EA033697B1 - Активаторы растворимой гуанилатциклазы и их применение - Google Patents
Активаторы растворимой гуанилатциклазы и их применение Download PDFInfo
- Publication number
- EA033697B1 EA033697B1 EA201790655A EA201790655A EA033697B1 EA 033697 B1 EA033697 B1 EA 033697B1 EA 201790655 A EA201790655 A EA 201790655A EA 201790655 A EA201790655 A EA 201790655A EA 033697 B1 EA033697 B1 EA 033697B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- piperidin
- pyridin
- carboxylic acid
- phenyl
- difluoro
- Prior art date
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- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 title abstract description 22
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 title abstract description 22
- 239000003119 guanylate cyclase activator Substances 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 238000000034 method Methods 0.000 claims abstract description 60
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 14
- 230000004406 elevated intraocular pressure Effects 0.000 claims abstract 2
- -1 3,5-difluoro-2 - ((2-methyl-4- (1 - (3,3,3-trifluoropropyl) piperidin-4-yl) benzyl) hydroxy) phenyl Chemical group 0.000 claims description 82
- 159000000000 sodium salts Chemical class 0.000 claims description 69
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 claims description 46
- 201000010099 disease Diseases 0.000 claims description 26
- 230000004410 intraocular pressure Effects 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 208000035475 disorder Diseases 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 241000124008 Mammalia Species 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
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- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 9
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- 238000002156 mixing Methods 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- XZIQSOZOLJJMFN-UHFFFAOYSA-N n-[4-[3,5-bis(trifluoromethyl)pyrazol-1-yl]phenyl]-3-fluoropyridine-4-carboxamide Chemical compound FC1=CN=CC=C1C(=O)NC1=CC=C(N2C(=CC(=N2)C(F)(F)F)C(F)(F)F)C=C1 XZIQSOZOLJJMFN-UHFFFAOYSA-N 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 239000002840 nitric oxide donor Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
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- 239000007800 oxidant agent Substances 0.000 description 1
- GSUBXIVOZXWGKF-UHFFFAOYSA-N oxolane-3-carbaldehyde Chemical compound O=CC1CCOC1 GSUBXIVOZXWGKF-UHFFFAOYSA-N 0.000 description 1
- BOTREHHXSQGWTR-UHFFFAOYSA-N oxolane-3-carboxylic acid Chemical compound OC(=O)C1CCOC1 BOTREHHXSQGWTR-UHFFFAOYSA-N 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
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- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Substances [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 229940005550 sodium alginate Drugs 0.000 description 1
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
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- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
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- 125000004434 sulfur atom Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 229920001187 thermosetting polymer Polymers 0.000 description 1
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- 238000004809 thin layer chromatography Methods 0.000 description 1
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- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462052537P | 2014-09-19 | 2014-09-19 | |
| PCT/IB2015/057219 WO2016042536A1 (en) | 2014-09-19 | 2015-09-18 | Novel soluble guanylate cyclase activators and their use |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201790655A1 EA201790655A1 (ru) | 2017-08-31 |
| EA033697B1 true EA033697B1 (ru) | 2019-11-18 |
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| EA201790655A EA033697B1 (ru) | 2014-09-19 | 2015-09-18 | Активаторы растворимой гуанилатциклазы и их применение |
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|---|---|
| US (2) | US9938260B2 (enExample) |
| EP (1) | EP3194384A1 (enExample) |
| JP (3) | JP6678656B2 (enExample) |
| KR (1) | KR20170054508A (enExample) |
| CN (1) | CN106687456B (enExample) |
| AU (1) | AU2015319724B2 (enExample) |
| BR (1) | BR112017005660A2 (enExample) |
| CA (1) | CA2961745A1 (enExample) |
| CL (1) | CL2017000640A1 (enExample) |
| CO (1) | CO2017002506A2 (enExample) |
| CR (1) | CR20170102A (enExample) |
| DO (1) | DOP2017000073A (enExample) |
| EA (1) | EA033697B1 (enExample) |
| IL (1) | IL251094A0 (enExample) |
| MA (1) | MA40583A (enExample) |
| MX (1) | MX2017003621A (enExample) |
| PE (1) | PE20170937A1 (enExample) |
| PH (1) | PH12017500481A1 (enExample) |
| SG (1) | SG11201701915TA (enExample) |
| WO (1) | WO2016042536A1 (enExample) |
| ZA (1) | ZA201701835B (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SMT202400446T1 (it) | 2014-02-06 | 2024-11-15 | Nxera Pharma Uk Ltd | Composti aza biciclici come agonisti del recettore muscarinico |
