2,10- 2, 45 (m, 5H) , 3, 37 (m, 1H) , 3, 68 (m, 1H) , 7, 45 (dd, 1H, J = 4, 0, 8, 0 Hz) , 7,53 (s ig, 1H) , 7,72 (t , 1H , J = 8, 0 Hz) r 7, 83 (d , 1H, J = 8,0 Hz) , 8,02 (d, 1H, , J = 8,0 Hz) , 8,: 18 (d l, 1H, J = 8, 0 Hz) , 8, 93 (d, 1H, J = 4, 0 Hz) . 207 1-158
pf: 253-255°C RMN de (CDC13) δ ppm: 1,20-1,40 (m, 2H) , 1,42 (s, 9H) , 1, 60-1, 90 (m, 2H) , 2,06-2,50 (m, 5H) , 2,72 (s, 3H), 3,33 (m, 1H), 3,78 (d, 1H, J = 9,2 Hz), 7,52 (t, 1H, J = 7,0 Hz), 7, 62-7, 80 (m, 2H) , 7,94 (s lg, 1H) , 8,05 (d, 1H, J = 8,5 Hz), 8,20 (s, 1H). 1-159
pf: 253-255°C RMN de XH (CDCls) δ ppm: 1,20-1,39 (m, 2H) , 1,40 (s, 9H) r 1, 60 -1,80 (m, 2H) , 1, 98- 2,30 (m, 5H) , 2,71 (s, 3H) , 3, 31 (m, 1H) , 3, 68 (d, 1H, J = 9,0 Hz) , 7,41 (s ig, 1H) , 7, 61 (d, 2H, J = 9,0 Hz) , 7,70 (d, 2H, J = 9,0 Hz) . 1-160
pf: 211-212 °C RMN de ΧΗ (CDCls) δ ppm : 1, ,20- -1,32 (m, 2H) , 1,39 (t, 3H, J = 7 , o Hz) , 1,40 (s, 9H) , - 1, 55- 1,79 (m, 2H), 1 , 98- 2,35 (m, 5H), 3 ,31 (m, 1H), 3 , 65 (d, 1H , J = 9,5 Hz) , 4,03 (q, 2H, J = 7 , o Hz) , 6,64 (d, 1H, J = = 8, 0 Hz) , 6, 92 (d, 1H, J = 8,0 Hz) , 7, 10 (s, 1H), 7, 19 (t, 1H, J = 8,0 Hz) , 7,30 (s lg, 1H). 208 1-161
pf: 202-203°C RMN de XH (CDC13) δ ppm: 0, 96 (t, 1H, J = 7,3 Hz) , 1, 29· -1,39 (m, 2H) , 1,40 (s, 9H) , 1, ,41- 1,58 (m, 2H) , 1, 60 -í, 80 (m, 4H) , 1,98-2,31 (m, 5H) , 3, 31 (m, 1H) , 3, 66 (d, 1H, J = 8, 5 Hz) , 3,96 (t, 2H, J = 6 ,4 Hz) , 6, 1 54 (d, . 1H, J = 8,0 Hz) , 6, 90 (d, 1H, J = 8,0 Hz) , 7 ,11 (s, 1H) , 7,19 (t, 1H, J = 8, 0 Hz) , 7,31 (s ig, 1H). 1-162
pf: 177-180°C RMN de ΧΗ (CDCls) δ ppm: 1 ,18- -1,38 (m , 2H) , 1,39 (s, 9H) , 1,59 -1/ 78 (m, 2H) , , 1,95-2, 05 (m, 2H) , 2,07- 2,25 (m, 3H) , 3,26 (m, 1H) , 3,46 (s, 3H) , 4, 17 (d, 1H, J = 9,5 Hz) , 5, 15 (s, 2H) , 6,77 (d, 1H, J = 8,0 Hz) , 7, 10-7,23 (m, 2H) , 7,34 (s, 1H) , 7,58 (s, 1H) . 1-163 pf: 175 -17 8 °C RMN de ΧΗ (DMSO-d e) δ ppm : 1 ,27 (s, 9H) , 1 ,28- 1,50 (m, 4H) , 1, 78-2,00 (m, 4H) , 2, 22 (m, 1H) , 2,96- 3, 15 209 (m, 2H) , 6,67 (m, 1H) , 6,79 (d, 1H, J = 8,5 Hz), 7,18 (m, 2H) , . 7,38 (s, 1H) , 9, 81 (s, 1H). 1-164
pf: 232-233 °C RMN de XH (CDCls) δ ppm: 0, 97 (t, 3H, J = 7,3 Hz), 1,22 -1,30 (m, 2H), 1,40 (s, 9H), 1,44- 1,51 (m, 2H) , 1,67-1,77 (m, 4H) , 2, 02-2,24 (m, 5H) , 3,22 (m, 1H) , 3, 62 (d, 1—1 C-I II 3Ω , 6 Hz) , 4,25 (t, 2H, J = = 6, 8 Hz) , 6,71 (d, 1H, J = 8,4 Hz), 7,01 (s lg, 1H), 7, 91 (dd, 1H, J = 8,4, 3,3 Hz) , . 8,08 (d, 1H, J = 3,3 Hz) . 1-165
pf: 199-200°C RMN < de ΧΗ (CDC13) δ ppm : 0, 96 (t , 3H, J = 7,4 Hz) , 1, 24- -1,50 (m, 4H) , 1, 40 (s, 9H) , 1 , 67 -1,76 (m, 3H) , 2,03 -2, 08 (m, 2H) , 2 ,24-2,: 35 (m, 3H) , 3, r 2 9 (m, 1H) , 3,76 (d, 1H, J = 9, 1 Hz) , 3, 91 (t, 2H, J = = 6 , 6 Hz) , 6,41 (dd, 1H, J = = 8 ,8, 2 ,5 Hz) , 6, 55 (d , 1H , J = 2,5 Hz) , 6, 82 (d, 1H, J = 8, 8 Hz) , 7,43 (s, 1H), 8, 95 (s, 1H) .
1-166 pf: 215-218 °C 210 (CDCI3+CD3OD) δ ppm: 0, 97 (t, , 3H , J = 7, 4 Hz) , 1, 24 -1,40 (m , 4H) , 1, 39 (s, . 9H), 1 ,42 -1, 50 (m, 2H) , 1,54- 1, 72 (m, 2H) , 1,76- 1, 82 (m, , 2H) , 1 , 91 -2, 00 (m, 2H) , 2,06- 2, 22 (m, 3H) , 3,24 (m , 1H), 4,00 (t , 2H, J = 6, 6 Hz) , 6,78 (d 1H, J 8,8 Hz) r 6, 98 (dd, 1H, J _ ( 3,8, 2, 5 Hz) , 7,09 (d, 1H, J = 8,8 Hz) . 1-167
pf: 212-213°C M (CDC13) δ ppm: 0,96 (t, 3H, J = 7,5 Hz), 1,26- 1,34 (m, 2H) , 1, 40 (s, 9H), 1, 45-1 , 50 (m, 2H) , 1 00 CO \—1 1 ,77 (m, 4H) , 2,03-2, 08 (m, 2H) , 2, . 17 (m, 1H) , 2,26 -2,29 (m, 2H) , 3,29 (m, 1H) , 3 , 60 (d, 1H, J = 9, 0 Hz) , 4,25 (t, 2H , J = 6, 8 Hz) , 6,71 (d, 1H, J = 8,4 Hz) , 7, 01 (s lg, 1H) , 7 , 91 (dd, 1H, J = 8,4, 3, 3 Hz), 8,08 (d, 1H, J = 3,3 Hz) . 1-168
pf: 230-232°C RMN de (CDCI3) δ ppm: 1 , 22- 1, 35 (m, 2H) r 1,40 (s, 9H) , 1, 63 -1, 77 (m, 2H) , 2,03-2, . 08 (m , 2H) , 1 LO \—1 CM 2,29 (m, 3H) , 3,31 (m , 1H), 3, 63 α 1—> íe J = 9 ,3 Hz) , 6, 89 (d, 1H, J = : 9,4 Hz), 7, 10 (d ig, 2H, J = 7, 4 Hz) , 7, 12 (s ig, 1H) , 7, 18 (t, 1H, J = 7 ,4 Hz) , 7,36 (t lg, 2H, . J = = 7, 4 Hz) , 8,09-8,15 (m, 2H) . 211 1-169
pf: 159-160°C RMN de XH (CDCls) δ ppm: 0 , 97 (t, 3H, , J = 7 ,3) , 1,20 -1,35 (m, 2H) , 1,40 (s, 9H), 1,37-1,49 (m, 2H) , 1 , 61- 1,78 (m, 4H) , 2, 05-2,08 (m , 2H), 2, 23- 2,26 (m, r 2H) , 2,36 (s, 3H) , 2, 97 (s lg, 1H) r 3,32 (m, 1H) , 3, 86 (s lg, 1H) , 4,30 (t, 2H, J 6,5 Hz) , 6, 25 (s, 1H), 7,92 (s lg, 1H) • 1-170 pf: 180 -181 ° C RMN de XH (CDCls) δ ppm: 0 , 88- -0,89 (m , 2H) , 1,39 (s, 9H) , 1,42 -i, 60 (m, 2H) , 1,86-1, 90 (m, 2H) , 2,04- 2,09 (m, 2H) , 2,42 (s, 3H), 2, 91 (m, 1H), 3,20 (m, , 1H) , 3,63 (d, 1H, J = 9,2 Hz), 6,38 (s, 1H), 7,15 (m, 2H) , 7, 2 8 (m, 1H) , 7,45 (m, 2H) , 7,84 (s lg, 1H) . 1-171 pf: 173 -17 4 ° C RMN de ΧΗ (CDC13) δ ppm: 0,98 (t , 3H, J = 7,5
Hz) , 1,29 O \—1 1 (m, 2H) , 1,40 (s, 9H) , 1,55 (m, 2H) , 1, 62- 1,83 (m, 4H) , 2,09 -2, 12 (m, 2H) , 2,24 -2,32 (m, 3H) , 3,32 (m, 1H) , 3, 63 (d, 1H, J = 9,5 Hz) , 3, 99 (t, 2H, J = 6,4 212
Hz) , 7,22 (dd, 1H, J = 9,4, 2,7 Hz), . 7,66 (d, 1H, J = 2,7 Hz) , 8, 63 (d, 1H, J = 9, 4 Hz) , 10,17 (s, 1H) . 1-172
pf: 238-242°C RMN de 1H-NMF (CDCls) δ ppm: 0,96 (t, 3H, J = : 7, Hz) , 1,23· -í, 52 (m, 4H) , 1, 40 (s, 9H) \—1 1 \—1 co \—1 ,78 (m, 4H) 1 LO O CM -2,28 (m , 5H) , 3,30 (m, 1H) r 3, 66 (d, 1H, J = 9, 4 Hz) 3, 84 (s lg, 2H) , 3, 90 (t, 2H, j = 6, 4 Hz), 6 , 32- -6, 35 (m 2H) , 6,96 (s ig, 1H), 6, 97 (d, 1H, r J = 9,4 Hz) . 1-173 pf: 165 -166°C RMN de XH (CDC13) δ ppm: 1 , 23 -1, 2 6 (m, 2H) , 1 ,40 (s, 9H) , 1, 67 -1/ 72 (m, 2H) , 2,01-2, 06 (m , 2H) , 2,11-2 ,28 (m, 3H) , 3,31 (m, 1H) , 3, 60 (s, 2H), 3, 69 (s, 3H) , 4,02 (s ií i—1 1H) , 7,01 (d , 1H, J = 8 ,0 Hz), 7, 25 (t, 1H, J = 8,0 Hz) , , 7,43 (d, 1H, J = 8 , 0 Hz) , 7,49 (s lg, 1H), 7, 51 (s ig, 1H) ,
1-174 pf: 264-265°C 213 RMN de XH (CDCI3+CD3OD) δ ppm: 1,26 -1, 29 (m, 2H), 1,39 (s, 9H) , 1,62- -1,69 (m, 2H) , 1 ,96-2, 00 (m, 2H), 2,18- 2,21 (m, 3H) , 3,25 (m, 1H) , 3,58 (s , 2H) , 7, 01 (d, 1H, J = 7,5 Hz) , 7,26 (t, 1H, J = 7,5 Hz), 7,42 (s lg , 1H), 7,50 (d, 1H, J = 7, 5 Hz) . 1-175
pf: 90-94 °C RMN de XH (CDCI3) δ ppm: 1, 16- 1,23 (m, 2H) , 1,37 (s, 9H) , 1,44- -1, 56 (m, 2H) , 1 ,73- -1,85 (m, 3H) , 2, 11- 2,15 (m, 2H) , 3,57 (t , 2H d J = 6, 4 Hz) , 3 ,21 (m, 1H) , 3 , 58 (m, 2H) , 3, 84 (d, 1H , J = 9,3 Hz) , 5, 56 (s ig, 1H) , 7 , 01 (s, 1H) , 7, 11 (t, 1H , J = 7,5 Hz) , , 7, 21 (t, . 1H, . J = 7 ,5 Hz) , 7,38 (d, 1H, J = 7,5 Hz) , 7 ,59 (d, 1H, r J = 7, 5 Hz) r 8,24 (s ig, 1H) . 1-176
pf: 116-118°C RMN de ΧΗ (CDCls) δ ppm: 1,18-1,38 (m, 2H) , 1,40 1,60-1,79 (m, 2H), 1, 95-2,30 (m, 5H) , 3, 30 (m, 1H) , 3,69 (m, 1H) , 3,80 (s, 3H) , 4,64 (s, 2H) , 6,67 (d, 1H, J = 8,0 Hz), 7,00 (d, 1H, J = 8,5 Hz), 7,15-7,24 (m, 2H), 7,32 (s lg, 1H) . 1-177 214 pf: 219-220 °C RMN de 1R (DMSO-d e) δ ppm: 1,27 (s, 9H) , 1, 28- 1, 50 (m, 4H) , 1,75-2, 01 (m, 4H) , 2,18-2,30 (m, 1H) , 2, 95- 3, 15 (m, 2H) , 4,61 (s , 2H) , 6,56 (m, 1H) , 6, . 80 (d, 1H, J = 8, 5 Hz) , 7,16 (m, 2H) , 7,28 (s lg , 1H), 9,87 (s ig, 1H) . 1-178
pf: 170-173°C RMN de (CDC13) δ ppm: 1,18-1,39 (m, 2H) , 1,40 (s, 9H) , 1,50-1, 80 (m, 2H) , 1, 90-2,33 (m, 5H) , 2,36 (s, 6H) , 2,75 (t, 2H, J = 5,5 Hz), 3,30 (m, 1H), 3,70 (m, 1H), 4,08 (t, 2H, J = 5,5 Hz), 6,68 (d, 1H, J = 8,0 Hz), 6,94 (d, 1H, J = 7,5 Hz), 7,15-7,23 (m, 2H), 7,33 (s lg, 1H) . 1-179
pf: 191-193°C RMN de XH (CDCI3) δ ppm: 1,20· -1,39 (m, 2H), 1,40 (s, 9H) , 1,58 -1, 80 (m, 2H) , 1, 98- 2,32 (m, 5H) , 3,30 (m, 1H) , 3,70 (d, 1H, J = 9, 5 Hz) , 4,77 (s, 2H) , 6, 73 (d, 1H, J = 8, 0 Hz) , 7, 04 (d, . 1H , J = 8,0 Hz) , 7,20 -7,31 (m, 2H) , 7,48 (s lg, 1H). 1-180 215
pf: 174-176°C RMN de ΧΗ (CDC13) δ ppm: 1 O \—1 \—1 -1,30 (m, 2H) , 1,40 (s, 9H) , 1,45 -1, 65 (m, 2H) , . 1,81- 2,02 (m, 3H) , 2,15- 2,30 (m, 2H) , 2,58 (t, 2H, J = 6, .5 Hz), 3,25 (m, 1H) , 3,37 (dt, 2H, J = = 5,5, 6, 5 Hz) , 3, 60 (d, 1H , J = 9,5 Hz) , 3,71 (s, 2H) , - 5, 73 (s lg, 1H), 7,20-7 ,40 (m, 5H) . 1-181
pf: 176-178°C RMN de ΧΗ (CDC13) δ ppm: 1 LO \—1 -1,30 (m, 2H) , 1, 39 (s, 9H) , 1,45 -1, 7 0 (m, 6H), . 1,85-2, 01 (m, 3H) , 2,15- -2, 28 (m, 2H) , 2, 63 (t , 2H, J = 7 ,0 Hz), 3,25 (dt , 2H, . J = 6, 0, 7,0 Hz) , 3,27 (m, r 1H) , 3,63 (m, 1H), 5, 35 (s ig, 1H) , 7, 17 (m, 3H) , 7,29 (m; 2H) . 1-182
pf: 152-154°C RMN de ΧΗ (CDCls) δ ppm: 1 ,15-1, 30 (m, 2H) , 1, 39 (s, 9H) , 1,45 -í, 65 (m, 2H) , 1, 85-2, 05 (m / 3H) , 2,09 -2, 25 (m, 2H) , 3,25 (m, 1H), 3,45 (dt, 2H, J = 5, ,0, . 5, 0 Hz) , 3, 55 (t, 2H, J = 5 ,0 Hz) , 3, 60 (m, 1H) , 4,51 (s , 2H) , 5, 81 (s ig, 1H) , 7,29- 7,40 (m, 5H). 216 1-183
pf: 208-211°C RMN de M (CDC13) δ ppm: 1,20-1,31 (m, 2H) , 1,39 (s, 9H) , 1, 62-1, 68 (m, 2H) , 1, 98-2,25 (m, 5H) , 3,30 (m, 1H) , 3,57 (d, 1H, J = 9,2 Hz), 4,59 (d, 2H, J = 5,8 Hz), 5,76 (s lg, 1H), 7,37 (dd, 1H, J = 8,4, 2,0 Hz), 7,46-7,52 (m, 2H) , 7,69 (s lg, 1H) , 7,78-7,83 (m, 3H) . 1-184
pf: 180-182°C RMN de M (CDC13) δ ppm: 1,22-1,37 (m, 2H) , 1,40 (s, 9H) , 1, . 60- 1, 69 (m, : 2H) , 2, CM 1 LO O 0 9 (m, 2H) , 2 ,21- 2,27 (m, 3H) , - 3, 45 (m, , 1H) , 3 , 64 (d, 1H, J = 9, .6 Hz), 4, 77 (d, 2H, J = 4,9 Hz) r 7, 43 (d, 1H, J = 8,6 Hz) , 7,46 (s ig, 1H) , 7, 61 (t, 1H , J = 1 ,7 Hz) , 7,73 (t , 1H, J = 7 ,7 Hz), 7, 87 (t, 1H, J = 7,7 Hz) r 8, 20 (t, 1H, J = 7,7 Hz) , 8,24 (d, 1H, J = 8, 6 Hz) . 1-185
pf: 260-261°C RMN de M (CDC13) δ ppm: 1,22-1,32 (m, 2H) , 1,39 1,60-1,70 (m, 2H), 1,97-2,01 (m, 2H) , 2, 11 (m, 1H) , 2,21-2,24 (m, 2H) , 3,30 (m, 1H) , 3,61 (d, 1H, J = 9,3 217
Hz),4,95 (d, 2H, J = 6,0 Hz), 5,85 (s lg, 1H), 7,33 (d, 1H,
J = = 4,8 Hz) , 7,62 (dd, 1H, J = 8,4, 6,9 Hz), 7,7 5 (dd, 1H, J = = 8,1, 6,9 Hz), 8,00 (d, 1H, J = 8,1 Hz), 8,20 (d, 1H, J = 8,4 Hz), 8,42 (d, 1H, J = 4,8 Hz). 1-186
pf: 231-233°C RMN de XH (CDC13) δ ppm: 1,23-1,40 (m, 2H) , 1,40 (s, 9H) , 1, 62-1,76 (m, 2H) , 2,04-2,10 (m, 2H) , 2,22-2,32 (m, 3H) , 3,30 (m, 1H) , 3, 95 (d, 1H, J = 9,3 Hz) , 5, 04 (d, 2H, J = 4 ,1 Hz), 7 , 61 (d, 1H, J = 5, 8 Hz) , r 7, 63 (s ig, 1H) , 7, 65 (dd, 1H, J = 8,2, 6,9 Hz) , 7, 73 (dd, 1H , J = 8,5, 6, 9 Hz) , 7,86 (d, 1H, J = 8,2 Hz) , 8, 10 (d, 1H, J = 8,5 Hz) , 8,42 (d, 1H, J = 5 ,8 Hz) . 1-187 pf: 184- 187 °C RMN de XH (CDC13: 1 δ ppm : 0 , 97 (t, . 3H, J = 7,3 Hz) , 1,18 :-1,30 i (m, γ 2H), 1, 39 (s, 9H) , 1 ,42- -1, 65 (m, 4H) , 1,70 -1,80 (m, 2H) , 1,94-2, 08 (m, 3H) , 2 ,18- -2,26 (m, 2H) , 3,29 (m, 1H) , 3,61 (d, 1H, J = 9, 5 Hz) , 3,93 (t, 2H, J = 6, 4 Hz) , 4,39 (d, 2H, J = 5,5 Hz) , r 5, . 67 (s lg, 1H), 6 ,79- 6, 83 (m, 3H) , 7,23 (t, 1H, J = 7, 6 Hz) . 1-188 218
pf: 224-226°C RMN de XH (CDC13) δ ppm: 1,16-1,31 (m, 2H) , 1,38 (s, 9H) , 1,55-1,70 (m, 2H) , 1, 92-2,07 (m, 3H) , 2,17-2,23 (m, 2H) , 3,21 (m, 1H) , 3,81 (s, 3H) , 3,83 (s, 6H) , 4,05 (d, 1H, J = 9,8 Hz), 4,34 (d, 2H, J = 5,8 Hz), 5,96 (s lg, 1H) , 6, 47 (s, 2H) . 1-189
pf: 217-218°C RMN de ΧΗ (CDC13) δ ppm: 1, 15- 1,30 (m, 2H) , 1,37 (s, 9H) , 1,52 -i, 66 (m, 2H) , 1, 90-2, 06 (m, 3H) , 2,13- 2,20 (m, 2H) , 2,93 (s , 6H), 3,24 (m, 1H) , 3, 94 (d, 1H , J = 9,5 Hz) , - 4, 30 (d, 2H , J = 5,5 Hz), 5,73 (s ig, 1H) , 6,69 (d, 2H, J = 8,9 Hz) , 7,12 (d, 2H, J = 8,9 Hz) . 1-190 pf: sólido amorfo RMN de ΧΗ (CDC13) δ ppm: 1,17-1,32 (m, 2H) , 1,39 (s, 9H) , 1,54-1,72 (m, 2H) , 1,96-2,13 (m, 3H) , 2,18-2,27 (m, 2H) , 3,30 (m, 1H) , 3,63 (d, 1H, J = 9,2 Hz), 4,51 (d, 2H, J = 5,8 Hz), 5,82 (s lg, 1H), 7,40 (d, 2H, J = 8,5 Hz), 8,02 (d, 2H, J = 8,5 Hz), 8,64 (s, 1H) . 219 1-191
pf: 126-128°C J = 7,4 (m, 9H) , 4,5 Hz), 7,26 (t, RMN de (CDC13) δ ppm: 0,97 (t, 3H,
Hz), 1,10-1,28 (m, 2H) , 1,36 (s, 9H) , 1,42-1,86 2,06-2,18 (m, 2H) , 3,22 (m, 1H) , 3,95 (t, 2H, J = 4,16 (s lg, 1H) , 4,85 (s, 2H) , 6, 82-6, 95 (m, 3H) , 1H, J = 7,8 Hz), 8,54 (s lg, 1H). 1-192
pf: 178-181°C RMN de XH (CDCI3) δ ppm : 0, .96 (t, 3H, J = 7,3 Hz) , 1, . 18· -1,52 : (m, 4H) , 1 ,39 (s, 9H) , r 1,58-1,76 (m, 4H) , 1, 92 -2, 00 (m, 2H) , 2,02-2, 29 (m, 3H) , 3,28 (m, 1H) , 3,78 (d, 1H, J = 9, 5 Hz) , 3,89 (t, 2H, J = 6,6 Hz), 6, 00 (s ig, 1H) , 6, 78 (s, 4H), 7 , 35 (s ig, 1H) . 1-193
pf: 187-188°C RMN de ΧΗ (CDC13+CD30D) δ ppm: 1,21-1,40 (m, 2H), 1,38 (s, 9H) , 1,52-1, 69 (m, 2H) , 1 , 90-2, r00 (m, 2H), 2,02- 2,20 (m, 3H) , 3,22 (m, 1H), 3,75 (s, r 3H) , 6,79 (s, 4H) . 1-194 220 pf: 251 -253 °C RMN de XH (DMSO-de ) δ ppm: 1,27 (s, 9H) , 1,24- 1,50 (m ., 4H) , 1, 72-1 , 83 (m, 2H) , 1, 91-1,99 (m , 2H) , 2,16 (m, 1H) , 3, 02 (m, . 1H) , 3, 82 (s, 3H) , 6,79 (d, 1H, J = 8,2 Hz) , 7, 01 (d, 2H , J = 8,8 Hz), 7,85 (d, 2H, J = 8,8 Hz) , 9, 72 (s lg, 1H), 8, 64 (s lg, 1H) . 1-195
pf: 183-185°C RMN de ΧΗ (CDC13) δ ppm: 1,22-1,37 (m, 2H) , 1,40 (s, 9H) , 1,58-1,75 (m, 2H) , 2,05-2,10 (m, 2H) , 2,20-2,30 (m, 3H), 3,32 (m, 1H), 3,70 (s, 2H), 3,73 (s, 3H) , 6,79 (s, 1H), 8,83 (s lg, 1H). 1-196
pf: 185-187°C RMN de ΧΗ (CDCls) δ ppm: 1 ,20-1,39 (m, 2H) O \—1 (s, 9H) , 1,44 (t, 6H, J = 7, ,0 Hz), 1, O 00 \—1 1 o qo (m, 2H) , 1, 95- 2,35 (m, 5H) , 3,30 (m, 1H) , 3,62 (d, 1—1 C-I II CO Hz) , 4,06 (q, 2H, J = 7,0 Hz), 4,09 (q, 2H, II o Hz) , • 6, 08 (s, 1H) , 7,02 (s, 1H) , 7,36 (s, 1H) . 1-197 221
pf: 211-213°C (s, 3H) , 7,43 (d, RMN de 1R (CDC13) δ ppm: 1 ,20- O \—1 (m, 2H) , 1,41 9H) , 1, 60 -1,80 (m, 2H), 2,00-2 ,36 (m, 5H) , 2, 61 (s, 3,32 (m, 1H) , 3, 64 (d, 1H, J = 9,2 Hz) , 7,28 (s, 1H) , (t, 1H, J = 7 ,5 Hz) , 7, 69 (d, 1H, J = 7,5 Hz) , 7,85 1H, J = 7, 5 Hz) , 8,02 (s, 1H) .
