HRP970664A2 - 6-phenylpyridyl-2-amine derivatives - Google Patents
6-phenylpyridyl-2-amine derivativesInfo
- Publication number
- HRP970664A2 HRP970664A2 HR60/032,793A HRP970664A HRP970664A2 HR P970664 A2 HRP970664 A2 HR P970664A2 HR P970664 A HRP970664 A HR P970664A HR P970664 A2 HRP970664 A2 HR P970664A2
- Authority
- HR
- Croatia
- Prior art keywords
- nmr
- cdcl
- disease
- phenyl
- mmol
- Prior art date
Links
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 113
- 150000001875 compounds Chemical class 0.000 claims description 92
- -1 hydroxy, methyl Chemical group 0.000 claims description 46
- 208000002193 Pain Diseases 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 21
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 241000124008 Mammalia Species 0.000 claims description 19
- 238000000034 method Methods 0.000 claims description 18
- 230000001154 acute effect Effects 0.000 claims description 16
- 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 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 230000005764 inhibitory process Effects 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 11
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 10
- 206010040070 Septic Shock Diseases 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 230000036303 septic shock Effects 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 230000006378 damage Effects 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 208000030507 AIDS Diseases 0.000 claims description 8
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 208000019901 Anxiety disease Diseases 0.000 claims description 8
- 208000000094 Chronic Pain Diseases 0.000 claims description 8
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 8
- 206010056370 Congestive cardiomyopathy Diseases 0.000 claims description 8
- 208000011231 Crohn disease Diseases 0.000 claims description 8
- 206010012335 Dependence Diseases 0.000 claims description 8
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 8
- 201000010046 Dilated cardiomyopathy Diseases 0.000 claims description 8
- 208000010412 Glaucoma Diseases 0.000 claims description 8
- 206010019196 Head injury Diseases 0.000 claims description 8
- 208000023105 Huntington disease Diseases 0.000 claims description 8
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 8
- 208000018737 Parkinson disease Diseases 0.000 claims description 8
- 208000028017 Psychotic disease Diseases 0.000 claims description 8
- 208000006011 Stroke Diseases 0.000 claims description 8
- 206010044541 Traumatic shock Diseases 0.000 claims description 8
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
- 206010047700 Vomiting Diseases 0.000 claims description 8
- 208000027418 Wounds and injury Diseases 0.000 claims description 8
- 208000005298 acute pain Diseases 0.000 claims description 8
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 8
- 230000036506 anxiety Effects 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 206010013663 drug dependence Diseases 0.000 claims description 8
- 206010015037 epilepsy Diseases 0.000 claims description 8
- 208000014674 injury Diseases 0.000 claims description 8
- 208000002780 macular degeneration Diseases 0.000 claims description 8
- 206010027599 migraine Diseases 0.000 claims description 8
- 229960005181 morphine Drugs 0.000 claims description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims description 8
- 230000004770 neurodegeneration Effects 0.000 claims description 8
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
- 230000007135 neurotoxicity Effects 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 201000008482 osteoarthritis Diseases 0.000 claims description 8
- 230000016087 ovulation Effects 0.000 claims description 8
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 8
- 230000010410 reperfusion Effects 0.000 claims description 8
- 230000000241 respiratory effect Effects 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 208000020431 spinal cord injury Diseases 0.000 claims description 8
- 208000011580 syndromic disease Diseases 0.000 claims description 8
- MNUHYQZBNHDABI-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-6-amine Chemical group C1NCC2C(N)C21 MNUHYQZBNHDABI-UHFFFAOYSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 208000007848 Alcoholism Diseases 0.000 claims description 6
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 208000011117 substance-related disease Diseases 0.000 claims description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 5
- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000002346 iodo group Chemical group I* 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 2
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 2
- 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 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 208000024891 symptom Diseases 0.000 claims 4
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 125000003386 piperidinyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 153
- 238000005160 1H NMR spectroscopy Methods 0.000 description 85
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 76
