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RU2219178C2 - Бициклические производные, фармацевтическая композиция на их основе и промежуточные соединения - Google Patents

Бициклические производные, фармацевтическая композиция на их основе и промежуточные соединения Download PDF

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RU2219178C2
RU2219178C2 RU2000110738/04A RU2000110738A RU2219178C2 RU 2219178 C2 RU2219178 C2 RU 2219178C2 RU 2000110738/04 A RU2000110738/04 A RU 2000110738/04A RU 2000110738 A RU2000110738 A RU 2000110738A RU 2219178 C2 RU2219178 C2 RU 2219178C2
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Суань ЧЭН (US)
Суань ЧЭН
Дейвид Майкл ГОЛДСТЕЙН (US)
Дейвид Майкл ГОЛДСТЕЙН
Тереза Александро Трехо МАРТИН (US)
Тереза Александро Трехо МАРТИН
Эрик Брайан ШУГРЕН (US)
Эрик Брайан ШУГРЕН
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Abstract

Изобретение относится к области органической химии, а именно к новым бициклическим производным. Описываются бициклические производные общей формулы (I)
Figure 00000001

где R1 обозначает пиримидинил или пиридил, каждый необязательно замещенный независимо одним, двумя или тремя заместителями, выбранными из алкила, алкокси, алкилтио, галоида, нитро, гидроксиамино, -NRR' (где R и R' независимо друг от друга означают водород, алкил, карбоксиалкил или гетероалкил) или -NHC(0)Rb[где Rb означает алкил, -(алкилен)-Х, где Х означает алкокси, алкиламино, диалкиламино, гетероциклил или гетероарил], --- обозначает связь между либо В и CR1, либо Q и CR1, вследствие чего (I) когда --- обозначает связь между Q и CR1, тогда В обозначает азот, R2 обозначает галоидфенил или пиридил, а Q обозначает -СН-, и (II) когда --- обозначает связь между В и CR1, тогда В обозначает углерод, R2 обозначает фенил, необязательно замещенный галоидом, алкилом, алкокси или галоидалкилом, а Q обозначает -NR4- или -О-, где R4 обозначает водород, алкил, галоидалкил, гетероалкил, гетероаралкил, гетероциклилалкил, -OR5 (где R5 обозначает водород, алкил, гетероалкил или гетероциклилалкил), -SO2R" (где R" обозначает алкил), -(алкилен)-Z- или -(алкилен)-СО-(алкилен)-Z, где обозначает цианогруппу; -COOR7, где R7 обозначает водород или алкил, -CONR8R9, где R8 обозначает водород или алкил, R9 обозначает водород, алкил, алкокси или -(алкилен)-СООR7; -C(=NH)NH2; или -COR13, где R13 обозначает алкил, обозначает группу формулы (S), (Т), (U), (V) или (W),
Figure 00000002

Figure 00000003

Figure 00000004

Figure 00000005

Figure 00000006

где R6 обозначает водород, алкил, гетероалкил, галоид, алкокси, моноалкиламиногруппу (необязательно замещенную гидрокси, алкокси или амино), диалкиламино, алкилтио, -NHC(О)R" [где R" обозначает алкил], и R3 обозначает водород, алкил, галоидалкил; причем "алкил" и "алкилен" во всех случаях и "алкокси" каждый содержат не более шести атомов углерода; "гетероалкилом" обозначают алкильную группу, содержащую не более шести атомов углерода и имеющую один или два заместителя, выбранных из гидрокси, гидроксиалкил, алкокси, алкилтио, -NRaRb и SО3Х+, где Ra означает водород, алкил, гдрокси, цианоалкил, гидроксиалкил, аминоалкил или диалкиламиноалкил, и Х+ означает атом щелочного металла; "гетероарилом" обозначают имидазолильную группу, которая может быть замещена алкилом или нитро; "гетероциклилом" обозначают циклический насыщенный радикал, содержащий от 3 до 8 кольцевых атома, в котором 1 или 2 кольцевых атома представляют собой гетероатомы, выбранные из N и О, и который может быть замещен одним или двумя заместителями, выбранными независимо из алкила, гидроксиалкила, гидрокси, амино и карбомоила, а также их фармацевтически приемлемые соли, индивидуальные изомеры и смеси изомеров. Также описывается фармацевтическая композиция на основе соединений формулы (I), предназначенная для лечения и профилактики воспалительных заболеваний, и промежуточные соединения. Технический результат - получены новые соединения, обладающие полезными биологическими свойствами. 3 с. и 12 з.п. ф-лы, 8 табл.