1-198 pf: 268-269°C (s, 1H) , = 8,
RMN de ΧΗ (CDCI3) δ ppm: 1,20-1,39 (m, 2H), 1,40 9H) , 1,42-2,32 (m, 7H) , 2,90-3,10 (m, 4H) , 3,30 (m, 3, 68 (d, 1H, J = 8,8 Hz), 6,59 (s, 1H) , 7,18 (d, 1H, J 7 Hz) , 7,59 (d, 1H, J = 8,7 Hz), 7,77 (s ig, 1H) . 1-199 pf: 221-224 °C 1-200 pf: 237-240 °C 1-201 pf: 87-90 °C 1-202 pf: 222-223°C 1-203 pf: 255-257°C
1-204 pf: 234-236°C 222 1-205 pf: 208-210°C 1-206 pf: 217-218°C 1-207 pf: 275-27 9°C 1-208 pf: 248-250°C 1-209 pf: 256-258 °C 1-210 pf: 270-271°C 1-211 pf: 219-220°C 1-212 pf: 260-261°C 1-213 pf: >300 °C 1-214
pf: 206-207°C RMN de ΧΗ (CDC13) δ ppm: 0, 93 (t, 3H, J = 7, 4 Hz) , 1, 30· -1,42 (m, 2H) , 1,49 (d , 6H, J = 6 ,9 Hz) , 1,53- -1, 65 (m, 2H) r 2, 61 (t, 2H, J = 7,7 Hz) , 4,15 (septeto, , 1H, J = 6, 9 Hz) r 7,04 (d, 1H, J = 8,2 Hz) , 7,20 (d, 2H, J = : 8, 2 Hz) , 7, 51 (d, 2H, J = 8,2 Hz), 7, 8S > (d, 1H, J = 8, 8 Hz) r 8,18 (s, 1H), 10,55 (s, 1H). 223 1-215 RMN de 1 H (CDCI3) δ ppm: 0, 93 (t, 3H, Hz) , 1, 30-1,41 (m, 2H), 1,52- 1, 63 (m, 2H) , 1, 95 2, 61 (t , 2H, J = 7, ,8 Hz), 6,99 (s lg , 1H) , 7, 20 (d, 8, 5 Hz) , 7,65 (d, 2H, J = 8,5 Hz) , 7, 93 (dd, 1H, 2, 5 Hz) , 8,28 (d, 1H, J = 8, 5 Hz) , 8,55 (d , 1H, J = (s, 2H, J = J = Hz) , 9,7 6 (s lg, 1H) . 7,3 6H) , J = 8,5, 2,5
Ia-1 pf:
RMN (s, 9H) , 1,62 J = 4,8 Hz) , 6,64-6,32 (m, 7,45 (s, 1H).
221-224 °C de XH (CDC13) -1,77 (m, 2H) , 3,21-3,38 (m, 2H) , 7,11 (s, δ ppm: 1,19-] 2,00-2,31 (m, 1H), 3,85 (t, 1H) , 7,20 (t, , 38 (m, 2H) , 5H) , 3, 18 (t 4H, J = 4,8 1H, J = 7,8 1,40 4H, Hz) , Hz) ,
Ia-3 pf: co 1 0 0 O RMN de ΧΗ (CDCI3) δ ppm: 1 , 25 (d, 6H , J = Hz) , r 1, 37 (d, 6H, J = 6, 9 Hz), 1, 59 -1, 70 (m, 2H) , 1,76- (m, 2H) r 2,32- -2,42 (m , 4H), 3,11- 3,. 23 (m, 3H) , 3, 39 (d, J = 10, 8 Hz) , 3,74-3, 8 6 (m, 2H), 4, 34 (t, 1H , J = 9,0 6, 3 1,88 2H, Hz) , 224 6,86 (d, 2H, J = 9,0 Hz), 7,30 (s, 1H) , 7,40 (d, 2H, J = 9,0 Hz) .
Ia-4
pf: 233-234°C RMN de XH (CDCls) δ ppm : 1 , 25 (d, 6H, J = 6,3 Hz) , 1, ,40 (s, 9H) r 1,26-1,37 (m, 2H) , i ., 62- 1,78 (m , 2H) , 2,00- -2, 22 (m, 5H) , 2 ,42 (t, 2H, J = = 11 ,7 Hz) , 3,20 -3, 40 (m, 1H) , 3, .46 (d, 2H, J = 10,5 Hz) , 3, . 67 (d, 1H, J = 9, 3 Hz) , 3,72- -3, 84 (m, 2H) r 6, 62-6,76 (m, 2H) , , 7 ,10 (s, 1H) , 7,18 (t, 1H, J = 7,8 Hz), 7,42 (s, 1H).
Ia-5
pf: 125-126°C RMN de ΧΗ (CDCls) δ ppm : 1,25 (d, 6H, J = = 6, 3 Hz) ; 1, 40 (s, 9H) \—1 1 CT3 LO \—1 70 (m, 2H) , 1 , 77-1 ,84 (m, 2H) r 2, 30- -2, 46 (m, 4H) , 3,24 (q, 2H, J = = 6,6 Hz) , 3 , 38 (d, 2H, j = 11, ,1 Hz) , 3 ,74- 3,88 (m, 2H) , 4, 08 (t, 1H, J = 5,7 Hz) r 6, 87 (d 2H, J = 8,7 Hz), 7,30 (s , 1H) , 7,41 (d, 2H , J = 8,7 Hz).
Ia- 6 pf: 22 9-230 °C 225 RMN de 1 H (CDC13) δ ppm: 1 , 25 (d, 6H, J = 6, 3 Hz) , 1,26 -1,34 (m, 2H) , 1,39 (d, 6H, J ' = 6 , 9 Hz), 1,61- -1,77 (m, 2H) , 1,98-1,26 (m, 5H) , 2,32- 2,46 (m, 2H) , 3, 15 (quinteto , 1H, J = 6, 6 Hz) , 3,22- -3,35 (m, 1H) , 3,39 (d, . 2H, J = 11,4 Hz) , 3,74 -3, 92 (m, 2H) , 3, 88 (d, 1H, J = 8, 4 Hz) , 6,96 -6,71 (m, 2H) , 7 , 05 (s ig, 1H) , 7,39 (d, 2H, J = = 9,3
Hz) .
Ia-7
pf: 253-254°C RMN de (DMSO) δ ppm: 1,24-1, 60 (m, 4H) , 1,27 (s, 9H) , 1,77-2,07 (m, 4H) , 2,16-2,34 (m, 1H) , 2,97-3,15 (m, 1H) , 6,78 (d, 1H, J = 7,2 Hz), 7,01 (t, 1H, J = 6,0 Hz), 7,27 (t, 2H, J = 6,6 Hz), 7,58 (d, 2H, J = 7,5 Hz), 9,78 (s, 1H).
Ia-8 pf: 257-258°C RMN de XH (DMSO) δ ppm: 1,22-1,54 (m, 4H) , 1,27 (s, 9H) , 1,77 00 00 \—1 1 2H), 1, 88-2,00 (m, 2H) , 2 ,16- 2,34 (m, 1H) , 2,23 (S, 3H), 2,92-3,14 (m, 1H) , 6,77 (d, 1H, J = 8,4 Hz) , 7,07 (d, 2H, J = 8,4 Hz), 7,46 (d, 2H, J = 8,1 Hz) , . 9, 68 (s, 1H) .
Ia- 9 226
pf: 231-232°C RMN de 1R (CDC13) δ ppm: 1, 21 (t, 3H, J Hz) , 1,22- -1,38 (m, 2H) , 1,40 (s, 9H) , 1, 62- -1,78 (m 1, 98 -2,31 (m, 5H) , 2,61 (q, 2H, . J = = 7, 5 Hz) , 3,24 -3, 1H) , 3,70 (d, 1H, J = 9, 9 Hz) , 7, 11 (s, 1H) , 7, 14 (d, = 8, 7 Hz) , 7, 40 (d, 2H, J = 8,7 Hz) . = 7,5 , 2H) , 38 (m,
2H, J
Ia-10 pf: 233-234°C RMN de 1H (CDCI3) δ ppm: 0, 96 (t, 3H, J Hz) , 1,20- -1,37 (m, 2H) , 1,40 (s, 9H) , 1,56- -1,78 (m 1, 98 -2,32 (m, 5H), 2,54 (t, 2H, , J = = 7, 2 Hz) , 3,23 -3, 1H) , 3, 66 (d, 1H, J = 9, 6 Hz) , 7,08 (s, 1H) , 7, 12 (d, = 8, 4 Hz) , 7, 39 (d, 2H, J = 8,4 Hz) . = 7,2 , 4H) ,
39 (m, 2H, J
Ia-11
pf: 243-244°C
RMN de ΧΗ (CDC13) δ ppm: 1,22 (d, 6H, J = 1,22 -1,77 (m, 4H) , 1,40 (s, 9H), 2, 01-2, 30 (m, 5H) , 2, 92 (m, 1H) , 3,24 -3,40 (m, • 1H), 3 , 66-3 , 69 (m, 1H) (s, 1H) , 7, 17 (d, 2H, J = 8,4 Hz), 7,41 - (d , 2H, J 6, 9) , 2,83-, 7,09 = 8,1
Hz) . 227
Ia-12 pf: 24 6-247 °C RMN de 1 H (CDC13) δ ppm: 0,80 (t, 3H, J = 7 ,5) , 1,20 (d, 3H, J = 7,2) , 1, 26- -1,77 (m, 6H) , 1,40 (s, 9H) , 2,01 -2,27 (m, 5H) , 2,51 -2, 60 (m, 1H) , 3,20- -3,38 (m, 1H) , 3, 64 -3, 69 (m, 1H) , 7,08 (s, 1H), 7, ,12 (d, 2H , J = = 8,4 Hz) , 7,41 (d, 2H, J = 8 ,4 Hz) • Ia-13 pf: 278- 2 7 9 ° C RMN de 1 H (CDC13) δ ppm: 1,22- -1,52 (m, 4H) , 1,29 (s, 9H) , 1,40 (s, 9H) , 1, 61- -1,77 (m, 2H) , 2,02 -2,30 (m, 5H) , 3,20 -3,30 1 (m , 1H) , 3, 66- -3, 69 (m, 1H) , 7,10 (s, 1H) , 7,33 (d, 2H, J = 9 , 0 Hz) , 7 ,42 (d, 2H, J ' = 8, 7 Hz) • Ia-14 pf: 263- 2 64 ° C RMN de 1 Ή (DMSO) δ ppm: 1,24- -1,51 (m, 4H) , 1,27 (s, 9H) , 1,82 -1,99 (m, 4H) / 2,19- 2,28 (m, 1H) , 2, 98- 3, 12 (m, 1H) , 6, 78 (d, 1H, J = 8, 7 Hz) , 7,: 33 (d , 2H, . J = 8,7 Hz) , 7, 61 (d, 2H, J = 9, 0 Hz) , 9, 94 (s, 1H) .
Ia-15 228
pf: 209-210°C RMN de XH (CDC13) δ ppm: 1,25 (d, 6H, J = 6,3 Hz), 1,40 (s, 9H) , 1,70-1, 98 (m, 8H) , 2,19-2,38 (m, 3H) , 3,39 (d, 2H, J = 11,7 Hz), 3,58-3, 92 (m, 3H) , 4,12-4,26 (m, 1H) , 6, 82-6, 96 (m, 2H) , 7,10 (lg, 1H) , 7,41 (d, 2H, J = 8,1 Hz) .
Ia-16
pf: 238-240°C RMN de 1H (DMSO) δ ppm: 1, 22-1, 52 (m, 4H) , 1,27 (s, 9H) , 1,81 -1,84 (m, 2H) , 1,93-1, 97 (m , 2H) , 2,16- -2,23 (m, 1H) , 2, 95- 3, 12 (m, 1H) , 3,70 (s, 3H) , 6,77 (d, 1H, J = 8,4 Hz) , 6, 85 (d, 2H, J = 9,0 Hz), 7,48 (d, 2H, J = : 9,3 Hz) , 9, 64 (s, 1H) .
Ia-17
pf: 245-246°C RMN de ΧΗ (DMSO) δ ppm: 1,22-1,52 (m, 4H) , 1,27 (s, 9H) , 1,83-1,87 (m, 2H) , 1, 94-1, 99 (m, 2H) , 2,20- 2,28 (m, 1H) , 2,98-3,12 (m, 1H), 6,78 (d, 1H, J = = 8,7 Hz) , 7,28 (d, 2H, J = 8,7 Hz) , 7,69 (d, 2H, J = 9,0 Hz) , 9, 64 (s, 1H) . 229
Ia-18 pf: 240-241°C 4H), 1,40 3,64-3,67 RMN de (CDC13) δ ppm: 1,22-1,78 (m, (s, 9H) , 2,05-2,33 (m, 5H) , 3,22-3,44 (m, 1H) , (m, 1H) , 6,61 (s, 1H) , 6, 69-6, 77 (m, 2H) .
Ia-19
pf: 240-241 C RMN de ΧΗ (CDC13) δ ppm: 1,24-1,77 (m, 4H), 1,40 (s, 9H) , (m, 1H), 1H) . 2,05-2,30 (m, 5H) , 3,22-3,38 (m, 1H) , 3,70-3,74 7,00-7,15 (m, 3H) , 7,36 (s, 1H) , 8,29-8,34 (m,
Ia-20
pf: 239-240 °C RMN de ΧΗ (CDC13) δ ppm: 1,24 -1,78 (m, 4H), 1,40 (s, 9H) , 2,02-2,30 (m, 5H) , 3,22-3,40 (m, 1H) , 3,63-3,66 (m, 1H) , 6,89-6, 84 (m, 1H) , 7,10-7,17 (m, 2H) , 7,22-7,34 (m, 1H) , 7,48-7,51 (m, 1H).
Ia-21 pf: 259-260°C 230 RMN de (CDCI3/DMSO) δ ppm: 1,21 (d, 6H, J = 6,0 Hz), 1,22-1,44 (m, 2H) , 1,40 (s, 9H) , 1, 60-1,78 (m, 2H), 1,87-2,03 (m, 2H), 2,08-2,29 (m, 3H), 2,39 (t, 2H, J = 10,2 Hz), 3,14-3,32 (m, 1H) , 3,19 (d, 2H, J = 11,4 Hz), 3,77-3, 93 (m, 2H) , 5,33 (d, 1H, J = 9,0 Hz), 6,84 (dd, 1H, JFH, HH = 8,1, 8,1 Hz), 7,20 (d, 1H, J = 7,8 Hz), 7,49 (d, 1H, JFH = 14,7 Hz), 8,86 (s, 1H) .
Ia-22 pf: 234-235°C RMN de v H (CDCI3) δ ppm: 1 ,20 (d, 6H, J = 5, Hz) , 1, 22- 1,44 (m, 2H) , 1, 38 (s, 9H) , 1 ,54- 1,76 (m , 2H) 1 σι \—1 2, 32 (m, 5H), 2,27 (s, 3H) , 2 ,39 (t, 2H, J = 10, 8 Hz) 2,87 (d , 2H, J = 11 -, 4 Hz) r 3,20-3, 40 (m, 1H) , 3,76 -3, 92 (m 2H) , 3, 91 (d, 1H, J = 9, 3 Hz) , 6 , 93 (d, 1H, J = 8, 1 Hz) 7,21 (s lg , 1H), 7, 27 (s lg , 1H), 7,36 (s ig, 1H) .
