BG103540A - Производни на 6-фенилпиридил-2-амин полезни като nоs инхибитори - Google Patents
Производни на 6-фенилпиридил-2-амин полезни като nоs инхибитори Download PDFInfo
- Publication number
- BG103540A BG103540A BG103540A BG10354099A BG103540A BG 103540 A BG103540 A BG 103540A BG 103540 A BG103540 A BG 103540A BG 10354099 A BG10354099 A BG 10354099A BG 103540 A BG103540 A BG 103540A
- Authority
- BG
- Bulgaria
- Prior art keywords
- phenyl
- alkyl
- disease
- ylamine
- pyridin
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 230000002969 morbid Effects 0.000 claims abstract 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 claims description 193
- 150000001875 compounds Chemical class 0.000 claims description 155
- -1 hydroxy, methyl Chemical group 0.000 claims description 106
- 238000005160 1H NMR spectroscopy Methods 0.000 claims description 65
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 claims description 62
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 62
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 33
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 241000124008 Mammalia Species 0.000 claims description 27
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 27
- 208000002193 Pain Diseases 0.000 claims description 25
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 22
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
- 230000001154 acute effect Effects 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 19
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 19
- 238000000354 decomposition reaction Methods 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 17
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 17
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 15
- 230000002401 inhibitory effect Effects 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 206010040070 Septic Shock Diseases 0.000 claims description 13
- 201000011510 cancer Diseases 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 208000027866 inflammatory disease Diseases 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 239000000126 substance Substances 0.000 claims description 13
- 208000024827 Alzheimer disease Diseases 0.000 claims description 12
- 208000019901 Anxiety disease Diseases 0.000 claims description 12
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 12
- 208000000094 Chronic Pain Diseases 0.000 claims description 12
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 12
- 206010012289 Dementia Diseases 0.000 claims description 12
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 12
- 206010019196 Head injury Diseases 0.000 claims description 12
- 206010021138 Hypovolaemic shock Diseases 0.000 claims description 12
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 12
- 208000019695 Migraine disease Diseases 0.000 claims description 12
- 206010063837 Reperfusion injury Diseases 0.000 claims description 12
- 206010044541 Traumatic shock Diseases 0.000 claims description 12
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 12
- 206010047700 Vomiting Diseases 0.000 claims description 12
- 208000005298 acute pain Diseases 0.000 claims description 12
- 230000036506 anxiety Effects 0.000 claims description 12
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 12
- 206010015037 epilepsy Diseases 0.000 claims description 12
- 208000002780 macular degeneration Diseases 0.000 claims description 12
- 206010027599 migraine Diseases 0.000 claims description 12
- 201000006417 multiple sclerosis Diseases 0.000 claims description 12
- 230000004770 neurodegeneration Effects 0.000 claims description 12
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 12
- 201000008482 osteoarthritis Diseases 0.000 claims description 12
- 230000016087 ovulation Effects 0.000 claims description 12
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
- 230000036303 septic shock Effects 0.000 claims description 12
- 230000008673 vomiting Effects 0.000 claims description 12
- 208000010412 Glaucoma Diseases 0.000 claims description 11
- 208000006011 Stroke Diseases 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
- 206010040560 shock Diseases 0.000 claims description 11
- 208000018737 Parkinson disease Diseases 0.000 claims description 10
- 208000028017 Psychotic disease Diseases 0.000 claims description 10
- 238000007792 addition Methods 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 208000011231 Crohn disease Diseases 0.000 claims description 9
- 206010012335 Dependence Diseases 0.000 claims description 9
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 9
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 9
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000001624 naphthyl group Chemical group 0.000 claims description 9
- 208000020431 spinal cord injury Diseases 0.000 claims description 9
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims description 8
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 8
- 125000006413 ring segment Chemical group 0.000 claims description 8