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Claims (18)

1. Бициклические соединения, выбранные из группы соединений формулы (I)
Figure 00000132
(I)
в которой R1 - пиримидинил или пиридил, каждый необязательно замещенный независимо одним, двумя или тремя заместителями, выбранными из алкила, алкокси, алкилтио, галоида, нитро, гидроксиламино, -NRR' (где R и R' независимо друг от друга означают водород, алкил, карбоксиалкил или гетероалкил) или -NHC(O)Rb [где Rb - алкил, -(алкилен)-Х, где Х - алкокси, алкиламино, диалкиламино, гетероциклил или гетероарил];
--- обозначает связь между либо В и CR1, либо Q и CR1, вследствие чего,
(I) когда --- обозначает связь между Q и CR1, тогда В - азот,
R2 обозначает галоидфенил или пиридил, а
Q - -СН-, и (II) когда --- обозначает связь между В и CR1, тогда В - углерод, R2 - фенил, необязательно замещенный галоидом, алкилом, алкокси или галоидалкилом, а Q обозначает -NR4- или -О-,
где R4 - водород, алкил, галоидалкил, гетероалкил, гетероаралкил, гетероциклилалкил, -OR5 (где R5 - водород, алкил, гетероалкил или гетероциклилалкил), -SO2R" (где R" - алкил), -(алкилен)-Z или -(алкилен)-СО-(алкилен)-Z, где Z - цианогруппа; -СОOOR7, где R7 обозначает водород или алкил, -CONR8R9, где R8 - водород или алкил, R9 - водород, алкил, алкокси или -(алкилен)-СООR7; - C(=NH)NH2 или -COR13, где R13 - алкил,
Figure 00000133
- группа формулы (S), (Т), (U), (V) или (W)
Figure 00000134
Figure 00000135
Figure 00000136
или
Figure 00000137
Figure 00000138
где R6 - водород, алкил, гетероалкил, галоид, алкокси, моноалкиламиногруппа (необязательно замещенная гидрокси, алкокси или амино), диалкиламино, алкилтио, -NHC(O)R" [где R" - алкил];
R3 - водород, алкил, галоидалкил;
причем "алкил" и "алкилен" во всех соединениях и "алкокси" каждый содержат не более шести атомов углерода;
"гетероалкилом" обозначают алкильную группу, содержащую не более шести атомов углерода и имеющую один или два заместителя, выбранных из гидрокси, гидроксиалкил, алкокси, алкилтио, -NRaRb и –SO3Х+, где Ra - водород, алкил, гидрокси, цианоалкил, гидроксиалкил, аминоалкил или диалкиламиноалкил и Rb - водород, алкил, гидроксиалкил, аминоалкил или диалкиламиноалкил, X+ - атом щелочного металла;
"гетероарилом" обозначают имидазолильную группу, которая может быть замещена алкилом или нитро;
"гетероциклилом" обозначают циклический насыщенный радикал, содержащий от 3 до 8 кольцевых атома, в котором 1 или 2 кольцевых атома представляют собой гетероатомы, выбранные из N и О, и который может быть замещен одним или двумя заместителями, выбранными независимо из алкила, гидроксиалкила, гидрокси, амино и карбамоила;
а также их фармацевтически приемлемые соли, индивидуальные изомеры и смеси изомеров.
2. Соединения по п. 1, в которых R6 - водород, алкил, галоид, алкокси, моноалкиламино (необязательно замещенный гидрокси, алкокси или амино), диалкиламино или гетероалкил.
3. Соединения по п. 1 или 2, выбранные из соединений формулы (Iа)
Figure 00000139
в которой R1, R2 и R3 имеют значения, указанные в п.1;
Q обозначает -NR4- или -О-, где R4 имеет значения, указанные в п.1, кроме –SO2R";
один из А и D - атом азота, а другой обозначает –CR6-, где R6 - водород, алкил, галоид, алкокси, моноалкиламино (необязательно замещенный гидрокси, алкокси или амино), диалкиламино или гетероалкил,
а также их фармацевтически приемлемые соли, индивидуальные изомеры и смеси изомеров.
4. Соединение по п. 1 или 2, в котором --- обозначает связь между В и -CR1-,
Figure 00000140
представляет собой группу формулы (S), (V) или (W), a Q обозначает -NR4-.
