BG109057A - N-[[5-метил-3-фенилизоксазол-4-ил]фенил]сулфонилпропиламид и негова натриева сол като прекурсори на инхибитори на сох-2 - Google Patents

N-[[5-метил-3-фенилизоксазол-4-ил]фенил]сулфонилпропиламид и негова натриева сол като прекурсори на инхибитори на сох-2 Download PDF

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Publication number
BG109057A
BG109057A BG109057A BG10905798A BG109057A BG 109057 A BG109057 A BG 109057A BG 109057 A BG109057 A BG 109057A BG 10905798 A BG10905798 A BG 10905798A BG 109057 A BG109057 A BG 109057A
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BG
Bulgaria
Prior art keywords
methyl
compounds
phenyl
phenylisoxazol
anhydride
Prior art date
Application number
BG109057A
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English (en)
Inventor
John Talley
James Malecha
Stephen Bertenshaw
Matthew Graneto
Jeffrey Carter
Jinglin Li
Srinivasan Nagarajan
David Brown
Jr. Donald Rogier
Thomas Penning
Ish Khanna
Xiangdong Xu
Richard Weier
Original Assignee
G.D.Searle & Co
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Publication date
Application filed by G.D.Searle & Co filed Critical G.D.Searle & Co
Publication of BG109057A publication Critical patent/BG109057A/bg

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    • C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
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Abstract

Изобретението се отнася до метод за получаване на прекурсори на инхибитори на СОХ-2, N-[[4- (5-метил-3- фенилизоксазол- 4-ил) фенил] сулфонил] пропанамид или N-[[4- (5-метил-3-фенилизоксазол-4- ил)]сулфонил] пропанамид, тяхна натриева сол и техни фармацевтично приемливи соли.

Description

СОЛ КАТО ПРЕКУРСОРИ НА ИНХИБИТОРИ НА СОХ-2
Област на техниката [0001] Настоящото изобретение се отнася до противовъзпалителни фармацевтични средства и, по-специално, до прекурсори на съединения, които селективно инхибират циклооксигеназа-2.
Предшестващо състояние на техниката [0002] Прилагането на нестероидални противовъзпалителни лекарства (NSAIDs) за успокояване на болка и за спадане на оток.
свързани с възпаление, могат да предизвика! тежки странични реакции, включващи появата на язви, застрашаващи живота. Неотдавнашното откритие на индуцируем ензим, свързан с възпаление (“простагландин
Ί ·· 4 · 4 ·· ·· 44 44
4 4 4 44 · 444
4 · · · · ·4···
44····· « · · * ** · 4·· · ··
44·· · ·· ···· ·····
G/Ή синтаза П” или “циклооксигеназа-2 (СОХ-2)”), обезпечава жизнеспособна мишена за инхибиране. която по-ефективно редуцира възпалението и води до появяване па по-слаби и по-малко драстични странични ефекти.
[0003] Описани са съединения, които селективно инхибират циклооксигеназа-2. В US-A~5.380.738 са описани оксазоли, които селективно инхибират циклооксигеназа-2. В US-A-5,344,991 са описани циклопентени, които селективно инхибират циклооксигеназа-2. В US-A5,393,790 (съответстващ на WO-A-9521817) са описани спиросъединения, които селективно инхибират циклооксигеназа-2 и, следователно, са приложими за лечение на възпаление. В WO-A-9415932 са описани производни на тиофен и фуран, които селективно инхибират циклооксигеназа-2. В WO-A-9427980 са описани оксазоли, които селективно инхибират циклооксигеназа-2. В WO-A-9413635 са описани съединения, които селективно инхибират циклооксигеназа-2. В WO-A9420480 са описани съединения, които селективно инхибират циклооксигеназа-2. В WO-A-9515316 са описани производни па пиразолилеулфоамид, които селективно инхибират циклооксигеназа-2. В някои случаи, обаче, са изгодни прекурсори на противовъзпаличелни съединения, особено, когато прекурсорите притежават повишена водоразтворимоет или забавено начало на действие.
[0004] Описани са заместени сулфонамиди. 11иразолилсулфонилкарбамидите са описани като имащи възможна хиногликемична активност (Н. Paid Allah, Н. Mokhtar, Ind. J. Chem., 27, 245 (1988)). B JP 1,045,374 са описани водоразтворими гетразолиеви съединения, приложими при анализи за определяне на редуциращи вещества. D. Mukerjec el al. {Acta. Pharma. Jugcsl., 31, 151 (1981)] описват гетразолиеви сулфонамиди като антивирусни средства. В JP 4,277,724 са описани грифенилпиразолини като нелинеен оптичен материал. В JP 1,045,374 е • · · · · · · • · · · ·· • · · · ·· • ······ « · • · ·· · съдинения за черно-бял са описани заместени
В US-A-5,387,592 са като антагонисти на ···· · ·· · · · · описано приложението на хетероциклични фотографски материал. В US-A-5,389,635 имидазоли, като антагонисти на ангиотензин II. описани производни на заместен бензимидазол, ангиотензин II. G. Dorofeenko et al., [Khim. Farm. Zh., 16, 920 (1982)] описва пиридиниеви соли като антивирусни агенти. В US-A-5,338,749 са описани диарилзаместени противоартритни средства. В съединения, които селективно хетероциклични съединения като
WO-A-9426731 са описани гиофепови инхибират циклооксигеназа-2. В WO-A
9500501 са описани съединения, които селективно инхибират циклооксигеназа-2 и, по-специално, описан е 3-(4-(трифлуорацетиламиносулфонил) фенил)-2-(4-флуорфенил)тиофен. Т. Ivanov [Mh. Chem., 97, 1499 (1966)] описва получаването на производни на диарилиндон като възможни индикатори, като специално е описан 2-(4-(Ъ1-метиламиносулфонил) фенил)-3-фенилиндон.
[0005] J. Larsen и Н. Bundgaard [Int. J. Pharmaceutics, 37, 87 (1987)] описват отделянето на N-ацилсулфонамиди като потенциални производни на прекурсор. J. Larsen et al., [Int. J. Pharmaceutics, 47, 103 (1988)] описва оценяването на N-метилсулфонамиди като потенциални производни на прекурсор.
[0006] В WO-A-9603388 са описани 1,2-заместени имидазолилови съединения за лечение на възпаление.
[0007] В Bioorganic & Medicinal Chemistry Letters, Vol. %, No. 18, pp. 2123-2128, 1995 е описан синтезът и биологичната оценка на 2,3диарилтиофени като селективни инхибитори на СОХ-2 и СОХ-1.
[0008] В WO-A-9619462 са описани производни на оксазол и тяхното приложение като антипиретици, аналгетици и противовъзпалителни средства. В WO-A-9619463 също са описани производни на оксазол.
[0009] Напоследък се чувства нужда от съединения, подходящи за инжектируеми противовъзпалителни състави. Установено е, че съеди ненията, съгласно настоящото изобретение, не са ефикасни като прекурсори.
Техническа същност на изобретението [0010] N-[[4-( 5-метил-3-фенилизоксазол-4-ил]фенил]сулфонилпропанамид и Ь1-[[4-(5-метил-3-фенилизоксазол-4-ил]пропанамид, натриева сол, са заместени сулфонамидни съединения с приложение като прекурсори.
[0011] Споменатите съединения могат да се използват за, но без да е ограничение, лечение на възпаление на пациент или за лечение на други нарушения, свързани с циклооксигеназа-2, като аналгетик при облекчаване на болка или главоболие, или като антипиретик за лечение на треска. Например, съединенията, съгласно настоящото изобретение, могат да бъдат полезни при лечение на артрит, включващ, но без да е ограничение, ревматоиден артрит, спондилоартропатии, подагрен артрит, остеоартрит, лупус еригематозус и юношески артрит. Тези съединения, съгласно настоящото изобретение, могат да бъдат полезни при лечение па астма, бронхит, менструални спазми, преждевременно раждане, тендинит, бурсит, състояния, свързани с кожата, като псориазис, екзема, изгаряния и дерматит, и при следоперативно възпаление, включващо офталмологична операция като отстраняване на перде и рефрактивна операция. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни също и при лечение на стомашно-чревни състояния, като възпаление на червата, болест на Crohn, гастрит, синдром на чувствителните черва и язвен колит. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни за превенция или лечение на рак, като колоректален рак и рак на гърдата, на белия дроб, на простатата, на цервикса и кожата.
• · · · • · • · · · • · • · • · ·
Съединенията, съгласно настоящото изобретение, могат да бъдат полезни при лечение на възпаление при такива заболявания, като васкуларни болести, главоболие вследствие мигрена, периартритна нодоза, тироидит, апластична анемия, болест на Hodgkin, склеродома, ревматична треска, диабет от тип I, болест на невромускулните връзки, включваща миастения гравис, болест на мозъка, включваща множествена склероза, саркодоза, нефротичен синдром, синдром на Behcek полимиозит, гипгивит, нефрит.