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 8
- 125000001246 bromo group Chemical group Br* 0.000 claims description 7
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 7
- 125000002346 iodo group Chemical group I* 0.000 claims description 7
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 6
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 230000007135 neurotoxicity Effects 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 229960005181 morphine Drugs 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- MNUHYQZBNHDABI-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-6-amine Chemical compound C1NCC2C(N)C21 MNUHYQZBNHDABI-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- ULNUZJQBLXAHCQ-UHFFFAOYSA-N 8-[4-(6-aminopyridin-2-yl)phenyl]-3-(2-methylpropyl)-3-azabicyclo[3.2.1]octan-8-ol Chemical compound C1N(CC(C)C)CC2CCC1C2(O)C(C=C1)=CC=C1C1=CC=CC(N)=N1 ULNUZJQBLXAHCQ-UHFFFAOYSA-N 0.000 claims description 3
- 230000010339 dilation Effects 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- JEIONJSEBLCOJW-UHFFFAOYSA-N 6-[4-[1-(1,3-benzodioxol-5-ylmethyl)piperidin-4-yl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C2CCN(CC=3C=C4OCOC4=CC=3)CC2)=N1 JEIONJSEBLCOJW-UHFFFAOYSA-N 0.000 claims description 2
- IREJNWMYFOEDGE-UHFFFAOYSA-N 8-[4-(6-aminopyridin-2-yl)phenyl]-3-(furan-2-ylmethyl)-3-azabicyclo[3.2.1]octan-8-ol Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C2(O)C3CCC2CN(CC=2OC=CC=2)C3)=N1 IREJNWMYFOEDGE-UHFFFAOYSA-N 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 210000002569 neuron Anatomy 0.000 claims 6
- 208000024891 symptom Diseases 0.000 claims 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 5
- 201000001881 impotence Diseases 0.000 claims 4
- 238000006467 substitution reaction Methods 0.000 claims 4
- 230000009692 acute damage Effects 0.000 claims 3
- 125000000623 heterocyclic group Chemical group 0.000 claims 3
- 210000000278 spinal cord Anatomy 0.000 claims 3
- 101100027896 Arabidopsis thaliana OCP3 gene Proteins 0.000 claims 2
- 239000005898 Fenoxycarb Substances 0.000 claims 2
- 125000003277 amino group Chemical group 0.000 claims 2
- 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 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000001786 isothiazolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- XPZYBFOYRKOKPL-UHFFFAOYSA-N 3-azabicyclo[3.2.1]octan-8-ol Chemical compound C1NCC2CCC1C2O XPZYBFOYRKOKPL-UHFFFAOYSA-N 0.000 claims 1
- MXNCJGDSGDBEBK-UHFFFAOYSA-N 8-[4-(6-aminopyridin-2-yl)phenyl]-3-benzyl-3-azabicyclo[3.2.1]octan-8-ol Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C2(O)C3CCC2CN(CC=2C=CC=CC=2)C3)=N1 MXNCJGDSGDBEBK-UHFFFAOYSA-N 0.000 claims 1
- 208000023105 Huntington disease Diseases 0.000 claims 1
- 239000000654 additive Substances 0.000 claims 1
- 125000002877 alkyl aryl group Chemical group 0.000 claims 1
- HJUFTIJOISQSKQ-UHFFFAOYSA-N fenoxycarb Chemical compound C1=CC(OCCNC(=O)OCC)=CC=C1OC1=CC=CC=C1 HJUFTIJOISQSKQ-UHFFFAOYSA-N 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- UHFXNKIOKXNMMJ-UHFFFAOYSA-N n-[2-[2-[2-(6-aminopyridin-2-yl)phenyl]ethyl]-4-phenylcyclohexyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound NC1=CC=CC(C=2C(=CC=CC=2)CCC2C(CCC(C2)C=2C=CC=CC=2)NC2C3CNCC32)=N1 UHFXNKIOKXNMMJ-UHFFFAOYSA-N 0.000 claims 1
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 13
- 230000000694 effects Effects 0.000 abstract description 4
- 210000003169 central nervous system Anatomy 0.000 abstract description 2
- 230000006806 disease prevention Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 138
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 99
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 32
- 238000005481 NMR spectroscopy Methods 0.000 description 31
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- 239000002904 solvent Substances 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 238000010992 reflux Methods 0.000 description 30
- 229910052938 sodium sulfate Inorganic materials 0.000 description 30
- 235000011152 sodium sulphate Nutrition 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- 239000000203 mixture Substances 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 20
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- 239000011780 sodium chloride Substances 0.000 description 18
- 230000001476 alcoholic effect Effects 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- HTNVCPGFIZOGBR-UHFFFAOYSA-N 6-(4-piperidin-4-ylphenyl)pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C2CCNCC2)=N1 HTNVCPGFIZOGBR-UHFFFAOYSA-N 0.000 description 12
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 239000002253 acid Substances 0.000 description 10
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 10
- 238000006268 reductive amination reaction Methods 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 7
