HRP980476A2 - Branched alkoxy-substituted 2-aminopyridines - Google Patents
Branched alkoxy-substituted 2-aminopyridinesInfo
- Publication number
- HRP980476A2 HRP980476A2 HR60/057,739A HRP980476A HRP980476A2 HR P980476 A2 HRP980476 A2 HR P980476A2 HR P980476 A HRP980476 A HR P980476A HR P980476 A2 HRP980476 A2 HR P980476A2
- Authority
- HR
- Croatia
- Prior art keywords
- disease
- alkyl
- phenyl
- pyridin
- compound according
- Prior art date
Links
- 150000003930 2-aminopyridines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 88
- 208000002193 Pain Diseases 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
- -1 chloro, fluoro, bromo, iodo Chemical group 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 241000124008 Mammalia Species 0.000 claims description 21
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 12
- 230000002401 inhibitory effect Effects 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 11
- 206010012335 Dependence Diseases 0.000 claims description 10
- 206010040070 Septic Shock Diseases 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011510 cancer Diseases 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 208000027866 inflammatory disease Diseases 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 230000036303 septic shock Effects 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
- 206010001497 Agitation Diseases 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 8
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 8
- 208000000094 Chronic Pain Diseases 0.000 claims description 8
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 8
- 208000011231 Crohn disease Diseases 0.000 claims description 8
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 8
- 208000032131 Diabetic Neuropathies 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
- 206010021138 Hypovolaemic shock 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
- 201000004681 Psoriasis Diseases 0.000 claims description 8
- 208000028017 Psychotic disease Diseases 0.000 claims description 8
- 206010063837 Reperfusion injury 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
- 208000005298 acute pain Diseases 0.000 claims description 8
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 8
- 238000013019 agitation Methods 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 8
- 208000033679 diabetic kidney disease Diseases 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 208000024732 dysthymic disease Diseases 0.000 claims description 8
- 206010015037 epilepsy Diseases 0.000 claims description 8
- 208000002780 macular degeneration Diseases 0.000 claims description 8
- 208000024714 major depressive disease 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
- 125000001624 naphthyl group Chemical group 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
- 201000008482 osteoarthritis Diseases 0.000 claims description 8
- 230000016087 ovulation Effects 0.000 claims description 8
- 230000000241 respiratory effect Effects 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
- 206010040560 shock Diseases 0.000 claims description 8
- 208000020431 spinal cord injury Diseases 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 8
- 208000011580 syndromic disease Diseases 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000000229 (C1-C4)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
- 125000003282 alkyl amino group Chemical group 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
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 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
- 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
- 230000002265 prevention Effects 0.000 claims 2
- MNUHYQZBNHDABI-UHFFFAOYSA-N 3-azabicyclo[3.1.0]hexan-6-amine Chemical class C1NCC2C(N)C21 MNUHYQZBNHDABI-UHFFFAOYSA-N 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 claims 1
- 150000003053 piperidines Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- 238000006243 chemical reaction Methods 0.000 description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000000243 solution Substances 0.000 description 37
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 24
- 239000003921 oil Substances 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 239000012267 brine Substances 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000012044 organic layer Substances 0.000 description 11
