CA2793125A1 - New enzyme inhibitor compounds - Google Patents
New enzyme inhibitor compounds Download PDFInfo
- Publication number
- CA2793125A1 CA2793125A1 CA2793125A CA2793125A CA2793125A1 CA 2793125 A1 CA2793125 A1 CA 2793125A1 CA 2793125 A CA2793125 A CA 2793125A CA 2793125 A CA2793125 A CA 2793125A CA 2793125 A1 CA2793125 A1 CA 2793125A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- compound
- mmol
- amino
- pyridin
- 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.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 276
- 239000002532 enzyme inhibitor Substances 0.000 title description 3
- 229940125532 enzyme inhibitor Drugs 0.000 title description 2
- -1 cyano, amino, hydroxyl Chemical group 0.000 claims description 201
- 238000000034 method Methods 0.000 claims description 87
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 85
- 239000000203 mixture Substances 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 17
- 125000001153 fluoro group Chemical group F* 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 208000027866 inflammatory disease Diseases 0.000 claims description 14
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 13
- 125000003277 amino group Chemical group 0.000 claims description 12
- 230000004054 inflammatory process Effects 0.000 claims description 12
- 206010061218 Inflammation Diseases 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 11
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 9
- 125000003386 piperidinyl group Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 230000004614 tumor growth Effects 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 229910052721 tungsten Inorganic materials 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 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 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 208000026278 immune system disease Diseases 0.000 claims description 5
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 5
- ZNGWEEUXTBNKFR-UHFFFAOYSA-N 1,4-oxazepane Chemical group C1CNCCOC1 ZNGWEEUXTBNKFR-UHFFFAOYSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005977 Ethylene Substances 0.000 claims description 4
- 206010047115 Vasculitis Diseases 0.000 claims description 4
- 201000008937 atopic dermatitis Diseases 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
- 206010003246 arthritis Diseases 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical group O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- BADLPWRPSDMYKM-UHFFFAOYSA-N 2-aminoethyl 4-[1-(4-chlorophenyl)pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate 3-(3,6-dihydro-2H-pyran-4-yl)-2-methyl-1-(4-methylphenyl)pyrrolo[2,3-c]pyridine Chemical compound O1CCC(=CC1)C1=C(N(C2=CN=CC=C21)C2=CC=C(C=C2)C)C.ClC2=CC=C(C=C2)N2C=C(C=1C2=CN=CC1)C1CCN(CC1)C(=O)OCCN BADLPWRPSDMYKM-UHFFFAOYSA-N 0.000 claims description 2
- YZTWDBUQPJNNLG-UHFFFAOYSA-N 4-[1-(4-chlorophenyl)pyrazolo[3,4-c]pyridin-3-yl]morpholine 1-[1-(4-methylphenyl)pyrazolo[3,4-c]pyridin-3-yl]piperidine-4-carboxamide 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CCOCC2.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CCC(CC1)C(=O)N YZTWDBUQPJNNLG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 2
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 2
- POOPWPIOIMBTOH-UHFFFAOYSA-N 8-oxa-3-azabicyclo[3.2.1]octane Chemical compound C1NCC2CCC1O2 POOPWPIOIMBTOH-UHFFFAOYSA-N 0.000 claims description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 2
- 208000022309 Alcoholic Liver disease Diseases 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010003827 Autoimmune hepatitis Diseases 0.000 claims description 2
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 2
- NTLQUFSAVDCBAN-UHFFFAOYSA-N CC1=CC=C(C=C1)N1C=C(C=2C1=CN=CC2)C2CCOCC2.ClC2=CC=C(C=C2)N2C=C(C=1C2=CN=CC1)C1CCOCC1.CC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CCC(CC2)O Chemical compound CC1=CC=C(C=C1)N1C=C(C=2C1=CN=CC2)C2CCOCC2.ClC2=CC=C(C=C2)N2C=C(C=1C2=CN=CC1)C1CCOCC1.CC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CCC(CC2)O NTLQUFSAVDCBAN-UHFFFAOYSA-N 0.000 claims description 2
