JP2001525322A - 胃酸分泌を抑制する複素環式化合物、それらの製造法およびそれらの医薬組成物 - Google Patents
胃酸分泌を抑制する複素環式化合物、それらの製造法およびそれらの医薬組成物Info
- Publication number
- JP2001525322A JP2001525322A JP2000523214A JP2000523214A JP2001525322A JP 2001525322 A JP2001525322 A JP 2001525322A JP 2000523214 A JP2000523214 A JP 2000523214A JP 2000523214 A JP2000523214 A JP 2000523214A JP 2001525322 A JP2001525322 A JP 2001525322A
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- Prior art keywords
- compound
- compound according
- pharmaceutically acceptable
- acceptable salt
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
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- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9704404A SE9704404D0 (sv) | 1997-11-28 | 1997-11-28 | New compounds |
| SE9704404-4 | 1997-11-28 | ||
| PCT/SE1998/002091 WO1999028322A1 (en) | 1997-11-28 | 1998-11-18 | Heterocyclic compounds for inhibition of gastric acid secretion, processes for their preparation and pharmaceutical compositions thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001525322A true JP2001525322A (ja) | 2001-12-11 |
| JP2001525322A5 JP2001525322A5 (https=) | 2006-01-12 |
Family
ID=20409181
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000523214A Pending JP2001525322A (ja) | 1997-11-28 | 1998-11-18 | 胃酸分泌を抑制する複素環式化合物、それらの製造法およびそれらの医薬組成物 |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US6518270B1 (https=) |
| EP (1) | EP1042324B1 (https=) |
| JP (1) | JP2001525322A (https=) |
| KR (1) | KR20010032559A (https=) |
| CN (1) | CN1142933C (https=) |
| AR (1) | AR016972A1 (https=) |
| AT (1) | ATE233263T1 (https=) |
| AU (1) | AU752187C (https=) |
| BR (1) | BR9814755A (https=) |
| CA (1) | CA2311798A1 (https=) |
| CZ (1) | CZ292349B6 (https=) |
| DE (1) | DE69811735T2 (https=) |
| DK (1) | DK1042324T3 (https=) |
| EE (1) | EE04060B1 (https=) |
| ES (1) | ES2191356T3 (https=) |
| HU (1) | HUP0100601A3 (https=) |
| ID (1) | ID24730A (https=) |
| IL (1) | IL136145A0 (https=) |
| IS (1) | IS5486A (https=) |
| MY (1) | MY121032A (https=) |
| NO (1) | NO315704B1 (https=) |
| NZ (1) | NZ504355A (https=) |
| PL (1) | PL340920A1 (https=) |
| PT (1) | PT1042324E (https=) |
| RU (1) | RU2241000C2 (https=) |
| SE (1) | SE9704404D0 (https=) |
| SK (1) | SK283904B6 (https=) |
| TR (1) | TR200001530T2 (https=) |
| TW (1) | TW515798B (https=) |
| UA (1) | UA70932C2 (https=) |
| WO (1) | WO1999028322A1 (https=) |
| ZA (1) | ZA9810468B (https=) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006011670A1 (ja) * | 2004-07-28 | 2006-02-02 | Takeda Pharmaceutical Company Limited | ピロロ［２，３－ｃ］ピリジン化合物、その製造方法および用途 |
| JP2008511619A (ja) * | 2004-09-03 | 2008-04-17 | ユーハン・コーポレイション | ピロロ［３，２−ｃ］ピリジン誘導体及びその製造方法 |
