SK70899A3 - 6-phenylpyridyl-2-amine derivatives useful as nos inhibitors - Google Patents

6-phenylpyridyl-2-amine derivatives useful as nos inhibitors Download PDF

Info

Publication number: SK70899A3
Authority: SK; Slovakia
Prior art keywords: phenyl; ylamine; pyridin; methyl; disease
Prior art date: 1996-12-06

Application number

SK708-99A

Other languages

English (en)

Slovak (sk)

Inventor

John Adams Lowe Iii

Original Assignee

Pfizer

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-12-06

Filing date

1997-11-17

Publication date

2002-04-04

1997-11-17 Application filed by Pfizer filed Critical Pfizer

2002-04-04 Publication of SK70899A3 publication Critical patent/SK70899A3/sk

Links

239000003112 inhibitor Substances 0.000 title abstract description 5
XDWUSBKLDNVDDQ-UHFFFAOYSA-N 6-phenylpyridin-2-amine Chemical class NC1=CC=CC(C=2C=CC=CC=2)=N1 XDWUSBKLDNVDDQ-UHFFFAOYSA-N 0.000 claims abstract description 18
238000011282 treatment Methods 0.000 claims abstract description 13
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
230000002265 prevention Effects 0.000 claims abstract description 7
150000001875 compounds Chemical class 0.000 claims description 126
-1 hydroxy, methyl Chemical group 0.000 claims description 93
ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 53
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 41
150000003839 salts Chemical class 0.000 claims description 41
125000001424 substituent group Chemical group 0.000 claims description 29
125000004432 carbon atom Chemical group C* 0.000 claims description 24
125000000217 alkyl group Chemical group 0.000 claims description 22
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 22
208000002193 Pain Diseases 0.000 claims description 21
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
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 20
230000001154 acute effect Effects 0.000 claims description 19
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 18
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 18
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 18
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 18
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 18
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 18
241000124008 Mammalia Species 0.000 claims description 17
125000003710 aryl alkyl group Chemical group 0.000 claims description 16
125000003118 aryl group Chemical group 0.000 claims description 14
206010040070 Septic Shock Diseases 0.000 claims description 12
208000027866 inflammatory disease Diseases 0.000 claims description 12
239000000126 substance Substances 0.000 claims description 12
206010012335 Dependence Diseases 0.000 claims description 11
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 11
208000023105 Huntington disease Diseases 0.000 claims description 11
208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 11
206010047700 Vomiting Diseases 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
230000007135 neurotoxicity Effects 0.000 claims description 11
229910052757 nitrogen Inorganic materials 0.000 claims description 11
230000036303 septic shock Effects 0.000 claims description 11
208000000094 Chronic Pain Diseases 0.000 claims description 10
206010009900 Colitis ulcerative Diseases 0.000 claims description 10
206010056370 Congestive cardiomyopathy Diseases 0.000 claims description 10
208000011231 Crohn disease Diseases 0.000 claims description 10
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206010021138 Hypovolaemic shock Diseases 0.000 claims description 10
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 10
208000019695 Migraine disease Diseases 0.000 claims description 10
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 10
206010063837 Reperfusion injury Diseases 0.000 claims description 10
206010044541 Traumatic shock Diseases 0.000 claims description 10
201000006704 Ulcerative Colitis Diseases 0.000 claims description 10
208000005298 acute pain Diseases 0.000 claims description 10
206010027599 migraine Diseases 0.000 claims description 10
229960005181 morphine Drugs 0.000 claims description 10
201000006417 multiple sclerosis Diseases 0.000 claims description 10
230000004770 neurodegeneration Effects 0.000 claims description 10
208000015122 neurodegenerative disease Diseases 0.000 claims description 10
201000008482 osteoarthritis Diseases 0.000 claims description 10
230000016087 ovulation Effects 0.000 claims description 10
206010039073 rheumatoid arthritis Diseases 0.000 claims description 10
208000024827 Alzheimer disease Diseases 0.000 claims description 9
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206010019196 Head injury Diseases 0.000 claims description 9
208000028017 Psychotic disease Diseases 0.000 claims description 9
230000036506 anxiety Effects 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
206010015037 epilepsy Diseases 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical group 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
208000020431 spinal cord injury Diseases 0.000 claims description 9
208000010412 Glaucoma Diseases 0.000 claims description 8
206010028980 Neoplasm Diseases 0.000 claims description 8
201000011510 cancer Diseases 0.000 claims description 8
206010040560 shock Diseases 0.000 claims description 8
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
208000018737 Parkinson disease Diseases 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 7
206010013663 drug dependence Diseases 0.000 claims description 7
208000011117 substance-related disease Diseases 0.000 claims description 7
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 7
206010065040 AIDS dementia complex Diseases 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 6
239000011737 fluorine Chemical group 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
208000002780 macular degeneration Diseases 0.000 claims description 6
125000001624 naphthyl group Chemical group 0.000 claims description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
239000011630 iodine Substances 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
208000030507 AIDS Diseases 0.000 claims description 4
206010012289 Dementia Diseases 0.000 claims description 4
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
208000033679 diabetic kidney disease Diseases 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
