PT2334672E - Compostos novos i - Google Patents
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- Publication number
- PT2334672E PT2334672E PT97830855T PT09783085T PT2334672E PT 2334672 E PT2334672 E PT 2334672E PT 97830855 T PT97830855 T PT 97830855T PT 09783085 T PT09783085 T PT 09783085T PT 2334672 E PT2334672 E PT 2334672E
- Authority
- PT
- Portugal
- Prior art keywords
- alkyl
- imidazo
- tetrahydro
- isopropyl
- carboxylate
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title description 7
- URMVFILWXLQJIP-UHFFFAOYSA-N 4,5,6,7-tetrahydro-3h-imidazo[4,5-c]pyridine Chemical class C1NCCC2=C1NC=N2 URMVFILWXLQJIP-UHFFFAOYSA-N 0.000 title 1
- -1 pyridine- tetrahydro-5H-imidazo [4,5-c] pyridine-5-carboxylate Chemical compound 0.000 claims description 81
- 150000001875 compounds Chemical class 0.000 claims description 78
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 36
- 201000010099 disease Diseases 0.000 claims description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 20
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 13
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
- 230000004054 inflammatory process Effects 0.000 claims description 13
- 206010061218 Inflammation Diseases 0.000 claims description 12
- 208000027866 inflammatory disease Diseases 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 206010047115 Vasculitis Diseases 0.000 claims description 4
- 206010003246 arthritis Diseases 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 208000026278 immune system disease Diseases 0.000 claims description 4
- 230000002685 pulmonary effect Effects 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 125000002252 acyl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- BJLVVNQWHJZXSZ-UHFFFAOYSA-N pyrazin-2-ylmethyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCC1=CN=CC=N1 BJLVVNQWHJZXSZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- WEEUMIAFJMZQBT-UHFFFAOYSA-N (2-chloro-2,2-difluoroethyl) 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound CC(C)C1N(C(=O)OCC(F)(F)Cl)CCC2=C1N=CN2 WEEUMIAFJMZQBT-UHFFFAOYSA-N 0.000 claims description 2
- HQYLBAHHQXRLJN-UHFFFAOYSA-N (3-chlorophenyl)methyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCC1=CC=CC(Cl)=C1 HQYLBAHHQXRLJN-UHFFFAOYSA-N 0.000 claims description 2
- SGZASQNKDIGCAN-UHFFFAOYSA-N (5-chloropyridin-2-yl)methyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCC1=CC=C(Cl)C=N1 SGZASQNKDIGCAN-UHFFFAOYSA-N 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- BNWCNSHBXPGXIS-UHFFFAOYSA-N 1,3-thiazol-2-ylmethyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCC1=NC=CS1 BNWCNSHBXPGXIS-UHFFFAOYSA-N 0.000 claims description 2
- XGYVJPDCZHHEDT-UHFFFAOYSA-N 2-(4-chlorophenoxy)ethyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCCOC1=CC=C(Cl)C=C1 XGYVJPDCZHHEDT-UHFFFAOYSA-N 0.000 claims description 2
- 206010001052 Acute respiratory distress syndrome 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
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 201000004624 Dermatitis Diseases 0.000 claims description 2
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 2
- 206010012442 Dermatitis contact 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
- 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
- 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
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000008937 atopic dermatitis Diseases 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
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000003176 fibrotic effect Effects 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 230000028709 inflammatory response Effects 0.000 claims description 2
- 210000000936 intestine Anatomy 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
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 230000007170 pathology Effects 0.000 claims description 2
- BRLXXVFUSZYJNB-UHFFFAOYSA-N pyridin-3-ylmethyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCC1=CC=CN=C1 BRLXXVFUSZYJNB-UHFFFAOYSA-N 0.000 claims description 2
- OMDOZAXSWPRNOK-UHFFFAOYSA-N pyridin-4-ylmethyl 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate Chemical compound C1CC=2NC=NC=2C(C(C)C)N1C(=O)OCC1=CC=NC=C1 OMDOZAXSWPRNOK-UHFFFAOYSA-N 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 2
- 208000011580 syndromic disease Diseases 0.000 claims description 2
- 201000004595 synovitis Diseases 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 5
- 230000001363 autoimmune Effects 0.000 claims 3
- MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
- 208000011623 Obstructive Lung disease Diseases 0.000 claims 1
- 206010040047 Sepsis Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 1
- 125000004093 cyano group Chemical group *C#N 0.000 claims 1
- 230000004761 fibrosis Effects 0.000 claims 1
- 208000023589 ischemic disease Diseases 0.000 claims 1
- 210000004185 liver Anatomy 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 125000006000 trichloroethyl group Chemical group 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 295
