ES2554228T3 - Ciclopenta[d]pirimidinas hidroxiladas como inhibidores de la proteína quinasa AKT - Google Patents

Ciclopenta[d]pirimidinas hidroxiladas como inhibidores de la proteína quinasa AKT Download PDF

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ES2554228T3
ES2554228T3 ES11166123.7T ES11166123T ES2554228T3 ES 2554228 T3 ES2554228 T3 ES 2554228T3 ES 11166123 T ES11166123 T ES 11166123T ES 2554228 T3 ES2554228 T3 ES 2554228T3
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piperazin
pyrimidin
dihydro
cyclopenta
hydroxy
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Ian S. Mitchell
James F. Blake
Rui Xu
Nicholas C. Kallan
Dengming Xiao
Keith Lee Spencer
Josef R. Bencsik
Jun Liang
Brian Safina
Birong Zhang
Christine Chabot
Steven Do
Eli W. Wallace
Anna L. Banka
Stephen T. Schlachter
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Genentech Inc
Array Biopharma Inc
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Array Biopharma Inc
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Abstract

Compuesto de fórmula I:**Fórmula** y tautómeros, enantiómeros separados, diastereoisómeros separados, solvatos y sales de los mismos, en la que: R1 es H, Me, Et, vinilo, CF3, CHF2 o CH2F; R2 es H; R5 es H, Me, Et o CF3; A se selecciona entre las fórmulas 2 y 4**Fórmula** G es fenilo opcionalmente sustituido con 1 a 4 grupos R9 o un heteroarilo de 5-6 miembros opcionalmente sustituido con un halógeno; R6 y R7 son independientemente H, OCH3, (cicloalquil C3-C6)-(CH2), (cicloalquil C3-C6)-(CH2CH2), V-(CH2)0-1 en el que V es un heteroarilo de 5-6 miembros, W-(CH2)1-2 en el que W es fenilo opcionalmente sustituido con F, Cl, Br, I, OMe, CF3 o Me, cicloalquilo C3-C6 opcionalmente sustituido con alquilo C1-C3 o O(alquilo C1-C3), hidroxi-(cicloalquilo C3-C6), fluoro-(cicloalquilo C3-C6), CH(CH3)CH(OH)fenilo, heterociclo de 4-6 miembros opcionalmente sustituido con F, OH, alquilo C1-C3, ciclopropilmetilo o C(>=O)(alquilo C1-C3), o alquilo C1-C6 opcionalmente sustituido con uno o más grupos seleccionados independientemente de OH, oxo, O(alquilo C1- C6), CN, F, NH2, NH(alquilo C1-C6), N(alquilo C1-C6)2, ciclopropilo, fenilo, imidazolilo, piperidinilo, pirrolidinilo, morfolinilo, tetrahidrofuranoilo, oxetanilo o tetrahidropiranilo, o R6 y R7 junto con el nitrógeno al que están unidos forman un anillo heterocíclico de 4-7 miembros opcionalmente sustituido con uno o más grupos seleccionados independientemente entre OH, halógeno, oxo, CF3, CH2CF3, CH2CH2OH, O(alquilo C1-C3), C(>=O)CH3, NH2, NHMe, N(Me)2, S(O)2CH3, ciclopropilmetilo y alquilo C1-C3; Rc y Rd son H o Me, o Rc y Rd junto con el átomo al que están unidos forman un anillo ciclopropilo; R8 es H, Me, F u OH, o R8 y R6 junto con los átomos a los que están unidos forman un anillo heterocíclico de 5-6 miembros que tiene uno o dos átomos de nitrógeno en el anillo; cada R9 es independientemente halógeno, alquilo C1-C6, cicloalquilo C3-C6, O(alquilo C1-C6), CF3, OCF3, S(alquilo C1-C6), CN, OCH2-fenilo, CH2O-fenilo, NH2, NH(alquilo C1-C6), N(alquilo C1-C6)2, piperidina, pirrolidina, CH2F, CHF2, OCH2F, OCHF2, OH, SO2(alquilo C1-C6), C(O)NH2, C(O)NH(alquilo C1-C6) y C(O)N(alquilo C1- C6)2; R10 es H o Me.

Description

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25 [0107] En ciertas realizaciones, los compuestos de la presente invención están representados por la fórmula 4B:
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en la que G y R5 son tal como se definen en el presente documento.