- 150000008282 halocarbons Chemical class 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- JXZYURNNBYDHOH-UHFFFAOYSA-N 2-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=CC=CC=2)=C1C JXZYURNNBYDHOH-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 125000001979 organolithium group Chemical group 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 238000006722 reduction reaction Methods 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N aminomethyl benzene Natural products NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 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 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 208000006673 asthma Diseases 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 206010013663 drug dependence Diseases 0.000 description 4
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 4
- 150000005826 halohydrocarbons Chemical class 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 208000011117 substance-related disease Diseases 0.000 description 4
- ZJPLEMDVDHDYOC-UHFFFAOYSA-N 2-[4-(1-benzyl-3,6-dihydro-2h-pyridin-5-yl)phenyl]-6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C=2CN(CC=3C=CC=CC=3)CCC=2)=C1C ZJPLEMDVDHDYOC-UHFFFAOYSA-N 0.000 description 3
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 3
- 208000007848 Alcoholism Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 206010057852 Nicotine dependence Diseases 0.000 description 3
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 3
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 3
- 208000025569 Tobacco Use disease Diseases 0.000 description 3
- 201000007930 alcohol dependence Diseases 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
- 229910052796 boron Inorganic materials 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 229910000510 noble metal Inorganic materials 0.000 description 3
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 2
- SWJPEBQEEAHIGZ-UHFFFAOYSA-N 1,4-dibromobenzene Chemical compound BrC1=CC=C(Br)C=C1 SWJPEBQEEAHIGZ-UHFFFAOYSA-N 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- LGQLFONOXOBPSW-UHFFFAOYSA-N 1-benzyl-2-[(4-bromophenyl)methyl]piperidine Chemical compound C1=CC(Br)=CC=C1CC1N(CC=2C=CC=CC=2)CCCC1 LGQLFONOXOBPSW-UHFFFAOYSA-N 0.000 description 2
- RPHPENJEEZCVAX-UHFFFAOYSA-N 2-(2,5-dimethyl-1h-pyrrol-3-yl)-6-(4-pyrrolidin-3-ylphenyl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C2CNCC2)=C1C RPHPENJEEZCVAX-UHFFFAOYSA-N 0.000 description 2
- JEDJZELSBSBBKI-UHFFFAOYSA-N 2-[(4-bromophenyl)methyl]piperidine Chemical compound C1=CC(Br)=CC=C1CC1NCCCC1 JEDJZELSBSBBKI-UHFFFAOYSA-N 0.000 description 2
- RLPGVOCDKUAXGM-UHFFFAOYSA-N 2-[4-[4-[6-(2,5-dimethyl-1H-pyrrol-3-yl)pyridin-2-yl]phenyl]phenyl]acetic acid Chemical compound CC=1NC(=CC1C1=NC(=CC=C1)C1=CC=C(C=C1)C1=CC=C(C=C1)CC(=O)O)C RLPGVOCDKUAXGM-UHFFFAOYSA-N 0.000 description 2
- GSMINZBNCZOLRK-UHFFFAOYSA-N 2-[6-[4-(3-methylphenyl)phenyl]pyridin-2-yl]isoindole-1,3-dione Chemical compound C1(C=2C(C(N1C1=NC(=CC=C1)C1=CC=C(C=C1)C=1C=C(C=CC=1)C)=O)=CC=CC=2)=O GSMINZBNCZOLRK-UHFFFAOYSA-N 0.000 description 2
- UIDJTQBFRQFCLI-UHFFFAOYSA-N 2-[[3-[6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridin-2-yl]phenyl]methyl]-n,n-dimethylcyclopentan-1-amine Chemical compound CN(C)C1CCCC1CC1=CC=CC(C=2N=C(C=CC=2)C2=C(NC(C)=C2)C)=C1 UIDJTQBFRQFCLI-UHFFFAOYSA-N 0.000 description 2
- SQWPRPIVUJCCHY-UHFFFAOYSA-N 2-bromo-6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=C(Br)C=CC=2)=C1C SQWPRPIVUJCCHY-UHFFFAOYSA-N 0.000 description 2
- WGTASENVNYJZBK-UHFFFAOYSA-N 3,4,5-trimethoxyamphetamine Chemical compound COC1=CC(CC(C)N)=CC(OC)=C1OC WGTASENVNYJZBK-UHFFFAOYSA-N 0.000 description 2
- IUIVIJDGFFYNKM-UHFFFAOYSA-N 3-[[3-[4-(6-aminopyridin-2-yl)phenyl]phenyl]methyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound C1C2C(N)C2CN1CC(C=1)=CC=CC=1C(C=C1)=CC=C1C1=CC=CC(N)=N1 IUIVIJDGFFYNKM-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- VCXPJIZDOYOACQ-UHFFFAOYSA-N 6-[3-[[2-(cyclohexylamino)cyclopentyl]methyl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=C(CC3C(CCC3)NC3CCCCC3)C=CC=2)=N1 VCXPJIZDOYOACQ-UHFFFAOYSA-N 0.000 description 2
- PHRZVIRPGDHKFL-UHFFFAOYSA-N 6-[3-[[2-(dimethylamino)cyclopentyl]methyl]phenyl]pyridin-2-amine Chemical compound CN(C)C1CCCC1CC1=CC=CC(C=2N=C(N)C=CC=2)=C1 PHRZVIRPGDHKFL-UHFFFAOYSA-N 0.000 description 2
- YJXDQBHVYMESQE-UHFFFAOYSA-N 6-[4-(1-benzyl-3,6-dihydro-2h-pyridin-5-yl)phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C=2CN(CC=3C=CC=CC=3)CCC=2)=N1 YJXDQBHVYMESQE-UHFFFAOYSA-N 0.000 description 2
- LLNJGUIIIBGBBQ-UHFFFAOYSA-N 6-[4-[(1-benzylpiperidin-2-yl)methyl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=CC(CC3N(CCCC3)CC=3C=CC=CC=3)=CC=2)=N1 LLNJGUIIIBGBBQ-UHFFFAOYSA-N 0.000 description 2
- MQKLGJVSLSPNNG-UHFFFAOYSA-N CC=1NC(=CC=1C1=NC(=CC=C1)C1=CC=C(C=C1)C1=CC=C(C=C1)C=O)C Chemical compound CC=1NC(=CC=1C1=NC(=CC=C1)C1=CC=C(C=C1)C1=CC=C(C=C1)C=O)C MQKLGJVSLSPNNG-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 208000001953 Hypotension Diseases 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 102000000589 Interleukin-1 Human genes 0.000 description 2
- 108010002352 Interleukin-1 Proteins 0.000 description 2