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 135
- 239000000243 solution Substances 0.000 description 73
- 239000011541 reaction mixture Substances 0.000 description 70
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 60
- 239000002904 solvent Substances 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 50
- 238000004128 high performance liquid chromatography Methods 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 30
- 238000000034 method Methods 0.000 description 29
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 239000012071 phase Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 19
- 238000004007 reversed phase HPLC Methods 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- 239000000377 silicon dioxide Substances 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 230000000694 effects Effects 0.000 description 15
- NXLNNXIXOYSCMB-UHFFFAOYSA-N (4-nitrophenyl) carbonochloridate Chemical compound [O-][N+](=O)C1=CC=C(OC(Cl)=O)C=C1 NXLNNXIXOYSCMB-UHFFFAOYSA-N 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 14
- 239000003550 marker Substances 0.000 description 14
- 239000000725 suspension Substances 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 12
- 108090000790 Enzymes Proteins 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 11
- 230000002441 reversible effect Effects 0.000 description 11
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 239000002480 mineral oil Substances 0.000 description 8
- 235000010446 mineral oil Nutrition 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- 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 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 235000019253 formic acid Nutrition 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 5
- MJVNWJUAUPLDGK-UHFFFAOYSA-N 4-propan-2-yl-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylic acid Chemical compound CC(C)C1N(C(O)=O)CCC2=C1N=CN2 MJVNWJUAUPLDGK-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- 101710149632 Pectinesterase A Proteins 0.000 description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
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- 230000006870 function Effects 0.000 description 5
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- 125000006239 protecting group Chemical group 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- DMQONDYIUCSREP-JAMMHHFISA-N (6S)-4-propan-2-yl-6,7-dihydro-4H-imidazo[4,5-c]pyridine-3,5,6-tricarboxylic acid Chemical compound CC(C)C1N(C(O)=O)[C@H](C(O)=O)CC2=C1N(C(O)=O)C=N2 DMQONDYIUCSREP-JAMMHHFISA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 4
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- JJNKKECPOPWYNY-UHFFFAOYSA-N (5-chloropyridin-2-yl)methanol Chemical compound OCC1=CC=C(Cl)C=N1 JJNKKECPOPWYNY-UHFFFAOYSA-N 0.000 description 3
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 3
- 101710132836 Membrane primary amine oxidase Proteins 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 150000001299 aldehydes Chemical class 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
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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 3
- 238000010790 dilution Methods 0.000 description 3
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- 238000001914 filtration Methods 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
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- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
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- 238000005259 measurement Methods 0.000 description 3
- PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
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- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
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- 229960001367 tartaric acid Drugs 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- 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
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- QERYCTSHXKAMIS-UHFFFAOYSA-N thiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=CS1 QERYCTSHXKAMIS-UHFFFAOYSA-N 0.000 description 1
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- 238000011269 treatment regimen Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
- JEJAMASKDTUEBZ-UHFFFAOYSA-N tris(1,1,3-tribromo-2,2-dimethylpropyl) phosphate Chemical compound BrCC(C)(C)C(Br)(Br)OP(=O)(OC(Br)(Br)C(C)(C)CBr)OC(Br)(Br)C(C)(C)CBr JEJAMASKDTUEBZ-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Gastroenterology & Hepatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0801979 | 2008-09-16 | ||
| US10673408P | 2008-10-20 | 2008-10-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2334672E true PT2334672E (pt) | 2014-01-02 |
Family
ID=41226693
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT97830855T PT2334672E (pt) | 2008-09-16 | 2009-09-16 | Compostos novos i |
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| Country | Link |
|---|---|
| US (7) | US8263616B2 (OSRAM) |
| EP (1) | EP2334672B1 (OSRAM) |
| JP (1) | JP5539989B2 (OSRAM) |
| CN (1) | CN102232073B (OSRAM) |