[0108] En ciertas realizaciones, los compuestos de la presente invención están representados por la fórmula 4C:
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oxopropilisopropilcarbamato de terc-butilo (283 mg, 0,502 mmol) en 1,4-dioxano (2,5 ml) y cloruro de metileno (2,5 ml) a 0°C. La mezcla se dejó calentar a temperatura ambiente y se agitó durante 1 hora. La mezcla se concentró a vacío. El residuo después se disolvió en un volumen mínimo de DCM (1 ml) y se añadió gota a gota a éter (10 ml) a 0°C con agitación. Precipitó un sólido blanco. Los disolventes se evaporaron con un rotavapor en un baño a 25°C. El
5 sólido blanquecino se secó con alto vacío durante la noche para dar el diclorhidrato de la (S)-2-(5-clorotiofen-2-il)-1(4-((5R,7R)-6,7-dihidro-7-hidroxi-5-metil-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3-(isopropilamino)-1-propanona (537 mg, 99,9%). MS (APCI+) [M+H]+ 464,1. RMN 1H (D2O, 400 MHz) δ 8,53 (s, 1H), 6,97 (d, J = 4,0 Hz, 1H), 6,96 (d, J = 4,0 Hz, 1H), 5,40 (t, J = 8,0 Hz, 1H), 4,78-4,71 (m, 1H), 4,31-4,27 (m, 1H), 4,09-3,97 (m, 2H), 3,84-3,42 (m, 10H), 2,36-2,30 (m, 1H), 2,21-2,13 (M, 1H), 1,33 (d, J = 6,4 Hz, 3H), 1,32 (d, J = 6,4 Hz, 3H), 1,14 (d, J = 6,4 Hz,
10 3H).
[00449] Los ejemplos 50-324 mostrados en la tabla 1 también se pueden fabricar de acuerdo con los procedimientos descritos antes.
Tabla 1
Ejemplo
Estructura Nombre LCMS o RMN 1H
50
(R)-2-amino-3-(4-clorofenil)-1-(4-((5R,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 416,2
51
1-(4-((SR,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(isopropilamino)-2-(4-(trifluorometil)fenil)-1propanona-ona 492,2
52
4-(1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(isopropilamino)-1-oxopropan-2-il)benzonitrilo 449,2
53
(S)-2-(4-clorofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(isopropilamino)-1-propanona 458,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
54
3-(azetidin-1-il)-2-(4-clorofenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 456,2
55
2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(3-hidroxiazetidin-1-il)-1-propanona 472,2
56
2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(neopentilamino)-1-propanona 486,3
57
imagen86 2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(isopropilamino)-1-propanona 504,2
58
imagen87 2-(4-clorofenil)-3-(4-fluoropiperidin-1-il)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 502,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
59
2-(4-clorofenil)-3-((S)-3-fluoropirrolidin-1-il)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 488,2
60
2-(4-clorofenil)-3-(etilamino)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 444,3
61
2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(isopropil(metil)amino)-1-propanona 472,2
62
imagen88 2-(4-clorofenil)-3-(4,4-difluoropiperidin-1-il)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 520,2
63
imagen89 2-(4-clorofenil)-3-(3,3-difluoropirrolidin-1-il)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 506,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
64
2-(4-bromo-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 520,2
65
(R)-2-amino-3-(4-fluorofenil)-1-(4-((5R,7S)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 400,2
66
(R)-2-amino-3-(3,4-diclorofenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 450,2
67
imagen90 (R)-2-amino-3-(3,4-difluorofenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 418,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
68
(R)-2-(4-clorofenil)-3-(ciclopropilmetilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 470 [M+H]+
69
(S)-2-(4-clorofenil)-3-(ciclopropilmetilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 470 [M+H]+
70
2-(4-clorofenil)-3-((R)-3-fluoropirrolidin-1-il)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 488,2
71
(S)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-l-il)-3(isopropilamino)-2-(4-(trifluorometoxi)fenil)-1propanona 508,3
72
imagen91 (S)-2-(4-clorofenil)-3-(ciclopropilamino)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 456,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
73
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(3-hidroxiazetidin-1-il)-1-propanona 472,1
74
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(3-hidroxiazetidin-1-il)-1-propanona 472,1
75
(R)-4-amino-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5 1H RMN
metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4
(CD3OD),
il)piperazin-1-il)-4-metil-1-pentanona
400 MHz, 8,51 (s, 1H), 7,40-7,33 (m, 4H), 5,17 (dd, J=14,9, 7,04 Hz, 1H), 4,26 (dd, J=9,4, 3,1 Hz, 1H), 4,06 (m, 1H), 3,85-3,60 (bm, 7H), 3,42 (m, 1H), 2,76 (dd, J=14,9, 10,1 Hz, 1H), 2,2 (m, 2H), 1,81 (dd, J=14,1, 3,1 Hz, 1H), 1,35 (s, 3H), 1,32 (s, 3H), 1,15 (d, J=7,04 Hz, 3H).