- 102000000588 Interleukin-2 Human genes 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- AMIMRNSIRUDHCM-UHFFFAOYSA-N Isopropylaldehyde Chemical compound CC(C)C=O AMIMRNSIRUDHCM-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- 238000006264 debenzylation reaction Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000036543 hypotension Effects 0.000 description 2
- 235000015110 jellies Nutrition 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N trihydridoboron Substances B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- ZYJPUMXJBDHSIF-NSHDSACASA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-phenylpropanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZYJPUMXJBDHSIF-NSHDSACASA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical compound CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LKUAPSRIYZLAAO-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine Chemical compound C1CNCCN1CCC1=CC=CC=C1 LKUAPSRIYZLAAO-UHFFFAOYSA-N 0.000 description 1
- UGYPXRGQGNLWOF-UHFFFAOYSA-N 1-(ethyliminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CCN=C=NC(CC)N(C)C UGYPXRGQGNLWOF-UHFFFAOYSA-N 0.000 description 1
- PXNAZQBPHRKZRL-UHFFFAOYSA-N 1-benzyl-4-(4-bromophenyl)piperidine Chemical compound C1=CC(Br)=CC=C1C1CCN(CC=2C=CC=CC=2)CC1 PXNAZQBPHRKZRL-UHFFFAOYSA-N 0.000 description 1
- NZVZVGPYTICZBZ-UHFFFAOYSA-N 1-benzylpiperidine Chemical compound C=1C=CC=CC=1CN1CCCCC1 NZVZVGPYTICZBZ-UHFFFAOYSA-N 0.000 description 1
- RSQUAQMIGSMNNE-UHFFFAOYSA-N 1-methyl-3h-indol-2-one Chemical compound C1=CC=C2N(C)C(=O)CC2=C1 RSQUAQMIGSMNNE-UHFFFAOYSA-N 0.000 description 1
- ZGABDPXDUGYGQE-UHFFFAOYSA-N 1-piperidin-1-ylpiperazine Chemical compound C1CCCCN1N1CCNCC1 ZGABDPXDUGYGQE-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- 125000000579 2,2-diphenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(C1=C([H])C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 description 1
- GWKPNEHDORAPJO-UHFFFAOYSA-N 2,5-diphenylhexanoic acid Chemical compound CC(CCC(C(O)=O)C1=CC=CC=C1)C1=CC=CC=C1 GWKPNEHDORAPJO-UHFFFAOYSA-N 0.000 description 1
- XGYOXWAFKQTSBK-UHFFFAOYSA-N 2-(2,5-dimethyl-1h-pyrrol-3-yl)-6-(4-piperidin-4-ylphenyl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C2CCNCC2)=C1C XGYOXWAFKQTSBK-UHFFFAOYSA-N 0.000 description 1
- IUYYGYBICBWHJY-UHFFFAOYSA-N 2-(2,5-dimethyl-1h-pyrrol-3-yl)-6-(4-pyridin-3-ylphenyl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C=2C=NC=CC=2)=C1C IUYYGYBICBWHJY-UHFFFAOYSA-N 0.000 description 1
- UDAARDAYKJUWAB-UHFFFAOYSA-N 2-(4-bromophenyl)-6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(Br)=CC=2)=C1C UDAARDAYKJUWAB-UHFFFAOYSA-N 0.000 description 1
- CEFVCNWQCJCMHZ-UHFFFAOYSA-N 2-(bromomethyl)furan Chemical compound BrCC1=CC=CO1 CEFVCNWQCJCMHZ-UHFFFAOYSA-N 0.000 description 1
- UALSQHSJANZRMN-UHFFFAOYSA-N 2-[4-(1-benzylpiperidin-3-yl)phenyl]-6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C2CN(CC=3C=CC=CC=3)CCC2)=C1C UALSQHSJANZRMN-UHFFFAOYSA-N 0.000 description 1
- FZTRNYCKHVVQMQ-UHFFFAOYSA-N 2-[4-(1-benzylpiperidin-4-yl)phenyl]-6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C2CCN(CC=3C=CC=CC=3)CC2)=C1C FZTRNYCKHVVQMQ-UHFFFAOYSA-N 0.000 description 1
- WSJVVCADMUDJSB-UHFFFAOYSA-N 2-[4-[(1-benzylpiperidin-2-yl)methyl]phenyl]-6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridine Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(CC3N(CCCC3)CC=3C=CC=CC=3)=CC=2)=C1C WSJVVCADMUDJSB-UHFFFAOYSA-N 0.000 description 1
- VDMGUVIZYWIANQ-UHFFFAOYSA-N 2-[[4-[6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridin-2-yl]phenyl]methyl]cyclopentan-1-one Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(CC3C(CCC3)=O)=CC=2)=C1C VDMGUVIZYWIANQ-UHFFFAOYSA-N 0.000 description 1
- PITSHUDTDNGKST-UHFFFAOYSA-N 2-amino-n-[3-[4-(6-aminopyridin-2-yl)phenyl]phenyl]-3-phenylpropanamide Chemical compound C=1C=CC(C=2C=CC(=CC=2)C=2N=C(N)C=CC=2)=CC=1NC(=O)C(N)CC1=CC=CC=C1 PITSHUDTDNGKST-UHFFFAOYSA-N 0.000 description 1
- SSOQAOUJVQDHOJ-UHFFFAOYSA-N 2-amino-n-[3-[4-(6-aminopyridin-2-yl)phenyl]phenyl]propanamide Chemical compound CC(N)C(=O)NC1=CC=CC(C=2C=CC(=CC=2)C=2N=C(N)C=CC=2)=C1 SSOQAOUJVQDHOJ-UHFFFAOYSA-N 0.000 description 1
- IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
- BPGIOCZAQDIBPI-UHFFFAOYSA-N 2-ethoxyethanamine Chemical compound CCOCCN BPGIOCZAQDIBPI-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- ZSYRDSTUBZGDKI-UHFFFAOYSA-N 3-(4-bromophenyl)pentanedioic acid Chemical compound OC(=O)CC(CC(O)=O)C1=CC=C(Br)C=C1 ZSYRDSTUBZGDKI-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- MWNICFXVCUVIBR-UHFFFAOYSA-N 3-[(6-aminopyridin-2-yl)-phenylmethyl]-1-[2-(dimethylamino)ethyl]-3h-indol-2-one Chemical compound C12=CC=CC=C2N(CCN(C)C)C(=O)C1C(C=1N=C(N)C=CC=1)C1=CC=CC=C1 MWNICFXVCUVIBR-UHFFFAOYSA-N 0.000 description 1
- BKSYILVEQJLAPP-UHFFFAOYSA-N 3-[4-[6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridin-2-yl]phenyl]aniline Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C=2C=C(N)C=CC=2)=C1C BKSYILVEQJLAPP-UHFFFAOYSA-N 0.000 description 1
