KR20170054508A - 신규 가용성 구아닐레이트 시클라제 활성화제 및 그의 용도 - Google Patents
신규 가용성 구아닐레이트 시클라제 활성화제 및 그의 용도 Download PDFInfo
- Publication number
- KR20170054508A KR20170054508A KR1020177010181A KR20177010181A KR20170054508A KR 20170054508 A KR20170054508 A KR 20170054508A KR 1020177010181 A KR1020177010181 A KR 1020177010181A KR 20177010181 A KR20177010181 A KR 20177010181A KR 20170054508 A KR20170054508 A KR 20170054508A
- Authority
- KR
- South Korea
- Prior art keywords
- piperidine
- carboxylic acid
- pyridin
- phenyl
- oxy
- 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.)
- Ceased
Links
- 102000007637 Soluble Guanylyl Cyclase Human genes 0.000 title abstract description 23
- 108010007205 Soluble Guanylyl Cyclase Proteins 0.000 title abstract description 23
- 239000003119 guanylate cyclase activator Substances 0.000 title description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims description 222
- -1 4- (1- (cyanomethyl) piperidin- Yl) piperidine-4-carboxylic acid Chemical compound 0.000 claims description 170
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 claims description 158
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 127
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 114
- 159000000000 sodium salts Chemical class 0.000 claims description 89
- 238000000034 method Methods 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 52
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 34
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 24
- 125000006179 2-methyl benzyl group Chemical group [H]C1=C([H])C(=C(C([H])=C1[H])C([H])([H])*)C([H])([H])[H] 0.000 claims description 23
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 22
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 17
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 13
- 208000010412 Glaucoma Diseases 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 241000124008 Mammalia Species 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 206010030043 Ocular hypertension Diseases 0.000 claims description 8
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
- QQJYBYUSURJAFG-UHFFFAOYSA-N ethyl 2h-pyridine-1-carboxylate Chemical compound CCOC(=O)N1CC=CC=C1 QQJYBYUSURJAFG-UHFFFAOYSA-N 0.000 claims description 6
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 claims description 5
- WMKYKQWKLILFBM-UHFFFAOYSA-N 2h-pyridine-1-carboxylic acid Chemical compound OC(=O)N1CC=CC=C1 WMKYKQWKLILFBM-UHFFFAOYSA-N 0.000 claims description 5
- FQYYIPZPELSLDK-UHFFFAOYSA-N ethyl pyridine-2-carboxylate Chemical compound CCOC(=O)C1=CC=CC=N1 FQYYIPZPELSLDK-UHFFFAOYSA-N 0.000 claims description 5
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 125000003944 tolyl group Chemical group 0.000 claims description 5
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
- 230000009467 reduction Effects 0.000 claims description 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 3
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Natural products OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 claims description 3
- 239000000203 mixture Substances 0.000 abstract description 33
- 239000012190 activator Substances 0.000 abstract description 6
- 241000894007 species Species 0.000 abstract description 5
- 241001465754 Metazoa Species 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 280
- 239000000243 solution Substances 0.000 description 233
- 229910001868 water Inorganic materials 0.000 description 163
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 162
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 155
- 230000002829 reductive effect Effects 0.000 description 152
- 235000019439 ethyl acetate Nutrition 0.000 description 138
- 239000011541 reaction mixture Substances 0.000 description 132
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 117
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 101
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 88
- 239000007787 solid Substances 0.000 description 87
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 81
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 81
- 239000011734 sodium Substances 0.000 description 77
- 239000012074 organic phase Substances 0.000 description 76
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 68
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 53
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 238000004440 column chromatography Methods 0.000 description 44
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 43
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 41
- 235000011121 sodium hydroxide Nutrition 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
- 239000000460 chlorine Substances 0.000 description 37
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 33
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 239000012043 crude product Substances 0.000 description 32
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
- 239000012071 phase Substances 0.000 description 28