76
(S)-4-amino-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5 1H RMN(CD3OD),
metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4
400 MHz, 8,51 (s,
il)piperazin-1-il)-4-metil-1-pentanona
1H), 7,40-7,32
(m, 4H), 5,17 (dd,
J=14,9, 7,04 Hz,
1H), 4,25 (dd,
J=9,4, 3,1 Hz,
1H), 4,03-3,52
(bm, 8H), 3,30
(m, 1H), 2,75 (dd,
J=14,9, 9,4 Hz,
1H), 2,18 (m, 2H),
1,82 (dd, J=14,1,
3.1 Hz, 1H), 1,35
(s, 3H), 1,32 (s,
3H), 1,18 (d,
J=6,3 Hz, 3H)
Ejemplo
Estructura Nombre LCMS o RMN 1H
77
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((R)-pirrolidin-3-ilamino)-1-propanona 485,2
78
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((S)-pirrolidin-3-ilamino)-1-propanona 485,2
79
(S)-3-((R)-1-acetilpirrolidin-3-ilamino)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 527,2
80
imagen92 (S)-3-((S)-1-acetilpirrolidin-3-ilamino)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 527,2
81
imagen93 (S)-2-(4-bromofenil)-3-(ciclopropilmetilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 514,0
Ejemplo
Estructura Nombre LCMS o RMN 1H
82
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(piperidin-4-ilamino)-1-propanona m/z 499 [M+H]+
83
(S)-3-(1-acetilpiperidin-4-ilamino)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 541 [M+H]+
84
imagen94 (S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(2-metoxietilamino)-1-propanona m/z 474 [M+H]+
85
imagen95 (R)-2-(4-clorofenil)-4-(dimetilamino)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-butanona 458,1
Ejemplo
Estructura Nombre LCMS o RMN 1H
86
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(tetrahidro-2H-piran-4-ilamino)-1-propanona m/z 500 [M+H]+
87
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((1r,4S)-4-hidroxiciclohexilamino)-1-propanona 514,3
88
(S)-3-(azetidin-1-il)-2-(4-clorofenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 456,3
89
imagen96 (R)-3-(azetidin-1-il)-2-(4-clorofenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 456,3
90
2-((S)-2-(4-clorofenil)-3-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-oxopropilamino)acetamida 473,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
91
2-((S)-2-(4-clorofenil)-3-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-oxopropilamino)-N,N-dimetilacetamida 501,3
92
2-((S)-2-(4-clorofenil)-3-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-oxopropilamino)-N-metilacetamida 487,2
93
(R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-4-(isopropilamino)-1-butanona 516,2/518,1
94
(R)-2-(4-bromofenil)-4-(dimetilamino)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-butanona 502,1/504,1
95
(R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)-piperazin-1il)-4-(isobutilamino)-1-butanona 530,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
96
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-((2-metoxietil)(metil)amino)-1-butanona 502,1
97
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-(isopropilamino)-1-butanona 472,2
98
imagen97 (R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-(3-hidroxiazetidin-1-il)1-butanona 486,2
99
2-((R)-3-(4-bromofenil)-4-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-4-oxobutilamino)-N,Ndimetilacetamida 559,1
Ejemplo
Estructura Nombre LCMS o RMN 1H
100
(R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-(2-hidroxietilamino)-1-butanona 518,2/520,1
101
(2R)-2-(4-bromofenil)-4-(2-hidroxi-1-(tetrahidro-2Hpiran-4-il)etilamino)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-butanona 604,2
102
(R)-2-amino-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-yodofenil)-1-propanona 508,1
103
4-((R)-2-amino-3-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3oxopropil)benzonitrilo 407,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
104
(R)-2-amino-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-(trifluorometil)fenil)-1-propanona 450,2
105
(S)-3-(4-acetilpiperazin-1-il)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)propan-ona 527,2
106
(R)-3-(4-acetilpiperazin-1-il)-2-(4-clorofenil)-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 527,2
107
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(metilamino)-1-propanona 430,2
108
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-(2-hidroxietil)piperazin-1-il)-1-propanona 529,4
Ejemplo
Estructura Nombre LCMS o RMN 1H
109
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-(2-hidroxietil)piperazin-1-il)-1-propanona 529,4
110
2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(3-metoxiazetidin-1-il)-1-propanona 486,2
111
(R)-2-(4-clorofenil)-4-(ciclohexilamino)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-butanona 512,3
112
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidrox-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-4(tetrahidro-2H-piran-4-ilamino)-1-butanona 514,2
113
(2R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-(2-hidroxipropilamino)-1-butanona 488,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
114
(2R)-2-(4-clorofenil)-4-(2-hidroxi-1-(tetrahidro-2Hpiran-4-il)etilamino)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-butanona 558,2
115
(2R)-2-(4-clorofenil)-4-(2-hidroxi-1-feniletilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-butanona 550,2
116