- 239000000047 product Substances 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 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 7
- 102100022397 Nitric oxide synthase, brain Human genes 0.000 description 7
- 101710111444 Nitric oxide synthase, brain Proteins 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 238000000668 atmospheric pressure chemical ionisation mass spectrometry Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 206010029350 Neurotoxicity Diseases 0.000 description 4
- 241000149788 Pseudophryne major Species 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 206010044221 Toxic encephalopathy Diseases 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000006260 foam Substances 0.000 description 4
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 231100000228 neurotoxicity Toxicity 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- XJGMXHIRLHNXQA-UHFFFAOYSA-N 1-[4-(6-aminopyridin-2-yl)-3-propan-2-yloxyphenyl]-2-[4-(2-phenylethyl)piperazin-1-yl]ethanol Chemical compound CC(C)OC1=CC(C(O)CN2CCN(CCC=3C=CC=CC=3)CC2)=CC=C1C1=CC=CC(N)=N1 XJGMXHIRLHNXQA-UHFFFAOYSA-N 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 3
- RPTOTWISMQOHGP-UHFFFAOYSA-N 6-[2-(2-methylpropoxy)-4-[2-[4-(2-phenylethyl)piperazin-1-yl]ethyl]phenyl]pyridin-2-amine Chemical compound C=1C=C(C=2N=C(N)C=CC=2)C(OCC(C)C)=CC=1CCN(CC1)CCN1CCC1=CC=CC=C1 RPTOTWISMQOHGP-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 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
- 102100028452 Nitric oxide synthase, endothelial Human genes 0.000 description 3
- 101710090055 Nitric oxide synthase, endothelial Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 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
- 239000003814 drug Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000003999 initiator Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- GZKQXVPTDMGYDX-UHFFFAOYSA-N n-[6-(2-fluoro-4-methylphenyl)pyridin-2-yl]-2,2-dimethylpropanamide Chemical compound FC1=CC(C)=CC=C1C1=CC=CC(NC(=O)C(C)(C)C)=N1 GZKQXVPTDMGYDX-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- JSGULGGTJKJYKP-UHFFFAOYSA-N (4-methyl-2-propan-2-yloxyphenyl)boronic acid Chemical compound CC(C)OC1=CC(C)=CC=C1B(O)O JSGULGGTJKJYKP-UHFFFAOYSA-N 0.000 description 2
- LKUAPSRIYZLAAO-UHFFFAOYSA-N 1-(2-phenylethyl)piperazine Chemical compound C1CNCCN1CCC1=CC=CC=C1 LKUAPSRIYZLAAO-UHFFFAOYSA-N 0.000 description 2
- SLFNGVGRINFJLK-UHFFFAOYSA-N 1-bromo-2-fluoro-4-methylbenzene Chemical compound CC1=CC=C(Br)C(F)=C1 SLFNGVGRINFJLK-UHFFFAOYSA-N 0.000 description 2
- HFCHJYQPPRDMSM-UHFFFAOYSA-N 1-bromo-4-methyl-2-propan-2-yloxybenzene Chemical compound CC(C)OC1=CC(C)=CC=C1Br HFCHJYQPPRDMSM-UHFFFAOYSA-N 0.000 description 2
- CTMBKSKRPWBTCB-UHFFFAOYSA-N 2,2-dimethyl-n-[6-(4-methyl-2-propan-2-yloxyphenyl)pyridin-2-yl]propanamide Chemical compound CC(C)OC1=CC(C)=CC=C1C1=CC=CC(NC(=O)C(C)(C)C)=N1 CTMBKSKRPWBTCB-UHFFFAOYSA-N 0.000 description 2
- QPUPPPPKBGBGDC-UHFFFAOYSA-N 2,2-dimethyl-n-[6-[4-(oxiran-2-yl)-2-propan-2-yloxyphenyl]pyridin-2-yl]propanamide Chemical compound CC(C)OC1=CC(C2OC2)=CC=C1C1=CC=CC(NC(=O)C(C)(C)C)=N1 QPUPPPPKBGBGDC-UHFFFAOYSA-N 0.000 description 2
- MDKLAQCKZQOKJJ-UHFFFAOYSA-N 2-[4-(6-aminopyridin-2-yl)-3-propan-2-yloxyphenyl]acetic acid Chemical compound CC(C)OC1=CC(CC(O)=O)=CC=C1C1=CC=CC(N)=N1 MDKLAQCKZQOKJJ-UHFFFAOYSA-N 0.000 description 2
- ISDGWTZFJKFKMO-UHFFFAOYSA-N 2-phenyl-1,3-dioxane-4,6-dione Chemical compound O1C(=O)CC(=O)OC1C1=CC=CC=C1 ISDGWTZFJKFKMO-UHFFFAOYSA-N 0.000 description 2
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
- PMEIIDDWZIOYKX-UHFFFAOYSA-N 3-[4-(6-aminopyridin-2-yl)-3-fluorophenyl]pyrrolidin-2-one Chemical compound NC1=CC=CC(C=2C(=CC(=CC=2)C2C(NCC2)=O)F)=N1 PMEIIDDWZIOYKX-UHFFFAOYSA-N 0.000 description 2
- YVTQRJWTWBGGRV-UHFFFAOYSA-N 6-(2-fluoro-4-pyrrolidin-3-ylphenyl)pyridin-2-amine Chemical compound NC1=CC=CC(C=2C(=CC(=CC=2)C2CNCC2)F)=N1 YVTQRJWTWBGGRV-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- 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
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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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Immunology (AREA)