5. Соединение по п. 1, 2 или 4, в котором R1 обозначает 4-пиридильное или 4-пиримидинильное кольцо, необязательно замещенное заместителем, выбранным из -NRR' (где каждый из R и R' независимо друг от друга - водород, алкил или гетероалкил) и -NHC(O)Rb [где Rb - алкил или -(алкилен)-Х, где Х - алкокси, алкиламино-, диалкиламиногруппу, гетероциклил или гетероарил].
6. Соединение по п. 1, 2, 4 или 5, в котором R2 обозначает фенильное кольцо, необязательно замещенное одним или двумя заместителями, выбранными из алкила, галоида или алкокси.
7. Соединение по любому из пп. 1, 2 и 4-6, в котором R6 - водород, метил, метокси, фтор или хлор, а R1 - 4-пиридильное кольцо, необязательно замещенное во 2-м положении заместителем, выбранным из амино-, метиламино-, диметиламино-, ацетиламино-, 2-гидроксиэтиламино-, 3-гидроксипропиламино-, 2-аминоэтиламино- и метоксигрупп.
8. Соединение по любому из пп. 1, 2 и 4-7, в котором R6 - водород, R2 - фенильное кольцо, замещенное одним или двумя заместителями, выбранными из метила, фтора, хлора и метокси, а R3 - водород, метил, хлор или фтор.
9. Соединение по любому из пп. 1, 2 и 4-8, в котором R4 - водород, метил, этил, 2-гидроксиэтил, 3-гидроксипропил, 2-аминоэтил, 3-аминопропил, 2-метиламиноэтил, 3-метиламинопропил, 2-диметиламиноэтил, 3 -диметиламинопропил, 2 - (морфолин - 4 - ил) этил, 3 - (морфолин- 4 - ил) пропил,
2-(пиперидин-1-ил)этил, 3-(пиперидин-1-ил) пропил, 2-(пиперазин-1-ил)этил, 3-(пиперазин-1-ил)пропил, гидроксил, метокси, 2-гидроксиэтокси, 3-гидроксипропокси, 2-метиламиноэтокси, 3-метиламинопропокси, 2-диметиламиноэтокси, 3-диметиламинопропокси, 2-(морфолин-4-ил)этокси, 3-(морфолин-4-ил)пропокси, 2-(пиперидин-1-ил)этокси, 3-(пиперидин-1-ил)пропокси, 2-(пиперазин-1-ил)этокси или 3-(пиперазин-1-ил)пропокси.
10. Соединения по любому из пп. 1 и 4-9, выбранные 3-(4-фторфенил)-2-[2- (2-гидроксиэтиламино)пиридин-4-ил]-1Н-пирроло[3,2-b] пиридина и 6-(2-ацетиламинопиридин-4-ил)-7-(4-фторфенил)-5Н-пирроло [2,3-b] пиразина.
11. Соединения по любому из пп. 2 и 4-9, выбранные из 3-(4-фторфенил)-1-метил-2-(пиридин-4-ил)-1Н-пирроло[3,2-b] пиридина и 7-(4-фторфенил) -6- (пиридин-4-ил) -5Н-пирроло [2,3-b] пиразина.
12. Соединения по любому из пп. 3-9, выбранные из 3-(4-фторфенил)-2-(пиридин-4-ил)-1Н-пирроло[3,2-b] пиридина, 3-(4-фторфенил)-1-метокси-2-(пиридин-4-ил)-1Н-пирроло[3,2-b] пиридина, 3-(4-фторфенил)-1-[2-(морфолин-4-ил)этокси]-2-(пиридин-4-ил)-1Н-пирроло[3,2-b] пиридина, 3-(4-фторфенил)-1-гидрокси-2-(пиридин-4-ил)-1Н-пирроло[3,2-b] пиридина, 3-(4-фторфенил)-1-[2-(пиперидин-1-ил)этокси]-2-(пиридин-4-ил)-lH-пирроло[3,2-b]пиридина, 3-(4-фторфенил)-1-[2-(пиперидин-1-ил)этил]-2-(пиридин-4-ил)-lH-пирроло13,2-b] пиридина и 3-(4-фторфенил)-1-[2-(морфолин-4-ил)этил] -2- (пиридин-4-ил) –1H-пирроло [3,2-b] пиридина.
13. Соединения по любому из пп. 1-12, предназначенные для применения в качестве фармацевтически действующих веществ, в частности для лечения воспалительных заболеваний.
14. Соединения формул
Figure 00000141
Figure 00000142
где Y - галоид, Z - -NH-CR1 =CHR2 , или
Y - -COR2 и Z - -NH-COR1, или
Y - атом водорода и Z - -NHN=CR1 –CH2R2 ; или
Y обозначает -C=CR1 и Z обозначает –NHR2;
R1 и R2 имеют значения, указанные в п.1.
15. Фармацевтическая композиция, включающая соединение по любому из п. 1 или 2 и терапевтически инертный носитель и предназначенная прежде всего для лечения и профилактики воспалительных заболеваний.
Приоритет по пунктам:
20.10.1997 по п.3;
20.02.1998 по пп.1-2, 4-9, 13-16;
18.08.1998 по пп.10-12.
RU2000110738/04A 1997-10-20 1998-10-13 Бициклические производные, фармацевтическая композиция на их основе и промежуточные соединения RU2219178C2 (ru)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2366659C2 (ru) * 2003-12-30 2009-09-10 Ск Кемикалз Ко., Лтд. Новые производные пиридина, способ их получения и содержащая их фармацевтическая композиция