| AU (1) | AU2009294660B2 (OSRAM) |
| BR (1) | BRPI0918602B8 (OSRAM) |
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| DK (1) | DK2334672T3 (OSRAM) |
| EA (1) | EA019167B1 (OSRAM) |
| ES (1) | ES2440279T3 (OSRAM) |
| MX (1) | MX2011002581A (OSRAM) |
| NZ (1) | NZ592238A (OSRAM) |
| PL (1) | PL2334672T3 (OSRAM) |
| PT (1) | PT2334672E (OSRAM) |
| WO (1) | WO2010031789A1 (OSRAM) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| PT2334672E (pt) | 2008-09-16 | 2014-01-02 | Proximagen Ltd | Compostos novos i |
| UA112154C2 (uk) | 2009-09-08 | 2016-08-10 | Біоті Терапіс Корп. | Застосування повністю людського анти-vap-1-антитіла для лікування фіброзних станів |
| GB201004311D0 (en) | 2010-03-15 | 2010-04-28 | Proximagen Ltd | New enzyme inhibitor compounds |
| CN102311396B (zh) * | 2010-07-05 | 2015-01-07 | 暨南大学 | 一种吡嗪类衍生物和其制备方法及在制药中的应用 |
| FI20115234A0 (fi) | 2011-03-08 | 2011-03-08 | Biotie Therapies Corp | Uusia pyridatsinoni- ja pyridoniyhdisteitä |
| US9150574B2 (en) | 2011-09-14 | 2015-10-06 | Proximagen Limited | Enzyme inhibitor compounds |
| GB201304526D0 (en) | 2013-03-13 | 2013-04-24 | Proximagen Ltd | New compounds |
| GB201304527D0 (en) | 2013-03-13 | 2013-04-24 | Proximagen Ltd | New compounds |
| US20160113893A1 (en) | 2013-06-12 | 2016-04-28 | Proximagen Limited | New therapeutic uses of enzyme inhibitors |
| WO2015189534A1 (en) | 2014-06-12 | 2015-12-17 | Proximagen Limited | Vap-1 inhibitors for treating muscular dystrophy |
| GB201416444D0 (en) * | 2014-09-17 | 2014-10-29 | Proximagen Ltd | New compounds |
| GB201416446D0 (en) * | 2014-09-17 | 2014-10-29 | Proximagen Ltd | New enzyme inhibitor compounds |
| WO2016139909A1 (ja) | 2015-03-02 | 2016-09-09 | 日本電気株式会社 | 復号装置、受信機器、送信機器、送受信システム、復号方法、および復号用プログラムが記憶された記憶媒体 |
| GB201507048D0 (en) * | 2015-04-24 | 2015-06-10 | Proximagen Ltd | Treatment of pain |
| GB201507036D0 (en) * | 2015-04-24 | 2015-06-10 | Proximagen Ltd | Crystalline enzyme inhibitor compound |
| GB201507031D0 (en) * | 2015-04-24 | 2015-06-10 | Proximagen Ltd | New pharmaceutical salt forms |
| GB201513115D0 (en) * | 2015-07-24 | 2015-09-09 | Proximagen Ltd | New therapeutic compound and use in therapy |
| EP3377493B1 (en) | 2015-11-20 | 2020-04-08 | Forma Therapeutics, Inc. | Purinones as ubiquitin-specific protease 1 inhibitors |
| CA3007768A1 (en) * | 2015-12-07 | 2017-06-15 | Benevolentai Cambridge Limited | Vap-1 inhibitors for treating pain |
| GB201618029D0 (en) | 2016-10-25 | 2016-12-07 | Proximagen Ltd | New process |
| US20220073525A1 (en) * | 2018-12-28 | 2022-03-10 | Forma Therapeutics, Inc. | Compositions for inhibiting ubiquitin specific protease 1 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4141899A (en) * | 1976-01-07 | 1979-02-27 | Societa' Farmaceutici Italia S.P.A. | 4,5,6,7-Tetrahydroimidazo-[4,5-c]-pyridine derivatives |
| JPS5285191A (en) * | 1976-01-07 | 1977-07-15 | Farmaceutici Italia | Novel 4*5*6*77tetrahydroimidazoo *4*55c*pyridine derivative process for preparing same and medicine having antiiulcer antiisecretion and antiicolline activities containing same |
| IT1098015B (it) * | 1978-08-07 | 1985-08-31 | Farmaceutici Italia | Nuovi 4,5,6,7,-tetraidroimidazo-aperta par.quadrata 4,5-c chiusa par.quadrata-piridin-derivati |
| US6908926B1 (en) | 1999-04-16 | 2005-06-21 | Novo Nordisk A/S | Substituted imidazoles, their preparation and use |
| SE0004101D0 (sv) * | 2000-11-09 | 2000-11-09 | Pharmacia Ab | New use |
| AU2002214505A1 (en) | 2000-11-09 | 2002-05-21 | Biovitrum Ab | New use of 4, 5, 6, 7-tetrahydroimidazo-(4,5-c)pyridine derivatives |
| US6576249B1 (en) * | 2000-11-13 | 2003-06-10 | El Gendler | Bone putty and method |
| PT2334672E (pt) | 2008-09-16 | 2014-01-02 | Proximagen Ltd | Compostos novos i |
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2009
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- 2009-09-16 AU AU2009294660A patent/AU2009294660B2/en not_active Ceased
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- 2009-09-16 PL PL09783085T patent/PL2334672T3/pl unknown
- 2009-09-16 EP EP09783085.5A patent/EP2334672B1/en not_active Not-in-force
- 2009-09-16 CN CN200980136970.1A patent/CN102232073B/zh not_active Expired - Fee Related
- 2009-09-16 WO PCT/EP2009/062011 patent/WO2010031789A1/en not_active Ceased
- 2009-09-16 US US13/062,318 patent/US8263616B2/en not_active Expired - Fee Related
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2012
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2013
- 2013-10-25 US US14/062,969 patent/US9035066B2/en active Active
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2015
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2016
- 2016-10-27 US US15/335,751 patent/US9890160B2/en not_active Expired - Fee Related
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2017
- 2017-12-29 US US15/858,407 patent/US10399973B2/en active Active
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2019
- 2019-07-17 US US16/514,413 patent/US11040969B2/en not_active Expired - Fee Related
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