CA3082337A1 - Dopamine-b-hydroxylase inhibitors - Google Patents
Dopamine-b-hydroxylase inhibitors Download PDFInfo
- Publication number
- CA3082337A1 CA3082337A1 CA3082337A CA3082337A CA3082337A1 CA 3082337 A1 CA3082337 A1 CA 3082337A1 CA 3082337 A CA3082337 A CA 3082337A CA 3082337 A CA3082337 A CA 3082337A CA 3082337 A1 CA3082337 A1 CA 3082337A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- pyrrolo
- thioxo
- hydrogen
- tetrahydro
- 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
- 239000003112 inhibitor Substances 0.000 title abstract description 16
- 108700006189 dopamine beta hydroxylase deficiency Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 351
- 150000003839 salts Chemical class 0.000 claims abstract description 37
- 239000012453 solvate Substances 0.000 claims abstract description 34
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 108010015720 Dopamine beta-Hydroxylase Proteins 0.000 claims abstract description 5
- 102100033156 Dopamine beta-hydroxylase Human genes 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 1283
- -1 hydroxy, methylsulfonyl Chemical group 0.000 claims description 518
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 173
- 239000001257 hydrogen Substances 0.000 claims description 164
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 114
- 125000001424 substituent group Chemical group 0.000 claims description 69
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 51
- 125000001153 fluoro group Chemical group F* 0.000 claims description 51
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 36
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 35
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 31
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- 125000004043 oxo group Chemical group O=* 0.000 claims description 26
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 23
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 21
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 19
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 16
- 125000002757 morpholinyl group Chemical group 0.000 claims description 16
- 125000003386 piperidinyl group Chemical group 0.000 claims description 16
- 125000003368 amide group Chemical group 0.000 claims description 15
- 210000003169 central nervous system Anatomy 0.000 claims description 15
- 230000005764 inhibitory process Effects 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 14
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 14
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 14
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 14
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 12
- 230000001668 ameliorated effect Effects 0.000 claims description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims description 7
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000004299 tetrazol-5-yl group Chemical group [H]N1N=NC(*)=N1 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000004500 isothiazol-4-yl group Chemical group S1N=CC(=C1)* 0.000 claims description 5
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 claims description 5
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 claims description 5
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 5
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- GSJJVNAPLSISFR-CQSZACIVSA-N (6S)-1-benzyl-6-(3,5-difluorophenyl)-2,5,6,7-tetrahydropyrrolo[1,2-c]imidazole-3-thione Chemical compound C(C1=CC=CC=C1)C1=C2N(C(N1)=S)C[C@@H](C2)C1=CC(=CC(=C1)F)F GSJJVNAPLSISFR-CQSZACIVSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 512