Ia-23
pf: 195-196°C RMN de ΧΗ (CDC13) δ ppm: 1 ,20- 1,44 (m, 4H) , 1 ,41 (s, 9H) , 1,59-1, ,76 (m, 2H) r 2,03-2, 14 (m, 2H) , 2,15-2 , 33 (m, 3H) , 3,20-3, 40 (m, 1H), 3, 64 (s, 1H, J = 9, 0 Hz), 7, 19- 7,24 (m, 1H), 7, 44 (s lg, 1H) , 7,52- 7, 63 (m, 2H) , 8,17 (d, 1H, J = 8,7 Hz). 231
Ia-24
pf: 209-210°C RMN de XH (CDC13) δ ppm: 1,22-1,39 (m, 2H) , 1,56 (s, 9H) , 1,61-1,78 (m, 2H) , 2,00-2,12 (m, 2H) , 2,17-2,33 (m, 3H) , 3,24-3,39 (m, 1H), 3, 67 (d, 1H, J = 9, 6 Hz), 6,90- 7,01 (m, 1H), 7,21 (s, 1H), 7, 95-8, 06 (m, 1H) .
Ia-25
pf: 278-281°C RMN de XH (DMSO-de) δ ppm: 1 ,10 (d, 6H, J = 6, 3 Hz) , 1,27 (s, 9H) , 1,28-1,55 (m, 4H) , 1, .78-2,00 (m, 4H) , 2,11 -2,26 (m, 1H) , 2 ,31 (t, 2H , J = 11, 1 Hz) , 3, 00- -3, 10 (m, 1H) , 3, 08 (d, 1H, J = 10,8 Hz) , 3, 67-3, 80 (m, 2H) , 6, 78 (d, 1H, J = 8, 7 Hz) , 7,08 (d, 1H, J = 9, 0 Hz) , 7, 41 (dd, 1H, J = 2, 4, 8,7 Hz) , 7 ,78 (d, 1H, J = 8 ,7 Hz), 9, 85 (s, 1H) .
Ia-26
pf: 253-255°C RMN de (DMSO-d6) δ ppm: 1,13 (d, 6H, J = 6, 0
Hz), 1,27 (s, 9H) , 1,28-1,52 (m, 4H) , 1,78-2,00 (m, 4H) , 2,21 (t, 2H, J = 11,1 Hz), 2,26-2,36 (m, 1H), 2,96-3,10 (m, 232 1Η) , 3,56 (d, 1H, J = 12,3 Hz), 3, 60-3,72 (m, 2H) , 6,66-6,84 (m, 4H) , 7,47 (t, 1H, J = 9,3 Hz), 9,28 (s, 1H) .
Ia-27
pf: 223-226°C RMN de XH (DMSO-d6) δ ppm: 1,09 (d, 6H, J = 6,3
Hz), 1,27 (s, 9H) , 1,28-1,54 (m, 4H) , 1,77-2,01 (m, 4H) , 2,32 (t, 2H, J = 11,1 Hz), 2,32-2,42 (m, 1H) , 2,90 (d, 1H, J = 11,4 Hz), 2,96-3,12 (m, 1H), 3,76-3,92 (m, 2H), 6,78-6,98 (m, 3H) , 7,68 (dd, 1H, J = 3,3, 8,7 Hz), 8,84 (s, 1H) .
Ia-28 pf: 237-238°C RMN de XH (CDC13) δ ppm: 1,22-1,44 (m, 2H) , 1,25 (d, 6H, J = 6,3 Hz), 1,40 (s, 9H) , 1,61-1,79 (m, 2H) , 2,05-2,32 (m, 5H) , 2,21 (s, 3H) , 2,38 (t, 2H, J = 10,2 Hz), 3,22-3,42 (m, 1H), 3,40 (d, 2H, J = 11,1 Hz), 3,65 (d, 1H, J = 9,3 Hz), 3,72-3, 90 (m, 2H) , 6, 70-6, 78 (m, 2H) , 6,81 (s lg, 1H) , 7,50 (d, 1H, J = 9,6 Hz).
Ia-29 pf: 208-209°C 233 RMN de XH (CDC13) δ ppm: 1 , 22 (d, 6H, J = Hz) , 1, 23- -1,40 (m , 2H) , 1,40 (s, 9H) , 1, 60- 1,78 (m, 2,00 -2, 16 (m, 2H) , 2,14 -2,33 (m , 3H) , 2,45 (t , 2H, J = Hz) , 3, 21 (d, 2H, J = 10,8 Hz), 3,24-3 , 38 (m, 1H) , 3, 63 1H, J = = 9 ,3 Hz), 3, 80- 3, 94 (m, 2H) , 5,33 (d , 1H, J = Hz) , 6, 66 (dd, 1H, JFH, HH = 6, 6, 6,6 Hz) , 7, 16 (s ig, 7,89 (dd, 1H, JFH, HH = 9,0, 9, 0 Hz) . 6, 0 2H) , 11,1 (d, 9, 0 1H) ,
Ia-30 pf: 284- 2 8 7 0 C RMN de XH (DMSO- d6) δ ppm: 1 , 08 (d , 6H, J = Hz) , 1, ,26 (s, 9H) r 1,28-1 , 53 (m, 4H) , 1,82- 2,22 (m , 2,25- -2, 39 (m, 1H) , 2 ,78 (t, , 2H , J = 10, 5 Hz) , 2, 97- -3, 14 1H) , 3, 18 (d, 2H, j = 11,4 Hz) , 3, 65-3, 76 (m, 2H) , 6, 79 6, 0 4H) , (m, (d, 1H, J = 8,7 Hz), 9,75 (s, 1H) .
Ia-31
pf: 200-201°C RMN de ΧΗ (CDC13) δ ppm: 1,22- O \—1 1 (m, 2H) , (s, 9H) , 1, 62-1,76 (m, 2H) , 2,04-2,32 (m, 5H) , 3,22- (m, 1H) , 3, 62-3, 66 (m, 1H) , 7,22-7,24 (m, 1H) , 7,38- (m, 1H) , 7,60 (s, 1H), 8,33-8, 36 (m, 1H) . 1.40 3.40 7,38
Ia-32 - 234 -
pf: 260-261°C
RMN de ΧΗ (CDCls/DMSO) δ ppm: 1, 25 -í, , 42 (m, 2H) 1, 38 (s, 9H) , 1, 64 (q, 2H, J = 13, 5 Hz) , 1, 95 (d, 2H r J 12 ,3 Hz) , 2, 16 (d, 2H, J = 10,5 Hz), 2, 18- -2, 32 (m, 1H) 3, 14- 3,30 (m, LO \—1 , 53 (d, 1H, J = 9,0 Hz), 7, 31 (d, 1H, = 8,7 Hz) , 7, 46 (dd, 1H, J = 2,4, 8 ,7 Hz), 7, 90 (d , 1H , J 2,1 Hz) , 9, 35 (s, 1H) . Ia-33 pf: 227 '°C RMN de ΧΗ (DMSO-i d6) δ ppm : 1, 27 (s, 9H) , 1,30- 1,56 (m, 4H) , 1, 78-2,01 (m , 2H), 2, 12-2 ,36 (m, 2H) , 2, 96- 3, 13 (m, 1H) , 3,70 (s, 3H), 3, 71 (s, 3H) , 6, 77 (d, 1H , J = 8,7 Hz) , 6, 85 (d , 1H, J = 8,7 Hz) , 7,06 (dd , 1H, J = 2,4, 8,7 Hz) , 7,33 (d, 1H, J = 2 ,4 Hz), 9, r 65 (s, 1H) . Ia-35 pf: 214 [ -216 ° C RMN de ΧΗ (CDCls) δ ppm: 1 , 23- 1,38 (m , 2H) , 1,40 (s, 9H) , 1, 6a -í, 76 (m, 2H) / 2,00-2, , 12 (m, 2H) , 2,20 -2,32 (m, 3H) , 3,24- -3,39 (m, 1H) , 3, 68 (d, 1H, J = : 9, 0 Hz) , 6, 77 (d, 1H, J = 8 ,7 Hz), 7,00 (dd , 1H, J = 2,4, 8, 7 Hz) , 7,77 (s, 1H), 8,45 (d, 1H, J = 2,4 Hz). 235
Ia-36 pf: 241-242 °C RMN de XH (CDCI3/DMSO) δ ppm : 1, 25-1 ,42 (m, 2H) , 1,37 (s, 9H) , 1, 62 (q, 2H, J = 11,7 Hz), 1, 93 (d, 2H, J = 12,0 Hz) , 2,12 (d, 2H, J = 10 ,8 Hz), 2, 16-2, r 30 (m, 1H) , 3, 12- 3,28 (m, 1H) , 3, 84 (s , 3H) , 6,07 (d, 1H, J = 8,4 Hz) , 6,89 (dd, 1H, JFH, HH = 9, 3, 9, 3 Hz) , 7,24 : (d, 1H, J = = 8,7 Hz) , 7,55 (d, 1H, JFH = 13, ,5 Hz) , 9,32 (s, 1H) .
Ia-37
pf: 248-249°C RMN de XH (CDC13) δ ppm: 0 ,60-0,73 (m, , 1H) , , 0 , 91 (d r 6H, J = 6, 6) , 1,12-1,40 (m, 2H) , 1,40 (s, 9H) , 1, 54- 1, 88 (m, 5H) , 1,98- -2,29 (m, 7H) , 3,: 22-3,37 (m, 1H) , 3, 51- 3, 54 (m, 2H) , 3,72 (d, 1H, J = 9,6), 6,88 (d, 1H , J = 8, 7) , 7, 06 (s, 1H) , 7,35 (d, 1H, J = 9,0) .
Ia-38
pf: 237-238°C RMN de ΧΗ (CDC13) δ ppm: 1,01 (d, 6H, J = 6, 6) , 1,20-1,40 (m, 2H) , 1,40 (s, 9H), 1,60-1,74 (m, 4H) , 1, 99- 2,28 (m, 7H) , 2,69- 2,82 (m, 2H), 3,02-3,14 (m, 2H) , 3, 20- 236 3,38 (m, 1H) , 3, 80-3, 90 (m, 1H) , 6, 83-6, 86 (m, 2H) , 7,14 (s, 1H) , 7,34 (d, 1H, J = 8,4) .
Ia-39
pf: 234-235°C RMN de M (CDCl3) δ ppm: 1,20-1,36 (m, 2H) , 1,40 (s, 9H) , 1, 60-1,77 (m, 2H) , 1, CM 1 O σι . 32 (m, 5H) , 3,21-3,39 (m, 1H) , 3,65 (d, 1H, J = 9, 6 Hz) , 6, , 87 (d, 1H, J = 8,7 Hz) , , 7,04 (s, 1H), 7,37 (dd, 1H, J = 2, 7, 8,7 Hz), 7,56 (d, 1H, J = 2 ,7 Hz).
Ia-40
pf: 257-258°C RMN de 1 H (DMSO-de) δ ppm: 1, 14 (d, 6H , J = 6 ,0 Hz) , 1,27 (s, 9H) , M 28-1,53 (m, 4H) , 1, 78-2, 00 (m, 4H) , 2,13 -2,256 (m , 1H) , 2 ,30 (t, 2H, J = 11, 7 Hz) r 2, 97- '3, 12 (m, 1H), 3, 53- -3, 67 (m, 2H), 4, 01 (d, 1H, , J = 12, r 3 Hz) , 6, 80 (dd, 1H, J = 3,0, 9, 0 Hz), 7, 79 (d, 1H , J ' = 9, 0 Hz) , 8, 27 (s, 1H), 9,66 (s, 1H) .
Ia-41 pf: 245-246°C 237 RMN de XH (CDCI3/DMSO) δ ppm: 1,25 -1,42 (m, 2H) 1,37 (s, 9H) , 1, 62 (q, 2H, J = 12 , 6 Hz) , 1, 94 (d, 2H, J : 11,1 Hz) , 2,13 (d, 2H, J = 11, 1 Hz) , 2,18- -2,35 (m, 1H) 3, 11- -3,29 (m, 1H) , 6, 07 (d , 1H, J = 8,1 Hz) , 6, 95- -7, 06 (m 1H) , 7, 14 -7,27 (m, 1H) , 7, 44 (d, 1H, J = = 7,2 Hz) , 7,79 (s 1Η), 9,48 (s, 1H).
Ia-43
pf: 294-295°C RMN de (DMSO-d6) δ ppm: 1,26 (s, 9H) , 1,28-1,53 (m, 4H) , 1,76-1, 87 (m, 2H) , 1, 89-2,00 (m, 2H) , 2,13-2,25 (m, 1H) , 2,96-3,10 (m, 5H) , 3,52-3, 60 (m, 4H) , 6,78 (d, 1H, J = 9,0 Hz), 6,88 (d, 2H, J = 9,0 Hz), 7,44 (d, 2H, J = 9,0
Hz) , 9,59 (s, 1H) .
Ia-44
pf: 250-252 °C RMN de XH (CDC13) δ ppm: 1 ,13 (d, 6H, J = 6, 3 Hz) , 1,21 -1, 38 (m, 2H) , 1 ,41 (s, 9H) , 1, 63 -1,80 (m, 2H) , 1, 93 (t, 2H, J = 10 ,8 Hz) , 2, 00-2 ,10 (m, 2H) , 2,16-2,32 (m -, 3H), 3,24 -3, 39 (m, 1H), 3, 54 (d, 2H, J = 10, 2 Hz) , 3,64 -3, 78 (m, 3H) , 7, 47 (s, 1H), 7, 69 (d, 2H, J = 9, 0 Hz), 7,73 (d, 2H, J = 9,0 Hz) .
Ia-45 238
pf: 193 °C RMN de 1R (DMSO-de) δ ppm: 1, 10 (t, 6H, J = = 7, Hz) , 1, ,26 (s, 9H) , 1,28-1,52 (m, 4H) , 1 , 75-1, ,86 (m, 2H) 1 CTl 00 \—1 -2, 01 (m, 2H) , 2,10-2,22 (m, 1H) , 2, ,96-3, , 10 (m, 1H) 3,30- -3, 52 (m, 12H) , 6,60 (d, 2H, J = 9, 0 Hz) , 6, 80 (d, 1H J = 9,0 Hz), 7,33 (d, 2H, J = 9,0 Hz), 9,46 (s, 1H) . Ia-46
pf > 300 °C RMN de ΧΗ (DMSO -d6) δ ppm: 1,28 (s, 9H), 1, 28- 1,58 (m, 4H) , 1,83- 2,04 (m, 4H) , 2, 23-2 ,36 (m, 1H), 2, r 46 (s, 3H) , , 3, 00 -3, 14 (m, 1H) , 6,79 (d, 1H, J = 8,7 Hz) , 7 ,34 (d, 1H, J = 8 ,7 Hz) , 7, 78 (d, . 2H, J = 8, 7 Hz) , 7, 89 (d, 1H, J = 8,4 Hz) , 7, 91 (s, 1H), 8 , 00 ( :d, 2H, J = 8,7 Hz), 10 , 13 (s, 1H) ,
Ia-47 pf: 236-237 °C RMN de ΧΗ (cdci3) δ ppm: : 0, 97 (d, 6H, J = 6, 6 Hz) , 1, 01 (d, 6H, J = 6, 6 Hz) , 1, 20-1 ,37 (m, , 2H) , 1 ,40 (s, 9H) , 1, 60- -1,84 (m, 3H) r 1,97-2, 31 (m, 5H) , 2 , 50 (t, 1H, J = 10,8 Hz) , 2,78 (dt, 1H, J = 3 ,3, 11, 4 Hz) , 3, 25-3, , 38 (m, 1H) , 3, 45 (d, 1H, J = 11 ,4 Hz), 3, . 75 (dt, 1H , J = 2, 4, 11, 4 Hz) , 239 4,02 (dt, 1H, J = 2,4, 11,4 Hz), 6,88 (d, 2H, J = 9,0 Hz), 7,05 (s, 1H) , 7,39 (d, 2H, J = 9,0 Hz).
Ia-48 pf: 228-229°C RMN de XH (CDCI3) δ ppm: 0,88 (t, 6H, J = 7 ,2 Hz) , 1, 19- LO \—1 (m, 4H) , 1, 40 (s, 9H) , 1 LO \—1 1,76 (m, 4H) , 1,76- 1, 92 (m, 1H) , 1,96- -2, 30 (m, 5H) , 2, 66- 3,20 (m, 3H) , 3,20- 3, 40 (m, 1H) , 3,78 (d, 1H, J = 9, 3 Hz) , 3, 82 (s, 1H) , 6,62- 6, 98 (m, 2H) , 7,09 (s \—1 ií 1—1 , 7, 37 (d, 2H, J = 7,8 Hz) .
Ia-49
pf: 262-263°C RMN de XH (CDC13/DMS0) δ ppm: 1,21 (d, 6H, J = 5,7
Hz), 1,26-1,34 (m, 2H), 1,37 (d, 6H, J = 5,4 Hz), 1,52-1,76 (m, 2H) , 1,85-2,03 (m, 2H) , 2,03-2,30 (m, 3H) , 2,30-2,53 (m, 2H), 3,02-3,33 (m, 4H), 3,75-3,98 (m, 2H), 5,70 (s lg, 1H) , 6, 73-6, 98 (m, 1H) , 7,14-7,25 (m, 1H) , 7,52 (d, 1H, JFH = 13,5 Hz), 8,86 (s lg, 1H) .
Ia-50 pf: 232-233 °C 240 RMN de XH (CDC13) δ ppm: 1, 21 (d, 6H, J = 6, 3 Hz) r 1,22-1 ,37 (m, 2H) r 1, 38 (d , 6H, J = 6, 9 Hz) , 1, 68 (q, 2H, j = 12, 6 Hz) , 1, 98- 2, 26 (m, 5H) , 2, 29 (s , 3H), 2,41 (t, 2H, j = 10,2 Hz) , 2, 88 (d, 2H, J = 11 ,1 Hz) , 3, 15 (septeto, 1H, j = 6,6 Hz) , - 3, 21- 3, 37 (m, 1H) , 3, 77- -3, 92 (m, 2H) , 3, 87 (d r 1—1 C-I = 7, 8 Hz) , 6, 88 1 <1 0 (m, 3H) , 7, 35 (s, 1H) .
Ia-51 pf: 211-212 °C RMN de XH (CDCI3) δ ppm: 1,20- -1,42 (m, 2H) , 1,26 (d, 6H, J = 6 , 3 Hz) , 1,38 (d, 6H, J = 6,9 Hz), 1, 62- 1,78 (m, 2H) r 1, 99- -2,28 (m, 5H) , 2,49 (dd, 2H, J = 10,5, 10,5 Hz) , 3, 17 (quinteto, 1H, J = 6,9 Hz) , 3,20-3,38 (m, 1H) , 3, 66 -3, 99 (m, 2H) , 3 ,90-4,01 (m, 3H) , 6, r62 (d, 1H , J = 9, 0 Hz) , 7, 06 (s, 1H), 7 ,90 (dd, 1H, J = 2,4 , 9,0 Hz), 8, 09 (d, 1H, J = 2, 4 Hz) .
Ia-52 pf: 247-249°C RMN de 1 H (CDCI3) δ ppm: 1, 21- 1,36 (m, 2H) , 1,40 (s, 9H) 1,62- 1,78 (m, 2H) , 1, 98- 2,32 (m, 5H) , r 2,55 (t, . 4H, J = 6, 0 Hz) , 3,23 -3,38 (m, 1H) , 3,55 (t , 4H, J = 6, 0 Hz) , 3,72 (d, 1H, J = 9, 6 Hz), 6, 94 (d, 2H, J = 9,0 Hz), 7,10 (s, 1H), 7,42 (d, 1H, J = 9,0 Hz). 241
Ia-53
pf: 234-235°C RMN de (CDC13) δ ppm: 1,22-1,38 (m, 2H) , 1,41 (s, 9H) 1,64-1,80 (m, 2H), 2,00-2,32 (m, 5H), 3,25-3,40 (m, 1H), 3,73 (d, 1H, J = 9,3 Hz), 7,43 (s, 1H), 7,48 (t, 2H, J = 7,5 Hz), 7,55-7, 66 (m, 3H) , 7, 68-7, 89 (m, 4H) .
Ia-54
pf: 235-236°C RMN de ΧΗ (CDC13) δ ppm: 1, 24- -1, 39 (m, 2H) , 1,25 (d, 6H, J = 6, 3 Hz), 1,39 (d, 6H, J = 6, 9 Hz) , 1, 60- 1,80 (m, 2H) , 2 ,00 1-2, 28 (m, 5H) , 2,21 (s, 3H) , 2, 38 (t , 2H, J = O \—1 8 Hz) , 3, 15 (septeto, 1H, J = 6 r 3 Hz) , 3,23 -3, 38 (m, 1H) , 3,40 (d, 2H , J = 11,7 Hz), 3,72- 3, 88 (m, 2H) , 3, 87 (d, 1H, J = 9 ,3 Hz) , 6, 78-6, 86 (m, 3H) , 7, 50 (d, 1H, . J = 9, 6 Hz) .
Ia-55
pf: 185-186°C RMN de XH (CDC13) δ ppm: 1,14 (d, 6H, J = 6, 3 Hz), 1,22-1,38 (m, 2H) , 1,41 (s, 9H) , 1, 62-1,78 (m, 2H) , 2,02 (t, 2H, J = 10,5 Hz), 2,02-2,10 (m, 2H), 2,16-2,31 (m, 3H), 3,24-3,39 (m, 1H) , 3,56 (d, 2H, J = 9,3 Hz), 3, 63-3, 80 (m, 242 3H) , 7,46 (dd, 1H, J = 1,5, 8,1 Hz), 7,51 (t, 1H, J = 8, 1 Hz) , 7, 63 (s, 1H), 7,81 (t, 1H, J = 1,8 Hz) , 7,98 (dt, 1H, J = 1,8, 8 ,1 Hz) .