- INNOXVKXTIMEAN-UHFFFAOYSA-N 3-[[4-[4-(6-aminopyridin-2-yl)phenyl]phenyl]methyl]-3-azabicyclo[3.1.0]hexan-6-amine Chemical compound C1C2C(N)C2CN1CC(C=C1)=CC=C1C(C=C1)=CC=C1C1=CC=CC(N)=N1 INNOXVKXTIMEAN-UHFFFAOYSA-N 0.000 description 1
- LFBVRERINNDIEJ-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-1-amine Chemical compound C1NCC2(N)C1C2 LFBVRERINNDIEJ-UHFFFAOYSA-N 0.000 description 1
- LWVFWYPZPKVCPQ-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-6-amine;tert-butylcarbamic acid Chemical compound C1NCC2C(N)C21.CC(C)(C)NC(O)=O LWVFWYPZPKVCPQ-UHFFFAOYSA-N 0.000 description 1
- DCDAOVIVXGHHHU-UHFFFAOYSA-N 3-benzyl-3-azabicyclo[3.2.1]octan-8-one Chemical compound O=C1C(C2)CCC1CN2CC1=CC=CC=C1 DCDAOVIVXGHHHU-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- ZNRGSYUVFVNSAW-UHFFFAOYSA-N 3-nitrophenylboronic acid Chemical compound OB(O)C1=CC=CC([N+]([O-])=O)=C1 ZNRGSYUVFVNSAW-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- UVZKTNHKBFICNI-UHFFFAOYSA-N 4-(4-bromophenyl)oxane-2,6-dione Chemical compound C1=CC(Br)=CC=C1C1CC(=O)OC(=O)C1 UVZKTNHKBFICNI-UHFFFAOYSA-N 0.000 description 1
- AKPSLMUFDIXDJJ-UHFFFAOYSA-N 4-(bromomethyl)-1,2-dimethoxybenzene Chemical compound COC1=CC=C(CBr)C=C1OC AKPSLMUFDIXDJJ-UHFFFAOYSA-N 0.000 description 1
- GOLLXDIOAVCCAO-UHFFFAOYSA-N 4-cyclohex-3-en-1-ylmorpholine Chemical compound C1COCCN1C1CC=CCC1 GOLLXDIOAVCCAO-UHFFFAOYSA-N 0.000 description 1
- KRSWPODJYNXIJP-UHFFFAOYSA-N 5,6-dimethoxy-1,2,3,4-tetrahydroisoquinoline Chemical compound C1NCCC2=C(OC)C(OC)=CC=C21 KRSWPODJYNXIJP-UHFFFAOYSA-N 0.000 description 1
- DKBISLDZVNXIFT-UHFFFAOYSA-N 5-(bromomethyl)-1,2-oxazole Chemical compound BrCC1=CC=NO1 DKBISLDZVNXIFT-UHFFFAOYSA-N 0.000 description 1
- UNYHRXLMTSXVIB-UHFFFAOYSA-N 5-(bromomethyl)-1,3-benzodioxole Chemical compound BrCC1=CC=C2OCOC2=C1 UNYHRXLMTSXVIB-UHFFFAOYSA-N 0.000 description 1
- XNONRNKAYRHZDJ-UHFFFAOYSA-N 5-bromo-1,2-thiazole Chemical compound BrC1=CC=NS1 XNONRNKAYRHZDJ-UHFFFAOYSA-N 0.000 description 1
- DWUPYMSVAPQXMS-UHFFFAOYSA-N 5-bromo-1,3-thiazole Chemical compound BrC1=CN=CS1 DWUPYMSVAPQXMS-UHFFFAOYSA-N 0.000 description 1
- ZRAOQEFNQJBCGD-UHFFFAOYSA-N 6-(2-piperidin-4-ylphenyl)pyridin-2-amine Chemical compound N1CCC(CC1)C1=C(C=CC=C1)C1=CC=CC(=N1)N ZRAOQEFNQJBCGD-UHFFFAOYSA-N 0.000 description 1
- KMMNYCOYYZWPDM-UHFFFAOYSA-N 6-[3-[[2-(2-phenylethylamino)cyclopentyl]methyl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=C(CC3C(CCC3)NCCC=3C=CC=CC=3)C=CC=2)=N1 KMMNYCOYYZWPDM-UHFFFAOYSA-N 0.000 description 1
- BTPGCGVNFGPTNZ-UHFFFAOYSA-N 6-[3-[[2-(4-methylpiperazin-1-yl)cyclohexyl]methyl]phenyl]pyridin-2-amine Chemical compound C1CN(C)CCN1C1C(CC=2C=C(C=CC=2)C=2N=C(N)C=CC=2)CCCC1 BTPGCGVNFGPTNZ-UHFFFAOYSA-N 0.000 description 1
- JOWSHJWAELAJNM-UHFFFAOYSA-N 6-[3-[[2-(4-methylpiperazin-1-yl)cyclopentyl]methyl]phenyl]pyridin-2-amine Chemical compound C1CN(C)CCN1C1C(CC=2C=C(C=CC=2)C=2N=C(N)C=CC=2)CCC1 JOWSHJWAELAJNM-UHFFFAOYSA-N 0.000 description 1
- SEHVUADTDSPSSK-UHFFFAOYSA-N 6-[3-[[2-(benzylamino)cyclohexyl]methyl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=C(CC3C(CCCC3)NCC=3C=CC=CC=3)C=CC=2)=N1 SEHVUADTDSPSSK-UHFFFAOYSA-N 0.000 description 1
- FHZKYMVMMVGGLZ-UHFFFAOYSA-N 6-[4-(1-benzyl-3,6-dihydro-2h-pyridin-5-yl)phenyl]pyridin-2-amine;dihydrochloride Chemical compound Cl.Cl.NC1=CC=CC(C=2C=CC(=CC=2)C=2CN(CC=3C=CC=CC=3)CCC=2)=N1 FHZKYMVMMVGGLZ-UHFFFAOYSA-N 0.000 description 1
- FCABMRYQTZQJTO-UHFFFAOYSA-N 6-[4-[4-[(5,6-dimethoxy-3,4-dihydro-1h-isoquinolin-2-yl)methyl]phenyl]phenyl]pyridin-2-amine Chemical compound C1CC2=C(OC)C(OC)=CC=C2CN1CC(C=C1)=CC=C1C(C=C1)=CC=C1C1=CC=CC(N)=N1 FCABMRYQTZQJTO-UHFFFAOYSA-N 0.000 description 1
- RLSCAFUCZAEEFS-UHFFFAOYSA-N 6-[4-[4-[[4-(2-phenylethyl)piperazin-1-yl]methyl]phenyl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C=2C=CC(CN3CCN(CCC=4C=CC=CC=4)CC3)=CC=2)=N1 RLSCAFUCZAEEFS-UHFFFAOYSA-N 0.000 description 1
- QRGHRDCIGYJTSW-UHFFFAOYSA-N 6-[4-[[2-(2-ethoxyethylamino)cyclohexyl]methyl]phenyl]pyridin-2-amine Chemical compound CCOCCNC1CCCCC1CC1=CC=C(C=2N=C(N)C=CC=2)C=C1 QRGHRDCIGYJTSW-UHFFFAOYSA-N 0.000 description 1
- FKWYUVJVLJKLQO-UHFFFAOYSA-N 6-[4-[[2-(4-benzylpiperazin-1-yl)cyclohexyl]methyl]phenyl]pyridin-2-amine Chemical compound NC1=CC=CC(C=2C=CC(CC3C(CCCC3)N3CCN(CC=4C=CC=CC=4)CC3)=CC=2)=N1 FKWYUVJVLJKLQO-UHFFFAOYSA-N 0.000 description 1
- QRXCJCWYQDRFNB-UHFFFAOYSA-N 8-[4-(6-aminopyridin-2-yl)phenyl]-3-azabicyclo[3.2.1]octan-8-ol Chemical compound NC1=CC=CC(C=2C=CC(=CC=2)C2(O)C3CCC2CNC3)=N1 QRXCJCWYQDRFNB-UHFFFAOYSA-N 0.000 description 1
- XFHJVCXODKPBNW-UHFFFAOYSA-N 8-[4-[6-(2,5-dimethyl-1h-pyrrol-3-yl)pyridin-2-yl]phenyl]-3-azabicyclo[3.2.1]octan-8-ol Chemical compound N1C(C)=CC(C=2N=C(C=CC=2)C=2C=CC(=CC=2)C2(O)C3CCC2CNC3)=C1C XFHJVCXODKPBNW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 101100500467 Arabidopsis thaliana EAAC gene Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- WHPLCRGHKLYJJQ-UHFFFAOYSA-N CC=1NC(=CC=1C1=NC(=CC=C1)C1=CC=C(C=C1)C1=CC(=CC=C1)[N+](=O)[O-])C Chemical compound CC=1NC(=CC=1C1=NC(=CC=C1)C1=CC=C(C=C1)C1=CC(=CC=C1)[N+](=O)[O-])C WHPLCRGHKLYJJQ-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 206010008120 Cerebral ischaemia Diseases 0.000 description 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 238000005361 D2 NMR spectroscopy Methods 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 235000011941 Tilia x europaea Nutrition 0.000 description 1