(S)-2-(4-clorofenil)-3-(etil(tetrahidro-2H-piran-4il)amino)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-1propanona m/z 528 [M+H]+
117
(R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-4-(2-metoxietilamino)-1-butanona 534,1
Ejemplo
Estructura Nombre LCMS o RMN 1H
118
(2R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-(3,3,3-trifluoro-2-hidroxipropilamino)-1-butanona 586,2
119
(R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-((1-hidroxiciclopropil)metilamino)-1-butanona 544,2/546,2
120
imagen98 2-((R)-3-(4-bromofenil)-4-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-4-oxobutilamino)acetamida 531,1/533,1
121
(R)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-4-(tetrahidro-2H-piran-4-ilamino)-1-butanona 558,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
122
(R)-4-(3-(1H-imidazol-1-il)propilamino)-2-(4bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-1butanona 584,2
123
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3morfolinopropan-1-ona 486,3
124
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-morfolinopropan-1-ona 486,3
125
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-metilpiperazin-1-il)-1-propanona 499,4
126
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-metilpiperazin-1-il)-1-propanona 499,4
Ejemplo
Estructura Nombre LCMS o RMN 1H
127
(S)-3-(3-aminoazetidin-1-il)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5,metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 471,2
128
(R)-3-(3-aminoazetidin-1-il)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 471,2
129
(S)-2-(4-clorofenil)-1-(4-((SR,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-tiomorfolinopropan-1-ona 502,2
130
(S)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(piperazin-1-il)-1-propanona 485,3
131
imagen99 (R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(piperazin-1-il)-1-propanona 485,3
132
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-tiomorfolinopropan-1-ona 502,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
133
(R)-2-(4-clorofenil)-3-(4-fluoropiperidin-1-il)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 502,2
134
(S)-2-(4-clorofenil)-3-(4-fluoropiperidin-1-il)-1-(4(5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 502,2
135
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(3-metoxiazetidin-1-il)-1-propanona 486,2
136
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(3-metoxiazetidin-1-il)-1-propanona 486,2
137
(S)-2-(3,4-diclorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(isopropilamino)-1-propanona 492,2
138
(S)-2-(4-clorofenil)-3-(dimetilamino)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 444,1
Ejemplo
Estructura Nombre LCMS o RMN 1H
139
(S)-2-(4-fluoro-3-(trifluorometil)fenil)-1-(4-((SR,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 510,2
140
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 510,4
141
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(metoxiamino)-1-propanona 446,2
142
(S)-2-(4-clorofenil)-1-(4-(5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-metoxipiperidin-1-il)-1-propanona 514,3
143
(R)-2-(4-clorofenil)-1-(4-((SR,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-metoxipiperidin-1-il)-1-propanona 514,3
144
(S)-2-(4-clorofenil)-1-(4-(5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-hidroxipiperidin-1-il)-1-propanona 500,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
145
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-hidroxipiperidin-1-il)-1-propanona 500,3
146
(S)-3-(4-aminopiperidin-1-il)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 499,3
147
(R)-3-(4-aminopiperidin-1-il)-2-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 499,3
148
(S)-2-(4-clorofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(tetrahidro-2H-piran-4-ilamino)-1-propanona 500,2
149
(S)-2-(4-clorofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(metilo(tetrahidro-2H-piran-4-il)amino)-1-propanona m/z 514 [M+H]+
150
imagen100 (S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3(isopropilo(metil)amino)-1-propanona 472,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
151
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-(metilsulfonil)piperazin-1-il)-1-propanona 563,2
152
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-(metilamino)piperidin-1-il)-1-propanona 513,3
153
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-(metilamino)piperidin-1-il)-1-propanona 513,3
154
(S)-2-(4-cloro-3-(trifluorometoxi)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 542,2
155
(S)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(isopropilamino)-1-propanona 526,3
156
(S)-2-(4-cloro-3-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin--il)-3-(isopropilamino)-1-propanona 526,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
157
(R)-2-(4-clorofenil)-3-(4-etilpiperazin-1-il)-1-(-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 513,3
158
(S)-2-(4-clorofenil)-3-(4-etilpiperazin-1-il)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 513,3
159
(S)-2-(4-clorofenil)-1-4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-isopropilpiperazin-1-il)-1-propanona 527,6
160
imagen101 (R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-isopropilpiperazin-1-il)-1-propanona 527,6