Families Citing this family (89)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998022457A1 (en) * 1996-11-19 1998-05-28 Amgen Inc. Aryl and heteroaryl substituted fused pyrrole antiinflammatory agents
WO2000002561A1 (en) * 1998-07-13 2000-01-20 University Of South Florida Modulation of the phospholipase a2 pathway as a therapeutic
WO2000019824A1 (en) 1998-10-07 2000-04-13 Smithkline Beecham Corporation Novel treatment for stroke management
EP1058549A4 (en) * 1998-12-23 2003-11-12 Bristol Myers Squibb Pharma Co FACTOR Xa OR THROMBIN INHIBITORS
EP1226144B1 (en) * 1999-10-21 2006-12-27 F. Hoffmann-La Roche Ag Alkylamino substituted bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase
CZ20021744A3 (cs) * 1999-10-21 2002-08-14 F. Hoffmann-La Roche Ag Bicyklické dusíkové heterocykly substituované heteroalkylaminoskupinou jako inhibitory P38 proteinkinázy
DE60024480T2 (de) * 1999-10-27 2006-07-27 Novartis Ag Thiazol und imidazo[4,5-b]pyridin verbindungen und ihre verwendung als pharmazeutika
GB9930698D0 (en) * 1999-12-24 2000-02-16 Rhone Poulenc Rorer Ltd Chemical compounds
CN100379734C (zh) * 1999-12-24 2008-04-09 阿文蒂斯药物有限公司 氮杂吲哚类化合物
GB0112348D0 (en) * 2001-05-19 2001-07-11 Smithkline Beecham Plc Compounds
GB0115109D0 (en) 2001-06-21 2001-08-15 Aventis Pharma Ltd Chemical compounds
US20030216396A1 (en) 2002-02-11 2003-11-20 Bayer Corporation Pyridine, quinoline, and isoquinoline N-oxides as kinase inhibitors
US20090306182A1 (en) * 2002-02-20 2009-12-10 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF MAP KINASE GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
MXPA04008592A (es) * 2002-03-07 2004-12-06 Hoffmann La Roche Inhibidores de piridina biciclica y pirimidina p38 cinasa.
WO2003082868A1 (en) * 2002-03-28 2003-10-09 Eisai Co., Ltd. 7-azaindoles as inhibitors of c-jun n-terminal kinases for the treatment of neurodegenerative disorders
AU2003241925A1 (en) * 2002-05-31 2003-12-19 Eisai R&D Management Co., Ltd. Pyrazole compound and medicinal composition containing the same
SG135051A1 (en) * 2002-06-20 2007-09-28 Aventis Pharma Ltd Azaindoles
JP4252534B2 (ja) * 2002-08-06 2009-04-08 エフ．ホフマン−ラ ロシュ アーゲー ｐ−３８ＭＡＰキナーゼインヒビターとしての６−アルコキシ−ピリド−ピリミジン類
EP1388541A1 (en) * 2002-08-09 2004-02-11 Centre National De La Recherche Scientifique (Cnrs) Pyrrolopyrazines as kinase inhibitors
CA2511763A1 (en) * 2002-12-06 2004-06-24 Scios Inc. Methods for treating diabetes
JP2006516548A (ja) 2002-12-30 2006-07-06 アンジオテック インターナショナル アクツィエン ゲゼルシャフト 迅速ゲル化ポリマー組成物からの薬物送達法
US7135575B2 (en) 2003-03-03 2006-11-14 Array Biopharma, Inc. P38 inhibitors and methods of use thereof