| JP2008511618A (ja) * | 2004-09-03 | 2008-04-17 | ユーハン・コーポレイション | ピロロ［３，２−ｃ］ピリジン誘導体及びその製造方法 |
| JP2008511620A (ja) * | 2004-09-03 | 2008-04-17 | ユーハン・コーポレイション | ピロロ［３，２−ｂ］ピリジン誘導体及びその製造方法 |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2324093A (en) | 1996-01-04 | 1998-10-14 | Rican Limited | Helicobacter pylori bacterioferritin |
| SE9704404D0 (sv) | 1997-11-28 | 1997-11-28 | Astra Ab | New compounds |
| HU230030B1 (hu) | 1999-10-08 | 2015-05-28 | Debiopharm International Sa | Fab I inhibitorok |
| EP1560584B1 (en) * | 2001-04-06 | 2009-01-14 | Affinium Pharmaceuticals, Inc. | Fab i inhibitors |
| JP2003119140A (ja) * | 2001-08-08 | 2003-04-23 | Sankyo Co Ltd | ピロロピリダジン化合物を含有する医薬 |
| KR20050008691A (ko) * | 2002-04-19 | 2005-01-21 | 셀룰러 지노믹스 아이엔씨 | 이미다조[1,2-ａ]피라진-8-일 아민, 그의 제조방법 및사용방법 |
| AU2003270489A1 (en) | 2002-09-09 | 2004-03-29 | Cellular Genomics, Inc. | 6-ARYL-IMIDAZO(1,2-a)PYRAZIN-8-YLAMINES, METHOD OF MAKING, AND METHOD OF USE THEREOF |
| WO2004029058A1 (ja) * | 2002-09-25 | 2004-04-08 | Sankyo Company, Limited | 血中ガストリン濃度上昇の抑制のための医薬組成物 |
| TW200418479A (en) * | 2002-09-25 | 2004-10-01 | Sankyo Co | Pharmaceutical compositions for the treatment or prevention of visceral pains |
| EP1575951B1 (en) * | 2002-12-06 | 2014-06-25 | Debiopharm International SA | Heterocyclic compounds, methods of making them and their use in therapy |
| WO2004072080A1 (en) | 2003-02-10 | 2004-08-26 | Cellular Genomics, Inc. | Certain 8-heteroaryl-6-phenyl-imidazo[1,2-a]pyrazines as modulators of hsp90 complex activity |
| AR043002A1 (es) * | 2003-02-18 | 2005-07-13 | Altana Pharma Ag | Imidazopirazinas 6-substituidos |
| WO2004082586A2 (en) * | 2003-03-17 | 2004-09-30 | Affinium Pharmaceuticals, Inc. | Phamaceutical compositions comprising inhibitors of fab i and further antibiotics |
| US7405295B2 (en) | 2003-06-04 | 2008-07-29 | Cgi Pharmaceuticals, Inc. | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
| WO2005005429A1 (en) | 2003-06-30 | 2005-01-20 | Cellular Genomics, Inc. | Certain heterocyclic substituted imidazo[1,2-a]pyrazin-8-ylamines and methods of inhibition of bruton’s tyrosine kinase by such compounds |
| US7259164B2 (en) | 2003-08-11 | 2007-08-21 | Cgi Pharmaceuticals, Inc. | Certain substituted imidazo[1,2-a]pyrazines, as modulators of kinase activity |
| KR20060099524A (ko) | 2003-11-03 | 2006-09-19 | 아스트라제네카 아베 | 무증상 위식도 역류의 치료를 위한 이미다조[1,2-ａ]피리딘유도체 |
| DK1828167T3 (da) * | 2004-06-04 | 2014-10-20 | Debiopharm Int Sa | Acrylamidderivater som antibiotiske midler |
| CA2575345A1 (en) * | 2004-08-02 | 2006-02-09 | Altana Pharma Ag | 5-substituted 1h-pyrrolo[3,2-b]pyridines |
| KR100958829B1 (ko) | 2004-09-03 | 2010-05-25 | 주식회사유한양행 | 피롤로[2,3-ｃ]피리딘 유도체 및 그의 제조방법 |