- 238000006243 chemical reaction Methods 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- 235000019439 ethyl acetate Nutrition 0.000 description 52
- 239000000243 solution Substances 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 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 33
- 239000003921 oil Substances 0.000 description 33
- 235000019198 oils Nutrition 0.000 description 33
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 229910052938 sodium sulfate Inorganic materials 0.000 description 32
- 235000011152 sodium sulphate Nutrition 0.000 description 32
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 30
- 239000012044 organic layer Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000012267 brine Substances 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
- 239000000203 mixture Substances 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 20
- 229910002027 silica gel Inorganic materials 0.000 description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
- 230000001476 alcoholic effect Effects 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 15
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 14
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 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 13
- 239000003153 chemical reaction reagent Substances 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-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
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 150000008282 halocarbons Chemical class 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 238000006268 reductive amination reaction Methods 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000012265 solid product Substances 0.000 description 8
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 7
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 239000010410 layer Substances 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
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 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
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 125000001979 organolithium group Chemical group 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 239000004215 Carbon black (E152) Substances 0.000 description 4
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 4
- 208000007271 Substance Withdrawal Syndrome Diseases 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
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-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
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 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 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 description 4
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 4
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 3
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 239000003112 inhibitor Substances 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
- 238000002360 preparation method Methods 0.000 description 3
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
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Classifications
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- 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
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- 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
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- 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
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- 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
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Landscapes
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- Addiction (AREA)
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- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3279396P | 1996-12-06 | 1996-12-06 |
Publications (1)
Publication Number | Publication Date |
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HRP970664A2 true HRP970664A2 (en) | 1998-10-31 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR60/032,793A HRP970664A2 (en) | 1996-12-06 | 1997-12-04 | 6-phenylpyridyl-2-amine derivatives |
Country Status (42)
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US (3) | US6235750B1 (fr) |
EP (1) | EP0946512B1 (fr) |
JP (2) | JP3604399B2 (fr) |
KR (1) | KR100360633B1 (fr) |
CN (1) | CN1117077C (fr) |
AP (1) | AP848A (fr) |
AR (1) | AR010331A1 (fr) |
AT (1) | ATE251612T1 (fr) |
AU (2) | AU4791797A (fr) |
BG (1) | BG103540A (fr) |
BR (1) | BR9714381A (fr) |
CA (1) | CA2273479C (fr) |
CZ (1) | CZ293863B6 (fr) |
DE (1) | DE69725465T2 (fr) |
DK (1) | DK0946512T3 (fr) |
DZ (1) | DZ2361A1 (fr) |
EA (1) | EA002907B1 (fr) |
ES (1) | ES2206691T3 (fr) |
HN (2) | HN1997000027A (fr) |
HR (1) | HRP970664A2 (fr) |
HU (1) | HUP0001848A3 (fr) |
ID (1) | ID19056A (fr) |
IL (1) | IL130111A0 (fr) |
IS (1) | IS5053A (fr) |
MA (1) | MA26453A1 (fr) |
NO (1) | NO313517B1 (fr) |
NZ (1) | NZ335733A (fr) |
OA (1) | OA11123A (fr) |
PA (1) | PA8442201A1 (fr) |
PE (1) | PE46499A1 (fr) |
PL (1) | PL333918A1 (fr) |
PT (1) | PT946512E (fr) |
SI (1) | SI0946512T1 (fr) |
SK (1) | SK70899A3 (fr) |
TN (1) | TNSN97198A1 (fr) |
TR (1) | TR199901259T2 (fr) |
TW (1) | TW491840B (fr) |
UA (1) | UA59379C2 (fr) |
UY (1) | UY24799A1 (fr) |