AU2004218463B2 (en) * 2003-03-03 2009-07-16 Array Biopharma, Inc. p38 inhibitors and methods of use thereof
GB0305142D0 (en) 2003-03-06 2003-04-09 Eisai London Res Lab Ltd Synthesis
US7432375B2 (en) 2003-03-06 2008-10-07 Eisai R & D Management Co., Ltd. JNK inhibitors
US7687506B2 (en) * 2003-04-11 2010-03-30 The Regents Of The University Of California Selective serine/threonine kinase inhibitors
JP2006524254A (ja) * 2003-04-24 2006-10-26 メルク　エンド　カムパニー　インコーポレーテッド Ａｋｔ活性の阻害剤
AU2004247626B8 (en) 2003-05-15 2011-05-19 Arqule, Inc. Imidazothiazoles and imidazoxazole derivatives as inhibitors of p38
WO2004101565A2 (en) * 2003-05-16 2004-11-25 Eisai Co., Ltd. Jnk inhibitors
EP1631145A4 (en) * 2003-06-06 2009-12-23 Univ Pennsylvania COMPOSITIONS COMPRISING P38 KINASE INHIBITORS AND METHODS OF USE
SE0301906D0 (sv) * 2003-06-26 2003-06-26 Astrazeneca Ab New compounds
US20050026944A1 (en) * 2003-07-24 2005-02-03 Patrick Betschmann Thienopyridine and furopyridine kinase inhibitors
US7202363B2 (en) * 2003-07-24 2007-04-10 Abbott Laboratories Thienopyridine and furopyridine kinase inhibitors
EP3235384B1 (en) * 2003-11-25 2019-08-28 Virginia Tech Intellectual Properties, Inc. Composition for animal consumption
EP1716150B1 (en) * 2004-01-22 2008-04-23 Amgen Inc. Substituted heterocyclic compounds and methods of use
GB0405055D0 (en) * 2004-03-05 2004-04-07 Eisai London Res Lab Ltd JNK inhibitors
US20050203111A1 (en) * 2004-03-12 2005-09-15 Vvii Newco 2003, Inc. Compositions and methods for preventing and treating skin and hair conditions
CA2558439A1 (en) * 2004-03-11 2005-10-06 Kythera Biopharmaceuticals, Inc. Compositions and methods for preventing and treating skin and hair conditions
WO2006010082A1 (en) 2004-07-08 2006-01-26 Arqule, Inc. 1,4-disubstituted naphtalenes as inhibitors of p38 map kinase
US20080113016A1 (en) * 2004-07-26 2008-05-15 Gary Steven Firestein Method for Prevention or Treatment of Inflammatory Disease
WO2006017443A2 (en) * 2004-08-02 2006-02-16 Osi Pharmaceuticals, Inc. Aryl-amino substituted pyrrolopyrimidine multi-kinase inhibiting compounds
WO2006044869A1 (en) 2004-10-19 2006-04-27 Arqule, Inc. Synthesis of imidazooxazole and imidazothiazole inhibitors of p38 map kinase
US20090131430A1 (en) * 2004-11-23 2009-05-21 Palle Venkata P Pyrido'2,3-dipyrimidines as anti-inflammatory agents
US20090036472A1 (en) * 2005-02-02 2009-02-05 Palle Venkata P Azabicyclo derivatives as anti-inflammatory agents
KR101142363B1 (ko) * 2005-06-27 2012-05-21 주식회사유한양행 피롤로피리딘 유도체를 포함하는 항암제 조성물
GB0516156D0 (en) * 2005-08-05 2005-09-14 Eisai London Res Lab Ltd JNK inhibitors
WO2007031098A1 (en) 2005-09-12 2007-03-22 Xigen S.A. Cell-permeable peptide inhibitors of the jnk signal transduction pathway