- MRUMHBYSCPWXAY-UHFFFAOYSA-N CC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CC(NCC2)=O.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CCOCCC1.N1C(COCC1)C(=O)O Chemical compound CC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CC(NCC2)=O.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CCOCCC1.N1C(COCC1)C(=O)O MRUMHBYSCPWXAY-UHFFFAOYSA-N 0.000 claims description 2
- 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 2
- BJWKMIUJDVPMLT-UHFFFAOYSA-N ClC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)C2CCOCC2.ClC2=CC=C(C=C2)C2=NC(=C1N2C=CN=C1)N1CCOCC1.CC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)N2CCOCC2 Chemical compound ClC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)C2CCOCC2.ClC2=CC=C(C=C2)C2=NC(=C1N2C=CN=C1)N1CCOCC1.CC1=CC=C(C=C1)C1=NC(=C2N1C=CN=C2)N2CCOCC2 BJWKMIUJDVPMLT-UHFFFAOYSA-N 0.000 claims description 2
- TXECSGCRZNTCJL-UHFFFAOYSA-N ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CC(CC2)O.ClC2=CC(=C(C=C2)N2N=C(C=1C2=CN=CC1)C1CCOCC1)F Chemical compound ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CC(CC2)O.ClC2=CC(=C(C=C2)N2N=C(C=1C2=CN=CC1)C1CCOCC1)F TXECSGCRZNTCJL-UHFFFAOYSA-N 0.000 claims description 2
- MNBJMFGAJFQOJH-UHFFFAOYSA-N ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CCC(CC2)O.COC2CN(CC2)C2=NN(C1=CN=CC=C12)C1=CC=C(C=C1)C Chemical compound ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2CCC(CC2)O.COC2CN(CC2)C2=NN(C1=CN=CC=C12)C1=CC=C(C=C1)C MNBJMFGAJFQOJH-UHFFFAOYSA-N 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 206010012442 Dermatitis contact Diseases 0.000 claims description 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 2
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 2
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 2
- OUGZXFITWWSNQB-UHFFFAOYSA-N NCCC(=O)N1CCC(CC1)C1=CN(C2=CN=CC=C21)C2=CC=C(C=C2)Cl.NCC(=O)N2CCC(CC2)C2=CN(C1=CN=CC=C12)C1=CC=C(C=C1)Cl Chemical compound NCCC(=O)N1CCC(CC1)C1=CN(C2=CN=CC=C21)C2=CC=C(C=C2)Cl.NCC(=O)N2CCC(CC2)C2=CN(C1=CN=CC=C12)C1=CC=C(C=C1)Cl OUGZXFITWWSNQB-UHFFFAOYSA-N 0.000 claims description 2
- ZCULWKRHIPCQMY-UHFFFAOYSA-N NCCCC(=O)N1CCC(CC1)C1=CN(C2=CN=CC=C21)C2=CC=C(C=C2)Cl.ClC2=CC=C(C=C2)N2C=C(C=1C2=CN=CC1)N1CCOCC1 Chemical compound NCCCC(=O)N1CCC(CC1)C1=CN(C2=CN=CC=C21)C2=CC=C(C=C2)Cl.ClC2=CC=C(C=C2)N2C=C(C=1C2=CN=CC1)N1CCOCC1 ZCULWKRHIPCQMY-UHFFFAOYSA-N 0.000 claims description 2
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 2
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 2
- 206010063837 Reperfusion injury Diseases 0.000 claims description 2
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 2
- 206010039710 Scleroderma Diseases 0.000 claims description 2
- 206010040047 Sepsis Diseases 0.000 claims description 2
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 2
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 2
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 201000004810 Vascular dementia Diseases 0.000 claims description 2
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- 208000006673 asthma Diseases 0.000 claims description 2
- 230000001363 autoimmune Effects 0.000 claims description 2
- 208000018093 autoimmune cholangitis Diseases 0.000 claims description 2
- 230000009787 cardiac fibrosis Effects 0.000 claims description 2
- 208000019069 chronic childhood arthritis Diseases 0.000 claims description 2
- 208000010247 contact dermatitis Diseases 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 230000003176 fibrotic effect Effects 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 2
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 2
- 208000023589 ischemic disease Diseases 0.000 claims description 2
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 2
- 210000004185 liver Anatomy 0.000 claims description 2
- 208000010125 myocardial infarction Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 230000002685 pulmonary effect Effects 0.000 claims description 2
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 2
- 201000004595 synovitis Diseases 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 2
- 108091008638 NR4A Proteins 0.000 claims 9
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 5