| WO2016042536A1 (en) * | 2014-09-19 | 2016-03-24 | Glaxosmithkline Intellectual Property Development Limited | Novel soluble guanylate cyclase activators and their use |
| TN2017000092A1 (en) | 2014-09-19 | 2018-07-04 | Bayer Pharma AG | Benzyl substituted indazoles as bub1 inhibitors. |
| CN109890379A (zh) | 2016-10-11 | 2019-06-14 | 拜耳制药股份公司 | 包含sGC活化剂和盐皮质激素受体拮抗剂的组合产品 |
| WO2019081456A1 (en) | 2017-10-24 | 2019-05-02 | Bayer Aktiengesellschaft | USE OF SGC ACTIVATORS AND STIMULATORS COMPRISING A BETA2 SUBUNIT |
| EP3498298A1 (en) | 2017-12-15 | 2019-06-19 | Bayer AG | The use of sgc stimulators and sgc activators alone or in combination with pde5 inhibitors for the treatment of bone disorders including osteogenesis imperfecta (oi) |
| CA3098475A1 (en) | 2018-04-30 | 2019-11-07 | Bayer Aktiengesellschaft | The use of sgc activators and sgc stimulators for the treatment of cognitive impairment |
| EA202092680A1 (ru) | 2018-05-15 | 2021-04-13 | Байер Акциенгезельшафт | 1,3-тиазол-2-ил-замещенные бензамиды для лечения заболеваний, ассоциированных с сенситизацией нервных волокон |
| EP3574905A1 (en) | 2018-05-30 | 2019-12-04 | Adverio Pharma GmbH | Method of identifying a subgroup of patients suffering from dcssc which benefits from a treatment with sgc stimulators and sgc activators in a higher degree than a control group |
| EP3911675A1 (en) | 2019-01-17 | 2021-11-24 | Bayer Aktiengesellschaft | Methods to determine whether a subject is suitable of being treated with an agonist of soluble guanylyl cyclase (sgc) |
| WO2023237577A1 (en) | 2022-06-09 | 2023-12-14 | Bayer Aktiengesellschaft | Soluble guanylate cyclase activators for use in the treatment of heart failure with preserved ejection fraction in women |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009071504A1 (en) * | 2007-12-03 | 2009-06-11 | Smithkline Beecham Corporation | 2,6-disubstituted pyridines as soluble guanylate cyclase activators |
| WO2010015653A1 (en) * | 2008-08-07 | 2010-02-11 | Smithkline Beecham Corporation | Pyrimidine derivatives as activators of soluble guanylate cyclase |
| WO2010099054A2 (en) * | 2009-02-26 | 2010-09-02 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5602143A (en) | 1994-12-08 | 1997-02-11 | Allergan | Method for reducing intraocular pressure in the mammalian eye by administration of guanylate cyclase inhibitors |
| KR20140032505A (ko) | 2006-11-09 | 2014-03-14 | 알콘 리서치, 리미티드 | 약물 전달용 수불용성 폴리머 매트릭스 |
| DE102009012314A1 (de) * | 2009-03-09 | 2010-09-16 | Bayer Schering Pharma Aktiengesellschaft | Oxo-heterocyclisch substituierte Alkylcarbonsäuren und ihre Verwendung |
| JP5636296B2 (ja) | 2011-01-20 | 2014-12-03 | 公益財団法人微生物化学研究会 | 塩分含有有機廃液処理剤、並びに、塩分濃度低下剤、塩分含有有機廃液の処理方法、及び包括固定担体 |
| WO2016042536A1 (en) * | 2014-09-19 | 2016-03-24 | Glaxosmithkline Intellectual Property Development Limited | Novel soluble guanylate cyclase activators and their use |
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- 2015-09-18 KR KR1020177010181A patent/KR20170054508A/ko not_active Ceased
- 2015-09-18 CA CA2961745A patent/CA2961745A1/en not_active Abandoned
- 2015-09-18 JP JP2017515074A patent/JP6678656B2/ja active Active
- 2015-09-18 SG SG11201701915TA patent/SG11201701915TA/en unknown
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2017
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009071504A1 (en) * | 2007-12-03 | 2009-06-11 | Smithkline Beecham Corporation | 2,6-disubstituted pyridines as soluble guanylate cyclase activators |
| WO2010015653A1 (en) * | 2008-08-07 | 2010-02-11 | Smithkline Beecham Corporation | Pyrimidine derivatives as activators of soluble guanylate cyclase |
| WO2010099054A2 (en) * | 2009-02-26 | 2010-09-02 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
Also Published As
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| CO2017002506A2 (es) | 2017-07-28 |
| DOP2017000073A (es) | 2017-04-16 |
| ZA201701835B (en) | 2018-12-19 |
| PH12017500481A1 (en) | 2017-08-07 |
| EP3194384A1 (en) | 2017-07-26 |
| CN106687456B (zh) | 2019-12-03 |
| US10472350B2 (en) | 2019-11-12 |
| MX2017003621A (es) | 2017-07-14 |
| JP2021155450A (ja) | 2021-10-07 |
| AU2015319724B2 (en) | 2018-05-10 |
| PE20170937A1 (es) | 2017-07-13 |
| JP2017527602A (ja) | 2017-09-21 |
| WO2016042536A1 (en) | 2016-03-24 |
| CA2961745A1 (en) | 2016-03-24 |
| MA40583A (fr) | 2016-03-24 |
| JP6908747B2 (ja) | 2021-07-28 |
| EA201790655A1 (ru) | 2017-08-31 |
| US9938260B2 (en) | 2018-04-10 |
| KR20170054508A (ko) | 2017-05-17 |
| CR20170102A (es) | 2017-07-17 |
| JP6678656B2 (ja) | 2020-04-08 |
| US20170305888A1 (en) | 2017-10-26 |
| CL2017000640A1 (es) | 2017-10-06 |
| US20180194756A1 (en) | 2018-07-12 |
| IL251094A0 (en) | 2017-04-30 |
| AU2015319724A1 (en) | 2017-04-06 |
| CN106687456A (zh) | 2017-05-17 |
| JP2020105189A (ja) | 2020-07-09 |
| BR112017005660A2 (pt) | 2017-12-19 |
| SG11201701915TA (en) | 2017-04-27 |
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