161
(R)-2-(4-clorofenil)-3-((S)-3-(dimetilamino)pirrolidin-1il)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 513,6
162
(S)-2-(4-clorofenil)-3-((S)-3-(dimetilamino)pirrolidin-1il)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 513,6
Ejemplo
Estructura Nombre LCMS o RMN 1H
163
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((R)-tetrahidrofurano-3-ilamino)-1-propanona 486,2
164
(S)-2-(4-clorofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((R)-tetrahidrofurano-3-ilamino)-1-propanona 486,2
165
(S)-2-(4-clorofenil)-3-(2-fluoroetilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 462,2
166
(S)-2-(4-fluoro-3-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(isopropilamino)-1-propanona 526,4
167
(S)-2-(3,5-bis(trifluorometil)fenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 560,3
168
imagen102 (S)-2-(3-fluoro-4-metoxifenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 472,5
Ejemplo
Estructura Nombre LCMS o RMN 1H
169
4-((R)-2-(4-clorofenil)-3-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-oxopropil)piperazin-2-ona 499,3
170
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-((R)-3-hidroxipirrolidin-1-il)-1-propanona 486,3
171
(S)-2-(4-clorofenil)-3-(4-(dimetilamino)piperidin-1-il)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 527,3
172
(R)-2-(4-clorofenil)-3-(4-(dimetilamino)piperidin-1-il)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 527,3
173
imagen103 (S)-2-(3-cloro-5-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 476,2
174
(S)-2-(3-bromo-4-metoxifenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 532,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
175
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(piperidin-4-ilamino)-1-propanona 499,3
176
(R)-2-(1-acetilpiperidin-4-ilamino)-3-(4-clorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 541,3
177
2-((R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-oxopropan-2-ilamino)-N-isopropilacetamida 515,3
178
(R)-3-(4-clorofenil)-2-(dimetilamino)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 444,2
179
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(2-morfolinoetilamino)-1-propanona 529,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
180
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(isopropilamino)-1-propanona 458,2
181
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(tetrahidro-2H-piran-4-ilamino)-1-propanona 500,3
182
(R)-3-(4-clorofenil)-1-((S)-4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)-3metilpiperazin-1-il)-2-(isopropilamino)-1-propanona 472,3
183
2-((R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-oxopropan-2-ilamino)-N,N-dimetilacetamida 501,2
184
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(1,4-oxazepan-4-il)-1-propanona 500,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
185
(R)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(1,4-oxazepan-4-il)-1-propanona 500,3
186
(R)-2-(4-cloro-2-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 476,2
187
(S)-2-(4-cloro-2-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 476,2
188
(S)-2-(2-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 510,2
189
(S)-2-(4-clorofenil)-3-(ciclohexilamino)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 498,3
190
(S)-2-(4-clorofenil)-3-(ciclohexilamino)-1-(4-((5R,7S)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 498,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
191
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidina-4-il)piperazin-1-il)3-(4-metoxiciclohexilamino)-1-propanona 528,4
192
(S)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 568,3
193
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 552,2
194
(S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((S)-tetrahidrofurano-3-ilamino)-1-propanona 486,3
195
imagen104 (S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(4-metiltetrahidro-2H-piran-4-ilamino)-1-propanona 513,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
196
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(2-(tetrahidro-2H-piran-4-il)etilamino)-1propanona 528,3
197
(R)-3-(4-clorophenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(3,3,3-trifluoropropilamino)-1-propanona 512,2
198
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-((tetrahidro-2H-piran-4-il)metilamino)-1propanona 514,2
199
(R)-3-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(isopropil(metil)amino)-1-propanona 472,3
200
(S)-3-(terc-butilamino)-2-(4-clorofenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 472,1
Ejemplo
Estructura Nombre LCMS o RMN 1H
201
(R)-3-(terc-butilamino)-2-(4-clorofenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 472,1
202
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-metilpiperazin-1-il)-1-propanona 517,2
203
(R)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-metilpiperazin-1-il)-1-propanona 517,2
204
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 518,2
205
(R)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-morfolinopropan-1-ona 504,2
206
imagen105 (R)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 518,2
207
(S)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(4-metilpiperazin-1-il)-1propanona 567,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