- 238000005160 1H NMR spectroscopy Methods 0.000 description 298
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 297
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 255
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 238
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 222
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 203
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 190
- 239000000203 mixture Substances 0.000 description 173
- 239000007787 solid Substances 0.000 description 173
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
- 239000000843 powder Substances 0.000 description 150
- 239000000243 solution Substances 0.000 description 139
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 138
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 110
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 82
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 73
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- 235000019341 magnesium sulphate Nutrition 0.000 description 55
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 38
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- 125000000217 alkyl group Chemical group 0.000 description 31
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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 21
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- 125000004429 atom Chemical group 0.000 description 20
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 20
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- 230000017074 necrotic cell death Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- LAIZPRYFQUWUBN-UHFFFAOYSA-L nickel chloride hexahydrate Chemical compound O.O.O.O.O.O.[Cl-].[Cl-].[Ni+2] LAIZPRYFQUWUBN-UHFFFAOYSA-L 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- DGOYLVBDCVINQZ-UHFFFAOYSA-N oxane-4-carboxamide Chemical compound NC(=O)C1CCOCC1 DGOYLVBDCVINQZ-UHFFFAOYSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 208000004594 persistent fetal circulation syndrome Diseases 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- WVUCPRGADMCTBN-UHFFFAOYSA-M potassium;3-ethoxy-3-oxopropanoate Chemical compound [K+].CCOC(=O)CC([O-])=O WVUCPRGADMCTBN-UHFFFAOYSA-M 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000036593 pulmonary vascular resistance Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- XACWJIQLDLUFSR-UHFFFAOYSA-N pyrrolidine-1-carbonyl chloride Chemical compound ClC(=O)N1CCCC1 XACWJIQLDLUFSR-UHFFFAOYSA-N 0.000 description 1
- IQHXABCGSFAKPN-UHFFFAOYSA-N pyrrolidine-3-carboxamide Chemical compound NC(=O)C1CCNC1 IQHXABCGSFAKPN-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000010911 splenectomy Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- GDFJXVDBIUMJHD-DOPOYZHKSA-N tert-butyl (1S,5R)-1-(2,5-difluorophenyl)-4-(3-methoxy-3-oxopropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound FC1=C(C=C(C=C1)F)[C@]12CN(C([C@@H]2C1)C(CC(=O)OC)=O)C(=O)OC(C)(C)C GDFJXVDBIUMJHD-DOPOYZHKSA-N 0.000 description 1
- OVAHXXDRAMFDJX-PQSDXZOWSA-N tert-butyl (1S,5R)-1-(2,5-difluorophenyl)-4-(3-phenylpropanoyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C(C)(OC(=O)N1C([C@@H]2C[C@]2(C2=CC(=CC=C2F)F)C1)C(=O)CCC1=CC=CC=C1)(C)C OVAHXXDRAMFDJX-PQSDXZOWSA-N 0.000 description 1
- BCILFPQBZXSXPQ-LNAYPVCKSA-N tert-butyl (1S,5R)-1-(3,5-difluorophenyl)-4-[3-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxopropanoyl]-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C(C)(C)(C)OC(=O)NC(CC(=O)C1N(C[C@]2(C[C@@H]12)C1=CC(=CC(=C1)F)F)C(=O)OC(C)(C)C)=O BCILFPQBZXSXPQ-LNAYPVCKSA-N 0.000 description 1