| WO2007024294A2 (en) | 2005-05-03 | 2007-03-01 | Cgi Pharmaceuticals, Inc. | Certain substituted ureas, as modulators of kinase activity |
| JP2009507032A (ja) | 2005-09-02 | 2009-02-19 | アボット・ラボラトリーズ | 新規なイミダゾ系複素環 |
| KR20080075027A (ko) * | 2005-12-05 | 2008-08-13 | 아피늄 파마슈티컬스, 인크. | Ｆａｂｉ 억제제 및 항박테리아제로서의헤테로시클릴아크릴아미드 화합물 |
| EP2029605A1 (en) * | 2006-06-06 | 2009-03-04 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| JP5468899B2 (ja) | 2006-07-20 | 2014-04-09 | アフィニウム ファーマシューティカルズ， インク． | Ｆａｂｉインヒビターとしてのアクリルアミド誘導体 |
| EP2125802A4 (en) | 2007-02-16 | 2014-08-20 | Debiopharm Int Sa | SALTS, PRODRUGS AND POLYMORPHES OF FAB I INHIBITORS |
| WO2009102468A1 (en) | 2008-02-13 | 2009-08-20 | Cgi Pharmaceuticals, Inc. | 6-aryl-imidaz0[l, 2-a] pyrazine derivatives, method of making, and method of use thereof |
| US8450321B2 (en) | 2008-12-08 | 2013-05-28 | Gilead Connecticut, Inc. | 6-(1H-indazol-6-yl)-N-[4-(morpholin-4-yl)phenyl]imidazo-[1,2-A]pyrazin-8-amine, or a pharmaceutically acceptable salt thereof, as a SYK inhibitor |
| PE20120121A1 (es) | 2008-12-08 | 2012-02-20 | Gilead Connecticut Inc | Derivados de imidazopirazina como inhibidores de syk |
| PL2716157T3 (pl) | 2008-12-08 | 2017-06-30 | Gilead Connecticut, Inc. | Imidazopirazynowe inhibitory Syk |
| AU2011226689B2 (en) | 2010-03-11 | 2016-09-01 | Kronos Bio, Inc. | Imidazopyridines Syk inhibitors |
| AU2013279021C1 (en) | 2012-06-19 | 2017-03-16 | Debiopharm International Sa | Prodrug derivatives of (E)-N-methyl-N-((3-methylbenzofuran-2-yl)methyl)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylamide |
| PE20160605A1 (es) | 2013-07-30 | 2016-07-20 | Gilead Connecticut Inc | Formulaciones de inhibidores de la syk |
| KR101810798B1 (ko) | 2013-07-30 | 2017-12-19 | 질레드 코네티컷 인코포레이티드 | Ｓｙｋ 억제제의 다형체 |
| KR20160090903A (ko) | 2013-12-04 | 2016-08-01 | 길리애드 사이언시즈, 인코포레이티드 | 암을 치료하는 방법 |
| GB201321738D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| TWI735853B (zh) | 2013-12-23 | 2021-08-11 | 美商克洛諾斯生技有限公司 | 脾酪胺酸激酶抑制劑 |
| US9290505B2 (en) | 2013-12-23 | 2016-03-22 | Gilead Sciences, Inc. | Substituted imidazo[1,2-a]pyrazines as Syk inhibitors |
| SG11201610551TA (en) | 2014-07-14 | 2017-01-27 | Gilead Sciences Inc | Combinations for treating cancers |
| RS61312B1 (sr) | 2016-02-26 | 2021-02-26 | Debiopharm Int Sa | Lek za lečenje infekcija dijabetskog stopala |
| EP3672974A1 (en) | 2017-08-25 | 2020-07-01 | Gilead Sciences, Inc. | Polymorphs of syk inhibitors |
| TN2021000159A1 (en) | 2019-02-14 | 2023-04-04 | Debiopharm Int Sa | Afabicin formulation, method for making the same and uses thereof |
| US11339168B2 (en) | 2019-02-22 | 2022-05-24 | Kronos Bio, Inc. | Crystalline forms of 6-(6-aminopyrazin-2-yl)-N-(4-(4-(oxetan-3-yl)piperazin-1-yl)phenyl)imidazo[1,2-a]pyrazin-8-amine as Syk inhibitors |