- 206010044248 Toxic shock syndrome Diseases 0.000 description 1
- 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 150000001242 acetic acid derivatives Polymers 0.000 description 1
- 125000000218 acetic acid group Polymers C(C)(=O)* 0.000 description 1
- 150000001243 acetic acids Polymers 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- WMJYTLWNWAEDJD-UHFFFAOYSA-N bis(1-cyanocyclohexyl)azaniumylideneazanide Chemical compound C1CCCCC1(C#N)[N+](=[N-])C1(C#N)CCCCC1 WMJYTLWNWAEDJD-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 229960002173 citrulline Drugs 0.000 description 1
- 235000013477 citrulline Nutrition 0.000 description 1
- 229910052681 coesite Inorganic materials 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229910052906 cristobalite Inorganic materials 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- VRHAQNTWKSVEEC-UHFFFAOYSA-N ethyl 1,3-dioxoisoindole-2-carboxylate Chemical compound C1=CC=C2C(=O)N(C(=O)OCC)C(=O)C2=C1 VRHAQNTWKSVEEC-UHFFFAOYSA-N 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- PGLTVOMIXTUURA-UHFFFAOYSA-N iodoacetamide Chemical compound NC(=O)CI PGLTVOMIXTUURA-UHFFFAOYSA-N 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000004571 lime Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 210000001259 mesencephalon Anatomy 0.000 description 1
- AGJSNMGHAVDLRQ-HUUJSLGLSA-N methyl (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-HUUJSLGLSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- RISWCGKBVILZDK-UHFFFAOYSA-N n-[4-[4-(6-aminopyridin-2-yl)phenyl]piperidin-1-yl]acetamide Chemical compound C1CN(NC(=O)C)CCC1C1=CC=C(C=2N=C(N)C=CC=2)C=C1 RISWCGKBVILZDK-UHFFFAOYSA-N 0.000 description 1
- 239000000236 nitric oxide synthase inhibitor Substances 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- FVFPRIPVSPDCJE-UHFFFAOYSA-N phenyl 3-cyanopropanoate Chemical compound N#CCCC(=O)OC1=CC=CC=C1 FVFPRIPVSPDCJE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- CVEDVJRENZAPPJ-UHFFFAOYSA-N potassium;ethanol;2-methylpropan-2-olate Chemical compound [K+].CCO.CC(C)(C)[O-] CVEDVJRENZAPPJ-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- CSYSULGPHGCBQD-UHFFFAOYSA-N s-ethylisothiouronium diethylphosphate Chemical compound CCSC(N)=N.CCOP(O)(=O)OCC CSYSULGPHGCBQD-UHFFFAOYSA-N 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000000779 smoke Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229910052682 stishovite Inorganic materials 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- 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
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
-
- 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
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/10—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 two hetero rings linked by a carbon chain containing aromatic rings
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Urology & Nephrology (AREA)
- Obesity (AREA)
- Addiction (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3279396P | 1996-12-06 | 1996-12-06 | |
| PCT/IB1997/001446 WO1998024766A1 (en) | 1996-12-06 | 1997-11-17 | 6-phenylpyridyl-2-amine derivatives useful as nos inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BG103540A true BG103540A (bg) | 2000-12-29 |
Family
ID=21866837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BG103540A BG103540A (bg) | 1996-12-06 | 1999-06-30 | Производни на 6-фенилпиридил-2-амин полезни като nоs инхибитори |
Country Status (42)
| Country | Link |
|---|---|
| US (3) | US6235750B1 (cs) |
| EP (1) | EP0946512B1 (cs) |
| JP (2) | JP3604399B2 (cs) |
| KR (1) | KR100360633B1 (cs) |
| CN (1) | CN1117077C (cs) |
| AP (1) | AP848A (cs) |
| AR (1) | AR010331A1 (cs) |
| AT (1) | ATE251612T1 (cs) |
| AU (2) | AU4791797A (cs) |
| BG (1) | BG103540A (cs) |
| BR (1) | BR9714381A (cs) |
| CA (1) | CA2273479C (cs) |
| CZ (1) | CZ293863B6 (cs) |
| DE (1) | DE69725465T2 (cs) |
| DK (1) | DK0946512T3 (cs) |
| DZ (1) | DZ2361A1 (cs) |
| EA (1) | EA002907B1 (cs) |
| ES (1) | ES2206691T3 (cs) |
| HN (2) | HN1997000027A (cs) |
| HR (1) | HRP970664A2 (cs) |
| HU (1) | HUP0001848A3 (cs) |
| ID (1) | ID19056A (cs) |
| IL (1) | IL130111A0 (cs) |
| IS (1) | IS5053A (cs) |
| MA (1) | MA26453A1 (cs) |
| NO (1) | NO313517B1 (cs) |
| NZ (1) | NZ335733A (cs) |
| OA (1) | OA11123A (cs) |
| PA (1) | PA8442201A1 (cs) |
| PE (1) | PE46499A1 (cs) |
| PL (1) | PL333918A1 (cs) |
| PT (1) | PT946512E (cs) |
| SI (1) | SI0946512T1 (cs) |
| SK (1) | SK70899A3 (cs) |
| TN (1) | TNSN97198A1 (cs) |
| TR (1) | TR199901259T2 (cs) |
| TW (1) | TW491840B (cs) |
| UA (1) | UA59379C2 (cs) |
| UY (1) | UY24799A1 (cs) |
| WO (1) | WO1998024766A1 (cs) |
| YU (1) | YU25399A (cs) |