- IIHCNUPPRMEMQU-UHFFFAOYSA-N CC1(CN(CCO1)C1=NN(C2=CN=CC=C21)C2=CC=C(C=C2)C)C.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CC2CCC(C1)O2 Chemical compound CC1(CN(CCO1)C1=NN(C2=CN=CC=C21)C2=CC=C(C=C2)C)C.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CC2CCC(C1)O2 IIHCNUPPRMEMQU-UHFFFAOYSA-N 0.000 claims 1
- HWZDZNGXNVSNCO-UHFFFAOYSA-N ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2C(COCC2)C.ClC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CC(OCC1)C Chemical compound ClC1=CC=C(C=C1)N1N=C(C=2C1=CN=CC2)N2C(COCC2)C.ClC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CC(OCC1)C HWZDZNGXNVSNCO-UHFFFAOYSA-N 0.000 claims 1
- SMOBSXJKURQTTC-UHFFFAOYSA-N FC1=C(C=CC(=C1)C)N1N=C(C=2C1=CN=CC2)N2CCOCC2.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CCOCC1 Chemical compound FC1=C(C=CC(=C1)C)N1N=C(C=2C1=CN=CC2)N2CCOCC2.CC2=CC=C(C=C2)N2N=C(C=1C2=CN=CC1)N1CCOCC1 SMOBSXJKURQTTC-UHFFFAOYSA-N 0.000 claims 1
- 108020002144 NR4 subfamily Proteins 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- 102100027159 Membrane primary amine oxidase Human genes 0.000 abstract description 11
- 239000003112 inhibitor Substances 0.000 abstract description 11
- 108010028700 Amine Oxidase (Copper-Containing) Proteins 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- 239000000543 intermediate Substances 0.000 description 123
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- 238000004128 high performance liquid chromatography Methods 0.000 description 70
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 68
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 67
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 42
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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 32
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 18
- 230000000694 effects Effects 0.000 description 18
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- 239000012071 phase Substances 0.000 description 17
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- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 16
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 14
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- 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
- C07D405/02—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 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
- 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
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- C—CHEMISTRY; METALLURGY
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- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
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- 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
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| GB201115853D0 (en) * | 2011-09-14 | 2011-10-26 | Proximagen Ltd | New enzyme inhibitor compounds |
| CN103889983B (zh) * | 2011-09-14 | 2015-12-09 | 普罗克西梅根有限公司 | 酶抑制剂化合物 |
| WO2013052417A1 (en) | 2011-10-03 | 2013-04-11 | The University Of North Carolina At Chapel Hill | Pyrrolopyrimidine compounds for the treatment of cancer |
| PL2844637T3 (pl) | 2012-05-02 | 2018-09-28 | Boehringer Ingelheim International Gmbh | Podstawione 3-haloalliloaminowe inhibitory ssao i ich zastosowania |
| EP2852579A4 (en) | 2012-05-22 | 2015-12-30 | Univ North Carolina | PYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| WO2014026330A1 (en) * | 2012-08-15 | 2014-02-20 | Merck Sharp & Dohme Corp. | 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF |
| EP2909211A4 (en) | 2012-10-17 | 2016-06-22 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
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| AU2014279863A1 (en) | 2013-06-12 | 2016-01-28 | Proximagen Limited | New therapeutic uses of enzyme inhibitors |
| JP2017510663A (ja) | 2014-04-11 | 2017-04-13 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | Ｍｅｒｔｋ特異的ピリミジン化合物 |
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| GB201416446D0 (en) | 2014-09-17 | 2014-10-29 | Proximagen Ltd | New enzyme inhibitor compounds |
| KR102412146B1 (ko) | 2015-02-11 | 2022-06-22 | 주식회사 아이엔테라퓨틱스 | 소디움 채널 차단제 |
| GB201507031D0 (en) * | 2015-04-24 | 2015-06-10 | Proximagen Ltd | New pharmaceutical salt forms |
| HK1256174A1 (zh) | 2015-12-07 | 2019-09-13 | Benevolentai Cambridge Limited | 用於治疗疼痛的 vap-1 抑制剂 |