свръхчувствителност, селинг, появяващ се след нараняване, миокардиална исхемия. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни също и при лечение на очни болести, като ретинит, регинонагии. увеит, очна фотофобия и силно нараняване на очната тъкан. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни също и при лечение на белодробно възпаление, като такова, свързано с вирусни инфекции и цистична фиброза. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни също и при лечение на някои нарушения на централната нервна система, като кортикални деменции, включващи болест на Alzheimer, и увреждане на централната нервна система, вследствие на удар, исхемия или травма. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни като противовъзпалителни средства, например, за лечение на артрит при значително по-малко вредни странични реакции. Съединенията, съгласно настоящото изобретение, moi ат да бъдат полезни също и при лечение на алергични риниги, синдром на респираторен дистрес, синдром на ендотоксичен шок и атеросклероза. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни също и при облекчаване на болка, без да се ограничава до следоперативна болка, зъбобол, мускулна болка и болка в резултат на раково заболяване. Съединенията, съгласно настоящото изобретение, могат да бъдат полезни за превенция на деменции, като болеет на Alzheimer.
··· 6·· ·· · ···· • · · · · · · · · · ··· · · · · ···· ······· · · ·· · · • · ··· ·· · ···· · ·· ···· ·· ··· [0012] Освен че са ефикасни при лечение па хора, съединенията, съгласно настоящото изобретение, са ефикасни също и във ветеринарната медицина за лечение на домашни животни, екзотични животни и селскостопански животни, включващи бозайници и гризачи. По-предночитаншс животни включват коне, кучета и котки.
[0013] Съединенията, съгласно настоящото изобретение, могат да се използват също и при комбинирана терапия, частично или напълно, вместо други конвенционални противовъзпалителни средства, например, заедно със стероиди, ттестероидални противовъзпалителни лекарства (NSAlDs), инхибитори на 5-липоксигеназа, антагонисти на LTB4 и инхибитори па 1ТА} хидролиза.
[0014] Подходящите инхибитори на LTB4 включват, освен други, и ебселен, Bayer Вау-х-1005, Ciba Geigy съединение CGS-25019C, Leo Denmark съединение 1-,111-615. Lilly съединение LY-293111, Ono съединение ONO-4057, Terumo съединение TMK-688, Lilly съединения Ι,Υ-213024, 264086 и 292728, ΟΝΟ съединение ONO-LB-457, Searle съединение SC-53228, калцитрол, Lilly съединения LY-210073, ! Y 223982, LY-233469 и LY-255283, ONO съединение ONO-LB-448, Searle съединения SC-41930, SC-50605 и SC-51146, и SK&F съдинение SKFO 104493. Предпочита се, инхибиторите на 1,ТВ4 да бъдат подбирани между ебселен, Bayer Вау-х-1005, Ciba Geigy съединение CGS-25019С, Leo Denmark съединение ЕТН-615, Lilly съединение LY-293111, Ono съединение ONO-4057 и Terumo съединение ТМК-688.
[00151 Подходящите инхибитори на 5-LO включват, освен други, и мазопрокол, тенидап, зилеутон, пранлукаст, тепоксалин, рилопирокс, флезетастин хидрохлорид, еназадрем фосфат и бунапроласт.
[0016] Съединенията, съгласно настоящото изобретение, могат да се използват също и при комбинирана терапия с опиати и други аналгетици, като морфин, меперидин или кодеин.
• · ·· · е · · ·· ··· ···· · · · • · · «· · · · ··· ••••••a · · · · · · • · ··· ··· «··· · ·· ···· ·· ··· [0017] Терминът “инхибитор на циклооксигеназа-2” включва съединения, които селективно инхибират циклооксигеназа-2, по-добре от циклооксигеназа-1. Предпочита се съединенията да притежават 1С50 на циклооксигеназа-2 по-малък от около 0.5 μΜ и, също така, да имат селективно съотношение на инхибиране на циклооксигеназа-2 по-голямо от това на циклооксигеназа-1 с поне 50, за предпочитане, поне 100. Даже повече се предпочита, съединенията да притежават 1С5о на циклооксигеназа-1, по-голям от около 1 μΜ, като още повече се предпочита, по-голям от 20 μΜ. Такава предпочитана селективност може да индикира способност за намаляване на появата па обичайни индуцирани от несгероидални противовъзпалителни лекарства странични реакции.
[0018] Фразата “терапевтично активен” служи за окачествяване на количеството на всяко лекарствено средство за използване в комбинираната терапия, с което ще се постигне подобряване в тежестта и честотата на появяване на странични ефекти в по-голяма степен, отколкото при лечение с всяко лекарствено средство поотделно, доколкото избягването на вредните странични ефекти обикновено се свързва с алтернативно лечение.
[0019] Фразата “комбинирана терапия”, с която се дефинира използването на инхибитор на циклооксигеназа-2 заедно с друго лекарствено средство, се отнася до последователно администриране на всяко лекарствено средство при даден режим, който осигурява благоприятни ефекти на лекарст вената комбинация и, също така сс отнася до съвместно едновременно администриране на тези лекарствени средства, например в единична капсула, съдържаща фиксирано съотношение на тези активни лекарствени средства, или в множество отделни капсули, съдържащи всяко лекарствено средство.
·« ·· ····· • · · · v · · ··· · · ······ ···*··· · · · · ·· • · ··· · ·· ···· · ·· ···· ·· ··· [0020] Терминът “прекурсор” се отнася до съединения, които са прекурсори на лекарства, които при администриране върху пациент и следващо абсорбиране, in vivo се превръщат в активни съставки при някой процес, като метаболизъм. Другите продукти на процеса на превръщане лесно се отделят от тялото. От по-предпочитапите прекурсори се получават продукти на процеса на превръщане, които обикновено се приемат за безопасни.
[0021] Настоящото изобретение се отнася до метод за получаване на N-[ [4-( 5-метил- 3 -фенилизокса зо л-4 нл]фенил] сулфонилпропанамвд или N-[ [4-( 5-метил-3-фенилизоксазол-4-ил |сулфонил]пропана мид, тяхна натриева сол или тяхна фармацевтично приемлива сол.
Основни синтетични мегоди [0022] Прекурсорите на инхибитора на циклооксигеназа-2, съгласно настоящото изобретение, могат да бъдат синтезирани по следните методи:
1. М-[[4-(5-метил-3-фенилизоксазол-4-ил]фепил]сулфонилпропанамид:
а) третиране на Я-[[4-(5Метил-3'фенилизокса.зол~4-ил]фенил] сулфонамид е подходящ ацилиращ агент, подбран от групата, състояща се от анхидрид, киселинен хлорид, ацилимидазол или активен естер, в присъст вие на база и подходящ разтворител и
б) изолиране на съединението посредством хроматография или кристализация.
2. Н-[[4-(5-мстил-3-фсншшзоксазо;ъ4-ил]сулфонил]11ропанамид, натриева сол:
третиране на Н-[[4-(5-метил--3-фенилизоксазол-4-ил)фенил] сулфонил]нропанамид със силна натриева база, като натриев хидроксид.
·· · • * ··♦·
9.·· • ·
[0023] Широка гама от разтворители може да бъде използвана достатъчно дълго, докато разтворителите не взаимодействат с добавената силна база, като предпочитани са етанол и тетрахидрофуран.
[0024] Следващите примери включват подробно описание на методите за получаване на Щ[4-(5-метил-3-фенилизоксазол-4ил]фенил]сулфоиилиронанамид или и-[[4-(5-мстил-3-фенилизоксазол-4ил]сулфонил]пропанамид, натриева сол. Всички използвани части са тегловни и температурата е дадена в градуси по Целзий, ако не е посочено друго. NMR-спектрите на всички съединения са в съответствие с тяхната
показана структура.
Примери за изпълнение на изобретението
Пример 1
№[[4-(5-метил-3-фенилизоксазол-4-ил)фенил]сулфонил]пропанамил [0025] Анхидрид на пропионовата киселина (9.39 mmol) и триетиламин (3.97 mmol) се прибавят към разтвор на 4-[5-мстил-3фенилизоксазол-4-ил]бензенсулфонамид (3.31 mmol) и Ν,Ν-диметилпиридин (0.202 g) в сух тетрахидрофуран. След разбъркване в продължение на 18 часа при стайна температура реакционната смес се концентрира. Остатъкът се разтваря в етилацетат, промива се добре с 1N ·· · 10 ·· .·*. .·.!··“ ··· · · · · · · · • · · · · * · · *·· ······· · · ·· · · . · .♦· .·· ««··· ·· ···· ·» ··· солна киселина и разсол, суши се над безводен магнезиев сулфат и се концентрира до получаване на 1.0 g (81%) от желания продукт като кристално вещество.
[0026] Т. т. 148.9-151,0°С. Ή NMR (CDCI3/3OO MHz) 8.60 (brs,lH), 8.04 (d,2H,./=8.7 Hz), 7.38-7.31 (m,7H), 2.50 (s,3H), 2.32 (q,2H/-7.2 Hz), 1.10 (t,311,/-7.2 Hz). FABLRMS m/z 371 (M+H). FABHRMS m/z 371.1049 (М-ьН), изчислено 371.1066. Елементен анализ: изчислено за C19Hl8N2O4S: С, 61.61; Н, 4.90; N, 7.56. Намерено: С, 61.52; Н, 4.92; N, 7.53.
Пример 2
№-[[4-(5-метил-3-фенилизоксазол-4-ил)фенил]сулфонил]пропанамид, натриева сол [0027J Смес на Н-[[4-(5-метил-3-фенилизоксазол-4-ил)фенил] сулфонил]пропанамид (Пример 1) (0.83 mmol) и натриев хидроксид (0.33 ml, 2.5N) в етанол се концентрират до сухо. Остатъкът се разтваря в етанол и отново се концентрира. Остатъкът се суши под вакуум до получаване на 0.32 g (97%) кристален продукт.