208
(R)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihydra-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3-(4metilpiperazin-1-il)-1-propanona 567,2
209
(S)-3-(ciclopropilmetilamino)-2-(3-fluoro-4(trifluorometil)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 522,2
210
(S)-3-(ciclopropilmetilamino)-2-(3-fluoro-4(trifluorometoxi)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 538,2
211
(5)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4il)piperazin-1-il)-3(isopropilamino)-2-(4-(trifluorometil)fenil)-1-propanona 492,3
212
imagen106 (S)-3-amino-2-(4-bromofenil)-1-(4-((5R,7S)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona m/z 460/462 (isótopo de Br) [M+H]+
213
(S)-3-amino-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona m/z 434 [M+H]+
Ejemplo
Estructura Nombre LCMS o RMN 1H
214
(S)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(tetrahidro-2H-piran-4-ilamino)-1-propanona 546,2
215
3-((S)-2-(4-clorofenil)-3-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-oxopropilamino)propanamida 487,2
216
3-((S)-2-(4-clorofenil)-3-(4-((SR,7S)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-oxopropilamino)propanamida 487,2
217
(4-(4-clorofenil)piperidin-4-il)(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)metanona 456,2
218
(S)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(isopropilamino)-1-propanona 504,2
219
(S)-3-amino-2-(4-cloro-3-fluorofenil)-1-(4-((SR,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 434,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
220
(S)-3-amino-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 462,2
221
(S)-2-(4-bromofenil)-1-(4-((SR,7S)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(tetrahidro-2H-piran-4-ilamino)-1-propanona m/z 544/546 (Br) m/z 544/546 (isótopo de Br) [M+H]+
222
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((SR,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona m/z 518 [M+H]+
223
(S)-2-(3,4-diclorofenil)-1-(4-((5R,7R)-7-hidroxi-5,metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(tetrahidro-2H-piran-4-ilamino)-1-propanona 534,2
224
imagen107 (S)-3-amino-2-(3,4-diclorofenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 450,3
225
(R)-2-(3,4-diclorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-hidroxipiperidin-1-il)-1-propanona 534,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
226
(S)-2-(3,4-diclorofenil)-1-(4-((SR,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-isopropilpiperazin-1-il)-1-propanona 561,3
227
(S)2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 568,2
228
(R)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 568,2
229
(S)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(4-isopropilpiperazin-1-il)-1propanona 595,3
230
imagen108 (S)-2-(3,5-difluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 460,3
231
(S)-3-((R)-3-aminopirrolidin-1-il)-2-(4-clorofenil)-1-(4((SR,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 485,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
232
(R)-3-((R)-3-aminopirrolidin-1-il)-2-(4-clorofenil)-1-(4(5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 485,3
233
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-isopropilpiperazin-1-il)-1propanona 545,3
234
imagen109 (S)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-morfolinopropan-1-ona 554,3
235
imagen110 (R)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-morfolinopropan-1-ona 554,3
236
(S)-3-(4-etilpiperazin-1-il)-2-(3-fluoro-4(trifluorometoxi)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 581,3
237
(R)-3-(4-etilpiperazin-1-il)-2-(3-fluoro-4(trifluorometoxi)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 581,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
238
(S)-3-(4-acetilpiperazin-1-il)-2-(3-fluoro-4(trifluorometoxi)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 595,3
239
(R)-3-(4-acetilpiperazin-1-il)-2-(3-fluoro-4(trifluorometoxi)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 595,3
240
(S)-2-(3,4-diclorofenil)-1-(4-((5R,75)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)pipemzin-1il)-3-(tetrahidro-2H-piran-4-ilamino)-1-propanona 534,2
241
imagen111 (S)-2-(4-bromofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1il)-3-(isopropilamino)-1-propanona m/z 502/504 (isótopo de Br) [M+H]+
242
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((SR,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona m/z 476 [M+H]+
243
(S)-2-(4-cloro-3-fluorofenil)-3-(ciclopropilmetilamino)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 488 [M+H]+
Ejemplo
Estructura Nombre LCMS o RMN 1H
244
(S)-3-(bis(ciclopropilmetil)amino)-2-(4-cloro-3fluorofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7-dihidro5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-1propanona m/z 542 [M+H]+
245
(S)-2-(4-bromofenil)-3-(ciclopropilmetilamino)-1-(4((5R,7S)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 514/516 (isótopo de Br) [M+H]+
246
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona LCMS (APCI+) m/z 518 520 [M+H]+
247
imagen112 (S)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona LCMS (APCI+) m/z 476, 478 [M+H]+
248