125000002924 primary amino group Chemical group [H]N([H])* 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 3
125000002373 5 membered heterocyclic group Chemical group 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
125000003282 alkyl amino group Chemical group 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
230000015572 biosynthetic process Effects 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 2
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 2
AFXPRGRPBFUARV-UHFFFAOYSA-N 3-[(6-aminopyridin-2-yl)-phenylmethylidene]-1-[2-(dimethylamino)ethyl]indol-2-one Chemical compound C12=CC=CC=C2N(CCN(C)C)C(=O)C1=C(C=1N=C(N)C=CC=1)C1=CC=CC=C1 AFXPRGRPBFUARV-UHFFFAOYSA-N 0.000 claims description 2
RDUSFASPCBUTSL-UHFFFAOYSA-N 3-[(6-aminopyridin-2-yl)-phenylmethylidene]-1-methylindol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)C1=C(C=1N=C(N)C=CC=1)C1=CC=CC=C1 RDUSFASPCBUTSL-UHFFFAOYSA-N 0.000 claims description 2
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
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 description 2
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 description 2
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 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
125000003395 phenylethylamino group Chemical group [H]N(*)C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
238000003786 synthesis reaction Methods 0.000 claims description 2
206010012601 diabetes mellitus Diseases 0.000 claims 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims 5
125000001786 isothiazolyl group Chemical group 0.000 claims 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 2
206010038687 Respiratory distress Diseases 0.000 claims 2
208000017169 kidney disease Diseases 0.000 claims 2
238000003307 slaughter Methods 0.000 claims 2
208000011580 syndromic disease Diseases 0.000 claims 2
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 claims 1
ZOMWHUFJIVHYTM-UHFFFAOYSA-N 3-[(6-aminopyridin-2-yl)-phenylmethyl]-1-methyl-3h-indol-2-one Chemical compound C12=CC=CC=C2N(C)C(=O)C1C(C=1N=C(N)C=CC=1)C1=CC=CC=C1 ZOMWHUFJIVHYTM-UHFFFAOYSA-N 0.000 claims 1
XPZYBFOYRKOKPL-UHFFFAOYSA-N 3-azabicyclo[3.2.1]octan-8-ol Chemical group C1NCC2CCC1C2O XPZYBFOYRKOKPL-UHFFFAOYSA-N 0.000 claims 1
125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
206010019233 Headaches Diseases 0.000 claims 1
125000003545 alkoxy group Chemical group 0.000 claims 1
125000001309 chloro group Chemical group Cl* 0.000 claims 1
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 1
230000007850 degeneration Effects 0.000 claims 1
230000003412 degenerative effect Effects 0.000 claims 1
125000004663 dialkyl amino group Chemical group 0.000 claims 1
125000002541 furyl group Chemical group 0.000 claims 1
125000005843 halogen group Chemical group 0.000 claims 1
231100000869 headache Toxicity 0.000 claims 1
125000002883 imidazolyl group Chemical group 0.000 claims 1
208000014674 injury Diseases 0.000 claims 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
125000000842 isoxazolyl group Chemical group 0.000 claims 1
210000003097 mucus Anatomy 0.000 claims 1
201000008383 nephritis Diseases 0.000 claims 1
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125000000335 thiazolyl group Chemical group 0.000 claims 1
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
230000000694 effects Effects 0.000 abstract description 3
210000003169 central nervous system Anatomy 0.000 abstract description 2
102000008299 Nitric Oxide Synthase Human genes 0.000 abstract 2
108010021487 Nitric Oxide Synthase Proteins 0.000 abstract 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 156
238000005481 NMR spectroscopy Methods 0.000 description 143
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 110
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HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 73
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
239000000243 solution Substances 0.000 description 66
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239000000047 product Substances 0.000 description 47
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WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 34
238000000034 method Methods 0.000 description 34
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
229910001873 dinitrogen Inorganic materials 0.000 description 33
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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
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
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HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
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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 14
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229910000041 hydrogen chloride Inorganic materials 0.000 description 9
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 9
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102100022397 Nitric oxide synthase, brain Human genes 0.000 description 8
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CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
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KDZKRQOXTTXKLC-UHFFFAOYSA-N n-[4-[2-[[4-(6-aminopyridin-2-yl)phenyl]methyl]cyclohexyl]piperazin-1-yl]-n-propan-2-ylacetamide Chemical compound C1CN(N(C(C)C)C(C)=O)CCN1C1C(CC=2C=CC(=CC=2)C=2N=C(N)C=CC=2)CCCC1 KDZKRQOXTTXKLC-UHFFFAOYSA-N 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
238000012261 overproduction Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
239000000546 pharmaceutical excipient 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
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 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
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
239000011833 salt mixture Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
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150000004760 silicates Chemical class 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 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
239000008247 solid mixture Substances 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000001629 suppression Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 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
150000003892 tartrate salts Chemical class 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1