Ia-5 6
pf: 22 9-230 °C RMN de M (DMSO) δ ppm: 1,27 (s, 9H) r 1,28- LO \—1 (m, 4H) , 1,38 (s, 6H) , 1 ,78 00 \—1 1 (m, 2H) , 1, 90 O o CM 1 (m, 2H) , 2,15 -2,30 (m, 1H) , 2 , 97 -3, 13 (m, 1H) , 4, 90 (s, 1H) , 6,79 (d, 1H, J = 9 ,0 Hz), 7, 34 (d , 2H, J = : 8, 7 Hz) , 7,48 (d, 2H, J = 8,4 Hz) , 9,72 (s, 1H) .
Ia-57 pf: 211-212 °C RMN de ΧΗ (CDC13/DMS0) δ ppm: 1,24-1,40 (m, 2H) , 1,38 (s, 9H) , 1,57-1,74 (m, 2H) , 1 \—1 (s, 3H) , 1,92-2 \—1 o (m, 2H) , 2, 12- -2,24 (m, 2H) , 2,51 (s ig, 1H) , 3, 18 -3, 33 (m, 1H) , 4, 96 (d, 1H, J = 9, 3 Hz), 7, 16- -7,53 (m, 9H) , 7, 41 (s, 1H) .
Ia-58 pf: 298-299°C 243 243 RMN de (DMSO-d6) δ ppm: 1,24 (s, 9H) , 1, 27 9H) , 1, 28-1, 54 (m, 4H) , 1,75-2,02 (m, 4H) , 2,14- -2, 28 1H) , 2, 97-3, 11 (m, 1H) , 6,78 (d, 1H , J = 8,4 Hz) , 7, 18 2H, J = = 9, 0 Hz) , 7 ,48 (d, 2H, J = 9,0 Hz), 9,46 (s r 9,76 (s , 1H) . (s, (m, (d, 1H) ,
Ia-5 9
pf: 253-254°C RMN de ΧΗ (CDC13) δ ppm: 1 , 22- O \—1 (m, 2H) , (s, 9H) , 1,65-1,81 (m, 2H) r 2,04-2, 16 (m, 2H) , 2,22- (m, 2H) , 3,24-3,41 (m, 1H) , 3, r 74 (d, 1H, J = 9, 6 Hz) , 7 1,41 2,36 ,40-Hz) , 7,54 (m, 3H) , 7,88-8,01 (m, 3H) , 8,66 (d, 1H, J = 1,5 9, 57 (d, 1H, J = 1,2 Hz) .
Ia- 60
pf: 213-214 °C RMN de (DMSO) δ ppm: 1,32- 1,50 (m, 2H) , (s, 9H) , 1,52 -i, 70 (m, 2H) r 1, 88- 2,00 (m, 2H) , 2,04- (m, 2H) , 2,22 -2, 38 (m, 1H) r 2, 65 (s, 3H) , 2,99 -3, 15 1H) , 6, 46 (d, 1H r J = 9,3 Hz) , 7, 28 (d , 1H, J = 9, 0 7,81 (s , 1H), 8,20 (s, 1H) , 8 ,47 (s i, 1H) , 9,89 (s, 1H) . 1,35 2,16 (m, Hz) ,
Ia- 61 pf: 274-275°C 244 RMN de (DMSO) δ ppm: 1 ,27 (s, 1H) , 1,28-1,58 (m, 4H) , 1,84-2, 0 8 (m, 4H) , 2, 22-2 ,40 (m, 1H) , 2,99-3,15 (m, 1H) , 3,01 (s , 3H), 6, 81 (d, 1H, J = = 8, 1 Hz) , 7,78 (d, 2H, J = 7,8 Hz), 7,84 (d, 2H, J = 8,4 Hz) , 8,18 (s, 1H), 10,43 (s, 1H).
Ia- 62
pf: 235-236°C RMN de XH (CDCls) δ ppm: 1, 22- 1,39 (m, 2H) , 1,41 (s, 3H) , 1,66-1 , 80 (m, 2H) r 2,01- -2, 12 (m, 2H) , 2,14- -2,22 (m, 1H) , 2,23-2, 34 (m, 2H), 3, 24-3, r 42 (m , 1H), 3,69 (d, . 1H, J = 9,5 Hz), 6, 44 (d, 1H, J = 9, 3 Hz) , , 7,27 (s ig, 1H) , 7,28 (d, 1H, J = = 9, ,3 Hz), 7,37 (dd, 1H, J = 2,4, 9, 0 Hz) , 7, 68 (d, 1H, J = 9, 6 Hz), 8 ,04 (d, 1H , J = 2,4 Hz) .
Ia- 63
pf: 277-279°C RMN de XH (DMSO-de) δ ppm: 1,27 (s, 9H) , 1,28-1,54 (m, 4H) , 1,77-2,02 (m, 4H) , 2,15-2,29 (m, 1H) , 2, 90 (s, 3H) , 2,96-3,13 (m, 1H) , 6,79 (d, 1H, J = = 8,7 Hz) , 7, 12 (d, 2H, J = 9, 0 Hz) , 7 ,54 (d, 2H, J = 9,0 Hz) , 9, 50 (s, 1H) , 9, 81 (s, 1H) .
Ia- 64 245
pf: 259-260°C RMN de 1R (DMSO-de) δ ppm: 1,26 (s, 9H), 1,26-1,50 (m, 4H) , 1,74 -1, 99 (m, 4H) , 2 , 10-2 , 25 (m, 1H) , 2,95-3,10 (m, 1H) , 6,78 (d, 1H, J = 8,7 Hz) , 6, 97 (d, 2H, J = 9, 0 Hz) , 7, 42 (d, 2H, J = 9,0 Hz) , 7,50- -7,71 (m, 5H), 9,73 (s, 1H) , 10 ,05 (s, 1H) .
Ia- 65 pf: 292-293°C RMN de ΧΗ (DMSO -d6) δ ppm: 1,27 (s , 9H), 1, 28- 1 ,54 (m, 4H) , 1, 62 -1, 72 (m, 2H) , 1,77-1 ,87 (m, 2H) , 1, 91- 2 ,10 (m, 4H) , 2,13 -2, 25 (m, 1H) , 2,98-3 ,12 (m, 1H), 3, 41- 3 , 52 (m, 2H) , 5,09 (s r 1H) , e i, 79 (d, 1H, J = 9, 0 Hz), 6 , 91 (d, 2H, J = 9,0 Hz), 7, 37 (d, . 2H, J = 9, 0 Hz) , 7,42 (d, 2H, J = 9, 0 Hz) , 7,51 (d, 2H, J = = 9, 0 Hz) , 9 ,56 (s, 1H) . I a- 6 6
pf > 300 °C RMN de 1H (DMSO-dg) δ ppm: 1,27 (s, 9H) , 1,28-1,58 (m, 4H) , 1,85· -2,02 (m, 4H) , 2,40- -2,52 (m, 1H) , 3,00-3,16 (m, 1H) , 6, 81 (d, 1H, J = 9,0 Hz) , 7,50-7,58 (m, 3H) , 7,90- 7,97 (m, 2H), 12,58 (s, 1H). 246
Ia- 67 pf: 199-200°C RMN de XH (DMSO-d e) δ ppm: 1, 14 (d , 6H, J = 6, 3 Hz) , 1, 28 (s, 9H) , 1, 31-1, 48 (m, 4H) , 1,76- 1,88 (m, 2H) , 2,17 (t , 2H, J = 11, 1 Hz) , 2,82 (t, 2H, J = 11,7 Hz) , 3,46 (d, 2H, J = 11, 4 Hz) r 3,20- 3,36 (m, 1H) , 3, 62 -3,74 (m, 2H) , 4,02 (d , 2H, J = 12, , 9 Hz) , 6, 83 (d, 2H, r J = 9, 0 Hz) , 6,89 (d, 1H, J = 8, 7 Hz) r 7,28 (d, 2H, J = : 9, 0 Hz) , 8,27 (s, 1H) .
Ia- 68
pf: 237-239°C RMN de (CDC13/DMS0) δ ppm: 1,40 (s, 9H), 1,49- 1,65 (m, 2H) , 1,99-2,10 (m, 2H) , 2,95 (t, 2H, J = 11,1 Hz), 3,36-3, 52 (m, 1H) , 4, 17 (d, 1H, J = 12,9 Hz), 5,84 (d, 1H, J = 8,7 Hz) 6 ,39 (d, 1H, J = 9,6 Hz), 7,21 (d, 1H, J = 9,3 Hz), 7, 51 (dd, 1H, J = 2,4, 9,3 Hz), 7,72 (d, 1H, J = 9, 9
Hz), 7,85 (d, 1H, J = 2,7 Hz), 8,04 (s, 1H).
Ia-69
pf: 259-260°C RMN de XH (DMSO) δ ppm: 1,25-1,55 (m, 4H) , 1,27 (s, 9H) , 1,82-2,05 (m, 4H) , 2,22-2,36 (m, 1H) , 2,98-3,17 247 (m, 1H), 4,16 (s, 3H), 6,80 (d, 1H, J = 8,4 Hz), 7,77-7,87 (m, 4H) , 10,16 (s, 1H) .
Ia-7 0
pf: 259-260°C RMN de XH (DMSO) δ ppm: 1, .28 (s, 9H) , 1, 36- 1,56 (m, 2H) , 1,80 -1, 92 (m, 2H) , 2,86-3, 02 (m, 2H) , 3, 36- 3,52 (m, 1H) , 4,04- 4,20 (m, 2H) , 6, r 92 (d, 1H, J = = 7,5 Hz) , 7 , Se 7,58 (m, 3H) , 8,00 -8,14 (m, 2H) , 8 , 90 (s, 1H) , , 9 , 08 is, 1H) , 9, 63 (s, 1H) .
Ia-71
pf: 228.229°C RMN de (CDC13/DMS0) δ ppm: 1,27-1,42 (m, 2H) ,
1, 38 (s, 9H) , \—1 1 r- LO \—1 , 75 (m, 2H) O CT) \—1 -2, 02 (m, 2H) , 2,12 2, 34 (m, 3H) , 3,14-3, 32 (m, 1H) , 5, 37 (d, 1H, J = 9, 3 Hz) 7, 38- -7,43 (m, 3H), 7, 46 (d, 2H, J = 8, 7 Hz), 7, 51-7, 60 (m 2H) , 7, 68 (d, 2H, J = 9, 0 Hz), 9 ,33 (s, 1H) . Ia- 75 pf: 169-170 °C RMN de (CDC13) δ ppm: 0,58-0,72 (m, 1H) , 0,80 (d, 3H, J = 6,6 Hz), 0,94 (d, 3H, J = 6,0 Hz), 1,14-1,35 248 248 1,74-2,06 (m 3,64-3,74 (m (m, 3H) , 1,39 (s, 9H) , 1,48-1, 66 (m, 2H) , 5H) , 2,06-2,44 (m, 6H) , 3,18-3,35 (m, 1H) , 1H) , 4,46-4, 60 (m, 1H) , 6, 98-7,38 (m, 5H) .
Ia-7 6
pf: 236-237 °C RMN de ΧΗ (CDC13/DMS0) δ ppm: 1,27- -í, 42 (m, 2H) , 1,38 (d, 6H, J = 6,6 Hz) , 1,60-1 ,78 (m, 2H) , , 94 -2, 06 (m, 2H) , 2,12 -2,30 (m, 3H) , 3, 06,3,34 (m, 2H) , 5, 10 (s lg, 1H) , 6,41 (d, 1H, J = 9,9 Hz) , 7,25 (d, 1H, J = 8, 4 Hz) , 7,48 (dd, 1H, J = 2, 4, 8,7 Hz) , 7,68 (d, 1H, J = 9, 9 Hz) , 8,12 (d, 1H, J = 2 ,4 Hz), 8,88 (s lg, 1H) .
Ia-77 pf: 117-118 °C RMN de XH (CDC13) δ ppm: 1, 38 (d, 6H , J = : 6, 9 Hz) , LO LO \—1 (quintetO, 2H, J = 5 ,4 Hz) , , 1 ΟΊ 1 \—1 σι \—1 (m r 2H) , 2,42 (t, 2H, J = 7,4 Hz) , 3, 10 -3,24 (m, 3H) , 4,77 (s ig, 1H) , 6,41 (d, 1H, J = 9, 6 Hz) r 7,18-7, 26 (m, 1H) , 7, 48 (dd, 1H, J = 1,8, co Hz) , 7, 67 (d, 1H, J = 9, 9 Hz) , 8, 01 (s, 1H) , 8,23 (s lg, 1H).
Ia-7 8 pf: 138-139°C 249 RMN de (CDC13) δ ppm: 1,41 (s, 9H) , 1,64 (quinteto, 2H, J = 6,6 Hz), 1,84 (quinteto, 2H, J = 7,3
Hz) , 2, 42 (t, 2H, J = 7, 5 Hz) , 3,26 (q, 2H, J = 6, 5 Hz) 4,59 (s lg, 1H), 6 ,41 (d, 1H, J = = 9,3 Hz) , 7,23 (d, 1H, J 8,7 Hz) , 7,49 (dd, 1H, J = 2, 4, 9, 0 Hz) , 7, 67 (d, 1H, J 9, 9 Hz) , 8,03 (d, 1H, J = 2,4 Hz) , 8, 28 (s lg, 1H).
Ia-79
pf: 289-290°C RMN de XH (DMSO) δ ppm: 1,24-1,63 (m, 4H), 1,28 (s, 9H) , 1,84 -2, 08 (m, 4H), 2,24 -2,41 (m, 1H) , 3, 00-3,16 (m, 1H) , 6, 82 (d, 1H, J = 8, 1 Hz) , 7,36-7,60 (m, 5H), 7,86- 7,99 (m, 2H) , 8,28 (s, 1H) , 10,50 (s, 1H) . Ia-80
pf: 239-240 °C RMN de XH (DMSO) δ ppm: 1,22 (d, 1H, J = 6,6 Hz) , 1,23-1,40 (m, 2H) , 1,40-1,59 (m, 2H) , 1,83-2,04 (m, 4H) , 2,23-2,39 (m, 1H) , 2, 98-3, 23 (m, 2H) , 7,00 (d, 1H, J = 7, 8 Hz) , 7,36· -7,59 (m, 5H) , 7,85-7, 97 (m, 2H) , 8,29 (s, 1H), 10,50 (s, 1H).
Ia-81 250
pf: 205-206°C RMN de ΧΗ (CDC13/DMS0) δ ppm: 1,40 (s, 9H) ,
(quinteto, 2H, J = 7, 0 Hz) , 1, 85 (quinteto, 2H, J : Hz) , 2, 45 (t, 2H, J = 7 ,5 Hz) , 3,24 (t, 2H, J = 6, 5 5, 17 (s lg , 1H) r 7,36- -7, . 54 (m, 5H) , 7,85 (d, 1H, J Hz) , 8, 07 (dd, 1H , J = 1, r 8 , 8,1 Hz) , 8,23 (d, 1H, J 1, 66 7,2 Hz) , 8,4 1,8
Hz) , 9,61 (s, 1H) .
Ia-82
pf: 216-217°C 6, 3 1, 98 1H) , (m, (d, 6, 3 3H) , (m, (s, RMN de ΧΗ (DMSO-d6) δ ppm: 1,14 (d, 6H, J =
Hz), 1,22 (d, 6H, J = 6,9 Hz), 1,22-1,53 (m, 4H) , 1,76- (m, 2H) , 2,21 (t, 2H, J = 10,8 Hz), 2,22-2,36 (m, 2, 96-3,20 (m, 2H) , 3,57 (d, 2H, J = 12,0 Hz), 3,60-3,74 1H) , 6, 66-6, 85 (m, 2H) , 6,98 (d, 1H, J = 7,8 Hz), 7,47 1H, J = 8,7 Hz), 9,30 (s, 1H) .
Ia-83 pf: 118-119°C RMN de ΧΗ (DMSO-dg) δ ppm: 1,41 (d, 6H, J =
Hz), 1,26 (s, 9H) , 1,40-1, 67 (m, 4H) , 2,17-2,36 (m, 2,97-3,10 (m, 2H) , 3,57 (d, 2H, J = 12,0 Hz), 3,61-3,74 1H) , 6, 67-6, 92 (m, 3H) , 7,48 (t, 1H, J = 9,0 Hz), 9,37 1H) . 251
Ia-84 pf: 2 65-2 67 °C RMN de 1 H (DMSO -d6) δ ppm: 1,21 (d, 6H, J = 6, 6 Hz) , 1, 20 -1,57 (m , 4H) , 1, 60 -2, 30 (m, 9H), 2, 99 -3,20 (m, 4H) , 3, 40- -3,52 (m, 2H) , 5 ,09 (s, 1H) , 6,91 (d, 2H , J = : 8,7 Hz) , 6, 98 (d, 1H, J = 7, 5 Hz) , 7,37 (d, 2H, J = 8,7 Hz) , 7,42 (d r 2H, J = 8,7 Hz) , 7, 51 (d, 2H, J = 8, 7 Hz) , 9,56 (s, 1H) .
Ia-85 pf: 185-186°C XH (DMSO -d6) δ ppm: 1 ,26 (s, 9H) , 1,42- -1, 72 (m, 6H) , 1, 96 -2,10 (m, 2H) , 2 ,26 (t, 2H, J = 6 , 9 Hz) , 2, 96- 3, 12 (m, 4H) r 3,41- 3,52 (m, 2H) , 5,09 (s, 1H) , 6, 88 (d , 1H, J = 8,7 Hz) r 6, 92 (d, 2H, J = 9,0 Hz) , 7,37 (d , 2H, J = 8,7 Hz) , 7, 43 (d, 2H, J = 9, 0 Hz) , 7,52 (d, 2H, J = 8,7 Hz) , 9, 63 (s r 1H) . Ia-86 pf: 162- 1 64 °C RMN de 1: H (DMSO -d6) δ ppm: 1,21 (d , 6H, J = 6, 6 Hz) , 1, 41 -1,73 (m, 6H) , 1 ,96-2,10 (m, 2H) , 2, 26 (t , 2H, J = 252
Hz) , 2,91-3,20 (m, 5H) , 3, 42-3, 52 (m, 2H) , 5, 09 (s, 6, 92 (d, 2H, J = 9,3 Hz) , 6,99 (t, 1H, . J = = 6, 0 Hz) , (d, 2H, J = 8,7 Hz), 7,43 (d, 2H, J = 9,3 Hz) r 7,52 7,2 1Η) , 7,37 (d, 2H, J = 8, 7 Hz) , 9, 64 (s, 1H) . Ia-87
pf: 245-247°C
Hz) , 1H) , Hz) , 1H) . RMN de XH (DMSO-d6) δ ppm: 1,22 (d, 6H, J = 6, 6 1,22-1,58 (m, 4H) , 1,81 -2,02 (m, 4H) , 2,22,2,36 (m, 3,00-3,20 (m, 2H) , 3, 01 (s, 3H) , 6,99 (d, 1H, J = 8,4 7,75-7,88 (m, 2H) , 8,19 (d, 1H, J = 1, 2 Hz), 10,43 (s,
Ia-88 pf: 208-209°C
Hz) , 1H) , Hz) , 1H) . RMN de ΧΗ (DMSO-d6) δ ppm: 1,22 (d, 6H, J = 6, 9 1,22-1,55 (m, 4H), 1,75 -1,98 (m, 4H) , 2,11-2,24 (m, 2,98-3,20 (m, 2H) , 5,96 (s, 2H) , 6,82 (d, 1H, J = 8,4 6,91-7,03 (m, 2H) , 7,30 (d, 1H, J = 1, ,8 Hz), 9,72 (s,
Ia-89
pf: 142-143°C 253 RMN de XH (DMSO -d6 ) δ ppm: 1, r 2 7 (s r 9H), 1,40-1, 66 (m, 4H) , 2,26 (t, 2H, J = 7,5 Hz) r 3, 02 (q , 2H, J = 6 , 6 Hz) , . 5, 96 (s, 2H) , 6, 82 (d, 1H, J = 8, r 4 Hz) r 6,88 (t, 1H, J = 8, . 4 Hz) , 6,94 (dd , 1H, J = = 1,8, 8, . 4 Hz) , 7, 30 (d, 1H, J = 1,8 Hz) , 9,78 (s, 1H).
Ia- 90 pf: 100°C RMN de (DMSO-d6) δ ppm: 1,20 (d, 6H, J = 6, 9
Hz), 1,40-1, 66 (m, 4H) , 2,26 (t, 2H, J = 7,5 Hz), 2,89-2,99 (m, 2H) , 3,13 (quinteto, 1H, J = 6,6 Hz), 5,96 (s, 2H) , 6,83 (d, 1H, J = 8,1 Hz), 6,91-7,02 (m, 2H) , 7,30 (d, 1H, J = 1, 8 Hz) , 9,78 (s, 1H) .
Ia- 91 pf: 189- 190 °C RMN de XH : (DMSO-d6) δ ppm: 1, ,26 (s, 9H) , 1,43- -1,71 (m, 4H) , 2,40 (t, 2H, J = 7 ,5 Hz) , 2, 97- 3,09 (m, 2H) , 3, 01 (s, 3H) , 6, 85 -6, 93 (m, 1H), 7,76-7, 88 (m, . 2H) , 8, 20 (d, 1H, J = 1,2 Hz) , 10,49 (s, 1H).
