CN103649093B - 取代的咪唑并吡啶和咪唑并哒嗪及其用途 - Google Patents
取代的咪唑并吡啶和咪唑并哒嗪及其用途 Download PDFInfo
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- CN103649093B CN103649093B CN201280033572.9A CN201280033572A CN103649093B CN 103649093 B CN103649093 B CN 103649093B CN 201280033572 A CN201280033572 A CN 201280033572A CN 103649093 B CN103649093 B CN 103649093B
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- MJQSRSOTRPMVKB-UHFFFAOYSA-N 5h-imidazo[4,5-c]pyridazine Chemical class C1=NNC2=NC=NC2=C1 MJQSRSOTRPMVKB-UHFFFAOYSA-N 0.000 title abstract description 4
- 125000004857 imidazopyridinyl group Chemical class N1C(=NC2=C1C=CC=N2)* 0.000 title abstract 2
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- 150000001875 compounds Chemical class 0.000 claims description 280
- 239000002585 base Substances 0.000 claims description 196
- 239000011737 fluorine Substances 0.000 claims description 114
- 229910052731 fluorine Inorganic materials 0.000 claims description 114
- 229910052739 hydrogen Inorganic materials 0.000 claims description 110
- 239000001257 hydrogen Substances 0.000 claims description 110
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 95
- 238000000034 method Methods 0.000 claims description 88
- 150000003839 salts Chemical class 0.000 claims description 82
- 238000006467 substitution reaction Methods 0.000 claims description 80
- 239000002904 solvent Substances 0.000 claims description 78
- 238000006243 chemical reaction Methods 0.000 claims description 76
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 74
- 125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 claims description 54
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 229910052757 nitrogen Inorganic materials 0.000 claims description 40
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 38
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
- 239000003513 alkali Substances 0.000 claims description 28
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 28
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- 125000001028 difluoromethyl group Chemical class [H]C(F)(F)* 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 24
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 24
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- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical group C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 claims description 22
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- 239000000460 chlorine Substances 0.000 claims description 20
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 19
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
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- 206010059245 Angiopathy Diseases 0.000 claims description 5
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- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 4
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- 231100000956 nontoxicity Toxicity 0.000 claims 1
- 201000010099 disease Diseases 0.000 abstract description 22
- 238000002360 preparation method Methods 0.000 abstract description 19
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- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- -1 diphenyl hexafluorophosphoric acid salt Chemical class 0.000 description 138
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 125
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 99
- 239000000203 mixture Substances 0.000 description 91
- 235000002639 sodium chloride Nutrition 0.000 description 81
- 239000012453 solvate Substances 0.000 description 71
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 69
- 150000002431 hydrogen Chemical group 0.000 description 67
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 65
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 50
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 45
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 45
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 42
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 39
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 38
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 29
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 27
- 229910052799 carbon Inorganic materials 0.000 description 27
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 24
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 24
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- 125000004093 cyano group Chemical group *C#N 0.000 description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 20
- JMANUKZDKDKBJP-UHFFFAOYSA-N imidazo[1,5-a]pyridine Chemical compound C1=CC=CC2=CN=CN21 JMANUKZDKDKBJP-UHFFFAOYSA-N 0.000 description 20
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 19
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 19
- 229940079593 drug Drugs 0.000 description 19
- 235000019253 formic acid Nutrition 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 17
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
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- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 15