JP5131990B2 (ja) * 2006-01-31 2013-01-30 アレイ バイオファーマ、インコーポレイテッド キナーゼ阻害剤およびその使用方法
JP2009528991A (ja) * 2006-02-14 2009-08-13 バーテックス ファーマシューティカルズ インコーポレイテッド プロテインキナーゼの阻害剤として有用なピロロ（３，２−ｃ）ピリジン
CL2007002617A1 (es) 2006-09-11 2008-05-16 Sanofi Aventis Compuestos derivados de pirrolo[2,3-b]pirazin-6-ilo; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar inflamacion de las articulaciones, artritis reumatoide, tumores, linfoma de las celulas del manto.
US7687893B2 (en) 2006-12-27 2010-03-30 Amkor Technology, Inc. Semiconductor package having leadframe with exposed anchor pads
US20100104536A1 (en) * 2007-03-20 2010-04-29 Indravadan Ambalal Modi P38 inhibitors
GB0708141D0 (en) * 2007-04-26 2007-06-06 Syngenta Participations Ag Improvements in or relating to organic compounds
WO2009143864A1 (en) 2008-05-30 2009-12-03 Xigen S.A. Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of chronic or non-chronic inflammatory digestive diseases
WO2009143865A1 (en) 2008-05-30 2009-12-03 Xigen S.A. Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases
EP2313411A1 (en) * 2008-06-10 2011-04-27 Plexxikon, Inc. 5h-pyrr0l0 [2,3-b]pyrazine derivatives for kinase modulation, and indications therefor
WO2010046215A2 (en) * 2008-10-21 2010-04-29 Syngenta Participations Ag Diaza-indole derivatives and their use as fungicides
DE102008052943A1 (de) 2008-10-23 2010-04-29 Merck Patent Gmbh Azaindolderivate
JP5588458B2 (ja) 2008-12-05 2014-09-10 アッヴィ・バハマズ・リミテッド 癌の治療に使用するためのキナーゼ阻害剤としてのチエノ［３，２−ｃ］ピリジン誘導体
EP3312269A1 (en) 2008-12-17 2018-04-25 The Scripps Research Institute Generation and maintenance of stem cells
WO2010072228A1 (en) 2008-12-22 2010-07-01 Xigen S.A. Novel transporter constructs and transporter cargo conjugate molecules
US20170117214A1 (en) 2009-01-05 2017-04-27 Amkor Technology, Inc. Semiconductor device with through-mold via
EP2245936A1 (en) * 2009-04-27 2010-11-03 Bayer CropScience AG Use of 4-aza indole derivatives for the reduction of mycotoxin contamination
EP2338890A1 (en) 2009-12-22 2011-06-29 Bayer CropScience AG 4,7-Diazaindole derivatives and their use as fungicides
CN102933584A (zh) * 2010-04-16 2013-02-13 Abbvie公司 激酶的吡咯并吡嗪酮抑制剂
WO2011160653A1 (en) 2010-06-21 2011-12-29 Xigen S.A. Novel jnk inhibitor molecules
JP5857056B2 (ja) 2010-10-14 2016-02-10 ザイジェン インフラメーション エルティーディー 慢性又は非慢性の炎症性眼疾患を治療するためのｊｎｋシグナル伝達経路の細胞透過性ペプチド阻害剤の使用
US8436179B2 (en) 2011-07-20 2013-05-07 Abbvie Inc. Kinase inhibitor with improved solubility profile
EP3072555B1 (en) * 2011-09-02 2020-03-25 The Trustees of Columbia University in the City of New York Mk2/3 inhibitors to treat metabolic disturbances of obesity