WO (1) | WO1998024766A1 (fr) |
YU (1) | YU25399A (fr) |
ZA (1) | ZA9710906B (fr) |
Families Citing this family (36)
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UA49006C2 (uk) * | 1996-03-29 | 2002-09-16 | Файзер Інк. | Похідні 6-фенілпіридил-2-аміну, фармацевтична композиція, спосіб інгібування синтази оксиду нітрогену у ссавців та спосіб лікування |
HN1998000118A (es) * | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
US20010049379A1 (en) | 1997-08-27 | 2001-12-06 | Lowe John Adams | 2-aminopyridines containing fused ring substituents |
HN1998000125A (es) * | 1997-08-28 | 1999-02-09 | Pfizer Prod Inc | 2-aminopiridinas con sustituyentes alcoxi ramificados |
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 |
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 |
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 |
NZ509298A (en) * | 1998-08-11 | 2005-02-25 | 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 |
PT1155000E (pt) | 1999-02-25 | 2003-10-31 | Pfizer Prod Inc | 2-aminopiridinas contendo aneis fundidos substituintes |
AU763976B2 (en) * | 1999-07-23 | 2003-08-07 | Shionogi & Co., Ltd. | Th2 differentiation inhibitors |
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 (fr) * | 2001-04-09 | 2002-10-17 | Bristol-Myers Squibb Company | Inhibiteurs heterocycliques fusionnes du facteur xa |
US20030045449A1 (en) * | 2001-08-15 | 2003-03-06 | Pfizer, Inc. | Pharmaceutical combinations for the treatment of neurodegenerative diseases |
MXPA05011070A (es) * | 2003-04-14 | 2005-12-12 | Pfizer Prod Inc | Derivados de 3-azabiciclo [3.2.1] octano. |
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 |
EP1850838A2 (fr) * | 2005-02-21 | 2007-11-07 | Proximagen Ltd. | Inhibition ou traitement de la dyskinesie |
WO2006105795A1 (fr) * | 2005-04-08 | 2006-10-12 | Leo Pharma A/S | Nouveaux dérivés d'indolinone |
EP2054383A2 (fr) | 2006-08-09 | 2009-05-06 | SmithKline Beecham Corporation | Nouveaux composés comme antagonistes ou agonistes inverses à des récepteurs d'opioïdes |
CA2687912C (fr) | 2007-06-08 | 2015-11-03 | Janssen Pharmaceutica N.V. | Derives de piperidine/piperazine |
JO2972B1 (en) | 2007-06-08 | 2016-03-15 | جانسين فارماسوتيكا ان. في | Piperidine / piperazine derivatives |
EP2152269B1 (fr) | 2007-06-08 | 2014-04-23 | Janssen Pharmaceutica, N.V. | Dérivés de piperidine/piperazine |
WO2008148868A1 (fr) | 2007-06-08 | 2008-12-11 | Janssen Pharmaceutica N.V. | Dérivés de piperidine/piperazine |
AU2009253892B2 (en) | 2008-06-05 | 2015-07-30 | 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 |
JP5642661B2 (ja) * | 2009-03-05 | 2014-12-17 | 塩野義製薬株式会社 | Npyy5受容体拮抗作用を有するピペリジンおよびピロリジン誘導体 |
US11013844B2 (en) * | 2014-11-20 | 2021-05-25 | City Of Hope | Treatment device for plasma virus inactivation |
CA3032586A1 (fr) | 2016-08-12 | 2018-02-15 | Athenex, Inc. | Composes de biaryle et utilisation connexe pour la modulation d'une cascade de kinase |
CN111108105B (zh) | 2017-09-22 | 2023-03-31 | 朱比兰特埃皮帕德有限公司 | 作为pad抑制剂的杂环化合物 |
BR112020007607A2 (pt) | 2017-10-18 | 2020-09-29 | Jubilant Epipad LLC | compostos das fórmulas (i), (ii) e (iii); processos de preparação de compostos das fórmulas (i), (ii) e (iii); composição farmacêutica; compostos; método para a inibição de uma ou mais famílias de pad em uma célula; método de tratamento de uma afecção mediada por uma ou mais pad; composto da fórmula (i), fórmula (ii) e fórmula (iii); uso do composto; método para o tratamento e/ou prevenção de uma afecção; método para o tratamento de artrite reumatoide; e método de tratamento de câncer |
JP7279057B6 (ja) | 2017-11-06 | 2024-02-15 | ジュビラント プローデル エルエルシー | Pd1/pd-l1活性化の阻害剤としてのピリミジン誘導体 |
SG11202004537UA (en) | 2017-11-24 | 2020-06-29 | Jubilant Episcribe Llc | Heterocyclic compounds as prmt5 inhibitors |
AU2019234185A1 (en) | 2018-03-13 | 2020-10-01 | Jubilant Prodel LLC. | Bicyclic compounds as inhibitors of PD1/PD-L1 interaction/activation |
EP3983392A4 (fr) * | 2019-06-14 | 2023-12-06 | SRX Cardio, LLC | Composés pour la modulation de la proprotéine convertase subtilisine/kexine de type 9 (pcsk9) |
US20220193058A1 (en) * | 2020-12-16 | 2022-06-23 | Srx Cardio, Llc | Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (pcsk9) |
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WO1992014780A1 (fr) | 1991-02-19 | 1992-09-03 | Akzo N.V. | Copolymers stabilises de monoxyde de carbone et d'olefine |
JPH08504798A (ja) * | 1992-12-18 | 1996-05-21 | ザ ウエルカム ファウンデーション リミテッド | 酵素阻害薬としての,ピリミジン,ピリジン,プテリジノンおよびインダゾール誘導体 |
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 |
UA49006C2 (uk) * | 1996-03-29 | 2002-09-16 | Файзер Інк. | Похідні 6-фенілпіридил-2-аміну, фармацевтична композиція, спосіб інгібування синтази оксиду нітрогену у ссавців та спосіб лікування |
US6093743A (en) | 1998-06-23 | 2000-07-25 | Medinox Inc. | Therapeutic methods employing disulfide derivatives of dithiocarbamates and compositions useful therefor |
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1997
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1999
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2001
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2004
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