| US10709708B2 (en) | 2016-03-17 | 2020-07-14 | The University Of North Carolina At Chapel Hill | Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor |
| CN106045876B (zh) * | 2016-06-07 | 2018-02-09 | 四川福思达生物技术开发有限责任公司 | 一种对氯苯肼盐酸盐的合成方法 |
| AU2017326006B2 (en) * | 2016-09-16 | 2021-10-28 | Vitae Pharmaceuticals, LLC. | Inhibitors of the menin-MLL interaction |
| AU2019234574A1 (en) | 2018-03-12 | 2020-09-03 | Abbvie Inc. | Inhibitors of tyrosine kinase 2 mediated signaling |
| IL308862A (en) | 2021-06-01 | 2024-01-01 | Janssen Pharmaceutica Nv | Altered phenyl-1H-pyrrolo[3,2-c]pyridine histories |
| AU2022357057A1 (en) * | 2021-10-01 | 2024-04-11 | Yuhan Corporation | Bicyclic fused ring derivative or salt thereof and pharmaceutical composition comprising same |
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| CA2383332C (en) | 1999-09-14 | 2006-01-10 | Aventis Pharmaceuticals Inc. | Benzisoxazolyl-, pyridoisoxazolyl- and benzthienyl-phenoxy derivatives useful as d4 antagonists |
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| AR037211A1 (es) | 2001-11-07 | 2004-10-27 | Schering Corp | Derivados de heteroarilo como ligandos superiores para el receptor de nociceptina orl-1 |
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| US20050096360A1 (en) | 2003-08-08 | 2005-05-05 | Salter-Cid Luisa M. | Inhibitors of semicarbazide-sensitive amine oxidase (SSAO) and VAP-1 mediated adhesion useful for treatment of diseases |
| SG146683A1 (en) | 2003-09-17 | 2008-10-30 | Janssen Pharmaceutica Nv | Fused heterocyclic compounds as serotonin receptor modulators |
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| TW200538453A (en) | 2004-04-26 | 2005-12-01 | Bristol Myers Squibb Co | Bicyclic heterocycles as kinase inhibitors |
| AU2006239632B2 (en) * | 2005-04-25 | 2012-03-15 | Merck Patent Gmbh | Novel AZA- heterocycles serving as kinase inhibitors |
| SI1906965T1 (sl) * | 2005-06-22 | 2015-09-30 | Chemocentryx, Inc. | Azaindolne spojine in postopki uporabe |
| EP2004166A2 (en) | 2006-03-31 | 2008-12-24 | La Jolla Pharmaceutical Company | Inhibitors of semicarbazide-sensitive amine oxidase (ssao) and vap-1 mediated adhesion useful for treatment and prevention of diseases |
| AU2007234408B2 (en) | 2006-04-04 | 2011-05-19 | Fibrogen, Inc. | Pyrrolo- and thiazolo-pyridine compounds as HIF modulators |
| GB0610242D0 (en) | 2006-05-23 | 2006-07-05 | Novartis Ag | Organic compounds |
| CN101568527A (zh) | 2006-10-31 | 2009-10-28 | 先灵公司 | 作为蛋白激酶抑制剂的2-氨基噻唑-4-羧酰胺 |
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| WO2008088744A1 (en) * | 2007-01-17 | 2008-07-24 | Merck & Co., Inc. | Decahydroquinoline analogs as cb2 receptor modulators |
| JP2010525032A (ja) | 2007-05-02 | 2010-07-22 | ノバルティス アーゲー | ヘテロ環化合物及び殺有害生物剤としてのそれらの使用 |
| GB0725103D0 (en) | 2007-12-21 | 2008-01-30 | Glaxo Group Ltd | Novel compounds |
| ES2430621T3 (es) | 2008-01-31 | 2013-11-21 | Sanofi | Azaindol-3-carboxamidas cíclicas, su preparación y su uso como productos farmacéuticos |
| WO2009108551A2 (en) | 2008-02-25 | 2009-09-03 | H. Lundbeck A/S | Heteroaryl amide analogues |
| US8633318B2 (en) * | 2008-09-16 | 2014-01-21 | Proximagen Ltd | Compounds for treatment or prevention of inflammation, an inflammatory disease, or an immune or an autoimmune disorder |
| JP5539989B2 (ja) | 2008-09-16 | 2014-07-02 | プロキシマジェン エルティーディー | 新規化合物ｉ |
| US20120010188A1 (en) | 2008-12-04 | 2012-01-12 | Promimagen Ltd. | Imidazopyridine Compounds |
| JP2012211085A (ja) * | 2009-08-12 | 2012-11-01 | Kyowa Hakko Kirin Co Ltd | ヘッジホッグシグナル阻害剤 |
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| GB201004311D0 (en) | 2010-04-28 |
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| ZA201206424B (en) | 2013-06-26 |
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| SG183936A1 (en) | 2012-10-30 |
| EA023038B1 (ru) | 2016-04-29 |
| ES2538526T3 (es) | 2015-06-22 |
| US9227967B2 (en) | 2016-01-05 |
| NZ602141A (en) | 2014-09-26 |
| CN103180319A (zh) | 2013-06-26 |
| BR112012023315A2 (pt) | 2016-05-24 |
| EP2547677A2 (en) | 2013-01-23 |
| WO2011113798A3 (en) | 2011-11-17 |
| KR20130057971A (ko) | 2013-06-03 |
| EP2547677B1 (en) | 2015-05-06 |
| JP2015017141A (ja) | 2015-01-29 |
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