[0028] Т.т. 271.9-272.7°С. Ή NMR (D20/300 MHz) 7.57 (d,211,/-8.4 Hz), 7.30-6.90 (m,7H), 2.12 (s,3H), 2.00 (q,2H/-7.8 Hz), 0.83 (t,3H,/-7.8 Hz). FABLRMS m/z 393 (M+H). Елементен анализ: изчислено за C19H17N2O4SNa: С, 58.61; Η, 4.37; Ν, 7.14. Намерено: С, 57.92; Η, 4.53; Ν, 6.95.

Claims (9)

11.··
ПАТЕНТНИ ПРЕТЕНЦИИ
1. Метод за получаване на парекоксиб, Ь1-[[4-(5-метил-3фенилизоксазол-4-ил)фенил]сулфонил]пропанамид, съединение с Формула:
характеризиращ се с това, че включва взаимодействие на [4-(5-метил-3фенилизоксазол-4-ил]бензенсулфонамид с ацилиращ агент в присъствие на база и разтворител.
2. Метод, съгласно претенция 1, характеризиращ се е това, че ацилиращият агент с подбран между анхидриди, киселинни хлориди, ацилимидазоли и активни естери на пропионова киселина.
3. Метод, съгласно претенция I, характеризиращ се с това, че ацилиращият агент е пропионов анхидрид.
4. Метод, съгласно претенция 1, характеризиращ се с това, че разтворителят е теграхидрофуран.
5. Метод за получаване на парекоксиб, Ь1-[[4-(5-метил-3фенилизоксазол-4-ил)фенил]сулфонил]пропанамид, или негова фармацевтично приемлива сол, характеризиращ се с това, че включва получаване на Ь18(М-ацилиран)сулфонамид посредством взаимодействие на [4-(5метил-3-фенилизоксазол-4-ил]бензенсулфонамид с излишък от анхидрид, киселинен хлорид или карбамилхлорид, в присъствие на трегична аминна база и третиране на споменатия Ьщ(№-ацилиран)сулфонамид с около два еквивалента силна база до получаване на солта.
12..
6. Метод, съгласно претенция 5, характеризиращ се с това, че анхидридът или киселинния! хлорид е нропионов анхидрид или пропионилхлорид.
7. Метод, съгласно претенция 5, характеризиращ се с това, че третичната аминна база е триетиламин или Ν,Ν-диметилпиридин.
8. Метод, съгласно претенция 5, характеризиращ се с това, че разтворителят е тетрахидрофуран.
9. Метод, съгласно претенция 5, характеризиращ се с това, че силната база е натриев хидроксид.
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Families Citing this family (287)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996038418A1 (en) 1995-06-02 1996-12-05 G.D. Searle & Co. Heterocyclo substituted hydroxamic acid derivatives as cyclooxygenase-2 and 5-lipoxygenase inhibitors
US5908858A (en) * 1996-04-05 1999-06-01 Sankyo Company, Limited 1,2-diphenylpyrrole derivatives, their preparation and their therapeutic uses
WO1997038986A1 (en) * 1996-04-12 1997-10-23 G.D. Searle & Co. Substituted benzenesulfonamide derivatives as prodrugs of cox-2 inhibitors
US6586458B1 (en) 1996-08-16 2003-07-01 Pozen Inc. Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs
US8022095B2 (en) 1996-08-16 2011-09-20 Pozen, Inc. Methods of treating headaches using 5-HT agonists in combination with long-acting NSAIDs
AU725697B2 (en) * 1997-04-03 2000-10-19 G.D. Searle & Co. Method of using cyclooxygenase-2 inhibitors in the treatment and prevention of dementia
US20040072889A1 (en) * 1997-04-21 2004-04-15 Pharmacia Corporation Method of using a COX-2 inhibitor and an alkylating-type antineoplastic agent as a combination therapy in the treatment of neoplasia
RS49982B (sr) 1997-09-17 2008-09-29 Euro-Celtique S.A., Sinergistička analgetička kombinacija analgetičkog opijata i inhibitora ciklooksigenaze-2
NZ333399A (en) 1997-12-24 2000-05-26 Sankyo Co Cyclooxygenase-2 inhibitors (COX-2) for the prevention and treatment of tumors, cachexia and tumor-metastasis
JP2002506024A (ja) * 1998-03-13 2002-02-26 メルク エンド カムパニー インコーポレーテッド 急性冠動脈虚血症候群および関連状態に対する併用療法および組成物
US6136804A (en) * 1998-03-13 2000-10-24 Merck & Co., Inc. Combination therapy for treating, preventing, or reducing the risks associated with acute coronary ischemic syndrome and related conditions
WO1999063939A2 (en) 1998-06-08 1999-12-16 Advanced Medicine, Inc. Multibinding inhibitors of cyclooxygenase-2
AR024222A1 (es) * 1998-10-16 2002-09-25 Palau Pharma Sa Imidazoles con actividad antiinflamatoria un procedimiento para su preparacion y composiciones farmaceuticas que lo contienen
ATE284691T1 (de) * 1998-11-02 2005-01-15 Merck & Co Inc Zusammensetzungen aus einem 5ht1b/1d agonisten und einem selektiven cox-2 hemmer zur behandlung von migräne
AU1398899A (en) * 1998-11-12 2000-06-05 Algos Pharmaceutical Corporation Cox-2 inhibitors in combination with centrally acting analgesics
US6649645B1 (en) 1998-12-23 2003-11-18 Pharmacia Corporation Combination therapy of radiation and a COX-2 inhibitor for treatment of neoplasia
US20040122011A1 (en) * 1998-12-23 2004-06-24 Pharmacia Corporation Method of using a COX-2 inhibitor and a TACE inhibitors as a combination therapy
US20030119895A1 (en) * 1998-12-23 2003-06-26 Pharmacia Corporation Methods using a combination of a 3-heteroaryl-2-indolinone and a cyclooxygenase-2 inhibitor for the treatment of neoplasia
US20030013739A1 (en) * 1998-12-23 2003-01-16 Pharmacia Corporation Methods of using a combination of cyclooxygenase-2 selective inhibitors and thalidomide for the treatment of neoplasia
AU3596500A (en) * 1999-02-19 2000-09-04 Pozen, Inc. Formulation of 5-ht agonists with cox-2 inhibitors
US20010024664A1 (en) * 1999-03-19 2001-09-27 Obukowicz Mark G. Selective COX-2 inhibition from edible plant extracts
US6323226B1 (en) 1999-10-19 2001-11-27 Texas Heart Institute Treatment of heart disease with cox-2 inhibitors
EA008242B1 (ru) * 1999-12-08 2007-04-27 Фармация Корпорейшн Композиции на основе ингибитора циклооксигеназы-2 с быстро наступающим терапевтическим действием и способы лечения заболеваний
ES2258988T3 (es) * 1999-12-22 2006-09-16 Pharmacia Corporation Composiciones de liberacion dual de un inhibidor de la ciclooxigenasa-2.
US6649629B2 (en) * 1999-12-23 2003-11-18 Nitromed, Inc. Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use
EP1762557B1 (en) 2000-02-16 2011-04-06 The Brigham And Women's Hospital, Inc. Aspirin-triggered lipid mediators
CA2401697A1 (en) * 2000-03-03 2001-09-07 Pfizer Products Inc. Pyrazole ether derivatives as anti-inflammatory/analgesic agents
US20070072861A1 (en) * 2000-03-27 2007-03-29 Barbara Roniker Method of using cyclooxygenase-2 inhibitors in the prevention of cardiovascular disorders
AU2001253749A1 (en) * 2000-04-25 2001-11-07 Pharmacia Corporation 2-fluorobenzenesulfonyl compounds for the treatment of inflammation
ES2166710B1 (es) * 2000-04-25 2004-10-16 J. URIACH & CIA, S.A. Nuevos compuestos heterociclicos con actividad antiinflamatoria.