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- 150000002170 ethers Chemical class 0.000 description 15
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 14
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- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 13
- 125000003226 pyrazolyl group Chemical group 0.000 description 13
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical group C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 12
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- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 12
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- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 9
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- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 8
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
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- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 6
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- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 description 6
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- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 6
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- BZCGWAXQDLXLQM-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O.ClP(Cl)(Cl)=O BZCGWAXQDLXLQM-UHFFFAOYSA-N 0.000 description 6
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- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 6
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- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 6
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
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Landscapes
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| DE102011075399A DE102011075399A1 (de) | 2011-05-06 | 2011-05-06 | Substituierte Imidazopyridine und Imidazopyridazine und ihre Verwendung |
| DE102011075399.0 | 2011-05-06 | ||
| DE201210200356 DE102012200356A1 (de) | 2012-01-11 | 2012-01-11 | Substituierte Imidazopyridine und Imidazopyridazine und ihre Verwendung |
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| PCT/EP2012/058046 WO2012152629A1 (de) | 2011-05-06 | 2012-05-02 | Substituierte imidazopyridine und imidazopyridazine und ihre verwendung |
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| ES2720594T3 (es) | 2008-12-18 | 2019-07-23 | Univ Oregon Health & Science | Anticuerpos anti-fXI y métodos de uso |
| EP3699180A1 (de) | 2009-11-27 | 2020-08-26 | Adverio Pharma GmbH | Verfahren zur herstellung von methyl-{4,6-diamino-2-[1-(2-fluorobenzyl)-1h-pyrazolo[3,4-b]pyridin-3-yl]pyrimidin-5-yl}methylcarbamat und dessen aufreinigung für die verwendung als pharmazeutischer wirkstoff |
| CN103180327B (zh) | 2010-07-09 | 2016-08-10 | 拜耳知识产权有限责任公司 | 稠环的4-氨基嘧啶及其作为可溶性鸟甘酸环化酶的刺激物的用途 |
| MX2013000198A (es) | 2010-07-09 | 2013-01-28 | Bayer Ip Gmbh | Pirimidinadas y triazinas condensadas y su uso. |
| DE102010040233A1 (de) | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| WO2012152629A1 (de) * | 2011-05-06 | 2012-11-15 | Bayer Intellectual Property Gmbh | Substituierte imidazopyridine und imidazopyridazine und ihre verwendung |
| JP6005134B2 (ja) | 2011-04-21 | 2016-10-12 | バイエル・インテレクチュアル・プロパティ・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツングＢａｙｅｒ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ ＧｍｂＨ | フルオロアルキル置換ピラゾロピリジンおよびその使用 |
| US8859569B2 (en) * | 2011-09-02 | 2014-10-14 | Bayer Pharma Aktiengesellschaft | Substituted annellated pyrimidines and use thereof |
| EP2594270A3 (en) * | 2011-11-18 | 2013-07-31 | BIP Patents | The use of sGC stimulators, sGC activators, alone and combinations with PDE5 inhibitors for the treatment of systemic sclerosis (SSc) |
| DE102012200360A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte Triazine und ihre Verwendung |
| DE102012200352A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte, annellierte Imidazole und Pyrazole und ihre Verwendung |
| DE102012200349A1 (de) | 2012-01-11 | 2013-07-11 | Bayer Intellectual Property Gmbh | Substituierte annellierte Pyrimidine und Triazine und ihre Verwendung |
| US9498480B2 (en) | 2012-03-06 | 2016-11-22 | Bayer Intellectual Property Gmbh | Substituted azabicycles and use thereof |
| WO2013167669A1 (en) | 2012-05-10 | 2013-11-14 | Bayer Pharma Aktiengesellschaft | Antibodies capable of binding to the coagulation factor xi and/or its activated form factor xia and uses thereof |
| US9278968B2 (en) | 2012-11-30 | 2016-03-08 | Astellas Pharma Inc. | Imidazopyridine compounds |
| WO2014131760A1 (de) | 2013-03-01 | 2014-09-04 | Bayer Pharma Aktiengesellschaft | Trifluormethyl-substituierte annellierte pyrimidine und ihre verwendung |
| ES2625744T3 (es) | 2013-06-04 | 2017-07-20 | Bayer Pharma Aktiengesellschaft | Imidazo[1,2-a]piridinas sustituidas con 3-arilo y su uso |
| KR101811549B1 (ko) * | 2013-06-19 | 2017-12-26 | 에프. 호프만-라 로슈 아게 | 인돌린-2-온 또는 피롤로-피리딘/피리미딘-2-온 유도체 |