- REZIRRNNUSQROU-OEBHRJGQSA-N tert-butyl (1S,5R)-4-[3-[benzyl(methyl)amino]-3-oxopropanoyl]-1-(2,5-difluorophenyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C(C1=CC=CC=C1)N(C(CC(=O)C1N(C[C@]2(C[C@@H]12)C1=C(C=CC(=C1)F)F)C(=O)OC(C)(C)C)=O)C REZIRRNNUSQROU-OEBHRJGQSA-N 0.000 description 1
- HUZXENNYKIFAKL-YMNIQAILSA-N tert-butyl (4R)-2-(2-bromoacetyl)-4-(2,3,5,6-tetrafluorophenyl)pyrrolidine-1-carboxylate Chemical compound BrCC(=O)C1N(C[C@H](C1)C1=C(C(=CC(=C1F)F)F)F)C(=O)OC(C)(C)C HUZXENNYKIFAKL-YMNIQAILSA-N 0.000 description 1
- BHRGSCCXZKNLSD-VCANKDNSSA-N tert-butyl (4S)-2-[cyano(hydroxy)methyl]-4-(3,5-difluorophenyl)pyrrolidine-1-carboxylate Chemical compound C(#N)C(C1N(C[C@@H](C1)C1=CC(=CC(=C1)F)F)C(=O)OC(C)(C)C)O BHRGSCCXZKNLSD-VCANKDNSSA-N 0.000 description 1
- BZUMXXCFQUZQAV-UHFFFAOYSA-N tert-butyl 6-(aminomethyl)-3-azabicyclo[3.1.0]hexane-3-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC2C(CN)C21 BZUMXXCFQUZQAV-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 108700012359 toxins Proteins 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
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
- C07D487/12—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 three hetero rings
- C07D487/14—Ortho-condensed systems
-
- 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
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1720189.8 | 2017-12-04 | ||
| GBGB1720189.8A GB201720189D0 (en) | 2017-12-04 | 2017-12-04 | Dopamine-B-hydroxylase inhibitors |
| GB1804439.6 | 2018-03-20 | ||
| GBGB1804439.6A GB201804439D0 (en) | 2018-03-20 | 2018-03-20 | Dopamin-b-hydroxylase inhibitors |
| PCT/PT2018/050043 WO2019112457A1 (en) | 2017-12-04 | 2018-11-30 | Dopamine-β-hydroxylase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3082337A1 true CA3082337A1 (en) | 2019-06-13 |
Family
ID=65012066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3082337A Pending CA3082337A1 (en) | 2017-12-04 | 2018-11-30 | Dopamine-b-hydroxylase inhibitors |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US11434242B2 (https=) |
| EP (1) | EP3720856A1 (https=) |
| JP (1) | JP7167155B2 (https=) |
| KR (1) | KR20200096584A (https=) |
| CN (1) | CN111479812A (https=) |
| AU (1) | AU2018379646A1 (https=) |
| BR (1) | BR112020010216A2 (https=) |
| CA (1) | CA3082337A1 (https=) |
| CL (1) | CL2020001461A1 (https=) |
| IL (1) | IL274550B2 (https=) |
| MX (1) | MX2020005864A (https=) |
| PH (1) | PH12020500542A1 (https=) |
| RU (1) | RU2020121820A (https=) |
| SG (1) | SG11202004231YA (https=) |
| TW (1) | TW201925193A (https=) |
| WO (1) | WO2019112457A1 (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111479812A (zh) | 2017-12-04 | 2020-07-31 | 巴尔-波特拉及康邦亚股份有限公司 | 多巴胺-b-羟化酶抑制剂 |
| GB201908044D0 (en) | 2019-06-05 | 2019-07-17 | Bial Portela & Ca Sa | Dopamine-B-Hydroxylase inhibitors |
| US20250122171A1 (en) * | 2023-09-20 | 2025-04-17 | Deep Apple Therapeutics, Inc. | Substituted Amine Compounds, Compositions and Methods of Use |
| CN120383599A (zh) * | 2024-01-29 | 2025-07-29 | 上海深势唯思科技有限责任公司 | 芳基杂环类Kv1.3抑制剂及其制备方法和用途 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3647790A (en) | 1969-04-08 | 1972-03-07 | American Home Prod | Ouinoxalinyl-oxazolidines and -oxazines |
| FR2449689A1 (fr) | 1979-02-20 | 1980-09-19 | Logeais Labor Jacques | Nouveaux derives condenses de pyrrolidine ou de piperidine, leur procede de preparation et leurs applications en therapeutique |
| US4628059A (en) | 1985-10-31 | 1986-12-09 | Smithklein Beckman Corporation | Dopamine-β-hydroxylase inhibitors |