Ia-104 pf: 238-241°C 254 RMN de M (DMSO) δ ppm: 1,27 (s, 9H), 1,3-1,5 (m, 4H) , r 1, 8-2,0 (m, 4H) , 2,50 (m, 1H) , 3,05 (m, 1H), 6,55 (s ig, 1H) , 6,79 (d, 1H, J= 8,2), 7,15 (t, 1H, J= 4,8), 8,64 (d, 2H, J= 4,8).
Ia-105
pf: 232-234 °C M (DMSO) δ ppm: 1,26 (s, 9H) , LO \—1 1 CM \—1 (m, 4H) O CM 1 00 \—1 (m, 4H) , 2,55 (m, 1H) , 3, 05 (m, 1H) , 6,77 (d, 1H II co 9,92 (s, 2H) , 10,93 (s, 1H) .
Ia-106 pf: 226-228°C RMN de M (DMSO) δ ppm: 1,28 (s, 9H) r 1,22- 00 LO \—1 1 (m, 4H) , 1, 82- -2, 04 (m, 4H) , 2,29 (m, 1H) , 3, 07 (m, 1H) , 6,79 (d, 1H, J = 8,7 Hz), 7, 6 1 (dd, 1H, J = 1, 8 Hz, 8,7 Hz) , 8,04 (d, 1H, , J,= 8,7 Hz) , 8, 48 (d , 1H, 2, 1 Hz) , 9, 35 (s, 1H) , 10,05 (s , 1H) .
Ia-107
pf: 282-283°C RMN de M (DMSO) δ ppm: 1,22-1,57 (m, 4H) , 1,27 (s, 9H) , 1,80-2,04 (m, 4H) , 2,27 (m, 1H) , 3,06 (m, 1H) , 255 6,81 (d, 1H, J = 8,7 Hz), 7,32 (m, 1H) , 7,44 (t, 2H, J = 7,5 Hz), 7,57-7,72 (m, 6H) , 9,91 (s, 1H) .
Ia-108
pf: 191-192°C RMN de XH (DMSO) δ ppm: 1,24 -1,58 (m, 4H) , 1,28 (s, 9H) , 1,86-2, 04 (m, 4H) , 2,70 (m, 1H) , 3,08 (m, 1H) , 6,83 (d, 1H, J = 8,7 Hz), 7,63-7,79 (m, 2H) , 8,31 (d, 1H, J = 7,2 Hz) , 10,27 (s, 1H) .
Ia-109
pf: 283-285°C RMN de XH (DMSO) δ ppm: 1,24- O \—1 (m, 4H) , 1,28 (s, 9H) , 1, 87 -2 ,04 (m , 4H) , 2,42 (m, 1H) , 3,09 (m, 1H) , 3, 87 (s, 2H) , 6, 82 (d, 1H, J = 8,7 Hz) , 7,28 -7,43 (m, 3H) , 7, 60 (d, 2H, J = 7 ,8 Hz) , 7, 68 (d, , 1H, J = 7,2 Hz) , 7,89 (d, 1H, J = 7, 5 Hz) , 9 ,48 (s, 1H) .
Ia-110
pf: 2 63-2 65 °C RMN de XH (DMSO) δ ppm: 1,24-1,54 (m, 4H) , 1,27 (s, 9H) , 1,76-1, 87 (m, 2H) , 1,89-2,01 (m, 2H) , 2,17 (m, 1H) , 3, 04 (m, 1H), 4,01 (s, 4H) , 6,01 (s, . 2H) , 6,44 (d, 2H, 256 J = 8,7 Hz), 6,77 (d, 1H, J = 8,7 Hz), 7,39 (d, 2H, J = 9,0
Hz) , 9, 44 (s, 1H) .
Ia-111
pf: 239-241°C RMN de XH (DMSO) δ ppm: 1,24- -1,54 (m, 4H) , 1,27 (s, 9H) , 1,62-1, 76 (m, 4H) , i, 80- 2,02 (m, 4H) , 2,30 (m, 1H) , 2, 47-2,59 (m, 2H), 2, 66-2, 76 (m, 2H) , 6, 08 (m, 1H) , 6,79 (d , 1H, J = 9, 0 Hz) , 6, 88 (d , 1H, J = 6, 9 Hz) , 7,02 (t, 1H, J = 7,5 Hz) , 7,13 (d, 1H, J = : 7,5 Hz) , 8, 98 (s, 1H) .
Ia-124
pf: 247-249°C RMN de ΧΗ (DMSO) δ ppm : 1,15 (d, 6H, J = 6,3 Hz) , 1, 30 (s, 9H) , 2,15- -2,26 (m, 2H) , 3,48-3,57 (m , 2H) , 3 , 63- 3, 76 (m, 2H) , 6, 92 (d, 2H, J = 8,7 Hz), 7,59 (d, 2H, J = 9, 0 Hz) , 7,38 (d, 2H, J = 9, 0 Hz) , 7,87 (d, 2H, J = 8,7
Hz) , 9, 92 (s lg, 1H) , 9, 98 (s lg, 1H) .
Ia-125 pf: 228-232 °C 257 RMN de (DMSO) δ ppm: 1, 30 (s, 9H) , 1 LO \—1 2,08 (m, 2H) , 2,77 -2,89 (m, 4H), 7, 17 (d, 1H, J = = 8,4 Hz) , 7,39 (d, 2H, J = 9,0 Hz), 7,42- 7,48 (m, 1H) , 7, ' 64 (s ig, 1H) , 7,87 (d, 2H, J = 9, 0 Hz), 9 ,99 (s ig, 2H) • Ia- 126 pf: 244-246°C RMN de XH (DMSO) δ ppm: 1 ,31 (s, 9H) , 7, 42 (d, 2H, J = 8,4 : Hz) , 7 ,81 (dd, 1H, J = 2,1 Hz, 8,7 Hz) , 7, 93 (d, 2H, J = 9 , 0 Hz) , 8,05 (d, 1H, j = = 9, 0 Hz) , 8,66 (d, 1H, J = 2,1 Hz) , 9,29 (s, 1H), 10,05 (s ig, 1H) , io, 39 (s ig, 1H) .
Ia-127 pf: 238-239°C RMN de XH (DMSO) δ ppm: 1,30 (s, 9H) , 4,18- -4,27 (m, 4H) , . 6, 81 (d, 1H, J = 8,4 Hz), 7,16 (dd, 1H, J = = 2,7 Hz, 9, 0 Hz) , 7,34-7,42 (m, 3H) , 7,85 (d, 2H, J = 8, 4 Hz) , 9, 94 (s lg, 1H), 9,99 (s lg, 1H) .
Ia-128 pf: 286-287°C 258 RMN de (DMSO) δ ppm: 1,31 (s, 9H) , 7,41 (d, 2H, J = 8,7 Hz), 7,71 (d, 2H, J = 8,4 Hz), 7,91 (d, 2H, J = 8,7 Hz), 7,99 (d, 2H, J = 8,7 Hz), 10,05 (s lg, 1H), 10,44 (s lg, 1H).
Ia-129 pf: 232-234 °C RMN de XH (DMSO) δ ppm: 1,27 (s, 9H), 1,3-1,5 (m, 4H) , 1,8-2,0 (m, 4H) , 2,25 (1H, m) , 3,07 (m, 1H) , 6,80 (d, 1H, J=9, 0) , 7,37 (d, 1H, J= 8,1), 7,53 (t, 1H, J=8,l), 7,75 (t, 1H, J= 8,1), 8,12 s, 1H), 10,16 (s, 1H) .
Ia-130
pf: 274-277°C RMN de ΧΗ (DMSO) δ ppm: 1,27 (s, 9H) , 1,23- OD LO \—1 1 (m, 4H) , 1, 81 -2,03 (m , 4H) , 2,28 (m, 1H) , 3 ,07 (m, 1H) , 6, 80 (d, 1H, J = 8,4 Hz) , 7,36 (dd, 1H, J = 0, 9 Hz, 5,7 Hz) , 7,43 (dd, r 1H, J = = 2,1 Hz, 8, 7 Hz), 7, 60 (d , 1H, J = LO Hz) , 7,78 (d, 1H, J = 8,7 Hz) , 8,40 (d r 1H, 1, 8 Hz) , 9, 97 (s lg, 1H) .
Ia-131 pf: 259-260°C 259 RMN de (DMSO) δ ppm: 1,31 (s, 9H) , 7,40 (d, 1H, J = 4,8 Hz), 7,41 (d, 2H, J = 8,7 Hz), 7,66 (d, 1H, J =
5,1 Hz), 7,67 (dd, 1H, J = 1,8 Hz, 8,7 Hz), 7,84 (d, 1H, J = 9,0 Hz), 7,92 (d, 2H, J = 8,7 Hz), 8,50 (s, 1H) , 10,03 (s lg, 1H) , 10,27 (s lg, 1H) .
Ia-132 pf: 265-266°C RMN de XH (DMSO) δ ppm: 1, 17 (d, . 6H , J = 6,6 Hz) , (s, 9H) , 4, 10 (m, 1H), 7,35- -7,46 (m, 3H) , 7, 54 (d, 1H, 7,5 Hz), 7,87- 7,97 (m, 3H) , 8,15 (s ig, 1H) , 8,20 (d, 1H, J = 7,5 Hz), 10,03 (s lg, 1H), 10,25 (s lg, 1H).
Ia-133 pf: 249-250°C RMN de XH (DMSO) δ ppm: 1,31 (s, 9H) , 7,41 (d,
2H, J = 8,7 Hz), 7,45 (d, 1H, J = 5,4 Hz), 7,67 (dd, 1H, J
= 1,8 Hz, 8,7 Hz), 7,76 (d, 1H, J = 5,4 Hz), 7,92 (d, 2H, J = 8,7 Hz), 7,95 (d, 1H, J = 8,1 Hz), 8,39 (d, 1H, J = 1,8
Hz), 10,02 (s lg, 1H), 10,23 (s lg, 1H).
Ia-134 pf: 305-306°C 260 RMN de ΧΗ (DMSO) δ ppm : 1,25 (m, 2H) , 1,25 (s, 9H) , 1,52 (m, 2H) , 1,82 (m, 2H, ) , 1, 94 (m, 2H) , 2,13 (m, 1H) , 3, 04 (m, 1H) , 6,00 (d, 1H, J= 8,1) , 6, 74 (d, 1H, J= co 7,3- -7,5 (m, 6H) , 7,85 (d, 2H, J=7 ,5) , 8, 31 (d, 1H, J=8,4).
Ia-135
pf: 220-222 °C RMN de ΧΗ (DMSO) δ ppm: 1,27 (s, 9H) , 1,3- LO \—1 m, 4H), 1,8-2, 0 (m, 4H) , 2,37 (m, 1H) , 3, 03 (m, 1H) , 6, 80 a 1—1 J=8,7) r 7,04 (m, 1H), 7,29 (m, 1H) , 7,79 (m, 1H) , 9, 60 (s, 1H) .
Ia-136
pf: 2 63-2 64 °C RMN de (DMSO) δ ppm: 1,27 ( s, 9H) , 1,3-1,5 (m, 4H) , 1,8-2,0 (m, 4H) , 2,20 ( m, 1H) , 3,03 (m, 1H) , 6,80 (d, 1H, J= 8,4), 6,87 (m, 1H) , 7,31 (m, 2H) , 10,21 (s, 1H) .
Ia-137 pf: 2 60-2 62 °C RMN de ΧΗ (DMSO) δ ppm: m, 4H) , 1,8-2,0 (m, 4H) , 2,30 (m, 1,27 (s, 9H) , 1,3-1,5 ( 1H) , 3,05 (m 1H) , 6,80 261 (d, 1H, J= 8,4), 7,13 (t, 2H, J= 8,1), 7,31 (m, 1H) , 9,52 (s, 1H).
Ia-138 pf: 270-273°C RMN de (DMSO) δ ppm: 1,27 (s, 9H), 1,3-1,5 (m, 4H) , 1,8-2,0 (m, 4H) , 2,12 (m, 1H) , 3,05 (m, 1H) , 6,79 (d, 1H, J=9, 0) , 7,31 (m, 2H) , 7,80 (m, 1H) , 10,05 (s, 1H) .
Ia-139 pf: 267 -27C )°C RMN de XH (DMSO) δ ppm: 1, 30 (s, 9H), 4,05 (s, 4H) , 6, 04 (s, 2H) , 6, 51 (d, 2H, J = 8, , 7 Hz), 7,34 (d, 2H, J = 8, 4 Hz) , 7, 54 (d, 2H, J = 8,4 Hz) , 7, ,87 (d, 2H , J = 8,4 Hz) , 9, 82 (s ig, 1H) , 9, 97 (s lg, 1H) ,
Ia-140 pf: 227-229°C RMN de 1H (DMSO) δ ppm: 1,22 (d, 6H, J = 6,6 Hz) , 1,20- -1,57 (m 4H) , 1,80-2, 01 (m, 4H) , 2,27 (m, 1H) , 2, 95- 3,22 (m, 2H) , 6,99 (d,1H, J = = 7,8 Hz) , 7, 65 (d, 2H, J = 8,7 Hz) , 7,80 (d, 2H, J = 8,4 Hz) , io, ,18 (s ig, 1H) . 262
Ia-141
pf: 205-207 °C RMN de XH (DMSO) δ ppm: 1,22 (d, 6H, J = 6,9 Hz) , 1, 20- 1,55 (m, 4H) , 1,75· -2, 05 (m, 6H) , 2, 21 (m, 1H), 2,72- 2, 85 (m, 4H) , 2, 93· -3,20 (m , 2H) , 6, 98 (d, 1H, J = 8,1 Hz) , 7, 10 (d, 1H, J = 8,1 Hz), 7,26 (dd, 1H, J = 2 ,1 Hz, 8,1 Hz) , 7,51 (s, 1H) , 9, 67 (s ig, 1H) φ
Ia-142
pf: 295-296°C RMN de (DMSO) δ ppm: 1,15 (d, 6H,J=6,6), 1,27 (s, 9H) , 1,3-1,5 (m, 4H) , 1,8-2,0 (m, 4H) , 2,27 (m, 1H) , 3,05 (m, 1H) , 4,07 (m, 1H) , 6,80 (d, 1H, J=8,7), 7,64 (d, 2H, J=8,7), 7,79 (d, 2H, J=8,7), 8,06 (d, 1H, J=7,5), 10,01 (s, 1H).
Ia-143
pf: 146-147°C RMN de 1H (DMSO) δ ppm: 1,26 (s, 9H), 1,5-1,7 (m, 4H) , 2,36 (t, 2H, J=7,8), 3,03 (q, 2H, J=6,3), 6,89 (t, 1H, J=6,3), 7,66 (d, 2H, J=8,4), 7,80 (d, 2H, J=8,4), 10,25 (s, 1H) . 263
Ia-144 pf: 138-140°C RMN de 1 H (DMSO) δ ppm: 1,21 O II "D Ί3 1 \—1 1,7 (m, 4H) , 2,37 (t, 2H, J=7,5), 2,96 (q, 2H, J=6,3) , 3,14 (m, 1H), 6,99 (t, 1H, J=5,4) , 7,66 (d, 2H, J=7,8), 7, 81 (d, 2H, J=7,8), 10,26 (s, 1H) .
Ia-145
pf: 134-136°C RMN de ΧΗ (DMSO) δ ppm: 1 ,26 (s, 9H) , 1,39 (m 2H), 1,4-1,7 (m, 4H), 2,28 (t, 2H, J=7,2), 2,79 (m, 4H) 3,02 (q, 2H, J= 7,2), 6,88 (t, 1H, J=6,0), 7,10 (t, 1H J=6, 0) , 7,51 (s, 1H) , 9,73 (s, 1H).
Ia-146 pf: 135-137°C RMN de 1R (DMSO) δ ppm: 1,20 (d, 6H, J=6 , 6) , 1,4· 1,7 (m, 4H) , 1, 99 (m, 2H) , 2,28 (t, 2H, J=7 ,2) , 2,79 (m 4H) , 2 , 94 (q , 2H, J=6,3), 3,13 (m, 1H) / 6, 98 (t, 1H J=6, 9) , 7, 10 (d, 2H , J=8,l), 7,26 (d, 2H, J=8 ,D , 7,51 (s 1H) , 9, 73 (s, 1H) .
Ia-147 264
pf: 206-207 °C RMN de XH (DMSO) δ ppm: 1,29 (s, 9H) , 4,54 (d, 2H, J = 5,7 Hz), 7,35 (d, 2H, J = 9, 0 Hz) , 7,52 (d, 2H, J = 7,8 Hz), 7,69 (d, 2H, J = 8, 1 Hz) , , 7,83 (d, 2H, J = 8,7 Hz) , . 9, 02 (t, 1H, J = 5,7 Hz) , 9, 97 (s lg, 1H) .
Ia-148
pf: 250-251°C RMN de XH (DMSO) δ ppm: 1,30 (s, 9H) , 7,18 (t,
2H, J = 9,3 Hz), 7,40 (d, 2H, J = 8,7 Hz), 7,76 (dd, 2H, J = 5,1 Hz, 9,3 Hz), 7,88 (d, 2H, J = 9,0 Hz), 10,02 (s lg, 1H), 10,17 (s lg, 1H).
Ia-149 pf: 220- -222 °C RMN de XH (DMSO) δ ppm: 1 , 30 (s, 9H) , 3, 74 (s, 3H) , 6, 92 (d, 2H, J = 9, 0 Hz), 7,38 (d, 2H, J = 9, 0 Hz) , 7, 64 (d, 2H, J = 9,0 Hz), 7,87 (d, 2H, J = 9, 0 Hz) , 9, 99 (s, 2H) .
Ia-150 pf: 264-266°C 265 RMN de XH (DMSO) δ ppm: 1,31 (s, 9H), 1,66-1,76 (m, 4H) , 2,57-2,66 (m, 2H), 2,71-2,80 (m, 2H), 6, 98 (m, 1H) , 7,06-7,16 (m, 2H) , 7,38 (d, 2H, J = 9,0 Hz) , 7,90 (d, 2H, J = 8,7 Hz), 9, 60 (s, 1H) , 9,99 (s, 1H) .
Ia-151
pf: 235-236°C RMN de XH (DMSO) δ ppm: 1, 03-1, 39 (m, 5H) , 1,27 (s, 9H) , 1,55- -1,87 (m, 5H) , 3,73 (m, 1H) , 7,31 (d, 2H, J = 8,7 Hz) , 7,76 (d, 2H, J = 8,4 Hz), 8,01 (d, 1H, J = : 7,8 Hz) , 9, 90 (s, 1H) .
Ia-152 pf: 244-246°C RMN de XH (DMSO) δ ppm: 0, 50-0,72 (m, 4H) , 1,27 (s, 9H) , , 2,81 (m, 1H) , 7,31 (d, 2H, J = 8,7 Hz) , 7,73 (d, 2H, J = 8,7 Hz), 8,30 (d, 1H, J = 4,2 Hz), 9, 91 (s lg, 1H) .
Ia-153 pf > 300 °C RMN de (DMSO) δ ppm: 1,06 (m, 6H) , 1,27 (s, 9H) , 1,2-1,5 (m, 4H) , 1,8-2,0 (m, 4H) , 2,25 (m, 1H) , 2,7 266 266 (m, 1H) , 6, 80 (d, 2H, J=8,4), 10,01 (m, 1H) , 3,05 (m, 1H) , 3,51 (m, 4H) , 4,30 1H, J=8,4), 7,34 (d, 2H, J=8,4), 7,65 (d; (s, 1H).
Ia-154
pf: 247-249°C RMN de ΧΗ (DMSO) δ ppm: 1,05 (m, 6H) , 1,27 (s, 9H) , r 1,2-1, 5 (m, 4H) , r 1, 8-2,0 (m, 4H) , 2, 23 (m, 1H) , 2,77 (m, 1H), 3, 05 (m, 1H) , 3, .52 (m, 4H) , 4, , 33 (m, 1H) , 6, 80 (d, 1H, II o 7,03 (d, 1H, II <1 co , 7, , 35 (t, 1H, J= 7,8) , 7,59 (d, 1—' C-I II ^1 ,8) , 7 , 68 (s, 1H), 9, , 96 (s, 1H) .
Ia-155
pf: 258-259°C RMN de ΧΗ (DMSO) δ ppm: 1,25 (m, 2H) , 1,50 (m, 2H) , 1,86 (m, 2H) , 1,99 (m, 2H) , 2,28 (m , 1H) , 2, 93 (s 3H), 3,10 (m, 1H), 7,02 (d, 1H, J=7, 5) , 7, 65 (d, 2H J=8,4), 7,80 (d, 2H, J=8,4), 10,20 (s, 1H). Ia-156 pf: 250-253°C RMN de ΧΗ (DMSO) δ ppm: 1,28 (m, 2H) , 1,50 (m 2H) , 1,82 (m, 2H) , 2,00 (m, 4H) , 2,22 (m, 1H) , 2,79 (m 267 4Η) , 2,92 (s, 3H) , 3,11 (m, 1H) , 7,01 (d, 1H, J= (,1), 7,26 (d, 1—1 C-i = 8,1), 7 ,51 (s, 1H) 9 68 (s, 1H) . Ia- 157 pf: 259 -262 °C RMN de ΧΗ (DMSO) δ ppm : 1 ,13 (d, 6H, . J=6, 0) , 1,25 (m, 2H), : L, 50 (m, 2H) , 1 , 80 (m, 2H) , 1 , 95 (m, 2H) , 2, 17 (m, 3H) , 2, 92 (s, 3H) , 3, 10 (m, 1H) , 3, 70 (m,2H), 3, 68 (m, 2H) , 6,86 (d, 2H J=9 ,3) , 7, 00 (d, 1H , J = 7,2) , 7,43 (d, 2H, J=9, 3), 9, , 58 (s, 1H) .