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| EP3079700B1 (en) | 2013-12-11 | 2020-11-25 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| WO2015088885A1 (en) | 2013-12-11 | 2015-06-18 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| WO2015106268A1 (en) | 2014-01-13 | 2015-07-16 | Ironwood Pharmaceuticals, Inc. | USE OF sGC STIMULATORS FOR THE TREATMENT OF NEUROMUSCULAR DISORDERS |
| CN106459090A (zh) | 2014-02-19 | 2017-02-22 | 拜耳制药股份公司 | 3‑(嘧啶‑2‑基)咪唑并[1,2‑a]吡啶 |
| CN106715426A (zh) * | 2014-03-21 | 2017-05-24 | 拜耳医药股份有限公司 | 氰基取代的咪唑并[1,2‑a]吡啶甲酰胺及其用途 |
| CN106103438A (zh) * | 2014-03-21 | 2016-11-09 | 拜耳医药股份有限公司 | 取代的咪唑并[1,2‑a]吡啶甲酰胺及其用途 |
| WO2015187470A1 (en) | 2014-06-04 | 2015-12-10 | Merck Sharp & Dohme Corp. | Imidazo-pyrazine derivatives useful as soluble guanylate cyclase activators |
| CN107074883A (zh) | 2014-08-29 | 2017-08-18 | 拜耳医药股份有限公司 | 氨基取代的环状嘧啶及其用途 |
| CA2959202A1 (en) | 2014-08-29 | 2016-03-03 | Bayer Pharma Aktiengesellschaft | Substituted annulated pyrimidines and use thereof |
| TW201625635A (zh) | 2014-11-21 | 2016-07-16 | 默沙東藥廠 | 作為可溶性鳥苷酸環化酶活化劑之三唑并吡基衍生物 |
| US10292970B2 (en) | 2014-12-02 | 2019-05-21 | Bayer Pharma Aktiengesellschaft | Heteroaryl-substituted imidazo[1,2-A]pyridines and their use |
| WO2016177660A1 (en) | 2015-05-06 | 2016-11-10 | Bayer Pharma Aktiengesellschaft | The use of sgc stimulators, sgc activators, alone and combinations with pde5 inhibitors for the treatment of digital ulcers (du) concomitant to systemic sclerosis (ssc) |
| WO2016191334A1 (en) | 2015-05-27 | 2016-12-01 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
| US10213429B2 (en) | 2015-05-28 | 2019-02-26 | Merck Sharp & Dohme Corp. | Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators |
| LT3325013T (lt) | 2015-07-23 | 2020-11-10 | Bayer Pharma Aktiengesellschaft | Tirpios guanilatciklazės (sgc) stimuliatoriai/aktyvatoriai derinyje su nep inhibitoriumi ir (arba) angiotenzino aii antagonistu ir jų naudojimas |
| JP2019502686A (ja) | 2015-12-14 | 2019-01-31 | アイアンウッド ファーマシューティカルズ インコーポレイテッド | 消化管括約筋機能障害の治療へのｓＧＣ刺激薬の使用 |
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| AU2019301683B9 (en) | 2018-07-11 | 2025-04-24 | Tisento Therapeutics Inc. | Use of sGC stimulators for the treatment of mitochondrial disorders |
| CR20210336A (es) | 2018-12-20 | 2021-12-06 | Incyte Corp | Compuestos de imidazopiridazina e imidazopiridina como inhibidores de quinasa-2 de tipo receptor de activina |
| WO2020164008A1 (en) | 2019-02-13 | 2020-08-20 | Bayer Aktiengesellschaft | Process for the preparation of porous microparticles |
| TWI895442B (zh) | 2020-06-12 | 2025-09-01 | 美商英塞特公司 | 咪唑并嗒嗪化合物及其用途 |
| CN113735849B (zh) * | 2021-07-22 | 2022-10-11 | 安徽中医药大学 | 1-氰基咪唑并[1,5-a]吡啶类化合物及其合成方法 |
| CN113603687A (zh) * | 2021-08-02 | 2021-11-05 | 北京工业大学 | 一种氰基取代的咪唑[1,5-a]并吡啶合成新方法 |
| TW202448469A (zh) * | 2023-06-09 | 2024-12-16 | 大陸商西藏海思科製藥有限公司 | 吡咯並[2,3-d]嘧啶-4-胺衍生物及其在醫藥上的應用 |
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| CN1317005A (zh) * | 1998-07-29 | 2001-10-10 | 拜尔公司 | 与六元杂环稠合的取代的吡唑衍生物 |
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| DE19642255A1 (de) | 1996-10-14 | 1998-04-16 | Bayer Ag | Verwendung von 1-Benzyl-3-(substituierten-hetaryl) -kondensierten Pyrazol-Derivaten |
| DE10220570A1 (de) | 2002-05-08 | 2003-11-20 | Bayer Ag | Carbamat-substituierte Pyrazolopyridine |
| DE102006043443A1 (de) | 2006-09-15 | 2008-03-27 | Bayer Healthcare Ag | Neue aza-bicyclische Verbindungen und ihre Verwendung |
| EP2108641A1 (en) * | 2008-04-11 | 2009-10-14 | Laboratorios Almirall, S.A. | New substituted spiro[cycloalkyl-1,3'-indo]-2'(1'H)-one derivatives and their use as p38 mitogen-activated kinase inhibitors |
| WO2010065275A1 (en) * | 2008-11-25 | 2010-06-10 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| PE20130222A1 (es) | 2010-05-27 | 2013-03-14 | Merck Sharp & Dohme | Activadores de guanilato ciclasa soluble |
| DE102010040233A1 (de) * | 2010-09-03 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Bicyclische Aza-Heterocyclen und ihre Verwendung |
| WO2012152629A1 (de) * | 2011-05-06 | 2012-11-15 | Bayer Intellectual Property Gmbh | Substituierte imidazopyridine und imidazopyridazine und ihre verwendung |
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- 2012-05-02 WO PCT/EP2012/058046 patent/WO2012152629A1/de not_active Ceased
- 2012-05-02 CN CN201280033572.9A patent/CN103649093B/zh not_active Expired - Fee Related
- 2012-05-02 US US14/115,870 patent/US20140171434A1/en not_active Abandoned
- 2012-05-02 ES ES12717331.8T patent/ES2592267T3/es active Active
- 2012-05-02 JP JP2014508787A patent/JP5976788B2/ja not_active Expired - Fee Related
- 2012-05-02 CA CA2834901A patent/CA2834901A1/en not_active Abandoned
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| CN1317005A (zh) * | 1998-07-29 | 2001-10-10 | 拜尔公司 | 与六元杂环稠合的取代的吡唑衍生物 |
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| ES2592267T3 (es) | 2016-11-29 |
| JP2014513112A (ja) | 2014-05-29 |
| EP2705037A1 (de) | 2014-03-12 |
| JP5976788B2 (ja) | 2016-08-24 |
| CN103649093A (zh) | 2014-03-19 |
| US20140171434A1 (en) | 2014-06-19 |
| CA2834901A1 (en) | 2012-11-15 |
| WO2012152629A1 (de) | 2012-11-15 |
| EP2705037B1 (de) | 2016-06-22 |
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