| ZA (1) | ZA9710906B (cs) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3455229B2 (ja) * | 1996-03-29 | 2003-10-14 | ファイザー インク． | ６―フェニルピリジル―２―アミン誘導体 |
| US20010049379A1 (en) | 1997-08-27 | 2001-12-06 | Lowe John Adams | 2-aminopyridines containing fused ring substituents |
| HN1998000118A (es) | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
| HN1998000125A (es) * | 1997-08-28 | 1999-02-09 | Pfizer Prod Inc | 2-aminopiridinas con sustituyentes alcoxi ramificados |
| NZ508057A (en) | 1998-06-03 | 2003-07-25 | Pfizer Prod Inc | 2-aminopyridines containing fused ring substituents as nitric oxide synthase inhibitors |
| FR2791674A1 (fr) * | 1999-04-02 | 2000-10-06 | Sod Conseils Rech Applic | Nouveaux derives de 2-aminopyridines, leur utilisation en tant que medicaments et compositions pharmaceutiques les contenant |
| FR2780971B1 (fr) * | 1998-07-08 | 2001-09-28 | Sod Conseils Rech Applic | Nouveaux derives de 2-aminopyridines, leur application en tant que medicaments et compositions pharmaceutiques les contenant |
| AR019190A1 (es) * | 1998-07-08 | 2001-12-26 | Sod Conseils Rech Applic | Derivados de 2-aminopiridinas, productos intermedios para su preparacion, medicamentos y composiciones farmaceuticas que los contienen y su uso para preparar medicamentos |
| AP2001002067A0 (en) * | 1998-08-11 | 2001-03-31 | Pfizer Prod Inc | New pharmaceutical uses for nos inhibitors. |
| SE9803710L (sv) | 1998-09-25 | 2000-03-26 | A & Science Invest Ab | Användning av vissa substanser för behandling av nervrotsskador |
| US7115557B2 (en) | 1998-09-25 | 2006-10-03 | Sciaticon Ab | Use of certain drugs for treating nerve root injury |
| ES2200813T3 (es) | 1999-02-25 | 2004-03-16 | Pfizer Products Inc. | 2-aminopiridinas que contienen sustituyentes de anillo condesado. |
| HK1046645A1 (zh) * | 1999-07-23 | 2003-01-24 | 盐野义制药株式会社 | Th2分化抑制剂 |
| FR2804429B1 (fr) * | 2000-01-31 | 2003-05-09 | Adir | Nouveaux derives de 4-sulfonamides piperidine, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| WO2002080853A2 (en) * | 2001-04-09 | 2002-10-17 | Bristol-Myers Squibb Company | Fused heterocyclic inhibitors of factor xa |
| US20030045449A1 (en) * | 2001-08-15 | 2003-03-06 | Pfizer, Inc. | Pharmaceutical combinations for the treatment of neurodegenerative diseases |
| CA2522323C (en) * | 2003-04-14 | 2009-09-15 | Pfizer Products Inc. | 3-azabicyclo[3.2.1]octane derivatives as opioid receptor ligands |
| CN1295216C (zh) * | 2003-07-04 | 2007-01-17 | 中国人民解放军军事医学科学院毒物药物研究所 | 吲哚酮类衍生物及其用于制备抗肿瘤药物的用途 |
| US20080070952A1 (en) * | 2005-02-21 | 2008-03-20 | Proximagen Ltd., | Inhibition or Treatment of Dyskinesia |
| WO2006105795A1 (en) * | 2005-04-08 | 2006-10-12 | Leo Pharma A/S | Novel indolinone derivatives |
| WO2008021849A2 (en) * | 2006-08-09 | 2008-02-21 | Smithkline Beecham Corporation | Novel compounds as antagonists or inverse agonists at opioid receptors |
| US8835437B2 (en) | 2007-06-08 | 2014-09-16 | Janssen Pharmaceutica N.V. | Piperidine/piperazine derivatives |
| JO2972B1 (en) | 2007-06-08 | 2016-03-15 | جانسين فارماسوتيكا ان. في | Piperidine / piperazine derivatives |
| EP2152270B1 (en) | 2007-06-08 | 2015-03-04 | Janssen Pharmaceutica, N.V. | Piperidine/piperazine derivatives |
| EP2152269B1 (en) | 2007-06-08 | 2014-04-23 | Janssen Pharmaceutica, N.V. | Piperidine/piperazine derivatives |
| CA2725933C (en) | 2008-06-05 | 2018-01-16 | Janssen Pharmaceutica Nv | Drug combinations comprising a dgat inhibitor and a ppar-agonist |
| UA105182C2 (ru) | 2008-07-03 | 2014-04-25 | Ньюрексон, Інк. | Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность |
| US8889674B2 (en) * | 2009-03-05 | 2014-11-18 | Shionogi & Co., Ltd. | Piperidine and pyrrolidine derivatives having NPY Y5 receptor antagonism |
| US11013844B2 (en) * | 2014-11-20 | 2021-05-25 | City Of Hope | Treatment device for plasma virus inactivation |
| TWI874960B (zh) | 2016-08-12 | 2025-03-01 | 美商亞瑟尼克斯公司 | 聯芳組成物和調控激酶級聯之方法 |
| PT3684767T (pt) | 2017-09-22 | 2024-07-29 | Jubilant Epipad LLC | Compostos heterocíclicos como inibidores de pad |
| ES2941512T3 (es) | 2017-10-18 | 2023-05-23 | Jubilant Epipad LLC | Compuestos de imidazo-piridina como inhibidores de PAD |
| SG11202004143XA (en) | 2017-11-06 | 2020-06-29 | Jubilant Prodel LLC | Pyrimidine derivatives as inhibitors of pd1/pd-l1 activation |
| KR102780935B1 (ko) | 2017-11-24 | 2025-03-12 | 주빌런트 에피스크라이브 엘엘씨 | Prmt5 억제제로서의 헤테로사이클릭 화합물 |
| JP7279063B6 (ja) | 2018-03-13 | 2024-02-15 | ジュビラント プローデル エルエルシー | Ｐｄ１／ｐｄ－ｌ１相互作用／活性化の阻害剤としての二環式化合物 |
| CN114206843A (zh) * | 2019-06-14 | 2022-03-18 | Srx心脏有限责任公司 | 用于调节前蛋白转化酶枯草杆菌蛋白酶/Kexin 9型(PCSK9)的化合物 |
| US12115154B2 (en) * | 2020-12-16 | 2024-10-15 | Srx Cardio, Llc | Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992014780A1 (en) | 1991-02-19 | 1992-09-03 | Akzo N.V. | Stabilized carbon monoxide-olefin copolymers |
| EP0674627A1 (en) * | 1992-12-18 | 1995-10-04 | The Wellcome Foundation Limited | Pyrimidine, pyridine, pteridinone and indazole derivatives as enzyme inhibitors |
| US5621004A (en) | 1994-06-03 | 1997-04-15 | Robert W. Dunn | Method for treating emesis |