AU5754701A (en) * 2000-07-13 2002-01-30 Pharmacia Corp Method of using cox-2 inhibitors in the treatment and prevention of ocular cox-2mediated disorders
NZ524252A (en) 2000-07-20 2004-03-26 Lauras As Cox-2 inhibitors for treating HIV and AIDS
US20030219461A1 (en) * 2000-09-12 2003-11-27 Britten Nancy J. Parenteral combination therapy for infective conditions
JP2004508401A (ja) * 2000-09-18 2004-03-18 メルク　エンド　カムパニー　インコーポレーテッド シクロオキシゲナーゼ−２阻害剤およびインテグリンアルファ−ｖアンタゴニストの組合せを用いる炎症の治療
US20020173524A1 (en) * 2000-10-11 2002-11-21 Tularik Inc. Modulation of CCR4 function
US20020136784A1 (en) * 2000-12-15 2002-09-26 Pharmacia Corporation Selective COX-2 inhibition from plant extracts
EP1363649A1 (en) * 2000-12-15 2003-11-26 Pharmacia Corporation Selective cox-2 inhibition from non-edible plant extracts
DE60122939T2 (de) 2000-12-21 2007-01-11 Nitromed, Inc., Bedford Substituierte arylverbindungen als neue, cyclooxygenase-2-selektive inhibitoren, zusammensetzungen und verwendungsverfahren
US7115565B2 (en) * 2001-01-18 2006-10-03 Pharmacia & Upjohn Company Chemotherapeutic microemulsion compositions of paclitaxel with improved oral bioavailability
EP1363669A2 (en) * 2001-02-02 2003-11-26 Pharmacia Corporation Method of using a cyclooxygenase-2 inhibitor and sex steroids as a combination therapy for the treatment and prevention of dismenorrhea
WO2002078625A2 (en) * 2001-03-28 2002-10-10 Pharmacia Corporation Therapeutic combinations for cardiovascular and inflammatory indications
PE20021017A1 (es) * 2001-04-03 2002-11-24 Pharmacia Corp Composicion parenteral reconstituible
ITMI20010733A1 (it) 2001-04-05 2002-10-05 Recordati Chem Pharm Uso di inibitori dell'isoenzina cox-2 per il trattamento dell'incontinenza urinaria
US20030105144A1 (en) 2001-04-17 2003-06-05 Ping Gao Stabilized oral pharmaceutical composition
US6673818B2 (en) 2001-04-20 2004-01-06 Pharmacia Corporation Fluoro-substituted benzenesulfonyl compounds for the treatment of inflammation
WO2002094264A1 (en) * 2001-05-23 2002-11-28 Tularik Inc. Ccr4 antagonists
US20030153801A1 (en) * 2001-05-29 2003-08-14 Pharmacia Corporation Compositions of cyclooxygenase-2 selective inhibitors and radiation for inhibition or prevention of cardiovascular disease
HUP0600294A2 (en) * 2001-05-31 2007-02-28 Pharmacia Corp Skin-permeable selective cyclooxygenase-2 inhibitor composition
DE10129320A1 (de) * 2001-06-19 2003-04-10 Norbert Mueller Verwendung von COX-2 Inhibitoren zur Behandlung von Schizophrenie, wahnhaften Störungen, affektiven Störungen oder Ticstörungen
US20060167074A1 (en) * 2001-06-19 2006-07-27 Norbert Muller Methods and compositions for the treatment of psychiatric disorders
UA80682C2 (en) * 2001-08-06 2007-10-25 Pharmacia Corp Orally deliverable stabilized oral suspension formulation and process for the incresaing physical stability of thixotropic pharmaceutical composition
EP1414522A2 (en) * 2001-08-10 2004-05-06 Pharmacia Corporation Carbonic anhydrase inhibitors
US20040067992A1 (en) * 2001-08-10 2004-04-08 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a carbonic anhydrase inhibitor for the treatment of neoplasia
US20050101563A1 (en) * 2001-08-14 2005-05-12 Pharmacia Corporation Method and compositions for the treatment and prevention of pain and inflammation
US20030114416A1 (en) * 2001-08-14 2003-06-19 Pharmacia Corporation Method and compositions for the treatment and prevention of pain and inflammation with a cyclooxygenase-2 selective inhibitor and chondroitin sulfate
AR038957A1 (es) 2001-08-15 2005-02-02 Pharmacia Corp Terapia de combinacion para el tratamiento del cancer
EP1436259A1 (en) * 2001-09-10 2004-07-14 Congxin Liang 3-(4,5,6,7-tetrahydroindol-2-ylmethylidiene)-2-indolinone derivatives as kinase inhibitors
WO2003024958A2 (en) * 2001-09-18 2003-03-27 Onconova Therapeutics, Inc. Processes for the preparation of 1,5-diaryl-3-substituted-pyrazoles
US20030236308A1 (en) * 2001-09-18 2003-12-25 Pharmacia Corporation Compositions of cyclooxygenase-2 selective inhibitors and acetaminophen for treatment and prevention of inflammation, inflammation-mediated disorders and pain
US20030114483A1 (en) * 2001-09-18 2003-06-19 Pharmacia Corporation Compositions of chromene cyclooxygenase-2 selective inhibitors and acetaminophen for treatment and prevention of inflammation, inflammation-mediated disorders and pain
WO2003024400A2 (en) 2001-09-18 2003-03-27 Onconova Therapeutics, Inc. Process for the preparation of 1,5-diarylpyrazoles
ATE363473T1 (de) 2001-09-19 2007-06-15 Pharmacia Corp Substituierte pyrazoloverbindungen zur behandlung von entzündungen
RU2284324C2 (ru) * 2001-10-02 2006-09-27 Фармация Корпорейшн Способ получения бензолсульфонилов
AR037097A1 (es) 2001-10-05 2004-10-20 Novartis Ag Compuestos acilsulfonamidas, composiciones farmaceuticas y el uso de dichos compuestos para la preparacion de un medicamento
AU2002337843A1 (en) * 2001-10-12 2003-04-22 Onconova Therapeutics, Inc. Processes for the preparation of substituted isoxazoles and 2-isoxazolines
US20030162824A1 (en) * 2001-11-12 2003-08-28 Krul Elaine S. Methods of treating or preventing a cardiovascular condition using a cyclooxygenase-1 inhibitor
US20030100595A1 (en) * 2001-11-13 2003-05-29 Aziz Karim Oral dosage form of a sulfonamide prodrug
ATE424388T1 (de) 2001-12-06 2009-03-15 Merck & Co Inc Mitotische kinesinhemmer
US20040126438A1 (en) * 2001-12-13 2004-07-01 Obukowicz Mark G. Selective cox-2 inhibition from plant extracts
AU2002353147A1 (en) * 2001-12-13 2003-06-30 Abbott Laboratories 3-(phenyl-alkoxy)-5-(phenyl)-pyridine derivatives and related compounds as kinase inhibitors for the treatment of cancer
US20040062823A1 (en) * 2001-12-13 2004-04-01 Obukowicz Mark G. Selective cox-2 inhibition from non-edible plant extracts
MXPA04006572A (es) * 2002-01-10 2005-11-04 Upjohn Co Terapia de combinacion antivirica.
US20030220374A1 (en) * 2002-01-14 2003-11-27 Pharmacia Corporation Compositions and methods of treatment involving peroxisome proliferator-activated receptor-gamma agonists and cyclooxygenase-2 selective inhibitors
US20030212138A1 (en) * 2002-01-14 2003-11-13 Pharmacia Corporation Combinations of peroxisome proliferator-activated receptor-alpha agonists and cyclooxygenase-2 selective inhibitors and therapeutic uses therefor
TW200403072A (en) * 2002-01-23 2004-03-01 Upjohn Co Combination therapy for the treatment of bacterial infections
US20050025791A1 (en) * 2002-06-21 2005-02-03 Julius Remenar Pharmaceutical compositions with improved dissolution
WO2004026235A2 (en) * 2002-09-20 2004-04-01 Transform Pharmaceuticals, Inc. Pharmaceutical compositions with improved dissolution
US7790905B2 (en) * 2002-02-15 2010-09-07 Mcneil-Ppc, Inc. Pharmaceutical propylene glycol solvate compositions
WO2003074474A2 (en) * 2002-03-01 2003-09-12 University Of South Florida Multiple-component solid phases containing at least one active pharmaceutical ingredient
US7927613B2 (en) * 2002-02-15 2011-04-19 University Of South Florida Pharmaceutical co-crystal compositions
US20100311701A1 (en) * 2002-02-15 2010-12-09 Transform Pharmaceuticals, Inc Pharmaceutical Co-Crystal Compositions
EP1915992A1 (en) 2002-02-19 2008-04-30 Pharmacia Corporation Use of cyclooxygenase inhibitors and antimuscarinic agents for the treatment of incontinence
AU2003220180A1 (en) * 2002-03-15 2003-09-29 Pharmacia Corporation Crystalline parecoxib sodium
US8481772B2 (en) 2002-04-01 2013-07-09 University Of Southern California Trihydroxy polyunsaturated eicosanoid derivatives
US7902257B2 (en) * 2002-04-01 2011-03-08 University Of Southern California Trihydroxy polyunsaturated eicosanoid
AR039391A1 (es) 2002-04-08 2005-02-16 Glaxo Group Ltd Compuesto de ciclopenteno, composicion farmaceutica que lo comprende y su uso para la fabricacion de un medicamento
WO2003088959A2 (en) * 2002-04-18 2003-10-30 Pharmacia Corporation Treatment of parkinson's disease with cyclooxygenase-2 (cox 2) inhibitor(s)
AU2003223579A1 (en) * 2002-04-18 2003-11-03 Pharmacia Corporation Combinations of cox-2 inhibitors and other agents for the treatment of parkinson's disease
US7273616B2 (en) * 2002-05-10 2007-09-25 The Trustees Of Columbia University In The City Of New York Genetically engineered cell lines and systems for propagating Varicella zoster virus and methods of use thereof
JP2005535644A (ja) * 2002-06-26 2005-11-24 ファルマシア コーポレイション 安定な非経口パレコキシブ液体製剤
CA2489428A1 (en) 2002-06-27 2004-01-08 Nitromed, Inc. Cyclooxygenase-2 selective inhibitors, compositions and methods of use
US7211598B2 (en) 2002-06-28 2007-05-01 Nitromed, Inc. Oxime and/or hydrozone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use
MXPA05000259A (es) * 2002-07-02 2005-04-11 Pharmacia Corp Uso de inhibidores selectivos de ciclooxigenasa-2 y agentes tromboliticos para el tratamiento o prevencion de un evento vaso-oclusivo.