- 238000000746 purification Methods 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 239000012267 brine Substances 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 26
- 229910002027 silica gel Inorganic materials 0.000 description 26
- 238000006243 chemical reaction Methods 0.000 description 25
- 238000004128 high performance liquid chromatography Methods 0.000 description 25
- 239000008346 aqueous phase Substances 0.000 description 24
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 22
- 201000010099 disease Diseases 0.000 description 22
- 238000000605 extraction Methods 0.000 description 22
- 239000002244 precipitate Substances 0.000 description 22
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 21
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 21
- 239000001099 ammonium carbonate Substances 0.000 description 21
- 239000012535 impurity Substances 0.000 description 21
- 230000004410 intraocular pressure Effects 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- 208000035475 disorder Diseases 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 238000002953 preparative HPLC Methods 0.000 description 14
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 13
- 239000007821 HATU Substances 0.000 description 13
- 239000007788 liquid Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000007858 starting material Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 125000004093 cyano group Chemical group *C#N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- CPTNXTSDQJQEFA-ZKOWQLKRSA-N mastoparan-A Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)[C@@H](C)CC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)=CNC2=C1 CPTNXTSDQJQEFA-ZKOWQLKRSA-N 0.000 description 9
- NSFBOCKFBVQQKB-CQWNSWRRSA-N mastoparan-B Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@H](CO)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC(C)C)[C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)=CNC2=C1 NSFBOCKFBVQQKB-CQWNSWRRSA-N 0.000 description 9
- 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 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 208000022873 Ocular disease Diseases 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 229910052786 argon Inorganic materials 0.000 description 7
- 125000003118 aryl group Chemical group 0.000 description 7
- 239000000872 buffer Substances 0.000 description 7
- 239000006184 cosolvent Substances 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 239000002808 molecular sieve Substances 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 7
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 7
- 241000400611 Eucalyptus deanei Species 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 235000019441 ethanol Nutrition 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
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- 230000001404 mediated effect Effects 0.000 description 6
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- 239000000377 silicon dioxide Substances 0.000 description 6
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- 239000013543 active substance Substances 0.000 description 5
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- SOGHURLUBLPHCJ-UHFFFAOYSA-N ethyl 1-[6-(3,5-difluoro-2-hydroxyphenyl)pyridin-2-yl]piperidine-4-carboxylate Chemical compound FC=1C(=C(C=C(C=1)F)C1=CC=CC(=N1)N1CCC(CC1)C(=O)OCC)O SOGHURLUBLPHCJ-UHFFFAOYSA-N 0.000 description 5
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- YLVUELSYOLYDBE-UHFFFAOYSA-N 1-(2,2,2-trifluoroethyl)piperidine Chemical compound FC(F)(F)CN1CCCCC1 YLVUELSYOLYDBE-UHFFFAOYSA-N 0.000 description 3
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- LLJBDRKENRHAPS-UHFFFAOYSA-N BrC1=CC(=C(C=O)C=C1)OC1COC1 Chemical compound BrC1=CC(=C(C=O)C=C1)OC1COC1 LLJBDRKENRHAPS-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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- 239000000150 Sympathomimetic Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 3
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- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 3
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 230000004382 visual function Effects 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
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
-
- Y10S514/913—
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462052537P | 2014-09-19 | 2014-09-19 | |
| US62/052,537 | 2014-09-19 | ||
| PCT/IB2015/057219 WO2016042536A1 (en) | 2014-09-19 | 2015-09-18 | Novel soluble guanylate cyclase activators and their use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20170054508A true KR20170054508A (ko) | 2017-05-17 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020177010181A Ceased KR20170054508A (ko) | 2014-09-19 | 2015-09-18 | 신규 가용성 구아닐레이트 시클라제 활성화제 및 그의 용도 |
Country Status (21)
| Country | Link |
|---|---|
| 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 |
|---|---|---|---|---|
| RU2685230C2 (ru) | 2014-02-06 | 2019-04-17 | Хептарес Терапьютикс Лимитед | Бициклические азотсодержащие соединения как агонисты М1 мускариновых рецепторов |