Ia-158 pf: 298-300°C RMN de (DMSO) δ ppm: 1,31 (s, 9H) , 7,30-7,50 (m, 5H) , 7,63-7, 71 (m, 4H) , 7,87 (d, 2H, J = 8,7 Hz), 7,91 (d, 2H, J = 9,0 Hz), 10,03 (s lg, 1H), 10,22 (s lg, 1H).
Ia-159 pf: 278-281°C RMN de XH (DMSO) δ ppm: 0,74-1,87 (m, 20H), 1,29 (s, 9H) , 3,76 (m, 1H) , 7,32 (d, 2H, J = 8,4 Hz), 7,75 (d, 2H, J = 8,7 Hz), 7,75 (d, 1H, J = 8,7 Hz), 7,90 (s lg, 1H). 268
Ia-160 pf: 227-228 °C RMN de XH (DMSO) δ ppm: 1,22-1,55 (m, 4H) , 1,27 (s, 9H) , 1, 80-2,02 (m, 4H) , 2,23 (m, 1H) , 3,06 (m, 1H) , 6,78 (d, 1H, J = 8,7 Hz), 7 ,45 (t, 1H, J = 9, 9 Hz) , 7,82 (m, 1H) , 8,12 (dd, 1H, J = 2,4 Hz, 6,3 Hz), 10, 17 (s ig, 1H) . Ia-161 pf: 259-260°C RMN de XH (DMSO) δ ppm: 1,22-1,54 (m, 4H) , 1,27 (s, 9H) , 1,78-2,01 (m, 4H) , 2,16 (s, 3H) , 2,21 (m, 1H) , 3, 05 (m, 1H) , 6,77 (d, 1H, J = 8,4 Hz) , 7,12- -7,21 (m, 2H) , 7,53 (m, 1H) , 9, 90 (s lg, 1H) • Ia-162 pf: 222-226°C RMN de ΧΗ (DMSO) δ ppm: 1,15 (d, 6H ,J = 6, 3 Hz) , 1,26 (d, 6H, J = 6, 9 Hz) , 2, 16-2,26 (m, 2H), 3,31 (m, 1H) , 3,48-3,58 (m, 2H) , 3, 63-3, 76 (m, 2H) , 6,92 (d, 2H, J = 9,0 H) , 7,32 (d, 2H, J = 8,7 Hz), 7,59 (d, 2H, 9,0 Hz), 7,89 (d, 2H, J = 9,0 Hz), 9,92 (s, 1H) , 10,13 (s lg, 1H) . 269
Ia-163 pf: 197-200°C RMN de XH (DMSO) δ ppm: 1,26 (d, 6H, J = 6,3 LO σι \—1 -2, 0 9 (m, 2H) , 2,77-2,90 (m, 4H) , 3, 32 (m, 1H) , (d, 1H, J = 8 ,1 Hz) , 7,32 (d, 2H, J = 8, 7 Hz) , 7,45 1H, J = : 1,8 Hz j r 8,1 Hz) , 7,64 (s lg, 1H) , 7, 90 (d, 2H co Hz) , 9, 99 (s ig, 1H), 10,13 (s lg, 1H) φ
Hz) , 7, 17 (dd, J =
Ia-164
pf: 145-247°C (m, (d, 9, 63 1,27 (d, J = RMN de (DMSO) δ ppm: 1,27 (s, 9H), 1,3-2,0 16H), 2,19 (m, 1H) , 3,05 (m, 1H) , 4,74 (m, 1H) , 6,79 1H, J=9, 0) , 6,80 (d, 2H, J=9,0), 7,47 (d, 2H, J=9,0), (s, 1H).
Ia-165 pf > 300 °C RMN de ΧΗ (DMSO) δ ppm: 1,03-2,02 (m, 18H) , (s, 9H) , 2,26 (m, 1H) , 3,06 (m, 1H) , 3,73 (m, 1H) , 6,78 1H, J = 8,7 Hz), 7,63 (d, 2H, J = 9,0 Hz), 7,78 (d, 2H, 8,7 Hz), 8,02 (d, 1H, J = 8,1 Hz), 10,00 (s lg, 1H) .
Ia-16 6 270
pf: 200-201°C RMN de XH (DMSO) δ ppm: 1,03-2,02 (m, 18H), 1,27 (s, 9H), 2,25 (m, 1H), 3,06 (m, 1H), 3,73 (m, 1H), 6,78 (d, 1H, J = 8,7 Hz), 7,33 (t, 1H, J = 8,1 Hz), 7,46 (d, 1H, J = 8,1 Hz), 7,76 (m, 1H) , 7,94 (m, 1H) , 8,14 (d, 1H, J = 8,1 Hz) , 9, 92 (s lg, 1H) .
Ia-167
pf: 282-285°C (m, 4H) , 1,27 3,07 (m, 1H) , RMN de ΧΗ (DMSO) δ ppm: 1,22-1,57 (s, 9H) , 1, 87-2,03 (m, 4H) , 2,49 (m, 1H) , 6,83 (d, 1H, J = 8,7 Hz), 13,20 (s lg, 1H) .
Ia-168
pf: 120-124 °C RMN de XH (DMSO) δ ppm: 0,94-1,66 (m, 14H), 1,27 (s, 9H) , 1 O 00 \—1 -2,04 (m, 4H) , 2,25 (mlH), 2, 92 (m, 1H) , 3, 06 (m, 1H) , 6,78 (d, 1H, J = 8,7 Hz), 7,42- 7,53 (m, 2H) , 7, 63 (d, 1H, J = 7 ,2 Hz), 7,73 (m, 1H), 8,17 (m, 1H) , . 10, 11 (s ig, 1H) .
Ia-169 - 271 -
pf: 256-257 °C RMN de ΧΗ (DMSO) δ ppm: 0,93-1,20 (m, 5H), 1,24- 1,64 (m, 9H) , 1,27 (s, 9H) , 1, 80-2,02 (m, 4H) , 2,27 (m, 1H) , 2,87 (m, 1H) , 3,06 (m, 1H) , 6,79 (d, 1H, J = 9,0 Hz), 7,48 (d, 1H, J = 7,2 Hz), 7, 68-7,79 (m, 4H) , 10,17 (s lg, 1H) .
Ia-171
pf: 242-244°C RMN de XH (DMSO) δ ppm: 1,27 (m, 12H) , LO \—1 (m 4H) , 1, 90 (m, 4H) , 2,25 (m, 1H) , 3,07 (m, 1H) , 3, 67 (m 2H) , 6, 77 (d, 1H, J=8,7) , 6,90 (d, 1H, J=7,8), 7, 31 (t, 1H C-I II ^1 5), 7, 53 1—1 C-I II <1 co 7,59 (s, 1H) , 9,89 (s , 1H) .
Ia-172 pf > 310 °C RMN de ΧΗ (DMSO) δ ppm: 1, 27 (m, 12H) , 1,38 (m 4H) , 1,84 (m, 2H) , 1,97 (m, 2H) , 2 , 25 (m, 1H) , 3,07 (m 1H) , 3, 66 (m , 2H) , 6,81 (d, 1H r J=8, 7) , 7,20 (d, 2H J=6, 7), 7, 61 (d, 2H, <^l II co (s, 1H)
Ia-173 pf: 279-281°C 272 RMN de 1R (DMSO) δ ppm: 1- , 27 (s , 9H), 1,3-1,5 (m, 4H) , 1, 83 (m, 6H) , 1, 93 (m, , 2H) r 2,21 (m, 1H) , 2,36 (m, 2H) , - 3, 05 (m, 1H) , 3,54 (m, 2H) , 6, • 79 (d, , 1H, J=8,7), 7 ,16 (d, 2H, J= = 9, 0) , 7,56 (d, 2H, J=9, 0) , 9, 83 (s, 1H).
Ia-174
pf: 258-2 62 °C RMN de (DMSO) δ ppm: 0,29 (m, 2H), 0,53 (m, 2H) , 1,20 (m, 1H) , 1,27 (s, 9H), 1,3-1,5 (m, 4H) , 1,7- 2,0 (m, 4H) , 2, 20 (m, 1H) , 3 ,05 (m, 1H), 3,75 (d, 2H, J=6 , 9) , 6,79 (d, 1H, J=9,0) , 6, 83 (d, 2H, J= = 9,0), 7,46 (d, 2H, J=9, 0), 9, r 64 (s, 1H) .
Ia-175 pf: 246-248°C RMN de (DMSO) δ ppm: 1,27 (s, 9H), 1,3-2,0 (m, 18H) , 2,19 (m, 1H) , 3,04 (m, 1H) , 4,23 (m, 1H) , 6,79 (d, 1H, J=8,7), 6,84 (d, 2H, J=9, 0) , 7,45 (d, 2H, J=9,0), 9, 64 (s, 1H) .
Ia-176 pf: 200-202 °C 273 RMN de (DMSO) δ ppm: 1,27 (s, 9H), 1,3-2,0 (m, 18H) , 2,21 (m, 1H), 3, 05 (m, 1H) , 4,23 (m, 1H) , 6, 57 (d, 1H, J= 6,9), 6,80 (d, 1H, J=9,0), 7,0-7,2 (m, 2H) , 7,28 (s, 1H) , 9, 74 (s, 1H) .
Ia-177 pf: 2 66-2 68 °C RMN de ΧΗ (DMSO) δ ppm: 1,22-1,56 (m, 4H) , 1,27 (s, 9H) , 1,79-2,02 (m, 4H), 2,25 (m,1H), 3,05 (m, 1H) , 6,56 (m, 1H) , 6, 77-6, 84 (m, 2H) , 7,58-7,71 (m, 5H) , 9,92 (s lg, 1H)
Ia-178 pf: 223-224°C RMN de ΧΗ (DMSO) δ ppm: 1,26 -1 ,54 (m ,4H) , 1,27 (s, 9H) , 1, 81 -2,02 (m,4H), 2 ,45 (m, 1H) , 3 ,06 (m, 1H) , 6, 80 (d, 1H, J = 8,7 Hz), 8,15 I—1 C-I 2,4 Hz, r 9, 0 Hz) , 8,27 (d, 1H, J = 9,0 Hz), 8, 70 (m, 1H) , 10 , 85 (s ig, 1H) .
Ia-179 pf: 224-227°C RMN de ΧΗ (DMSO) δ ppm: 1,24-1,56 (m, 4H) , 1,27 (s, 9H) , 1,80-2,03 (m, 4H) , 2,27 (m, 1H) , 3,06 (m, 1H) , 274 274 6, 80 (d, 1H, J = 8,7 Hz) , 6,90 (d, , 1H, J = 1,8 Hz) 7,84 (m, 4H) , 8,60 (d, . 1H, J = 1, 8 Hz) , 10, .09 (s ig, 7,72-1H) .
Ia-180
pf: 22 6-227 °C 6 Hz) , , 2,27 = 8,7 ,19 (s RMN de (DMSO) δ ppm: 0,92 (d, 6H, J = 6,
1,26-1,55 (m, 4H) , 1,27 (s, 9H) , 1, 80-2,03 (m, 4H) (m, 1H) , 3,05 (m, 1H) , 3,20 (m, 1H) , 6,80 (d, 1H, J
Hz), 7,42 (d, 1H, J = 7,2 Hz), 7,67-7,79 (m, 4H), 10 lg, 1H).
Ia-181 pf: 191- -192 ° C RMN de 1 H (DMSO) δ ppm: 0,95 (d, 6H, J = = 6, 1,26 -í, 55 (m, 4H) , 1,27 (s, 9H) , 1,80-2,03 (m, 4H) (m, 1H) r 3,06 (m, 1H), 3, 23 (m, 1H) , 6,80 (d , 1H , J Hz) , 7, 41 -7,53 (m, , 2H), 7 , 58 (d, 1H, J = 7,2 Hz) , 7, 1H) , 8, 18 (m, 1H) , 10,13 (s lg, 1H). 6 Hz) , , 2,25 = 8,4 73 (m,
Ia-182 pf: 192-193 °C RMN de XH (DMSO) δ ppm: 0,30 (m, 2H) , 0,55 (m, 2H) , 1,2-1,5 (m, 5H) , 1,27 (s, 1H) , 1,8-2,0 (m, 4H) , 2,20 275 (m, 1H) , 3,04 (m, 1H) , 3,75 (d, 2H, J=6,9), 6, 58 (m, 1H) , 6,79 (d, 1H, J=8,7), 7,0-7,2 (m, 2H) , 7,31 (s, 1H) , 9,76 (s, 1H) .
Ia-183 pf > 310 °C RMN de ΧΗ (DMSO) δ ppm: 1,27 (s, 9H), 1,3- í, (m,4H), 1,82 (m, 2H) , 1,97 (m, 2H) , 2,04 (m, 2H) , 2,39 (m 1H), 2, 46 (t , 2H, J=7,8) , 3,07 (m, 1H) , 3,79 (t, 2H J=7,5), 6,79 (d, 1H, J=8,7) , 7,56 (m, 4H) , 9,80 (s, 1H) .
Ia-184
pf: 281-283°C RMN de ΧΗ (DMSO) δ ppm: 1,24-1,57 (m, 4H) , 1,27 (s, 9H) , 1,80-2, 04 (m, 4H) , 2,27 (m, 1H) , 3,06 (m, 1H) , 6, 80 (d, 1H, J = 9,0 Hz), 7 j , 33 (s , 1H), 7, 75 (d , 2H , J = 9,3 Hz) , 7,91 (d , 2H, J = 8, 7 Hz) , 8,16 (s, 1H) , 10, 09 (s ií 1-1 1H) .
Ia-185
pf: 22 6-227 °C RMN de (DMSO) δ ppm: 1,24-1,58 (m, 10H), 1,27 (s, 9H) , 1,81-2,02 (m, 4H) , 2,28 (m, 1H) , 2,78-2, 88 (m, 276 4Η) , 3,06 (m, 1H) , 6,80 (d, 1H, J = 8,7 Hz), 7,64 (d, 2H, J = 8,7 Hz), 7,82 (d, 2H, J = 8,7 Hz), 10,25 (s lg, 1H).
Ia-186 pf: 148-150°C RMN de XH (DMSO) δ ppm: 1,25-1,60 (m, 10H), 1,27 (s, 9H) , 1,82-2,03 (m, 4H) , 2,24 (m, 1H) , 2,82-2, 92 (m, 4H) , 3,06 (m, 1H) , 6,79 (d, 1H, J = 8,4 Hz), 7,36 (m, 1H) , 7,55 (t, 1H, J = 7,8 Hz), 7,84 (m, 1H) , 8,06 (m, 1H) , 10,18 (s lg, 1H).
Ia-187
pf > 310 °C RMN de XH (DMSO) δ ppm: 1,27 (s, 9H) , 1, 36 (s, 9H) , 1,43 (m, 4H) , 1,85 (m, 2H) , 1,93 (m, 2H) , 2, 27 (m, 1H) , 3,06 (m, 1H) , 6,80 (d, 1H, J=8,7), 7,58 (s, 1H) r 7, 62 (d, 2H), 7,75 (d, 2H, J=9,0), 10,00 (s, 1H) .
Ia-188 pf: 285-292°C RMN de ΧΗ (DMSO) δ ppm: 0,85 (t , 3H C-i II ^1 ,5) r 1, 11 (d, 3H, J=6,3) , 1, 26 (s, 9H) , 1,3-1,6 (m, 6H) , 1, 85 (m, 2H) , 1,95 (m, 2H) , 2, 27 (m, 1H) , 3,06 (m, 1H) , 3, 90 (m, 277 277 1Η) , J=8, 17H) 7,3 (s, 7,48 6,80 (d, 1H, J=8,4), 7,64 (d, 2H, J=8,7), 7,79 (d, 2H, 7), 7,99 (d, 1H, J=8,1), 10,02 (s, 1H).
Ia-189
pf: 278-281°C RMN de (DMSO) δ ppm: 1,27 (s, 9H), 1,2-2,0 (m, , 2,03 (m, 2H) , 3,03 (m, 1H) , 6,79 (d, 1H, J=8,4), 7,1-(m, 3H) , 7,94 (s, 1H) , 9,78 (m, 2H) .
Ia-190
pf > 310 °C (m, 17H) , 1,27 (d, 1H, J=8,7 ) , RMN de ΧΗ (DMSO) δ ppm: 1,1-2,0 9H) , 2,25 (m, 2H) , 3,03 (m, 1H) , 6,79 (m, 4H) , 9,71 (m, 2H) .
Ia-191
pf: 275-277 °C 1,31 (s, Hz) , RMN de ΧΗ (DMSO) δ ppm: 1,16 (d, 6H, J = 6,6 Hz) , (s, 9H) , 4,09 (m, 1H) , 7,41 (d, 2H, J = 8,7 Hz), 7,84 4H) , 7,90 (d, 2H, J = 9,0 Hz), 8,11 (d, 1H, J = = 7,5 O \—1 04 (s Ig, 1H), 10,30 (s lg, 1H).
Ia-192 278
pf: 204-205°C RMN de XH (DMSO) δ ppm: 1,15 (d, 6H, J = 6,6 Hz), 1,20-1,56 (m, 4H) , 1,22 (d, 6H, J = 6,6 Hz), 1,78-2, 00 (m, 4H) , 2,25 (m, 1H) , 2, 98-3,22 (m, 2H) , 4,06 (m, 1H) , 6,99 (d, 1H, J = 8, , 1 Hz) , 7,34 (t, 1H, J = 8,1 Hz) , 7,46 (d, 1H J = 7,8 Hz) , 7,75 (m 1H), , 7, 96 (m, 1H) , 8,17 (d, 1H, J 8,7 Hz) , 9, 94 (s lg , 1H) .
Ia-193
pf: 285-286°C RMN de XH (DMSO) δ ppm: 1,15 (d, 6H , J = 6,6 Hz) , 1,20 -1,56 (m, 4H) , 1,22 (d, 6H, J = 6 ,9 Hz) , 1, 79-2,00 (m, 4H) , 2,26 (m, 1H) , 2,97-3,20 (m, 2H) , 4, 07 (m, 1H) , 6,99 (d, 1H, J = 7, 8 Hz) , 7,64 (d, 2H, J = 8,7 Hz) , 7 ,79 (d, 2H, J = 8,7 Hz), 8 ,06 (d, 1H, J = 7,5 Hz) , 10, 02 (s lg, 1H) φ
Ia-194
pf: 248-250°C RMN de 1H (DMSO) δ ppm: 1,22-1,57 (m, 4H) , 1,22 (d, 6H, J = 6, 6 Hz) , 1,78-2,00 (m, 4H), 2,25 (m, 1H), 2,98- 3,22 (m, 2H), 6,56 (m, 1H) , 6, 82 (d, 1H, J = 3,3 Hz) , 6,99 (d, 1H, J = 7,8 Hz), 7,58-7,71 (m, 5H) , 9,92 (s lg, 1H) . 279
Ia-195 pf: 271-275°C RMN de (DMSO) δ ppm: 1,27 (s, 9H) , 1,28-1,56 (m, 4H) , 1,80-2,02 (m, 4H) , 2,25 (m, 1H) , 3,06 (m, 1H) 6, 80 (d, 1H, J = 9, 0 Hz) , 7, 57 (s, 1H) , 7, 62 -7,74 (m, 4H) 8,39 (s, 1H) , 9, 99 (s lg, 1H) . Ia- 196 pf: 226-228°C RMN de 1H (CDC13) δ ppm: 0,30 (m, 2H) , 1,23 (d 6H, J=6, 9), : 1,2-2,0 (m, 4H) , 2,20 (m, 1H) , 3, 10 (m, 2H) 3,76 (d, 2H, J=6, 9) , 6, 83 (d, 2H, J= 8,7) , 6,99 (d, 1H J=8, D , 7,46 (d, 2H, J=8, 7) , 9,65 (ε d 1H) .
Ia-197
pf: 173-175°C RMN de ΧΗ (DMSO) δ ppm :0,31 (m, 2H) , 0,56 (m 2H) , 1,22 (d, 6H, J= = 6,6), 1,2-1,5 (m, 4H) , 1,8-2,0 (m, 4H) 2,22 (m, 1H), 3, 10 (m, 1H) , 3,7 6 (d, 1H, J=7,2) , 6, 58 (d 1H, J=8,l), 7, 0-7,2 (m, 2H) , 7,32 (s, 1H), 9,78 (s , 1H) .