US7759395B2 (en) 2002-08-12 2010-07-20 The Brigham And Women's Hospital, Inc. Use of docosatrienes, resolvins and their stable analogs in the treatment of airway diseases and asthma
AU2003258194B2 (en) * 2002-08-12 2009-11-12 The Brigham And Women's Hospital, Inc. Resolvins: biotemplates for therapeutic interventions
UY27939A1 (es) 2002-08-21 2004-03-31 Glaxo Group Ltd Compuestos
KR100484525B1 (ko) * 2002-10-15 2005-04-20 씨제이 주식회사 이소티아졸 유도체, 그 제조방법 및 약제학적 조성물
US20040082543A1 (en) * 2002-10-29 2004-04-29 Pharmacia Corporation Compositions of cyclooxygenase-2 selective inhibitors and NMDA receptor antagonists for the treatment or prevention of neuropathic pain
GB0225548D0 (en) 2002-11-01 2002-12-11 Glaxo Group Ltd Compounds
US20040092566A1 (en) * 2002-11-12 2004-05-13 Graneto Matthew J. Celecoxib prodrug
US20040147581A1 (en) * 2002-11-18 2004-07-29 Pharmacia Corporation Method of using a Cox-2 inhibitor and a 5-HT1A receptor modulator as a combination therapy
US20050020658A1 (en) * 2002-11-21 2005-01-27 Katsuyuki Inoo Selective cyclooxygenase-2 inhibitor patch
US20040126415A1 (en) * 2002-11-21 2004-07-01 Lu Guang Wei Dermal delivery of a water-soluble selective cyclooxygenase-2 inhibitor
US20040127531A1 (en) * 2002-11-21 2004-07-01 Lu Guang Wei Adhesive coated sheet for dermal delivery of a selective cyclooxygenase-2 inhibitor
DE60332387D1 (de) 2002-12-13 2010-06-10 Warner Lambert Co Alpha-2-delta-ligand zur behandlung vonsymptomen der unteren harnwege
US20040204411A1 (en) * 2002-12-17 2004-10-14 Pharmacia Corporation Method for the treatment, prevention, or inhibition of a CNS disorder and/or pain and inflammation using a combination of reboxetine and a cyclooxygenase-2 selective inhibitor and compositions thereof
US20040235925A1 (en) * 2002-12-17 2004-11-25 Pharmacia Corporation Method for the treatment, prevention, or inhibition of a CNS disorder and/or pain and inflammation using a combination of duloxetine, venlafaxine or atomoxetine and a cyclooxygenase-2 selective inhibitor and compositions thereof
US20080153894A1 (en) * 2002-12-19 2008-06-26 Pharmacia Corporation Cyclooxygenase-2 inhibitor and antibacterial agent combination for intramammary treatment of mastitis
PL377427A1 (pl) * 2002-12-19 2006-02-06 Pharmacia Corporation Sposoby i kompozycje do leczenia infekcji wirusem opryszczki z zastosowaniem inhibitorów selektywnych względem cyklooksygenazy-2 lub inhibitorów cyklooksygenazy-2 w połączeniu ze środkami przeciwwirusowymi
US20040171664A1 (en) * 2002-12-20 2004-09-02 Pharmacia Corporation Compositions of cyclooxygenase-2 selective inhibitors and selective serotonin reuptake inhibitors for the treatment or prevention of a vaso-occlusive event
ES2215474B1 (es) * 2002-12-24 2005-12-16 J. URIACH & CIA S.A. Nuevos derivados de fosforamida.
ES2380827T3 (es) 2002-12-26 2012-05-18 Pozen, Inc. Formas de dosificación con múltiples capas que contienen naproxeno y triptanes
US8183290B2 (en) * 2002-12-30 2012-05-22 Mcneil-Ppc, Inc. Pharmaceutically acceptable propylene glycol solvate of naproxen
WO2004060367A1 (en) * 2002-12-30 2004-07-22 Fujisawa Pharmaceutical Co., Ltd. Imidazole and triazole derivatives useful as selective cox-1 inhibitors
US20050026902A1 (en) * 2003-01-31 2005-02-03 Timothy Maziasz Methods and compositions for the treatment or prevention of human immunodeficiency virus and related conditions using cyclooxygenase-2 selective inhibitors and antiviral agents
US20040176378A1 (en) * 2003-02-12 2004-09-09 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and an amphetamine for the treatment of reduced blood flow to the central nervous system
WO2004078143A2 (en) * 2003-03-05 2004-09-16 The Brigham And Women's Hospital Inc. Methods for identification and uses of anti-inflammatory receptors for eicosapentaenoic acid analogs
US20050004098A1 (en) * 2003-03-20 2005-01-06 Britten Nancy Jean Dispersible formulation of an anti-inflammatory agent
US20040214753A1 (en) * 2003-03-20 2004-10-28 Britten Nancy Jean Dispersible pharmaceutical composition for treatment of mastitis and otic disorders
US20050009931A1 (en) * 2003-03-20 2005-01-13 Britten Nancy Jean Dispersible pharmaceutical composition for treatment of mastitis and otic disorders
CN1761487A (zh) * 2003-03-20 2006-04-19 法玛西雅公司 抗炎剂的可分散制剂
US20040214861A1 (en) * 2003-03-28 2004-10-28 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitors and 5-HT1B1D antagonists for the treatment and prevention of migraine
US20040220155A1 (en) * 2003-03-28 2004-11-04 Pharmacia Corporation Method of providing a steroid-sparing benefit with a cyclooxygenase-2 inhibitor and compositions therewith
US20050143431A1 (en) * 2003-04-04 2005-06-30 Hetero Drugs Limited Novel crystalline forms of parecoxib sodium
WO2004092146A2 (en) * 2003-04-14 2004-10-28 The Institutes For Pharmaceutical Discovery, Llc N- (((((1,3-thiazol-2-yl) amino) carbonyl) phenyl) sulfonyl) phenylalanine derivatives and related compounds for the treatment of diabetes
US20050159403A1 (en) * 2003-04-22 2005-07-21 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a calcium modulating agent for the treatment of central nervous system damage
WO2004093811A2 (en) * 2003-04-22 2004-11-04 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of central nervous system damage
US20040220187A1 (en) * 2003-04-22 2004-11-04 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a sodium ion channel blocker for the treatment of pain, inflammation or inflammation mediated disorders
US20050009733A1 (en) * 2003-04-22 2005-01-13 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a potassium ion channel modulator for the treatment of central nervous system damage
US20060135506A1 (en) * 2003-04-22 2006-06-22 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a calcium modulating agent for the treatment of pain, inflammation or inflammation mediated disorders
US20040229803A1 (en) * 2003-04-22 2004-11-18 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a potassium ion channel modulator for the treatment of pain, inflammation or inflammation mediated disorders
WO2004099168A2 (en) 2003-04-30 2004-11-18 The Institutes For Pharmaceutical Discovery, Llc Substituted carboxylic acids
US20040220167A1 (en) * 2003-05-02 2004-11-04 Nasrollah Samiy Methods of treating neuralgic pain
ES2275218T3 (es) 2003-05-07 2007-06-01 Osteologix A/S Sales de estroncio hidrosolubles para el tratamiento de afecciones de cartilagos y/o huesos.