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- Endocrinology (AREA)
- Hematology (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5773997P | 1997-08-28 | 1997-08-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP980476A2 true HRP980476A2 (en) | 1999-06-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/057,739A HRP980476A2 (en) | 1997-08-28 | 1998-08-28 | Branched alkoxy-substituted 2-aminopyridines |
Country Status (32)
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| US (2) | US6362195B1 (da) |
| EP (1) | EP1007512B1 (da) |
| JP (1) | JP3441714B2 (da) |
| CN (1) | CN1268122A (da) |
| AP (1) | AP9801331A0 (da) |
| AR (1) | AR016644A1 (da) |
| AT (1) | ATE215532T1 (da) |
| AU (1) | AU8458698A (da) |
| BR (1) | BR9811921A (da) |
| CA (1) | CA2302436C (da) |
| DE (1) | DE69804635T2 (da) |
| DK (1) | DK1007512T3 (da) |
| EA (1) | EA200000165A1 (da) |
| ES (1) | ES2172173T3 (da) |
| GT (1) | GT199800135A (da) |
| HN (1) | HN1998000125A (da) |
| HR (1) | HRP980476A2 (da) |
| HU (1) | HUP0002803A2 (da) |
| ID (1) | ID24318A (da) |
| IL (1) | IL134302A0 (da) |
| IS (1) | IS5342A (da) |
| MA (1) | MA26538A1 (da) |
| NO (1) | NO20000957D0 (da) |
| OA (1) | OA11294A (da) |
| PA (1) | PA8458301A1 (da) |
| PE (1) | PE106699A1 (da) |
| PL (1) | PL339008A1 (da) |
| PT (1) | PT1007512E (da) |
| SI (1) | SI1007512T1 (da) |
| TN (1) | TNSN98157A1 (da) |
| WO (1) | WO1999011620A1 (da) |
| ZA (1) | ZA987788B (da) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20010049379A1 (en) | 1997-08-27 | 2001-12-06 | Lowe John Adams | 2-aminopyridines containing fused ring substituents |
| HUP0103113A3 (en) * | 1998-08-11 | 2002-02-28 | Pfizer Prod Inc | New pharmaceutical compositions uses for nos inhibitors |
| CZ20013036A3 (cs) | 1999-02-25 | 2002-03-13 | Pfizer Products Inc. | 2-aminopyridiny obsahující jako substituenty kondenzované kruhové skupiny |
| WO2001009307A2 (en) * | 1999-07-30 | 2001-02-08 | University College London | Screen for nitric oxide synthase modulators |
| WO2001009375A2 (en) * | 1999-07-30 | 2001-02-08 | University College London | Inducible screen for drug discovery |
| GB0004153D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004151D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
| GB0004152D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| GB0004149D0 (en) * | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
| US6469172B2 (en) * | 2000-03-08 | 2002-10-22 | Merck & Co., Inc. | Process for the preparation of chemical compounds |
| SE0102640D0 (sv) | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
| US20040077853A1 (en) * | 2001-10-10 | 2004-04-22 | Pfizer Inc. | 2-amino-6-(2,4,5-substituted-phenyl)-pyridines |
| AU2003241398A1 (en) * | 2002-05-06 | 2003-11-17 | Washington University | Methods of treatment of glaucoma and other conditions mediated by nos-2 expression via inhibition of the egfr pathway |
| WO2005007627A1 (ja) * | 2003-07-18 | 2005-01-27 | Nihon Nohyaku Co., Ltd. | フェニルピリジン誘導体、その中間体及びこれを有効成分とする除草剤 |
| TW200628463A (en) * | 2004-11-10 | 2006-08-16 | Synta Pharmaceuticals Corp | Heteroaryl compounds |
| US8604031B2 (en) * | 2006-05-18 | 2013-12-10 | Mannkind Corporation | Intracellular kinase inhibitors |
| UA105182C2 (ru) | 2008-07-03 | 2014-04-25 | Ньюрексон, Інк. | Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность |
| EP3002279A1 (de) | 2014-10-02 | 2016-04-06 | Bayer CropScience AG | Verfahren zur Herstellung von 3-(5-Aminotriazolyl)-Sulfid-Derivaten |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5892112A (en) * | 1990-11-21 | 1999-04-06 | Glycomed Incorporated | Process for preparing synthetic matrix metalloprotease inhibitors |
| AU4515696A (en) | 1994-12-12 | 1996-07-03 | Merck & Co., Inc. | Substituted 2-aminopyridines as inhibitors of nitric oxide synthase |
| US5972975A (en) * | 1995-12-08 | 1999-10-26 | Merck & Co., Inc. | Substituted 2-aminopyridines as inhibitors of nitric oxide synthase |
| JP4431638B2 (ja) * | 1996-01-29 | 2010-03-17 | アメリカ合衆国 | ジヒドロピリジン―、ピリジン―、ベンゾピラン―オン―およびトリアゾロキナゾリン誘導体、それらの製造およびそれらのアデノシン受容体アンタゴニストとしての用途 |
| SK113998A3 (en) * | 1996-03-29 | 2001-05-10 | Pfizer | 6-phenylpyridyl-2-amine derivatives |
| HN1997000027A (es) | 1996-12-06 | 1997-06-05 | Pfizer Prod Inc | Derivados de 6-fenil piridil - 2 amina |
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