| AU4515696A (en) * | 1994-12-12 | 1996-07-03 | Merck & Co., Inc. | Substituted 2-aminopyridines as inhibitors of nitric oxide synthase |
| JP3455229B2 (ja) * | 1996-03-29 | 2003-10-14 | ファイザー インク． | ６―フェニルピリジル―２―アミン誘導体 |
| US6093743A (en) | 1998-06-23 | 2000-07-25 | Medinox Inc. | Therapeutic methods employing disulfide derivatives of dithiocarbamates and compositions useful therefor |
-
1997
- 1997-02-18 HN HN1997000027A patent/HN1997000027A/es unknown
- 1997-11-17 PT PT97910587T patent/PT946512E/pt unknown
- 1997-11-17 DE DE69725465T patent/DE69725465T2/de not_active Expired - Fee Related
- 1997-11-17 AU AU47917/97A patent/AU4791797A/en not_active Abandoned
- 1997-11-17 PL PL97333918A patent/PL333918A1/xx unknown
- 1997-11-17 KR KR1019997004981A patent/KR100360633B1/ko not_active Expired - Fee Related
- 1997-11-17 CA CA002273479A patent/CA2273479C/en not_active Expired - Fee Related
- 1997-11-17 WO PCT/IB1997/001446 patent/WO1998024766A1/en active IP Right Grant
- 1997-11-17 SK SK708-99A patent/SK70899A3/sk unknown
- 1997-11-17 YU YU25399A patent/YU25399A/sh unknown
- 1997-11-17 JP JP52539798A patent/JP3604399B2/ja not_active Expired - Fee Related
- 1997-11-17 UA UA99063103A patent/UA59379C2/uk unknown
- 1997-11-17 EP EP97910587A patent/EP0946512B1/en not_active Expired - Lifetime
- 1997-11-17 AT AT97910587T patent/ATE251612T1/de not_active IP Right Cessation
- 1997-11-17 SI SI9730597T patent/SI0946512T1/xx unknown
- 1997-11-17 IL IL13011197A patent/IL130111A0/xx unknown
- 1997-11-17 CN CN97180350A patent/CN1117077C/zh not_active Expired - Fee Related
- 1997-11-17 ES ES97910587T patent/ES2206691T3/es not_active Expired - Lifetime
- 1997-11-17 TR TR1999/01259T patent/TR199901259T2/xx unknown
- 1997-11-17 BR BR9714381-2A patent/BR9714381A/pt not_active Application Discontinuation
- 1997-11-17 NZ NZ335733A patent/NZ335733A/xx unknown
- 1997-11-17 DK DK97910587T patent/DK0946512T3/da active
- 1997-11-17 HU HU0001848A patent/HUP0001848A3/hu unknown
- 1997-11-17 CZ CZ19992017A patent/CZ293863B6/cs not_active IP Right Cessation
- 1997-11-17 EA EA199900448A patent/EA002907B1/ru not_active IP Right Cessation
- 1997-11-18 HN HN1997000149A patent/HN1997000149A/es unknown
- 1997-11-22 TW TW086117501A patent/TW491840B/zh active
- 1997-12-01 PE PE1997001080A patent/PE46499A1/es not_active Application Discontinuation
- 1997-12-03 MA MA24884A patent/MA26453A1/fr unknown
- 1997-12-03 TN TNTNSN97198A patent/TNSN97198A1/fr unknown
- 1997-12-03 UY UY24799A patent/UY24799A1/es unknown
- 1997-12-03 DZ DZ970211A patent/DZ2361A1/xx active
- 1997-12-04 AR ARP970105713A patent/AR010331A1/es not_active Application Discontinuation
- 1997-12-04 AP APAP/P/1997/001156A patent/AP848A/en active
- 1997-12-04 ZA ZA9710906A patent/ZA9710906B/xx unknown
- 1997-12-04 HR HR60/032,793A patent/HRP970664A2/hr not_active Application Discontinuation
- 1997-12-04 PA PA19978442201A patent/PA8442201A1/es unknown
- 1997-12-05 ID IDP973838A patent/ID19056A/id unknown
-
1999
- 1999-05-18 IS IS5053A patent/IS5053A/is unknown
- 1999-06-01 OA OA9900115A patent/OA11123A/en unknown
- 1999-06-03 US US09/325,480 patent/US6235750B1/en not_active Expired - Fee Related
- 1999-06-04 NO NO19992725A patent/NO313517B1/no unknown
- 1999-06-30 BG BG103540A patent/BG103540A/bg unknown
-
2001
- 2001-03-08 US US09/802,086 patent/US20020032191A1/en not_active Abandoned
- 2001-09-13 AU AU72050/01A patent/AU766080B2/en not_active Ceased
- 2001-09-27 US US09/965,564 patent/US20020103227A1/en not_active Abandoned
-
2004
- 2004-06-24 JP JP2004186311A patent/JP2005170924A/ja active Pending
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BG103540A (bg) | Производни на 6-фенилпиридил-2-амин полезни като nоs инхибитори | |
| TWI344955B (en) | Heterocyclic rinf having nitrogen atom derivatives and medicament containing the derivatives as active ingredient | |
| JP4853965B2 (ja) | アダマンタン誘導体およびアザビシクロオクタン誘導体およびアザビシクロノナン誘導体、ならびにこれらの調製方法およびｄｐｐ−ｉｖ阻害剤としてのこれらの使用 | |
| JP3411271B2 (ja) | Ｎｏｓ阻害剤であり縮合環置換基を含む２−アミノピリジン類 | |
| EA002270B1 (ru) | Производные 6-фенилпиридил-2-амина | |
| JP2020507582A (ja) | キナーゼ阻害剤としてのアミノトリアゾロピリジン | |
| JP2004510819A (ja) | Ｈｉｖインテグラーゼ阻害薬として有用なアザ−およびポリアザ−ナフタレニルカルボキサミド類 | |
| CA2369103A1 (en) | Nitrogen-containing heterocyclic compounds and benamide compounds and drugs containing the same | |
| TW200524901A (en) | 6-membered heteroaryl compounds for the treatment of neurodegenerative disorders | |
| AU2015290007B2 (en) | Fused quinoline compunds as pi3k, mTor inhibitors | |
| AU2005300736B2 (en) | Anthranilamide pyridinureas as VEGF receptor kinase inhibitors | |
| JP2022551794A (ja) | 酵素阻害剤 | |
| SK12022001A3 (sk) | 2-aminopyridíny obsahujúce ako substituenty kondenzované kruhové skupiny | |
| AU765851B2 (en) | 2-aminopyridines containing fused ring substituents as nitric oxide synthase inhibitors | |
| US20010049379A1 (en) | 2-aminopyridines containing fused ring substituents | |
| US20040142924A1 (en) | 6-Phenylpyridyl-2-amine derivatives useful as NOS inhibitors |