WO2004100895A2 (en) * 2003-05-13 2004-11-25 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a peroxisome proliferator activated receptor agonist for the treatment of ischemic mediated central nervous system disorders
CA2525571A1 (en) * 2003-05-14 2004-12-02 Pharmacia Corporation Compositions of a benzenesulfonamide or methylsulfonylbenzene cyclooxygenase-2 selective inhibitor and a cholinergic agent for the treatment of reduced blood flow or trauma to thecentral nervous system
BRPI0410287A (pt) * 2003-05-14 2006-05-16 Pharmacia Corp composições para o tratamento de fluxo sanguìneo reduzido
WO2004103283A2 (en) * 2003-05-14 2004-12-02 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a central nervous system stimulant for the treatment of central nervous system damage
WO2004103286A2 (en) * 2003-05-14 2004-12-02 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a cholimergic agent
US20050113376A1 (en) * 2003-05-27 2005-05-26 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor, a xanthine compound and an alcohol for the treatment of ischemic mediated central nervous system disorders or injury
US20060160776A1 (en) * 2003-05-28 2006-07-20 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a cannabinoid agent for the treatment of central nervous system damage
CN1812983A (zh) 2003-05-30 2006-08-02 兰贝克赛实验室有限公司 取代的吡咯衍生物及其作为hmg－co抑制剂的用途
US20050054646A1 (en) * 2003-06-09 2005-03-10 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and an antioxidant agent for the treatment of central nervous system disorders
CA2528634A1 (en) * 2003-06-24 2005-01-06 Pharmacia Corporation Treatment of migraine accompanied by nausea
US20050101597A1 (en) * 2003-07-10 2005-05-12 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitior and a non-NMDA glutamate modulator for the treatment of central nervous system damage
US20050080083A1 (en) * 2003-07-10 2005-04-14 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and an angiotensin II receptor antagonist for the treatment of central nervous system damage
WO2005016249A2 (en) * 2003-07-11 2005-02-24 Pharmacia Corporation Compositions of a chromene or phenyl acetic acid cyclooxygenase-2 selective inhibitor and an ace inhibitor for the treatment of central nervous system damage
WO2005018541A2 (en) * 2003-07-11 2005-03-03 Pharmacia Corporation Cox-2 inhibitor and serotonin modulator for treating cns damage
WO2005009342A2 (en) * 2003-07-16 2005-02-03 Pharmacia Corporation Method for the treatment or prevention of dermatological disorders with a cyclooxygenase-2 inhibitor alone and in combination with a dermatological treatment agent and compositions therewith
WO2005009354A2 (en) * 2003-07-17 2005-02-03 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and an ikk inhibitor for the treatment of ischemic-mediated central nervous system disorders or injury
JPWO2005012268A1 (ja) * 2003-07-30 2006-09-14 塩野義製薬株式会社 イソオキサゾール環を有するスルホンアミド誘導体
EP1670459A4 (en) * 2003-08-20 2009-03-25 Nitromed Inc NITROSED AND NITROSYLATED CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND APPLICATION METHODS
US20050119262A1 (en) * 2003-08-21 2005-06-02 Pharmacia Corporation Method for preventing or treating an optic neuropathy with a cox-2 inhibitor and an intraocular pressure reducing agent
WO2005018569A2 (en) * 2003-08-22 2005-03-03 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a serotonin modulating agent for the treatment of neoplasia
US20050107350A1 (en) * 2003-08-22 2005-05-19 Pharmacia Corporation Method for the treatment or prevention of bone disorders with a cyclooxygenase-2 inhibitor alone and in combination with a bone disorder treatment agent and compositions therewith
WO2005018564A2 (en) * 2003-08-22 2005-03-03 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a low-molecular-weight heparin for the treatment of central nervous system damage
WO2005018563A2 (en) * 2003-08-22 2005-03-03 Pharmacia Corporation Compositions of a cyclooxygenase-2 selective inhibitor and a phosphodiesterase inhibitor for the treatment of ischemic mediated central nervous system disorders or injury
US20050085479A1 (en) * 2003-08-27 2005-04-21 Pharmacia Corporation Mediated central nervous system compositions of a cyclooxygenase-2 selective inhibitor and a corticotropin releasing factor antagonist for the treatment of ischemic disorders or injury
US20050187278A1 (en) * 2003-08-28 2005-08-25 Pharmacia Corporation Treatment or prevention of vascular disorders with Cox-2 inhibitors in combination with cyclic AMP-specific phosphodiesterase inhibitors
JP2007504136A (ja) * 2003-08-28 2007-03-01 ニトロメッド インコーポレーティッド ニトロソ化およびニトロシル化利尿化合物、組成物、ならびに使用方法
WO2005023189A2 (en) * 2003-09-03 2005-03-17 Pharmacia Corporation Method of cox-2 selective inhibitor and nitric oxide-donating agent
MXPA06003663A (es) * 2003-10-03 2006-06-05 Pharmacia Corp Composiciones de un inhibidor selectivo de la ciclooxigenasa - 2 administrado en condiciones hipotermicas para el tratamiento de trastornos o lesion del sistema nervioso central mediados por isquemicos.
JP2007510756A (ja) * 2003-11-12 2007-04-26 ファルマシア・アンド・アップジョン・カンパニー・エルエルシー 中枢神経系介在障害を治療するためのシクロオキシゲナーゼ−２選択的阻害剤及び神経栄養因子調節剤の組成物
EP1708700A1 (en) * 2003-12-24 2006-10-11 Pharmacia Corporation Metal salts of parecoxib as prodrugs of the cox-2 inhibitor valdecoxib for the treatment of inflammation, pain and/or fever
JP2007518788A (ja) 2004-01-22 2007-07-12 ファイザー・インク バソプレッシンのアンタゴニスト活性を阻害するトリアゾール誘導体
EP1755537A4 (en) * 2004-04-14 2009-12-09 Univ Boston METHOD AND COMPOSITIONS FOR PREVENTING OR TREATING PERIODONTOPATHIA
CA2563963A1 (en) * 2004-04-28 2005-11-10 Pfizer Inc. 3-heterocyclyl-4-phenyl-triazole derivatives as inhibitors of the vasopressin v1a receptor
AU2005262373B2 (en) 2004-07-01 2011-03-17 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
ES2257929B1 (es) * 2004-07-16 2007-05-01 Laboratorios Del Dr. Esteve, S.A. Derivados de pirazolina, procedimiento para su obtencion y utilizacion de los mismos como agentes terapeuticos.
KR20070035101A (ko) * 2004-07-22 2007-03-29 파마시아 코포레이션 Ｃｏｘ-2 선택적 억제제 및 ｌｔｂ4 수용체 길항제의조합을 이용한 염증 및 통증 치료 조성물
WO2006041855A2 (en) 2004-10-04 2006-04-20 Nitromed, Inc. Compositions and methods using apocynin compounds and nitric oxide donors
WO2006052899A2 (en) * 2004-11-08 2006-05-18 Nitromed, Inc. Nitrosated and nitrosylated compounds, compositions and methods for the treatment of ophthalmic disorders
CA2592442A1 (en) 2004-12-23 2006-06-29 Glaxo Group Limited Pyridine compounds for the treatment of prostaglandin mediated diseases
CA2595579A1 (en) * 2005-01-21 2006-07-27 Nitromed, Inc. Cardiovascular compounds comprising heterocyclic nitric oxide donor group compositions and methods of use
EP1858525A2 (en) * 2005-02-16 2007-11-28 Nitromed, Inc. Organic nitric oxide donor salts of antimicrobial compounds, compositions and methods of use
US7521435B2 (en) * 2005-02-18 2009-04-21 Pharma Diagnostics, N.V. Silicon containing compounds having selective COX-2 inhibitory activity and methods of making and using the same
WO2006093864A1 (en) * 2005-02-28 2006-09-08 Nitromed, Inc. Cardiovascular compounds comprising nitric oxide enhancing groups, compositions and methods of use
NZ562234A (en) 2005-04-26 2009-09-25 Pfizer P-cadherin antibodies
WO2006121887A2 (en) * 2005-05-05 2006-11-16 Cook Biotech Incorporated Implantable materials and methods for inhibiting tissue adhesion formation
US8362075B2 (en) 2005-05-17 2013-01-29 Merck Sharp & Dohme Corp. Cyclohexyl sulphones for treatment of cancer
US20080234252A1 (en) * 2005-05-18 2008-09-25 Pfizer Inc Compounds Useful in Therapy
WO2006127591A2 (en) * 2005-05-23 2006-11-30 Nitromed, Inc. Organic nitric oxide enhancing salts of nonsteroidal antiinflammatory compounds, compositions and methods of use
HUP0500730A2 (en) * 2005-07-29 2007-02-28 Richter Gedeon Vegyuszeti Gyar 1,2-diaryl-heterocyclic compounds, their preparation, pharmaceutical compositions comprising thereof and their use
WO2007016677A2 (en) 2005-08-02 2007-02-08 Nitromed, Inc. Nitric oxide enhancing antimicrobial compounds, compositions and methods of use
TW200804345A (en) * 2005-08-30 2008-01-16 Novartis Ag Substituted benzimidazoles and methods of preparation
KR101536506B1 (ko) * 2005-09-07 2015-07-14 암젠 프레몬트 인코포레이티드 액티빈 수용체 유사 키나제-1에 대한 인간 모노클로날 항체
US8273792B2 (en) 2005-10-03 2012-09-25 The Brigham And Women's Hospital, Inc. Anti-inflammatory actions of neuroprotectin D1/protectin D1 and it's natural stereoisomers
US20090054381A1 (en) * 2005-10-04 2009-02-26 Nitromed, Inc. Methods for treating respiratory disorders
SG166829A1 (en) 2005-11-08 2010-12-29 Ranbaxy Lab Ltd Process for (3r, 5r)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4- [(4-hydroxy methyl phenyl amino) carbonyl]-pyrrol-1-yl]-3, 5-dihydroxy-heptanoic acid hemi calcium salt
WO2007059311A2 (en) * 2005-11-16 2007-05-24 Nitromed, Inc. Furoxan compounds, compositions and methods of use
US8636986B2 (en) * 2005-11-18 2014-01-28 The Forsyth Institute Treatment and prevention of bone loss using resolvins
EP1968584A2 (en) * 2005-12-20 2008-09-17 Nitromed, Inc. Nitric oxide enhancing glutamic acid compounds, compositions and methods of use
NL2000351C2 (nl) 2005-12-22 2007-09-11 Pfizer Prod Inc Estrogeen-modulatoren.