| WO1995029165A2 (en) | 1994-04-26 | 1995-11-02 | Syntex (U.S.A.) Inc. | Benzocycloalkylaz0lethione derivatives as dopamin beta-hydroxylase inhibitors |
| US6482982B1 (en) | 2001-03-09 | 2002-11-19 | University Of Sciences Of Philadelphia | Halogenated antituberculosis agents |
| IL143379A (en) * | 2001-05-24 | 2013-11-28 | Yissum Res Dev Co | Oligonucleotide against human ache isoform r and its uses |
| US7125904B2 (en) | 2002-10-11 | 2006-10-24 | Portela & C.A., S.A. | Peripherally-selective inhibitors of dopamine-β-hydroxylase and method of their preparation |
| WO2008085008A1 (en) | 2007-01-11 | 2008-07-17 | Mogam Biotechnology Research Institute | T-cell inhibiting compounds and their use for the treatment of t-cell-mediated diseases |
| GB0708818D0 (en) * | 2007-05-08 | 2007-06-13 | Portela & Ca Sa | Compounds |
| JP2010534676A (ja) | 2007-07-23 | 2010-11-11 | シノシア・セラピューティクス | 心的外傷後ストレス障害の治療 |
| US8110578B2 (en) * | 2008-10-27 | 2012-02-07 | Signal Pharmaceuticals, Llc | Pyrazino[2,3-b]pyrazine mTOR kinase inhibitors for oncology indications and diseases associated with the mTOR/PI3K/Akt pathway |
| WO2014127350A1 (en) | 2013-02-18 | 2014-08-21 | The Scripps Research Institute | Modulators of vasopressin receptors with therapeutic potential |
| JOP20190050A1 (ar) | 2016-09-23 | 2019-03-20 | Bial Portela & C? S A | مثبطات دوبامين-b-هيدروكسيلاز تخترق حاجز المخ الدموي |
| CN111479812A (zh) | 2017-12-04 | 2020-07-31 | 巴尔-波特拉及康邦亚股份有限公司 | 多巴胺-b-羟化酶抑制剂 |
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2018
- 2018-11-30 CN CN201880080871.5A patent/CN111479812A/zh active Pending
- 2018-11-30 SG SG11202004231YA patent/SG11202004231YA/en unknown
- 2018-11-30 CA CA3082337A patent/CA3082337A1/en active Pending
- 2018-11-30 KR KR1020207019157A patent/KR20200096584A/ko not_active Withdrawn
- 2018-11-30 RU RU2020121820A patent/RU2020121820A/ru unknown
- 2018-11-30 BR BR112020010216-4A patent/BR112020010216A2/pt not_active IP Right Cessation
- 2018-11-30 WO PCT/PT2018/050043 patent/WO2019112457A1/en not_active Ceased
- 2018-11-30 EP EP18833340.5A patent/EP3720856A1/en not_active Withdrawn
- 2018-11-30 MX MX2020005864A patent/MX2020005864A/es unknown
- 2018-11-30 TW TW107143059A patent/TW201925193A/zh unknown
- 2018-11-30 JP JP2020530502A patent/JP7167155B2/ja active Active
- 2018-11-30 AU AU2018379646A patent/AU2018379646A1/en not_active Abandoned
- 2018-11-30 US US16/769,045 patent/US11434242B2/en active Active
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2020
- 2020-05-10 IL IL274550A patent/IL274550B2/en unknown
- 2020-06-01 CL CL2020001461A patent/CL2020001461A1/es unknown
- 2020-06-02 PH PH12020500542A patent/PH12020500542A1/en unknown
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2022
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Also Published As
| Publication number | Publication date |
|---|---|
| IL274550B2 (en) | 2023-06-01 |
| US11434242B2 (en) | 2022-09-06 |
| JP7167155B2 (ja) | 2022-11-08 |
| WO2019112457A1 (en) | 2019-06-13 |
| TW201925193A (zh) | 2019-07-01 |
| CN111479812A (zh) | 2020-07-31 |
| IL274550A (en) | 2020-06-30 |
| MX2020005864A (es) | 2020-09-09 |
| PH12020500542A1 (en) | 2021-01-25 |
| US20210171528A1 (en) | 2021-06-10 |
| SG11202004231YA (en) | 2020-06-29 |
| KR20200096584A (ko) | 2020-08-12 |
| BR112020010216A2 (pt) | 2020-09-15 |
| JP2021505568A (ja) | 2021-02-18 |
| CL2020001461A1 (es) | 2020-10-16 |
| AU2018379646A1 (en) | 2020-06-11 |
| US20230138795A1 (en) | 2023-05-04 |
| RU2020121820A (ru) | 2022-01-10 |
| EP3720856A1 (en) | 2020-10-14 |
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