(S)-2-(4-bromofenil)-3-((ciclopropilmetil)(metilamino)-1-(4-((SR,7S)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 528/530 (isótopo de Br) [M+H]+
Ejemplo
Estructura Nombre LCMS o RMN 1H
249
(S)-2-(4-cloro-3-fluorofenil)-3-(ciclopropilmetilamino)-1-(4-((SR,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona LCMS (APCI+) m/z 488 490 [M+H]+
250
(S)-3-(ciclopropilmetilamino)-2-(3,4-dichiorofenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 504,3
251
(S)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3-(tetrahidro2H-piran-4-ilamino)-2-(4-(trifluorometoxi)fenil)-1propanona 550,3
252
imagen113 (R)-2-(4-clorofenil)-3-((3S,5R)-3,5-dimetilpiperazin-1il)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 513,3
253
imagen114 (R)-2-(4-clorofenil)-3-((2S,6R)-2,6-dimetilmorfolino)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 514,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
254
(S)-2-(4-clorofenil)-3-((2S,6R)-2,6-dimetilmorfolino)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 514,3
255
(S)-2-(4-clorofenil)-3-((3S,SR)-3,5-dimetilpiperazin-1il)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 513,3
256
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 552,3
257
(R)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 552,3
258
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-metilpiperazin-1-il)-1-propanona 551,3
259
(R)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-metilpiperazin-1-il)-1-propanona 551,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
260
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((SR,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-isopropilpiperazin-1-il)-1propanona 579,3
261
(R)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((SR,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-isopropilpiperazin-1-il)-1propanona 579,3
262
(S)-3-(ciclopropilmetilamino)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-2-(4-(trifluorometoxi)fenil)-1propanona 520,3
263
(S)-3-amino-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 480,2
264
(S)-3-amino-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 480,1
265
(S)-2-(3,4-diclorofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(isopropilamino)-1-propanona 492,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
266
(S)-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona m/z 520, 522 [M+H]+
267
(S)-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7S)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona m/z 520, 522 [M+H]+
268
(S)-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7R)-7,hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona m/z 562, 564 [M+H]+
269
(S)-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7S)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona m/z 562, 564 [M+H]+
270
(S)-2-(4-bromo-3-fluorofenil)-3(ciclopropilmetilamino)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona m/z 532, 534 [M+H]+
Ejemplo
Estructura Nombre LCMS o RMN 1H
271
(S)-2-(4-bromo-3-fluorofenil)-3(ciclopropilmetilamino)-1-(4-((5R,75)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona m/z 532, 534 [M+H]+
272
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 510,3
273
(S)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-isopropilpiperazin-1-il)-1-propanona 571,3
274
(S)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(4-hidroxipiperidin-1-il)-1-propanona 546,2
275
(S)-3-(ciclopropilmetilamino)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-cyaopenta[d]pirimidin-4il)piperazin-1-il)-2-(4-(trifluorometil)fenil)-1-propanona 504,3
276
(S)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3-(tetrahidro2H-piran-4-ilamino)-2-(4-(trifluorometil)fenil)-1propanona 534,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
277
(S)-3-(ciclopropilmetilamino)-2-(2-fluoro-4(trifluorometil)fenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 522,3
278
(R)-2-(4-bromo-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-3H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(4-hidroxipiperidin-1-il)-1propanona 562,2
279
(S)-2-(4-bromofenil)-1-(4-((5R,7S)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(isopropilo(metilamino)-1-propanona 518,2
280
(S)-3-amino-2-(4-bromo-2-fluorofenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 478,2
281
(S)-3-amino-2-(4-bromo-2-fluorofenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 478,2
282
imagen115 (S)-2-(4-bromofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-3-(isopropil(metil)amino)-1-propanona 443,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
283
(S)-2-(4-bromo-2-fluorofenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 520,2
284
(S)-2-(4-bromo-2-fluorofenil)-1-(4-((SR,7S)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 520,2
285
(S)-3-amino-2-(4-cloro-2-fluorofenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 434,2
286
2-(4-clorofenil)-3-((3S,4R)-4-(dimetilamino)-3fluoropiperidin-1-il)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-1-propanona 545,3
287
imagen116 (S)-2-(4-bromo-2-fluorofenil)-3(ciclopropilmetilamino)-1-(4-((5R,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-1-propanona 532,2
288