WO2007075542A2 (en) * 2005-12-22 2007-07-05 Nitromed, Inc. Nitric oxide enhancing pyruvate compounds, compositions and methods of use
EP1978964A4 (en) 2006-01-24 2009-12-09 Merck & Co Inc JAK2 tyrosine kinase Inhibition
GB0603041D0 (en) 2006-02-15 2006-03-29 Angeletti P Ist Richerche Bio Therapeutic compounds
CA2647859C (en) * 2006-03-29 2016-01-05 Nitromed, Inc. Nitric oxide enhancing prostaglandin compounds, compositions and methods of use
DK2010528T3 (en) 2006-04-19 2018-01-15 Novartis Ag 6-O-Substituted Benzoxazole and Benzothiazole Compounds and Methods for Inhibiting CSF-1R Signaling
AU2007254179B2 (en) 2006-05-18 2013-03-21 Pharmacyclics Llc Intracellular kinase inhibitors
WO2008033931A1 (en) * 2006-09-13 2008-03-20 The Institutes For Pharmaceutical Discovery, Llc Para-xylylene carboxylic acids and isothiazolones useful as protein tyrosine phosphatases (ptps) in particular ptp-ib
US8173629B2 (en) 2006-09-22 2012-05-08 Merck Sharp & Dohme Corp. Method of treatment using fatty acid synthesis inhibitors
US20110218176A1 (en) 2006-11-01 2011-09-08 Barbara Brooke Jennings-Spring Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
ATE511860T1 (de) 2006-12-22 2011-06-15 Recordati Ireland Ltd Kombinationstherapie für erkrankungen der unteren harnwege mit 2 liganden und nsar
EA016079B1 (ru) 2007-01-10 2012-01-30 Институто Ди Ричерке Ди Биолоджиа Молеколаре П. Анджелетти Спа Амидзамещенные индазолы в качестве ингибиторов поли(adp-рибоза)полимеразы (parp)
KR100843351B1 (ko) * 2007-01-30 2008-07-03 한국과학기술연구원 중추신경계 질환 치료제로 유효한ｎ-벤질-ｎ-(2-디메틸아미노-에틸)-벤젠술폰아미드 화합물
ES2431163T3 (es) 2007-03-01 2013-11-25 Novartis Ag Inhibidores de PIM quinasa y métodos para su uso
GB0704407D0 (en) 2007-03-07 2007-04-18 Glaxo Group Ltd Compounds
BRPI0812159A2 (pt) 2007-05-21 2017-05-02 Novartis Ag inibidores de csf-1r, composições e métodos de uso
AU2008269154B2 (en) 2007-06-27 2014-06-12 Merck Sharp & Dohme Llc 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
MX2010000465A (es) 2007-07-12 2010-08-30 Tragara Pharmaceuticals Inc Metodos y composiciones para el tratamiento de cancer, tumores y alteraciones relacionadas con tumores.
US7943658B2 (en) 2007-07-23 2011-05-17 Bristol-Myers Squibb Company Indole indane amide compounds useful as CB2 agonists and method
JP5411141B2 (ja) 2007-09-10 2014-02-12 カルシメディカ，インク． 細胞内カルシウムを調節する化合物
CN102014631A (zh) 2008-03-03 2011-04-13 泰格尔医药科技公司 酪氨酸激酶抑制剂
GB0813142D0 (en) 2008-07-17 2008-08-27 Glaxo Group Ltd Novel compounds
GB0813144D0 (en) 2008-07-17 2008-08-27 Glaxo Group Ltd Novel compounds
CA2734500A1 (en) 2008-08-27 2010-03-11 Calcimedica Inc. Compounds that modulate intracellular calcium
EP2177215A1 (en) 2008-10-17 2010-04-21 Laboratorios Del. Dr. Esteve, S.A. Co-crystals of tramadol and NSAIDs
JP5212177B2 (ja) * 2009-02-27 2013-06-19 東レ株式会社 γ−ケトアセタール化合物及びピロール誘導体の製造方法
GB0903493D0 (en) 2009-02-27 2009-04-08 Vantia Ltd New compounds
KR101069175B1 (ko) 2009-04-19 2011-09-30 중앙대학교 산학협력단 신규 아미노설포닐아릴이소옥사졸계 화합물 및 이를 포함하는 다약제내성 억제용 약제학적 조성물
WO2011012622A1 (en) 2009-07-30 2011-02-03 Glaxo Group Limited Benzoxazinone derivatives for the treatment of glytl mediated disorders
WO2011023753A1 (en) 2009-08-27 2011-03-03 Glaxo Group Limited Benzoxazine derivatives as glycine transport inhibitors
JP5099731B1 (ja) 2009-10-14 2012-12-19 メルク・シャープ・アンド・ドーム・コーポレーション ｐ５３活性を増大する置換ピペリジン及びその使用
GB201000685D0 (en) 2010-01-15 2010-03-03 Glaxo Group Ltd Novel compounds
CN101805290A (zh) * 2010-04-01 2010-08-18 中国人民解放军第四军医大学 氨基磺酰吡唑类化合物及其用途
HUE029570T2 (en) 2010-04-27 2017-03-28 Calcimedica Inc Intracellular calcium modifying compounds
EP2563759B1 (en) 2010-04-27 2022-04-06 Calcimedica, Inc. Compounds that modulate intracellular calcium
GB201007789D0 (en) 2010-05-10 2010-06-23 Glaxo Group Ltd Novel Compound
GB201007791D0 (en) 2010-05-10 2010-06-23 Glaxo Group Ltd Novel compounds
CA2799708A1 (en) 2010-05-21 2011-11-24 Pfizer Inc. 2-phenyl benzoylamides
EP2584903B1 (en) 2010-06-24 2018-10-24 Merck Sharp & Dohme Corp. Novel heterocyclic compounds as erk inhibitors
JP5815029B2 (ja) 2010-07-09 2015-11-17 クオンベルゲンセ プハルマセウトイカルス リミテッド カルシウムチャネル遮断薬としてのテトラゾール化合物
AU2011285909B2 (en) 2010-08-02 2016-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA)
EP2606134B1 (en) 2010-08-17 2019-04-10 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF HEPATITIS B VIRUS (HBV) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
AR082492A1 (es) * 2010-08-20 2012-12-12 Allergan Inc N-alquil-2-(1-(5-sustituido-2-(3-oxo-3-(trifluorometilsulfonamido)propil)bencil)pirrolidin-2-il)oxazol-4-carboxamida y su uso para preparar un medicamento util para tratar enfermedades o afecciones mediadas por receptor dp, fp, ep, ep, tp y/o ep
US8883801B2 (en) 2010-08-23 2014-11-11 Merck Sharp & Dohme Corp. Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors
CN103180316A (zh) 2010-08-27 2013-06-26 钙医学公司 调节细胞内钙的化合物
EP2613782B1 (en) 2010-09-01 2016-11-02 Merck Sharp & Dohme Corp. Indazole derivatives useful as erk inhibitors
US9242981B2 (en) 2010-09-16 2016-01-26 Merck Sharp & Dohme Corp. Fused pyrazole derivatives as novel ERK inhibitors
EP3766975A1 (en) 2010-10-29 2021-01-20 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using short interfering nucleic acid (sina)
EP2654748B1 (en) 2010-12-21 2016-07-27 Merck Sharp & Dohme Corp. Indazole derivatives useful as erk inhibitors
JP6058556B2 (ja) 2011-01-19 2017-01-11 クオンベルゲンセ プハルマセウトイカルス リミテッド ＣａＶ２．２カルシウムチャンネルブロッカーとしてのピペラジン誘導体
CA2828343A1 (en) 2011-03-04 2012-09-13 The Scripps Research Institute Edn3-like peptides and uses thereof
EP2699567A1 (en) 2011-04-21 2014-02-26 Merck Sharp & Dohme Corp. Insulin-like growth factor-1 receptor inhibitors
WO2013063214A1 (en) 2011-10-27 2013-05-02 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
US9221809B2 (en) 2011-10-31 2015-12-29 Merck Sharp & Dohme Corp. Aminopyrimidinones as interleukin receptor-associated kinase inhibitors
EP2780009A4 (en) * 2011-11-17 2015-05-06 Univ Colorado Regents METHOD AND COMPOSITIONS FOR IMPROVED DRUG RELEASE INTO EYE AND FORMULATIONS WITH EXTENDED RELEASE
GB201122113D0 (en) 2011-12-22 2012-02-01 Convergence Pharmaceuticals Novel compounds
EP3358013B1 (en) 2012-05-02 2020-06-24 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
KR20150060724A (ko) 2012-09-28 2015-06-03 머크 샤프 앤드 돔 코포레이션 Erk 억제제인 신규 화합물
US9512116B2 (en) 2012-10-12 2016-12-06 Calcimedica, Inc. Compounds that modulate intracellular calcium
DK2925888T3 (en) 2012-11-28 2017-12-18 Merck Sharp & Dohme COMPOSITIONS AND METHODS OF CANCER TREATMENT
EP2935263B1 (en) 2012-12-20 2018-12-05 Merck Sharp & Dohme Corp. Substituted imidazopyridines as hdm2 inhibitors
US9540377B2 (en) 2013-01-30 2017-01-10 Merck Sharp & Dohme Corp. 2,6,7,8 substituted purines as HDM2 inhibitors
AU2014233185B2 (en) 2013-03-15 2018-03-15 University Of Southern California Methods, compounds, and compositions for the treatment of angiotensin-related diseases
WO2015006181A1 (en) 2013-07-11 2015-01-15 Merck Sharp & Dohme Corp. Substituted amidopyrazole inhibitors of interleukin receptor-associated kinases (irak-4)