Ia-198 280
pf: 233-235°C RMN de M (DMSO) δ ppm: 1,25 (d, 6H, J=6, 9) , 1 CM \—1 2,0 (m, 16H) , , 2,19 (m, 1H) , 3,10 (m, 2H), 4,73 (m, 1H) , 6, 80 (d, 2H, J=8,7) , 6,98 (d, 1H, d =7,8), 7,45 (d, 2H, C-I II co 7) , 9, 63 (s, 1H). Ia- 199 pf: 185-186°C RMN de M (DMSO) δ ppm: 1,22 (d, 6H, J=6, 9) , 1,2- 2,0 (m, 1 6H) , r 2,22 (m, 1H) , 3,10 (m, 2H), 4,73 (m, 1H) , 6, 54 (m, 1H) , 7,0-7,2 (m, 2H) , 7,3 (s, 1H), 9,75 (s , 1H) . Ia- 200 pf: 235-237°C RMN de M (DMSO) δ ppm: 1,27 (s, 9H), 1,3 -1,6 (m, 6H) , 1,8 -2,0 (m, 6H), 2,20 (m, 1H), 3, 05 (m, 1H), 3, 45 (m, 2H) , 3,82 (m, 2H), 4,47 (m, 1H) , 6,79 (d, 1H, J=9, 0) , 6,89 (d, 2H, J=9, 0) , 7,47 (d, 2H,J=9,0), 9,66 (s, 1H) .
Ia-201 pf: 300-301°C 281 RMN de XH (DMSO) δ ppm: 1, 15 (d, 6H, J = 6,6 Hz) , 1,26 -i, 5 6 (m, 4H) , 1, 27 (s, 9H) , 1 ,82-2, 03 (m, 4H) , 2,23 (s, 3H) , 2,37 (m, 1H), 3, 06 (m, 1H), 4,07 (m, 1H) , 6,81 (d, 1H, J = 8,7 Hz), 7, 52 (d, 1H , J = 8, 4 Hz) , 7,62 (d, 1H, J = 8,4 Hz) , 7,68 (s, 1H) , 8 ,09 (d, 1H , J = 7,5 Hz) , 9,22 (s ig, 1H).
Ia-202
pf: 269-270°C RMN de XH (DMSO) δ ppm: 1,25- -1,26 (m, 4H), 1,27 (s, 9H) , 1,80-2, 03 (m, 4H) , 2, 25 (m, 1H) , 3,07 (m, 1H) , 6, 80 (d, 1H, J = : 8,4 Hz), 7 ,11 (m, , 1H) , 7,42 (d , 1H, J = 3, 6 Hz) , 7,48 (m , 1H), 7,58 (d, 2H , J = = 8,7 Hz), 7,64 (d, 2H, J = 8 ,4 Hz), 9, 92 (s lg, 1H) φ
Ia-203 pf: 271-273°C RMN de XH (DMSO) δ ppm: 1,14-1,54 (m, 9H) , 1,26 (s, 9H) , 1,63-1, 88 (m, 7H) , 1,89-2,01 (m, 2H) , 2,21 (m, 1H) , 2,42 (m, 1H) , 3 ,04 (m, 1H) , 6,79 (d, 1H, J = 9, 0 Hz), 7,11 (d, 2H, J = 8,4 Hz) , 7,47 (d, 2H, J = 8,1 Hz) , 9,70 (s lg, 1H).
Ia-204 282 pf: 250-251 °C RMN de ΧΗ (DMSO) δ ppm: 1,22-1, 39 (m r 2H) , 1,22 (d, 6H, J = ( 5, 6 Hz) , 1, 40- 1,57 (m 2H) , 1 , 80- 2, 01 (m, 4H) , 2,28 (m, 1H) , 2, 98-3, 21 (m, . 2H) , 7 ,00 (d, 1H, J 7,8 Hz) , 7,34 (s, 1H) , 7, 75 (d, 2H, J = = 9, 0 Hz) , 7, 91 (d, , 2H, J = 8,7 Hz) , 8,17 (s , 1H) , 10,10 (s ig, 1H) . Ia- 205 pf: 239-240 °C RMN de ΧΗ (DMSO) i 5 ppm: 1 ,27 (s, 9H) r 1, 2-1,5 (m, 4H) , 1,8 -2,0 (m, 5H) , 2, 08 (m, 2H) , 3, 05 (m, 1H) , 3, 80 (m, 4H) , 4, 95 (m, 1H) , 6, 79 (d, 1H, - J=8,7), 6, 83 (d, 2H, J=8, 7) , 7,48 (d, 2H, J=8 ,7) , 9, 6 6 ( !s, 1H) .
Ia-206 pf: 236-238 °C RMN de ΧΗ (DMSO) δ ppm:1,27 (s, 9H), 1,2 -1,7 (m, 8H), 1, 8-2,0 (m, 6H) , 2,18 (m, 1H) , 3,04 (m, 1H) , 3,3- -3, 6 (m, 2H) , 3,85 (m, 3H) , 6,80 (d, 1H, J=9, 0) , 6,84 (d, 2H, C4 II o 7,47 (d, 2H, J=9,0), 9,65 (s, 1H) .
Ia-207 pf: 224-226°C 283 RMN de M (DMSO) δ ppm: 1,27 (s, 9H) , 1 LO \—1 1 CM (m, 4H) , 1, 8-2,0 (m, 4H) , 2,24 (m, 1H), 2, 39 (m, 2H) , 3, 06 (m, 1H) , 3, 50 (t, 2H, J=7, 5), 3, 70 (t, 2H, J=6,3), 6, 78 (d, 1H, J=6 , 6) , 6, 83 (m, 1H) , 7,25 (m, 1H), 7,27 (m, 1H) , 7 ,54 (s, 1H) , 9, 61 (s, 1H) .
Ia-208 pf: 275 -277 °C RMN de ' lH (DMSO) δ ppm: 1 ,27 (s, 9H) , 1 LO \—1 1 00 (m, 4H) , 1, 8-2,0 (m, 4H) , 2,22 (m, 1H) , 2, 38 (m, 2H) , 3,07 (m, 1H) , 3, 47 (t, 2H, J=6 ,9), 3, 69 (t, 2H, J=6 , 6) , 6, 80 (d, 1H, J=8, 7) , 7, 14 (d, 2H, J=8,4), r 7 , 58 (d, 2H, J=8 ,4) , 9,83 (s, 1H) .
Ia-209
pf: 214-215°C RMN de (DMSO) δ ppm: 1,26-1,56 (m, 4H) , 1,27 (s r 9H) , 1, 80 -2, 03 (m, 4H) , 2, 25 (m, 1H) , 3, 06 (m, 1H) , 6, 59 (m, 1H) , 6, 81 (d, 1H, J = 8, 4 Hz), 6, 86 (d, 1H, J = 2, 7 Hz) , 7,28 -7, 40 (m, 2H) , 7, 47 (m, 1H) , 7, 75 (s, 1H) , 8, 01 (s, 1H) , 9, 91 (s lg , 1H) .
Ia-210 284 pf: 272- -275 °C RMN de ΧΗ ( IDMSO) δ ppm: 1,31 (s, 9H) , 6,59 (m, 1H) , 6, 87 (d, 1H, J = 3,3 Hz), 7, 41 (d, 2H , J = 8,7 Hz) , 7, 68 (d, 2H, J = 8,7 Hz) , 7, 72 (m , 1H) , 7, 83 (d, 2H, J = 8,7 Hz) , 7, 90 (d, 2H, J = 8,7 Hz) , 10,03 (s ig, 1H), 10,22 (s lg, 1H).
Ia-211
pf: 251-255°C RMN de XH (DMSO) δ ppm: 1,31 (s, 9H) , 7,36 (s, 1H) , 7, 41 (d, 2H, J = 8,4 Hz) , 7,91 (d, 2H, J = 8,4 Hz) , 7, 92 -8, 00 (m, 4H), 8, - 19 (s, 1H) , 10,06 (s ig, 1H), 10,38 (s ig, 1H) φ
Ia-212 pf: 241-244°C RMN de XH (DMSO) δ ppm: 1 , 30 (s , 9H) 1 O LO \—1 1,78 (m, 6H) , 1,81- -1, 97 (m, 2H) , 4 ,78 (m, 1H) , 6, 87 (d, 2H, J = 9, 0 Hz) , 7,38 (d, 2H, J = 8, Ί Hz), 7, 61 (d, : 2H, J = 9, 0 Hz) , 7,87 (d, 2H, J = 8,7 Hz), . 9, 97 (s lg, 1H) , 9,99 (s ig, 1H) .
Ia-213 285 pf: 283- 286°C RMN de 1 H (DMSO) δ ppm: 1 ,31 (s, 9H) , 7 ,12 (dd, 1H, J = 3, 6 Hz , 5, 1 Hz), 7 ,41 (d, 2H , J = 9 ,0 Hz), 7,46 (m, 1H) , 7, 50 (dd, . 1H , J = 1, 2 Hz, 5,1 Hz) , 7 ,64 (d, 2H, J = 8,7 Hz) r 7,82 (d, 2H, J = = 8,7 Hz), 7, 90 (d, 2H, J = 9,3 Hz) , 10 ,01 > (s ig, O \—1 \—1 22 (s lg, 1H) .
Ia-216 pf: 224-225°C RMN de 1 H (CDC13) δ ppm: 1 , 22 (d, LO II "D LO , 9) , 1,2- LO \—1 (m, 4H) , 1,8- 2,0 (m, 4H) , 2,45 (m, 1H) , 3,12 (m, 2H) , 6,99 (d, 1H, J=8 ,1), 8,15 < !m, 1H) , 8, , 27 (d, 1H, , J=9 ,0) , 8, 69 (s, 1H) , 10, 86 (s, 1H). Ia-219 pf: 270· -212° Q. RMN de XH (DMSO) δ ppm: 1,28 (s, 9H) , 1,34- 1,51 (m, 2H) , 1, 80 -1,92 (m, 2H) , 2,83- 2,97 (m , 2H) , 3, 32 (m, 1H) , 3,99-4,12 (m . 2H), 6, 92 (d, 1H , J = 8, 7 Hz) , 7,57 (d, 2H, J = 8,7 Hz), 7,68 (d, 2H, J = 9,0 Hz), 8,90 (s lg, 1H) .
Ia-220 pf: 187-189 °C 286 RMN de XH (DMSO) δ ppm: 1,28 (s, 9H), \—1 LO \—1 1 \—1 cn \—1 (m, 2H) , 1,78-1,90 (m, 2H), 2,78-2,93 (m, 2H) , 3,30 (m, 1H) , 3, 97-4,09 (m, 2H) , 6,90 (d, 1H, J = 8,7 Hz), 7,06 (t, 2H, J = 9,0 Hz) , 7, 44 (dd, 2H , J = 4, 8 1 Hz, 9,0 Hz) , 8,53 (s ig, 1H).
Ia-221
pf: 2 60-2 62 °C RMN de XH (DMSO) δ ppm: 1,12- 1,50 (m, 7H) , 1,28 (s, 9H) r 1, 63 -1, 90 (m, 7H), 2, 40 (m, 1H) , 2,76-2,91 (m, 2H) , 3, 28 (m, 1H), 3 ,96-4,09 (m, 2H) , 6, , 90 (d, 1H, J = : 8,7 Hz) , 7, 06 (d, 2H, J = 8,4 Hz), 7,32 (d , 2H, J = 8,4 Hz) , 8,40 (s lg , 1H) .
Ia-222 pf: 2 65-2 67 °C RMN de (DMSO) δ ppm: 1,23 (d, 6H, J = 6,6 Hz), 1,31-1,48 (m, 2H) , 1,77-1, 90 (m, 2H) , 2,84-2, 98 (m, 2H) , 3,16 (m, 1H) , 3,33 (m, 1H) , 3,96-4,10 (m, 2H) , 7,11 (d, 1H, J = 7,8 Hz), 7,57 (d, 2H, J = 8,7 Hz), 7,67 (d, 2H, J = 8,4 Hz) , 8,90 (s lg, 1H) .
Ia-223 287
pf: 183-186°C RMN de ΧΗ (DMSO) δ ppm: 1,23 (d, 6H, J = 6, 9 Hz) , 1,28 -1,47 (m, 2H) , 1,76-1, 88 (m, 2H) , 2,80-3,16 (m, 2H) , 3,16 (m, 1H) , 3,32 (m, 1H) , 3,94-4,07 (m, 2H) , 7,00- 7, 14 (m, 3H) , 7,44 (dd, 2H, J = 4,8 Hz, 9 , 0 Hz), 8,53 (s ig, 1H) .
Ia-224
pf: 232-234 °C RMN de XH (DMSO) δ ppm: 1, 12- 1,46 (m , 7H) , 1,23 (d, 6H, J = 6 ,6 Hz) , , 1,63-1 ,87 (m, 7H) , 2,40 (m, 1H) , 2,78- 2, 93 (m, 2H) , 3, 15 (m,1H), 3, 31 (m , 1H) , 3, 94 -4, 07 (m, 2H) , 7,06 (d, 2H, J = 8, ,4 Hz), 7, 09 (d , 1H, J = 8, 1 Hz) , 7,32 (d, 2H, J = 8,4 Hz), 8,39 (s lg, 1H). Ia-225
pf: 222-224°C RMN de XH (DMSO) δ ppm: 1,28 (s, 9H) , 1, 30-1 , 61 (m, 4H) , 1,77-1,98 (m, 4H) r 2, r 66- 2, 90 (m, 2H) , 3, 28 (m, 1H) , 3,40-3,50 (m, 2H) , 3, 79· -3 , 88 (m, 2H) , 3, 96· -4, . 08 (m, 2H) , 4,44 (m, 1H), ( 5, 85 (d, 2H 0 J = 9, 0 Hz) , 6, 91 (d , 1H , J = 9, 0 Hz), 7,31 (d, 2H, J = 9, 3 Hz) , 8, . 34 (s lg, 1H) φ
Ia-226 288
pf: 194-195 °C
RMN de XH (CDC13/DMS0) δ ppm: 1,39 (d, 6H, J = 7,2 Hz), 1,66 (quinteto, 2H, J = 6,8 Hz), 1,87 (quinteto, 2H, J = 7, 7 Hz) , 2 ,47 (t, 2H, J = 7, 5 Hz) , 3, 11- 3,22 (m r 1H) , 3,21 (t ' / 2H, J = 6,2 Hz), . 5, 00 (s lg, 1H) , 7,35 -7, 56 (m, 5H) , 7, 86 (d, 1H, J = 8,4 Hz) , í ), 05 (dd, 1H, J = 1, 8, 8,1 Hz) , 8, 20 (d, 1H, J = 1,8 Hz), 9, 24 (s, 1H) . Ia- 227 pf > 300 °C RMN de XH (DMSO) δ ppm: 1,22 (d, 6H, J = 6, 3 Hz) , 1,20 -i, 40 (m, 4H) , 1,74-2 ,10 (m , 4H) , 2,20- 2,40 (m r 1H) , 2,39 (s r 3H) , 3,00-3,30 (m, 2H), 6, 25 (s, 1H) , 6, 99 (s ig, 1H) , 7, 43 -7,57 (m, 1H), 7, 71 (d, 1H, J = 8,1 Hz) , 7, 76 (s, 1H) , 10 ,27 (s , 1H) .
Ia-228
pf: 168-169°C RMN de ΧΗ (DMSO) δ ppm : 1 ,26 (s, r 9H) , 1, 49 (quinteto, 2H , J = 7,5 Hz), 1, 64 (quinteto r 2H , J = 7 ,4 Hz), 2,38 (t, 2H, J = = 7,2 Hz) , 2,40 (s, 3H) , 3, 04 (q, 2H, J = 6,5 Hz) , 6, 25 (s, 1H), 6, 89 (t, 1H, J = 6, ,0 Hz) , 7, 48 289 (dd, 1H, J = 1,8, 8,4 Hz), 7,71 (d, 1H, J = 8,4 Hz), 7,77 (d, 1H, J = 1,8 Hz), 10,33 (s, 1H).
Ia-229 pf: 174-175°C RMN de XH (DMSO) δ ppm: 1,21 (d, 6H, J = 6,6 Hz) , 1,42 -1,56 (m, 2H) , 1,56-1,70 (m, 2H) , 2,33-2,42 (m, 2H) , 2,40 (s, 3H) , 2,90-3,02 (m, 2H) , 3,14 (septeto, 1H, J: = 6,5 Hz) , 6,26 (s, 1H) , 6,99 (s lg, 1H), 7 ,48 (d, 1H, J = = 8,4 Hz) , 7,71 (d, 1H, J = 8,7 Hz), 7,77 (s, 1H) , 10,33 (s, 1H) . Ia-: 230 pf: 194-195 °C RMN de XH (DMSO) δ ppm: 0,86 (d, 6H, J = 6, 9 Hz) , 1,25 -1, 65 (m, 4H), 1,27 (s, 9H) , 1,81- -2,05 (m, 5H) , 2,23- 2,35 (m, 1H) , 2,99-3,15 (m, 1H) , 3,36 (d, 2H, J = 7,2 Hz) , 6, 80 (d, 1H, J = 8,4 Hz) , 7 ,80 (d, 1H , J = 8,4 Hz) , 7,87 (d, 1H, J = 8 ,4 Hz) , 8,19 (s, r 1H), 10,44 (s, 1H).
Ia-231 pf: 221-222 °C RMN de XH (DMSO) δ ppm: 0,86 (d, 6H, J = 6,9 Hz), 1,22-1,40 (m, 2H) , 1,23 (d, 6H, J = 6,9 Hz), 1,40-1,58 (m, 290 290 2H) , 1H) , Hz) , 7,86 1,82-2,04 (m, 5H), 2,22-2,37 (m, 1H), 3,00-3,16 (m, 3,15 (septeto, 1H, J = 6,6 Hz), 3,36 (d, 2H, J = 7,5 6,99 (d, 1H, J = 7,5 Hz), 7,80 (d, 1H, J = 8,4 Hz), (d, 1H, J = 8,4 Hz), 8,19 (s, 1H), 10,45 (s, 1H) .
Ia-232
pf: 196-197 °C RMN de XH (CDC13) δ ppm: 0, 93 (d, 6H , J = 6, 6 Hz) , 1,42 (s, 1H) , 1 , 60 -1, 70 (m, 2H) , 1 , 88 (quintetOo 2H, J = 7,4 Hz) , 2,02- -2, 20 (m, 1H) r 2,46 (t, r 2H, J = 7,7 Hz), 3,29 (q, 2H, J = 6, . 1 Hz) , 3 ,48 (d, . 2H, J = 7 , 8 Hz) , 4,26 (t, 1H, j = 6, 0 Hz) , 7, 76 (d, 1H, J = 8, . 1 Hz) , 7,90 (dd, 1H, J = 1,8, 8,1 Hz) , 8, 07 (d, 1H, J = l,i 3 Hz) , 8,39 (s, 1H).
Ia-233
pf: 151-152°C RMN de 1 H (CDCI3) δ ppm: 0,93 (d, 6H, J = 6,6 Hz) , 1,40 (d, 6H , J = 6,6 Hz), 1,62- 1,69 (m , 2H) , 1,88 (quinteto, 2H , J : = 7,3 Hz), 2,03-2,16 (m, 1H), 2,47 (t , 2H, J = 7,5 Hz) , 3,21 (septeto, 1H, J = 6, 8 Hz), 3 ,23 (q, 2H, J = 6, 3 Hz) , 3, 48 (d, 2H, J = 7,5 Hz), 4,43 (t, 1H, J : = 6,0 Hz) , 7,76 (d, 1H, J = 8,4 Hz), 7,91 1 (dd, 1H, J = 1, 8 , 8,4 Hz) , 8,06 (d, 1H, J =1,8 Hz), 8,36 (s, 1H) .
Ia-234 291
pf: 219-220°C RMN de 1R (DMSO- -d6) δ ppm: 1,28 (s, 9H) , 1,30 O LO \—1 1 (m, 2H) r 1,74 -1,88 (m, 2H) , 2,83 (t, 2H, J = 11, 1 Hz) , 3,20 -3, 32 (m, 1H) , 3, 94- 4,07 (m, 2H) , 5, 94 (s, 2H) , 6, 77 (d, 1H, 07 = 8, 8 Hz) , . 6, 82 (dd, 1H, J = 1,8, 8,7 Hz) , 6,89 (d, 1H, J = 8, 7 Hz) , , 7,11 (d, 1H, J = 1,8 Hz) , 8,38 (s, 1H) .
Ia-235
pf: 280-282 °C RMN de 1R (DMSO-d6) δ ppm: 1,27 (s, 9H) , 1,26-1,57 (m, 4H) , 1, 86-2,03 (m, 4H) , 2,38-2,50 (m, 1H) , 3,00-3,14 (m, 1H) , 6,81 (d, 1H, J = 8,4 Hz), 7,29 (t, 1H, J = 8,4 Hz), 7,43 (t, 1H, J = 7,5 Hz), 7,73 (d, 1H, J = 8,4 Hz), 7,96 (d, 1H, J = 7,5 Hz), 12,27 (s, 1H).
Ia-237
pf: 204-205°C RMN de ΧΗ (DMSO) δ ppm: 1,23 (d, 6H, J = 6, 6 Hz) , 1, 29 -1, 61 (m, 4H) , 1,75-1,98 (m, 4H) , 2, 78-2,92 (m, 2H) , 3, 15 (m, 1H) , 3,29 (m, 1H) r 3,38-3,51 (m , 2H) , 3,78- -3,89 (m r 2H) , 3, 94- -4,06 (m, 2H) , 4, ,44 (m, 1H), 6,85 (d , 2H, J = 9, 0 Hz) , 7,10 (d, 1H, J = 7, 8 Hz), 7,31 (d, 2H, J = = 9,3
Hz), 8,34 (s lg, 1H). 292
Ia-238 pf: 128-130°C RMN de XH (DMSO) δ ppm: 1 ,26 (s, 9H), 1,41-1,53 (m, 2H) , 1,55-1,68 (m, 2H) , 2,44 (t, 2H, J = = 7,2 Hz), 2,98- 3, 07 (m, 2H) , 6,90 (t, 1H, J = 6, 0 Hz) , 8, 16 (dd, 1H, J = 2,1 Hz, 8,7 Hz) , 8 ,29 (d, 1H, J = 8,7 Hz) , 8,70 (m, 1H), 10, 91 (s lg, 1H) .