WO2013091670A1 (en) 2011-12-21 2013-06-27 Xigen S.A. Novel jnk inhibitor molecules for treatment of various diseases
WO2013162027A1 (ja) 2012-04-27 2013-10-31 学校法人 慶應義塾 神経分化促進剤
GB201304526D0 (en) 2013-03-13 2013-04-24 Proximagen Ltd New compounds
DK2970265T3 (en) 2013-03-15 2018-10-01 Plexxikon Inc HETEROCYCLIC COMPOUNDS AND APPLICATIONS THEREOF
US20140303121A1 (en) 2013-03-15 2014-10-09 Plexxikon Inc. Heterocyclic compounds and uses thereof
WO2015197097A1 (en) 2014-06-26 2015-12-30 Xigen Inflammation Ltd. New use for jnk inhibitor molecules for treatment of various diseases
WO2014206427A1 (en) 2013-06-26 2014-12-31 Xigen Inflammation Ltd. New use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases
AU2014301631A1 (en) * 2013-06-26 2015-08-27 Xigen Inflammation Ltd. New use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
WO2015023811A2 (en) 2013-08-16 2015-02-19 The J. David Gladstone Institutes Compositions and methods for identifying latently infected cells
BR112016026556A8 (pt) 2014-05-16 2021-07-06 Atriva Therapeutics Gmbh inibidores de mek, de p38 e/ou de nfkb, seus usos, composição, sistema de teste in vitro, seu uso, e método para detecção de moléculas eficazes na profilaxia e/ou tratamento de uma co-infecção
AR103232A1 (es) 2014-12-22 2017-04-26 Bristol Myers Squibb Co ANTAGONISTAS DE TGFbR
EP3368052B1 (en) 2015-10-27 2021-12-08 Children's Hospital Medical Center Use of mapk inhibitors to reduce loss of hematopoietic stem cells during ex vivo culture and genetic manipulation
PT3691620T (pt) 2017-10-05 2022-10-06 Fulcrum Therapeutics Inc Os inibidores da quinase p38 reduzem a expressão de dux4 e genes a jusante para o tratamento de fshd
US10342786B2 (en) 2017-10-05 2019-07-09 Fulcrum Therapeutics, Inc. P38 kinase inhibitors reduce DUX4 and downstream gene expression for the treatment of FSHD
EP3694855A1 (en) 2017-10-13 2020-08-19 Plexxikon Inc. Solid forms of a compound for modulating kinases
PT3728252T (pt) 2017-12-18 2023-10-26 Bristol Myers Squibb Co Compostos 4-azaindol
CA3128946A1 (en) 2019-02-07 2020-08-13 Bayer Aktiengesellschaft 3-amino-2-[2-(acylamino)pyridin-4-yl]-1,5,6,7-tetrahydro-4h-pyrrolo[3,2-c]pyridin-4-one as csnk1 inhibitors
WO2022023339A1 (en) 2020-07-29 2022-02-03 Bayer Aktiengesellschaft Aryl substituted pyrrolo-pyridinones and therapeutic uses thereof
WO2023280911A1 (en) 2021-07-06 2023-01-12 Westfälische Wilhelms-Universität Münster P38-inhibitors for the treatment of coronavirus infections and/or covid-19 cytokine storm
US20250188075A1 (en) * 2022-01-27 2025-06-12 The Broad Institute, Inc. Substituted heterocyclic csnk1 inhibitors