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
CN104418818B (zh) * 2013-09-04 2017-01-11 天津汉瑞药业有限公司 帕瑞昔布钠无水化合物
WO2015054283A1 (en) 2013-10-08 2015-04-16 Calcimedica, Inc. Compounds that modulate intracellular calcium
CN105085425B (zh) * 2014-05-23 2018-01-30 昆药集团股份有限公司 一种制备帕瑞昔布的方法
JO3589B1 (ar) 2014-08-06 2020-07-05 Novartis Ag مثبطات كيناز البروتين c وطرق استخداماتها
GB201417499D0 (en) 2014-10-03 2014-11-19 Convergence Pharmaceuticals Novel use
GB201417500D0 (en) 2014-10-03 2014-11-19 Convergence Pharmaceuticals Novel use
GB201417497D0 (en) 2014-10-03 2014-11-19 Convergence Pharmaceuticals Novel use
CN104557754A (zh) * 2015-01-04 2015-04-29 成都克莱蒙医药科技有限公司 一种帕瑞昔布钠杂质的合成方法
WO2016144846A1 (en) 2015-03-12 2016-09-15 Merck Sharp & Dohme Corp. Pyrazolopyrimidine inhibitors of irak4 activity
EP3268003B1 (en) 2015-03-12 2020-07-29 Merck Sharp & Dohme Corp. Thienopyrazine inhibitors of irak4 activity
US10155765B2 (en) 2015-03-12 2018-12-18 Merck Sharp & Dohme Corp. Carboxamide inhibitors of IRAK4 activity
DK3328827T3 (da) * 2015-07-31 2023-10-02 Univ Johns Hopkins Prodrugs af glutaminanaloger
US9598361B1 (en) * 2016-04-12 2017-03-21 King Saud University Amino substituted acetamide derivative
CN109906082A (zh) 2016-09-07 2019-06-18 塔夫茨大学信托人 使用免疫dash抑制剂和pge2拮抗剂的组合治疗
WO2018071283A1 (en) 2016-10-12 2018-04-19 Merck Sharp & Dohme Corp. Kdm5 inhibitors
US11098059B2 (en) 2017-11-08 2021-08-24 Merck Sharp & Dohme Corp. PRMT5 inhibitors
WO2019094311A1 (en) 2017-11-08 2019-05-16 Merck Sharp & Dohme Corp. Prmt5 inhibitors
CN108299331A (zh) * 2018-03-02 2018-07-20 成都新恒创药业有限公司 一种帕瑞昔布钠光降解杂质及其制备、检测方法和应用
CN108164521B (zh) * 2018-03-02 2020-11-13 成都新恒创药业有限公司 一种帕瑞昔布钠降解杂质及其制备、检测方法和应用
BR112021002267A8 (pt) 2018-08-07 2023-02-07 Merck Sharp & Dohme Inibidores de prmt5
WO2020033285A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
EP3833668B1 (en) 2018-08-07 2025-03-19 Merck Sharp & Dohme LLC Prmt5 inhibitors
EP3833667B1 (en) 2018-08-07 2024-03-13 Merck Sharp & Dohme LLC Prmt5 inhibitors
CN110305071A (zh) * 2019-07-23 2019-10-08 成都通德药业有限公司 一种帕瑞昔布钠中间体帕瑞昔布的合成方法
EP4076460B1 (en) 2019-12-17 2026-01-21 Merck Sharp & Dohme LLC 1,4-dihydro-2h-spiro[isoquinoline-3,4'-piperidine derivatives as prmt5 inhibitors for the treatment of cancer
EP4076459B1 (en) 2019-12-17 2026-04-29 Merck Sharp & Dohme LLC Prmt5 inhibitors
CA3160153A1 (en) 2019-12-17 2021-06-24 Michelle Machacek Prmt5 inhibitors
BR112022012015A2 (pt) 2019-12-17 2022-08-30 Merck Sharp & Dohme Llc Inibidores de prmt5
CA3209491A1 (en) 2021-03-15 2022-09-22 Saul Yedgar Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory disease
CN115784991B (zh) * 2022-11-22 2025-01-24 合肥医工医药股份有限公司 N-(苯磺酰基)酰胺衍生物及其制备方法和用途

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US538738A (en) 1895-05-07 Measuring-faucet
GB911204A (en) 1960-07-28 1962-11-21 Unilever Ltd Bleaching compositions
US4146721A (en) 1969-09-12 1979-03-27 Byk Gulden Lomberg Chemische Fabrik Gmbh Pyrazol-4-acetic acid compounds
US3984431A (en) 1972-03-15 1976-10-05 Claude Gueremy Derivatives of pyrazole-5-acetic acid
DE3321082C2 (de) 1982-06-10 1996-08-22 Kao Corp Bleich-Reinigungsmittel
JPS59145300A (ja) 1983-02-07 1984-08-20 日本パ−オキサイド株式会社 漂白洗剤
JPS6015500A (ja) 1983-07-08 1985-01-26 ライオン株式会社 高嵩密度洗剤組成物
JPS60118606A (ja) 1983-11-28 1985-06-26 Mitsubishi Gas Chem Co Inc 安定化された過炭酸ナトリウム粒状物
US5051518A (en) 1987-05-29 1991-09-24 Ortho Pharmaceutical Corporation Pharmacologically active 2- and 3-substituted (1',5'-diaryl-3-pyrazolyl)-N-hydroxypropanamides
JP2590124B2 (ja) * 1987-08-12 1997-03-12 国際試薬株式会社 水溶性テトラゾリウム化合物およびその化合物を用いる還元性物質の測定方法
JPS6445374U (bg) 1987-09-10 1989-03-20
DE3903993A1 (de) * 1989-02-10 1990-08-16 Basf Ag Diarylsubstituierte heterocyclische verbindungen, ihre herstellung und arzneimittel daraus
JPH04277724A (ja) * 1991-03-06 1992-10-02 Sumitomo Electric Ind Ltd 有機非線形光学材料
GB9113628D0 (en) * 1991-06-25 1991-08-14 Ici Plc Heterocyclic derivatives
US5219856A (en) * 1992-04-06 1993-06-15 E. I. Du Pont De Nemours And Company Angiotensin-II receptor blocking, heterocycle substituted imidazoles
US5334991A (en) 1992-05-15 1994-08-02 Reflection Technology Dual image head-mounted display
JPH05323522A (ja) * 1992-05-20 1993-12-07 Fuji Photo Film Co Ltd 黒白ハロゲン化銀写真感光材料の処理方法
US5604260A (en) * 1992-12-11 1997-02-18 Merck Frosst Canada Inc. 5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
EP0679157B1 (en) * 1993-01-15 1997-11-19 G.D. Searle & Co. Novel 3,4-diaryl thiophenes and analogs thereof having use as antiinflammatory agents
US5409944A (en) * 1993-03-12 1995-04-25 Merck Frosst Canada, Inc. Alkanesulfonamido-1-indanone derivatives as inhibitors of cyclooxygenase
CA2161789A1 (en) * 1993-05-13 1994-11-24 Jacques Yves Gauthier 2-substituted-3,4-diarylthiophene derivatives as inhibitors of cyclooxygenase
US5380738A (en) * 1993-05-21 1995-01-10 Monsanto Company 2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents
US5474995A (en) * 1993-06-24 1995-12-12 Merck Frosst Canada, Inc. Phenyl heterocycles as cox-2 inhibitors
US5344991A (en) * 1993-10-29 1994-09-06 G.D. Searle & Co. 1,2 diarylcyclopentenyl compounds for the treatment of inflammation
RO118291B1 (ro) 1993-11-30 2003-04-30 Searle & Co Derivati de pirazol 1,3,4,5 - tetrasubstituiti si compozitie farmaceutica care ii contine
US5401765A (en) 1993-11-30 1995-03-28 G. D. Searle 1,4,5-triphenyl pyrazolyl compounds for the treatment of inflammation and inflammation-related disorders
US5434178A (en) 1993-11-30 1995-07-18 G.D. Searle & Co. 1,3,5 trisubstituted pyrazole compounds for treatment of inflammation
ES2133740T3 (es) * 1994-02-10 1999-09-16 Searle & Co Espiro-compuestos sustituidos para el tratamiento de la inflamacion.
US5393790A (en) * 1994-02-10 1995-02-28 G.D. Searle & Co. Substituted spiro compounds for the treatment of inflammation
US5486534A (en) 1994-07-21 1996-01-23 G. D. Searle & Co. 3,4-substituted pyrazoles for the treatment of inflammation
US5556019A (en) * 1994-07-25 1996-09-17 Sealed Air Corporation Bag separator and dispenser
US5616601A (en) * 1994-07-28 1997-04-01 Gd Searle & Co 1,2-aryl and heteroaryl substituted imidazolyl compounds for the treatment of inflammation
JP3181190B2 (ja) * 1994-12-20 2001-07-03 日本たばこ産業株式会社 オキサゾール誘導体
JP2636819B2 (ja) * 1994-12-20 1997-07-30 日本たばこ産業株式会社 オキサゾール系複素環式芳香族化合物
US5633272A (en) * 1995-02-13 1997-05-27 Talley; John J. Substituted isoxazoles for the treatment of inflammation
US5908858A (en) * 1996-04-05 1999-06-01 Sankyo Company, Limited 1,2-diphenylpyrrole derivatives, their preparation and their therapeutic uses
WO1997038986A1 (en) * 1996-04-12 1997-10-23 G.D. Searle & Co. Substituted benzenesulfonamide derivatives as prodrugs of cox-2 inhibitors
JPH1045374A (ja) 1996-08-01 1998-02-17 Nittetsu Mining Co Ltd ドラム缶吊り上げ装置
US20030105144A1 (en) * 2001-04-17 2003-06-05 Ping Gao Stabilized oral pharmaceutical composition

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