(S)-3-(terc-butilamino)-1-(4-((5R,7R)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1il)-2-(4-(trifluorometil)fenil)-1-propanona 506,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
289
(S)-2-(3-fluoro-4-(trifluorometoxi)fenil)-1-(4-((5R,7S)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 567,6
290
(S)-2-(3-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 552,3
291
(S)-2-(4-cloro-2-fluorofenil)-3-(ciclopropilmetilamino)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 488,3
292
(S)-2-(4-bromo-2-fluorofenil)-1-(4-((5R,7R)-7-hidroxi5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 562,2
293
(S)-2-(4-cloro-2-fluorofenil)-1-(4-((5R,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 518,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
294
(S)-2-(4-cloro-2-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 518,3
295
(S)-1-(4-((5R,7S)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3-(tetrahidro2H-piran-4-ilamino)-2-(4-(trifluorometil)fenil)-1propanona 534,2
296
(S)-3-(ciclopropilmetilamino)-1-(4-((5R,7S)-7-hidroxi5-metil-6,7-dihidro-5H-3-ciclopenta[d]pirimidin-4il)piperazin-1-il)-2-(4-(trifluorometil)fenil)-1-propanona 504,2
297
(S)-2-(4-bromofenil)-3-(tertbutilamino)-1-(4-((5R,7R)7-hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin4-il)piperazin-1-il)-1-propanona 516,2
298
(S)-2-(4-cloro-3-fluorofenil)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isobutilamino)-1-propanona m/z 490, 492 [M+H]+
Ejemplo
Estructura Nombre LCMS o RMN 1H
299
(S)-2-(4-cloro-3-fluorofenil)-3-(ciclopentilmetilamino)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 516, 518 [M+H]+
300
(S)-2-(4-cloro-3-fluorofenil)-3-(ciclopentilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona m/z 502, 504 [M+H]+
301
(S)-2-(2-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7R)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropil(metil)amino)-1-propanona 524,2
302
imagen117 (S)-2-(4-clorofenil)-1-(4-((5R,7R)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-3((2-hidroxietil)(isopropil)amino)-1-propanona 502,3
303
imagen118 (S)-2-(2-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,75)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 510,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
304
(S)-2-(2-fluoro-4-(trifluorometil)fenil)-1-(4-((5R,7S)-7hidroxi-5-metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 552,3
305
(S)-3-amino-2-(2-fluoro-4-(trifluorometil)fenil)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 467,2
306
(S)-3-(ciclopropilmetilamino)-2-(3-fluoro-4(trifluorometil)fenil)-1-(4-((5R,75)-7-hidroxi-5-metil-6,7dihidro-5H-ciclopenta[d]pirimidin-4-il)piperazin-1-il)-1propanona 552,2
307
(S)-3-(ciclopropilmetilamino)-2-(3-fluoro-4(trifluorometoxi)fenil)-1-(4-((5R,7S)-7-hidroxi-5-metil6,7-dihidro-5H-ciclopenta[d]piridin-4-il)piperazin-1-il)1-propanona 538,2
308
(S)-2-(4-bromofenil)-3-(4,4-dimetilciclohexilamino)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 572,3
309
(S)-2-(4-bromofenil)-3-(3,3-dimetilciclohexilamino)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 570,3
Ejemplo
Estructura Nombre LCMS o RMN 1H
310
(S)-2-(4-clorofenil)-3-(4,4-dimetilciclohexilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 526,4
311
(S)-2-(4-clorofenil)-3-(3,3-dimetilciclohexilamino)-1-(4((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 526,3
312
(S)-1-(4-((5R,7R)-7-hydioxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-3(isopropilamino)-2-(tiofen-2-il)-1-propanona 430,3
313
imagen119 (S)-2-(5-bromotiofen-2-il)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 508,2
314
imagen120 (S)-2-(5-bromotiofen-2-il)-1-(4-((5R,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 508,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
315
(S)-2-(5-bromotiofen-2-il)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 550,2
316
(R)-2-(5-bromopiridin-2-il)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 503,2
317
(S)-2-(5-bromopiridin-2-il)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamimo)-1-propanona 503,2
318
(S)-2-(5-bromotiofen-2-il)-1-(4-((5R,75)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 550,2
319
(S)-2-(5-bromotiofen-2-il)-3-(ciclopropilmetilamino)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 520,2
Ejemplo
Estructura Nombre LCMS o RMN 1H
320
(S)-2-(5-clorotiofen-2-il)-1-(4-((5R,7S)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 506,2
321
(S)-2-(5-clorotiofen-2-il)-1-(4-((5R,75)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(isopropilamino)-1-propanona 464,2
322
(S)-2-(5-clorotiofen-2-il)-1-(4-((5R,7R)-7-hidroxi-5metil-6,7-dihidro-5H-ciclopenta[d]pirimidin-4il)piperazin-1-il)-3-(tetrahidro-2H-piran-4-ilamino)-1propanona 506,2
323
(S)-2-(5-clorotiofen-2-il)-3-(ciclopropilmetilamino)-1(4-((5R,7R)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 476,2
324
(S)-2-(5-clorotiofen-2-il)-3-(ciclopropilmetilamino)-1(4-((5R,7S)-7-hidroxi-5-metil-6,7-dihidro-5Hciclopenta[d]pirimidin-4-il)piperazin-1-il)-1-propanona 476,2

Claims (1)

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ES11166123.7T 2006-07-06 2007-07-05 Ciclopenta[d]pirimidinas hidroxiladas como inhibidores de la proteína quinasa AKT Active ES2554228T3 (es)

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