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4767766A (en) * 1987-01-30 1988-08-30 Merck & Co., Inc. Derivatives of 3-hydroxyazabenzo(B)thiophene useful as 5-lipoxygenase inhibitors
WO1997005878A1 (en) * 1995-08-10 1997-02-20 Merck & Co., Inc. 2,5-substituted aryl pyrroles, compositions containing such compounds and methods of use

Family Cites Families (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU371228A1 (ru) 1971-04-02 1973-02-22 Всесоюзный научно исследовательский химико фармацевтический институт Серго Орджоникидзе Способ получения пирроло-
RO62428A (fr) 1971-05-04 1978-01-15 Thomae Gmbh Dr K Procede pour la preparation des thyeno-(3,2-d)-pyrimidines
JPS56104870A (en) 1980-01-25 1981-08-20 Dai Ichi Seiyaku Co Ltd 2-halogeno-3,4-dihydro-condensed pyrimidine and its preparation
EP0300688A1 (en) 1987-07-21 1989-01-25 FISONS plc Pyrrole derivatives, process for their preparation and pharmaceutical compositions containing them
US5236925A (en) 1991-10-24 1993-08-17 American Home Products Corporation Fused pyrimidines as angiotensin II antagonists
FR2687402B1 (fr) 1992-02-14 1995-06-30 Lipha Nouveaux azaindoles, procedes de preparation et medicaments les contenant.
US5502187A (en) 1992-04-03 1996-03-26 The Upjohn Company Pharmaceutically active bicyclic-heterocyclic amines
DE4304650A1 (de) 1993-02-16 1994-08-18 Thomae Gmbh Dr K Kondensierte 5-gliedrige Heterocyclen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
US6756388B1 (en) 1993-10-12 2004-06-29 Pfizer Inc. Benzothiophenes and related compounds as estrogen agonists
CA2134192A1 (en) 1993-11-12 1995-05-13 Michael L. Denney 5, 6-bicyclic glycoprotein iib/iiia antagonists
US5468757A (en) 1994-01-31 1995-11-21 Eli Lilly And Company 6-azaindole thromboxane synthase inhibitors
WO1995033752A1 (en) 1994-06-09 1995-12-14 Smithkline Beecham Corporation Endothelin receptor antagonists
US6075037A (en) 1994-06-09 2000-06-13 Smithkline Beecham Corporation Endothelin receptor antagonists
US5521213A (en) 1994-08-29 1996-05-28 Merck Frosst Canada, Inc. Diaryl bicyclic heterocycles as inhibitors of cyclooxygenase-2
US5589482A (en) 1994-12-14 1996-12-31 Pfizer Inc. Benzo-thiophene estrogen agonists to treat prostatic hyperplasia
GB2298199A (en) 1995-02-21 1996-08-28 Merck Sharp & Dohme Synthesis of azaindoles
FR2732969B1 (fr) 1995-04-14 1997-05-16 Adir Nouveaux composes pyridiniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
WO1997049706A1 (en) 1996-06-25 1997-12-31 Novartis Ag SUBSTITUTED 7-AMINO-PYRROLO[3,2-d]PYRIMIDINES AND THE USE THEREOF
WO1998022457A1 (en) * 1996-11-19 1998-05-28 Amgen Inc. Aryl and heteroaryl substituted fused pyrrole antiinflammatory agents
WO1998047899A1 (en) 1997-04-24 1998-10-29 Ortho-Mcneil Corporation, Inc. Substituted pyrrolopyridines useful in the treatment of inflammatory diseases

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4767766A (en) * 1987-01-30 1988-08-30 Merck & Co., Inc. Derivatives of 3-hydroxyazabenzo(B)thiophene useful as 5-lipoxygenase inhibitors
WO1997005878A1 (en) * 1995-08-10 1997-02-20 Merck & Co., Inc. 2,5-substituted aryl pyrroles, compositions containing such compounds and methods of use

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2366659C2 (ru) * 2003-12-30 2009-09-10 Ск Кемикалз Ко., Лтд. Новые производные пиридина, способ их получения и содержащая их фармацевтическая композиция

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EP1025102A1 (en) 2000-08-09
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