| EA033697B1 (ru) * | 2014-09-19 | 2019-11-18 | Glaxosmithkline Ip Dev Ltd | Активаторы растворимой гуанилатциклазы и их применение |
| WO2016042084A1 (en) | 2014-09-19 | 2016-03-24 | Bayer Pharma Aktiengesellschaft | Benzyl substituted indazoles as bub1 inhibitors |
| US11331308B2 (en) | 2016-10-11 | 2022-05-17 | Bayer Pharma Aktiengesellschaft | Combination containing sGC activators and mineralocorticoid receptor antagonists |
| 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) |
| CN112055584A (zh) | 2018-04-30 | 2020-12-08 | 拜耳公司 | sGC活化剂和sGC刺激剂用于治疗认知障碍的用途 |
| MA52616A (fr) | 2018-05-15 | 2021-03-24 | Bayer Ag | Benzamides à substitution 1,3-thiazol-2-yl pour le traitement de maladies associées à la sensibilisation de fibres nerveuses |
| US11508483B2 (en) | 2018-05-30 | 2022-11-22 | 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 |
| WO2020148379A1 (en) | 2019-01-17 | 2020-07-23 | Bayer Aktiengesellschaft | Methods to determine whether a subject is suitable of being treated with an agonist of soluble guanylyl cyclase (sgc) |
| CN119300815A (zh) | 2022-06-09 | 2025-01-10 | 拜耳公司 | 用于治疗女性射血分数保留型心力衰竭的可溶性鸟苷酸环化酶激活剂 |
Family Cites Families (8)
| 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 |
| JP5411703B2 (ja) * | 2006-11-09 | 2014-02-12 | アルコン リサーチ， リミテッド | 薬物送達のための水不溶性ポリマーマトリクス |
| PE20091258A1 (es) * | 2007-12-03 | 2009-09-12 | Smithkline Beecham Corp | Derivados de piridina como activadores de la guanilato ciclasa soluble |
| WO2010015653A1 (en) * | 2008-08-07 | 2010-02-11 | Smithkline Beecham Corporation | Pyrimidine derivatives as activators of soluble guanylate cyclase |
| CA2753434C (en) | 2009-02-26 | 2014-07-15 | Merck Sharp & Dohme Corp. | Soluble guanylate cyclase activators |
| 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 |
| EA033697B1 (ru) * | 2014-09-19 | 2019-11-18 | Glaxosmithkline Ip Dev Ltd | Активаторы растворимой гуанилатциклазы и их применение |
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2015
- 2015-09-18 EA EA201790655A patent/EA033697B1/ru not_active IP Right Cessation
- 2015-09-18 KR KR1020177010181A patent/KR20170054508A/ko not_active Ceased
- 2015-09-18 CN CN201580050717.XA patent/CN106687456B/zh active Active
- 2015-09-18 BR BR112017005660A patent/BR112017005660A2/pt not_active Application Discontinuation
- 2015-09-18 AU AU2015319724A patent/AU2015319724B2/en active Active
- 2015-09-18 JP JP2017515074A patent/JP6678656B2/ja active Active
- 2015-09-18 CR CR20170102A patent/CR20170102A/es unknown
- 2015-09-18 MA MA040583A patent/MA40583A/fr unknown
- 2015-09-18 MX MX2017003621A patent/MX2017003621A/es unknown
- 2015-09-18 US US15/509,895 patent/US9938260B2/en active Active
- 2015-09-18 SG SG11201701915TA patent/SG11201701915TA/en unknown
- 2015-09-18 CA CA2961745A patent/CA2961745A1/en not_active Abandoned
- 2015-09-18 WO PCT/IB2015/057219 patent/WO2016042536A1/en not_active Ceased
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- 2015-09-18 EP EP15772026.9A patent/EP3194384A1/en not_active Withdrawn
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2017
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- 2017-03-14 PH PH12017500481A patent/PH12017500481A1/en unknown
- 2017-03-14 ZA ZA2017/01835A patent/ZA201701835B/en unknown
- 2017-03-16 CO CONC2017/0002506A patent/CO2017002506A2/es unknown
- 2017-03-16 CL CL2017000640A patent/CL2017000640A1/es unknown
- 2017-03-16 DO DO2017000073A patent/DOP2017000073A/es unknown
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2018
- 2018-03-05 US US15/911,797 patent/US10472350B2/en active Active
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2020
- 2020-03-02 JP JP2020035272A patent/JP6908747B2/ja active Active
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2021
- 2021-06-30 JP JP2021109106A patent/JP2021155450A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020105189A (ja) | 2020-07-09 |
| CN106687456B (zh) | 2019-12-03 |
| AU2015319724B2 (en) | 2018-05-10 |
| US20170305888A1 (en) | 2017-10-26 |
| MA40583A (fr) | 2016-03-24 |
| ZA201701835B (en) | 2018-12-19 |
| DOP2017000073A (es) | 2017-04-16 |
| JP6678656B2 (ja) | 2020-04-08 |
| EA033697B1 (ru) | 2019-11-18 |
| MX2017003621A (es) | 2017-07-14 |
| JP2017527602A (ja) | 2017-09-21 |
| WO2016042536A1 (en) | 2016-03-24 |
| US9938260B2 (en) | 2018-04-10 |
| PE20170937A1 (es) | 2017-07-13 |
| CA2961745A1 (en) | 2016-03-24 |
| CL2017000640A1 (es) | 2017-10-06 |
| BR112017005660A2 (pt) | 2017-12-19 |
| JP6908747B2 (ja) | 2021-07-28 |
| SG11201701915TA (en) | 2017-04-27 |
| IL251094A0 (en) | 2017-04-30 |
| US10472350B2 (en) | 2019-11-12 |
| CO2017002506A2 (es) | 2017-07-28 |
| EP3194384A1 (en) | 2017-07-26 |
| CR20170102A (es) | 2017-07-17 |
| US20180194756A1 (en) | 2018-07-12 |
| JP2021155450A (ja) | 2021-10-07 |
| EA201790655A1 (ru) | 2017-08-31 |
| AU2015319724A1 (en) | 2017-04-06 |
| CN106687456A (zh) | 2017-05-17 |
| PH12017500481A1 (en) | 2017-08-07 |
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