Ia-239
pf: 256-258 °C RMN de XH (DMSO) δ ppm: 1,26- -1,53 (m, 4H) , 1,26 (s, 9H) , 1,76' -2, 00 (m, 4H) r 2,23 (s, 3H) , 2,39 (m, 1H) , 3, 04 (m, 1H) , 6, 80 (d, 1H, j = 8, 7 Hz) , 7,57 (dd , 1H, J = 2,4 Hz, 8,4 Hz), 7, 97 (d, 1H , J : = 8,4 Hz) , 8,12 (m, 1H) , 10,26 (s lg, 1H).
Ia-240
pf: 288-290°C RMN de ΧΗ (DMSO) δ ppm: 1,26- -1,53 (m, 4H) , 1,27 (s, 9H) , 1,78-1, 90 (m, 4H) , 2,40 (m, 1H) , 3, 04 (m, 1H) , 6,81 (d, 1H, J = 8, 7 Hz), 7, 07 (m, 1H) , 7,75 (m, 1H) , 8,07 (d, 1H, J = 8,4 Hz), 8,29 (m, 1H) , 10,36 (s lg, 1H) . 293
Ia-241 pf: 24 9-250 °C RMN de XH (DMSO) δ ppm: 1, 28 (s, 9H) , 1,34-1 O LO (m, 2H) , 1,79· -i, 90 (m, 2H) , 2,74-2, , 98 (m, 2H) , 3, 32 (m, 1H) , 4, 02-4,14 (m, 2H) , 6, 91 (d, 1H, J = = 8, 4 Hz) , 7, 94 (d, 1H, J = = 9,0 Hz), 8 ,04 (dd, 1—1 C-I II 2,1 Hz , 9,0 Hz) , 8 , 60 (s, 1H) , 9,76 (s lg , 1H) φ
Ia-242 pf: 250-252 °C RMN de (DMSO) δ ppm: 1,24 (s, 9H) , 1,27 (s, 9H) , 1,24 -1,54 (m, 4H) , 1, 76-1,88 (m, 2H) , 1, 90 -2, 01 (m, 2H) , 2,21 (m, 1H) r 3, 05 (m, 1H), 6 ,79 (d, 1H , J = 8, 7 Hz) , 6, 88 (d, 2H, J = 9, 0 Hz) , 7, 48 (d, 2H, J = 9, 0 Hz) , ‘ 3,72 (s ig, 1H) . 136- 0290 pf: 250 -252 °C RMN de XH (DMSO) δ ppm: 1 ,15 (d, 6H , J = : 6, 6 Hz) , 1,28 (s, 9H) , 1, 35 -1,52 (m, , 2H) , 1,78 -1, 92 (m, 2H) r 2,20 (s, 3H) , 2,81 -2, 96 (m, 2H) , 3,33 (m, 1H) , 3, 96 -4, 16 (m,
3H) , 6,92 (d, 1H, J
8,7 Hz), 7,27 (d, 1H, J 8,1 Hz) 294 7,60 (m, 1H) , 7,66 (m, 1H) , 8,06 (d, 1H, J = 7,8 Hz), 8,14 (s lg, 1H).
Ia-244
pf: 211-213°C RMN de XH (DMSO) δ ppm: 1,29 (s, 9H) , 1, 35- 1,52 (m, 2H) , 1,81· -1, 93 (m, 2H) , 2, 83- 2, 97 (m, 2H) , 3 , 32 (m, 1H) , , 4,03- 4, 14 (m, 2H) , 6,93 (d, 1H , J = 8,7 Hz) , 7, 55 (dd, 1H, J = 2 ,1 Hz, 9, 0 Hz), 7 , 94 (d, III, J = 9, 0 Hz) , 8,29 (d, 1H, J = 1,8 Hz) , 8,78 (s ig, 1H) , 9,19 1 (s, . 1H) φ
Ia-245 pf: 196-197 °C RMN de ΧΗ (DMSO) δ ppm: 1,27 (s , 9H), 1,2-1,6 (m 6H) , 1, 8-2,0 (m, 6H) , 2,23 (m, 1H), 3, 05 (m, 1H) , 3,73 (m 4h) , 4 ,99 (s , 1H) , 6,79 (d, 1H, J= = 8, 7), 7,13 (d, 1H J=6, 8) , 7,22 (t, 1H, J=6,8) , 7, 49 (d, 1H , J= 6,8), 7,72 (s 1H) , 9, 78 (s, 1H) .
Ia-246 pf: 242-244°C RMN de (DMSO) δ ppm: 1,27 (s, 9H), 1,2-1,5 (m, 4H) , 1,65 (m, 4H) , 1,8-2,0 (m, 4H) , 2,23 (m, 1H) , 2,71 (m, 295
1Η) , 3, 06 (m, 1H) , 3, 43 (m, 2H) , 3 , 93 (m, 2H) , 6,79 (d, 1H, J=8, 7) , 6, 91 (d, 1H, J=8,7), 7,20 (t, 1H, J=7 ,5), 7 ,40 (d, 1H, J=7 ,5) , 7 , 53 (s, 1H), 9, 76 (s, 1H) • Ia- 247 pf: 242 -245 °C RMN de ΧΗ (DMSO) δ ppm: ; L, 27 (s, 9H) , 1,2- 1,6 (m, 6H) , 1, 8-2 :,o (m, 6H) , 2,23 i (m, 1H) , 3 , 05 (m, 1H) , 3 ,74 (m, 4H) , 4, 94 (s ig, ih: 1, 6,79 (d, lh, J=8, 7) , 7,38 (d, 1H, J=8, 7) , 7, 52 (d, 1H, J=8,7), 9,76 (s, 1H) . Ia- 248 pf: 272 -274 °C RMN de ΧΗ (CDC13) δ ppm: 1,27 (s, , 9H) , 1,2- 1,5 (m, 4H) , 1, 62 (m, 4H) 1, .8-2,0 i (m, 4H) , 2 , 22 (m, 1H), 2 , 68 (m, 1H) , 3, 05 (m, 1H) , 3, 41 (m, 2H) , 3 , 92 (m, 2H) , 6,79 (d, 1H, J=9, 0) , 7, 15 (d, 2H, J=8,7), 7,50 (d, 2H, J=8 ,7), 9 ,73 (s, 1H) . Ia- 249 pf: 174-176 °C Ia- 250 pf: 255-257 °C Ia- 252 pf: 249-251 °C Ia- 253 pf: 120-121 °C Ia- 254 pf: 236-237 °C Ia- 255 pf: 172-174 °C Ia- 256 pf: 257-259 °C 296
Ia-257 pf: 179-180 °C
Ia-258 pf: 227-229 °C
Ia-259 pf: 135-136 °C
Experiência 1 Afinidade para o receptor Y5 de NPY
Clonou-se a sequência de cADN que codifica para um receptor humano Y5 de NPY (WO 96/16.542) no vector de expressão pME18S (Takebe et al., Mol. Cell. Biol. 8, 8957). Transfectou-se o vector de expressão obtido em células hospedeiras CHO utilizando um reagente Lipofect AMINE (Marca Registada, Gico BRL Co., Lda.), de acordo com um protocolo que integra instruções para se obterem as células que expressam o receptor Y5 de NPY de um modo estável.
Incubaram-se as membranas preparadas a partir das células CHO expressando o receptor Y5 de NPY, o composto da invenção presente e 30.000 cpm de péptido YY-[125I] (60 pM
de concentração final: Amersham) , no tampão da experiência (tampão de HEPES-Hanks 20 mM contendo 0,1 % de albumina de soro de bovino, pH 7,4), a 25°C durante 2 horas, e depois filtrou-se a mistura através de um filtro em vidro GF/C tratado com polietilenoimina. Depois de se lavar o filtro em vidro com tampão Tris-HCl 50 mM (pH 7,4), mediu-se a radioactividade no filtro com um contador gama. Detectou-se a ligação não especifica na presença de 200 nM de péptido YY. Calculou-se a concentração do composto em teste que inibia especificamente em 50 % a ligação do péptido YY (valor de IC5o) , (Inui, A. et al. Endocrinology 131, 2090 - 297 2096 (1992)). Os resultados estão listados nas Tabelas 1 e 2 . O composto da invenção presente inibia a ligação do péptido YY (homólogo da NPY) aos receptores Y5 de NPY. Por outras palavras, o composto da invenção presente evidenciava afinidade para o receptor Y5 de NPY.
Experiência 2 Actividade de produção de cAMP em células CHO
Depois de se incubarem células CHO que expressavam o receptor Y5 de NPY humano na presença de isobutilmetilxantina 2,5 mM (SIGMA) a 37°C durante 20 minutos, adicionou-se o composto da invenção presente e incubou-se durante 5 minutos. Em seguida adicionaram-se 50 nM de NPY e 10 μΜ de forscolina (SIGMA) às células e incubou-se durante mais 30 minutos. Terminada a reacção por adição de HC1 1 N, mediu-se a quantidade de cAMP no sobrenadante com o estojo EIA (Amersham LIFE SCIENCE). Considerou-se que a actividade inibitória da NPY contra o CAMP estimulado pela forscolina era 100 % e calcularam-se os valores das concentrações correspondentes a 50 % de inibição (valor de IC50) dos compostos da invenção presente contra a actividade de NPY. Os resultados estão listados nas Tabelas 1 a 4. 298 Tabela 1 valor de omposto IC50 da ligação cAMP ICsnínM) 1-2 7.5 72 1-7 3 <10 1-11 1.3 5 1-18 4.4 29 1-20 7 21 1-22 8.6 51 1-24 9.6 71 1-25 0.6 2.6 1-41 5.3 38.2 1-44 1.0 13.4 Γ-45 1.2 27.9 1-46 0.8 10.5 1-47 0.6 14.9 1-49 0.4 8.1 1-50 0.3 8.4 1-53 4.1 21 1-55 9.0 40 1-57 4.8 47 1-59 0.8 35 1-60 0.69 18 1-61 0.26 5.3 Γ-62 0.58 16 1-63 1.3 50 1-64 2.2 80 1-65 1.8 72 1-66 1.5 30 1-67 2 17 1-69 3.8 13 1-72 2.3 2.1 .1-75 0.55 3.4 1-76 0.61 5.5 1-77 1.8 28 1-79 0.59 25 1-83 0.61 29 1-84 1.3 25 1-86 3.4 100 1-87 0.66 21 1-90 2.8 50 1-92 7 61 1-101 3.9 38 1-102 1.7 14 1-106 6.4 ‘ 29 299 Tabela 2 1-109 1.2 3.2 1-110 4.3 13.6 1-111 1.8 6.1 1-114 7 30 1-116 1.2 11 1-120 1.4 4.8 1-123 1.8 168 1-126 0.6 13.2 1-127 1.4 30.4 1-128 1.3 10.2 1-129 2.1 174 1-130 1.1 42.5 1-131 1.1 34.8 1-132 2.2 30.4 1-133 0.9 21.1 1-134 0.5 10.0 1-135 0.7 22.0 1-136 2.8 - 1-137 1.4 68.2 1-138 1.0 18.6 1-139 0.41 7.6 1-140 0.48 8.9 1-141 0.42 7.4 1-142 0.49 28 1-143 3.5 44 1-144 3.4 - 52 1-146 2.3 20 1-147 7.1 63 1-149 0.83 15 1-150 0.17 5.2 1-151 0.17 2.6 1-152 0.88 46 1-153 1.7 29 1-154 1.1 11 1-156 0.81 17 1-160 0.61 8.8 1-161 0.49 3.1 1-162 1.7 32 1-163 2.3 83 1-164 0.71 5.9 1-165 0.44 47 1-166 0.37 9.7 1-167 0.72 39 1-168 2.1 32 1-171 2.4 71 1-172 0.91 36 T-187 0.58 13 1-191 1.1 11 1-196 1.4 6.8 1-197 6.7 38 1-198 7.2 33 1-199 4.8 · 31 1-202 . 6.7 67 1-204 1.0 6.3 1-205 2.9 17 1-206 5.9 54 1-207 4.6 23 1-210 1.1 13 1-212 0.67 7.5 1-213 0.44 4.0 Ia-1 4.8 31 la-3 9.2 150 Ia-4 1.4 15 Ia-5 1.6 43 Ia-6 2.4 23 Ia-8 2.9 34 Ia-9 0.94 11 Ia-10 0.47 2.7 Ia-11 0.64 7.2 Ia-12 0.94 5.5 Ia-13 1.5 3.3 Ia-14 4.8 28 Ia-16 0.1 - ía-17 0.1 1.9 Ia-20 4.9 100 300 Tabela 3 Ia-21 3.4 35 Ia-22 3.1 38 Ia-24 · 5.2 74 Ta-25 1.1 18 Ia-26 1.9 27 Ia-28 5.2 130 Ia-29 1 7.3 Ia-30 2.6 25 Ia-31 3.8 11 Ia-32 0.52 6.7 Ia-33 1.8 64 Ia-35 1.8 - Ia-36 1.6 86 Ia-37 0.73 3.8 Ia-38 1 2.2 Ia-39 1.5 3.5 Ia-40 2.2 9.3 Ia-41 2.5 9 Ia-42 3.6 20 Ia-44 4.8 27 Ia-45 4.8 42 Ia-46 0.87 8.3 Ia-47 0.82 3.8 Ia-48 1.2 6.1 Ia-49 2.6 83 Ia-50 1.7 24' Ia-51 1.3 3.4 Ia-52 1.9 22 Ia-53 0.22 8.1 Ia-54 0.44 9 Ia-55 1.1 27 Ia-56 2.3 96 Ia-57 0.93 31 Ia-58 2.5 110 Ia-59 0.71 16 Ia-60 0.95 10 Ia-61 0.68 19 Ia-62 1.1 29 Ia-63 3.9 370 Ia-64 7.1 96 · Ia-65 1.1 11
Ia-66 0.59 3.2 Ia-67 6.3 75 Ia-68 9.5 180 Ia-69 2.7 33 Ia-70 1.5 31 Ia-71 1.3 12 Ia-76 2.2 - Ia-78 2 150 Ia-79 0.82 - Ia-80 0.44 3.0 Ia-81 2.7 4.5 Ia-83 1.2 53 Ia-84 0.25 13 Ia-85 0.22 14 Ia-86 0.73 13 Ia-87 0.49 61 Ia-88 0.62 48 Ia-91 4 150 la-106 1.9 24 Ia-107 0.14 1.3 Ia-109 0.6 3.9 Ia-110 0.3 1.1 Ia-111 5.1 28 Ia-124 1.1 22 Ia-125 4.1 46 Ia-126 2.3 68 Ia-127 6.1 160 Ia-129 1.3 26 Ia-130 0.21 3 Ia-131 1.3 17 Ia-132 2.8 76 Ia-133 1.7 8.8 Ia-135 8.2 49 Ia-136 1.6 13 Ia-138 2.2 28 Ia-139 1.9 25 Ia-140 1 24 Ia-141 1 5.7 Ia-142 0.67 5.5 301
Tabela 4 301 Ia-143 7.8 39 Ia-144 6.1 57 Ia-145 7 86 Ia-146 9.9 79 Ia-158 0.71 1.7 Ia-160 0.76 140 Ia-161 1.9 18 Ia-163 7 400 Ia-164 0.38 4.7 Ia-168 0.95 13 Ia-169 1.9 88 Ia-173 6.9 140 Ia-174 0.35 5.4 Ia-175 0.49 9.2 Ia-176 0.63 5.1 Ia-177 0.49 7.5 Ia-178 4.'6 16 Ia-179 0.89 19 Ia-180 1.9 11 Ia-181 7.7 25 Ia-182 0.24 2.1 Ia-183 1.9 7.8 Ia-184 0.38 - Ia-185 0.94 4.4 Ia-186 0.93 12 Ia-187 1.9 60 Ia-188 0.75 28 Ia-189 3.5 95 Ia-190 0.34 1000 Ia-191 0.49 220 Ia-192 5.9 200 Ia-193 1.4 43 Ia-194 0.22 8.1 Ia-195 1.4 31 Ia-196 0.39 1.3 Ia-197 0.44 2.5 Ia-198 0.23 2.6 Ia-199 0.11 1.6 Ia-200 1.4 18 Ia-201 3.1 74 Ia-202 0.37 3.4
Ia-203 0.2 2.6 Ia-204 1 6.3 Ia-205 2.4 99 Ia-206 1.9 460 Ia-207 0.55 5.9 Ia-208 1.2 9.7 Ia-209 0.55 * I-a-210 2.8 99 Ia-211 4.8 240 Ia-212 0.52 2.6 Ia-213 0.91 28 Ia-219 2.5 28 Ia-221 0.47 1.5 Ia-222 3.7 18 Ia-224 0.1 1.2 Ia-225 3.4 20 Ia-226 0.37 21 Ia-227 0.59 . Ia-228 0.96 - Ia-229 1.9 - Ia-230 0.32 - Ia-231 0.29 - Ia-2.32 0.7 - Ia-233 0.63 - Ia-235 5.5 - Ia-237 1.1 15 Ia-241 1.9 - Ia-243 1.3 - Ia-246 0.26 20 Ia-247 0.79 31 Ia-248 0.27 17 Ia-250 1.9 Ia-252 1.2 Ia-253 0.53 Ia-254 2.0 Ia-255 3.2 Ia-256 5.7 Ia-257 8.6 Ia-258 1.8
Tal como se evidencia nas Tabelas 1 a 4, os compostos da invenção presente apresentam actividade antagonista em relação ao receptor Y5 de NPY.
Experiência 3 302
Utilizando as membranas preparadas a partir de células humanas que expressavam Yl (de neuroblastoma humano, SK-N-MC) e as membranas preparadas a partir de células de expressão de Y2 (neuroblastoma humano, SMS-KAN), levou-se a cabo a experiência de um modo semelhante ao utilizado na Experiência 1, para se determinar a afinidade em relação ao receptor Yl de NPY e em relação ao receptor Y2 de NPY.
Os valores de IC 5o para a ligação ao receptor Yl de NPY e ao receptor Y2, dos compostos 1-27, 1-32, 1-41, I-45, 1-46, 1-47, 1-48, 1-49, 1-59, 1-61, 1-63, 1-64, 1-66, 1-69, 1-72, 1-152, 1-154, 1-204, 1-205, 1-212, Ia-3, Ia-5, Ia-6, Ia-12, Ia-16, Ia-17, Ia-20, Ia-21, Ia-22, Ia-26, Ia-28, Ia-29, Ia-30, Ia-31, Ia-32, Ia-33, Ia-37, Ia-39, Ia-40, Ia-50, Ia-51, Ia-54, Ia-62, Ia-67, Ia-124, Ia-126, Ia-139, Ia-140, Ia-142, Ia-178, Ia-199 e Ia-200, foram de 100.000 nM ou maiores, e todos estes compostos eram selectivos em relação ao receptor Y5 de NPY. 303
Exemplo de Formulação 1 Comprimidos
Composto (1-1)
Amido
Lactose
Celulose Cristalina Ií::::::::::::::::::::::::::::::::::::::::::::::::::;::·:·
Poli (álcool vinilico) Água destilada
Estearato de Cálcio
Depois de se misturarem até à uniformidade todos os ingredientes acima excepto o estearato de cálcio, mói-se a mistura e granula-se, e seca-se para se obterem grânulos com dimensões adequadas. Depois de se adicionar estearato de cálcio aos grânulos, formam-se comprimidos por moldagem e compressão.
Exemplo de Formulação 2 Cápsulas 304 Composto (1-2) 10i |mg
Estearato de magnésio 10! smq
Lactose 80; |mq
Depois de se misturarem os ingredientes acima para se obterem pós ou grânulos, estes são utilizados como enchimento das cápsulas.
Exemplo de Formulação 3 Grânulos ;.................................................................................................................................................. Composto (1-3) 3 01 ? i Lactose 2 6 i Estearato de magnésio 5
Depois de se misturarem os ingredientes acima uniformemente, e de os enformar por moldagem sob compressão, mói-se o produto obtido, granula-se e peneira-se para se preparar um volume adequado de grânulos.
Aplicabilidade Industrial
Tal como se mostrou nas Experiências acima, os compostos da invenção presente apresentam uma actividade antagonista em relação ao receptor Y5 de NPY. Os compostos da invenção presente são portanto úteis como agentes contra a obesidade, e anoréxicos.
Lisboa, 13 de Julho de 2010.

Claims (3)

1 REIVINDICAÇÕES 1. Um composto com a fórmula:
sta um seu sal ou solvato aceitável do ponto de vi farmacêutico. um
2. Uma composição farmacêutica que inclua composto coma fórmula:
sta um seu sal ou solvato aceitável do ponto de vi farmacêutico. Um composto com a fórmula:
3. um farmacêutico, seu sal ou solvato aceitável do ponto de vista para utilização no tratamento da obesidade. Lisboa, 13 de Julho de 2010.
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