| SG11202113174SA (en) | 2019-06-14 | 2021-12-30 | Debiopharm Int Sa | Medicament and use thereof for treating bacterial infections involving biofilm |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4507294A (en) * | 1982-03-08 | 1985-03-26 | Schering Corp. | Imidazo[1,2-a]pyrazines |
| DE3269604D1 (en) * | 1981-06-26 | 1986-04-10 | Schering Corp | Novel imidazo(1,2-a)pyridines and pyrazines, processes for their preparation and pharmaceutical compositions containing them |
| US4725601A (en) * | 1985-06-04 | 1988-02-16 | Fujisawa Pharmaceutical Co., Ltd. | Certain imidazo[1,2-a]pyridines useful in the treatment of ulcers |
| WO1991017164A1 (de) * | 1990-04-27 | 1991-11-14 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue pyridazine |
| US5041442A (en) | 1990-07-31 | 1991-08-20 | Syntex (U.S.A.) Inc. | Pyrrolo(1,2-a)pyrazines as inhibitors of gastric acid secretion |
| WO1992006979A1 (de) * | 1990-10-15 | 1992-04-30 | Byk Gulden Lomberg Chemische Fabrik Gmbh | Neue diazine |
| JPH07500329A (ja) * | 1991-10-25 | 1995-01-12 | ビイク グルデン ロンベルク ヒエーミツシエ フアブリーク ゲゼルシヤフト ミツト ベシユレンクテル ハフツング | ピロロ−ピリダジン |
| ATE229020T1 (de) * | 1994-01-19 | 2002-12-15 | Sankyo Co | Pyrrolopyridazin-derivate |
| SE9602286D0 (sv) | 1996-06-10 | 1996-06-10 | Astra Ab | New compounds |
| SE9700661D0 (sv) | 1997-02-25 | 1997-02-25 | Astra Ab | New compounds |
| SE9704404D0 (sv) | 1997-11-28 | 1997-11-28 | Astra Ab | New compounds |
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- 1998-11-18 BR BR9814755-2A patent/BR9814755A/pt not_active Application Discontinuation
- 1998-11-18 JP JP2000523214A patent/JP2001525322A/ja active Pending
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- 1998-11-18 KR KR1020007005804A patent/KR20010032559A/ko not_active Ceased
- 1998-11-18 WO PCT/SE1998/002091 patent/WO1999028322A1/en not_active Ceased
- 1998-11-18 ES ES98957270T patent/ES2191356T3/es not_active Expired - Lifetime
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- 1998-11-18 DK DK98957270T patent/DK1042324T3/da active
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006011670A1 (ja) * | 2004-07-28 | 2006-02-02 | Takeda Pharmaceutical Company Limited | ピロロ［２，３－ｃ］ピリジン化合物、その製造方法および用途 |
| JPWO2006011670A1 (ja) * | 2004-07-28 | 2008-05-01 | 武田薬品工業株式会社 | ピロロ［２，３−ｃ］ピリジン化合物、その製造方法および用途 |
| JP2008511619A (ja) * | 2004-09-03 | 2008-04-17 | ユーハン・コーポレイション | ピロロ［３，２−ｃ］ピリジン誘導体及びその製造方法 |
| JP2008511618A (ja) * | 2004-09-03 | 2008-04-17 | ユーハン・コーポレイション | ピロロ［３，２−ｃ］ピリジン誘導体及びその製造方法 |
| JP2008511620A (ja) * | 2004-09-03 | 2008-04-17 | ユーハン・コーポレイション | ピロロ［３，２−ｂ］ピリジン誘導体及びその製造方法 |
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