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- C07—ORGANIC CHEMISTRY
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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
- C07D401/14—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
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- 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
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- 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)
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Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Pyridine Compounds (AREA)
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SK708-99A 1996-12-06 1997-11-17 6-phenylpyridyl-2-amine derivatives useful as nos inhibitors SK70899A3 (en)

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
SK70899A3 true SK70899A3 (en)	2002-04-04

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ID=21866837

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SK708-99A SK70899A3 (en)	1996-12-06	1997-11-17	6-phenylpyridyl-2-amine derivatives useful as nos inhibitors

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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)
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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)
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1997
- 1997-02-18 HN HN1997000027A patent/HN1997000027A/es unknown
- 1997-11-17 SK SK708-99A patent/SK70899A3/sk unknown
- 1997-11-17 UA UA99063103A patent/UA59379C2/uk unknown
- 1997-11-17 CZ CZ19992017A patent/CZ293863B6/cs not_active IP Right Cessation
- 1997-11-17 BR BR9714381-2A patent/BR9714381A/pt not_active Application Discontinuation
- 1997-11-17 WO PCT/IB1997/001446 patent/WO1998024766A1/en not_active Ceased
- 1997-11-17 CA CA002273479A patent/CA2273479C/en not_active Expired - Fee Related
- 1997-11-17 TR TR1999/01259T patent/TR199901259T2/xx unknown
- 1997-11-17 DK DK97910587T patent/DK0946512T3/da active
- 1997-11-17 EP EP97910587A patent/EP0946512B1/en not_active Expired - Lifetime
- 1997-11-17 DE DE69725465T patent/DE69725465T2/de not_active Expired - Fee Related
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- 1997-11-17 CN CN97180350A patent/CN1117077C/zh not_active Expired - Fee Related
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- 1997-12-01 PE PE1997001080A patent/PE46499A1/es not_active Application Discontinuation
- 1997-12-03 MA MA24884A patent/MA26453A1/fr unknown
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- 1997-12-03 DZ DZ970211A patent/DZ2361A1/xx active
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1999
- 1999-05-18 IS IS5053A patent/IS5053A/is unknown
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- 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
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Also Published As

Publication number	Publication date
DE69725465D1 (de)	2003-11-13
IS5053A (is)	1999-05-18
AP9701156A0 (en)	1998-01-31
AU7205001A (en)	2001-11-15
UY24799A1 (es)	2001-08-27
YU25399A (sh)	2001-07-10
AP848A (en)	2000-06-09
TR199901259T2 (xx)	1999-08-23
AU766080B2 (en)	2003-10-09
DE69725465T2 (de)	2004-05-06
SI0946512T1 (en)	2004-04-30
PT946512E (pt)	2004-01-30
CA2273479C (en)	2006-02-07
OA11123A (en)	2003-04-07
PE46499A1 (es)	1999-05-12
NO992725L (no)	1999-06-04
HN1997000149A (es)	1997-12-26
ID19056A (id)	1998-06-11
US6235750B1 (en)	2001-05-22
EA002907B1 (ru)	2002-10-31
BR9714381A (pt)	2000-05-02
HRP970664A2 (en)	1998-10-31
PA8442201A1 (es)	2000-05-24
PL333918A1 (en)	2000-01-31
KR20000057413A (ko)	2000-09-15
CA2273479A1 (en)	1998-06-11
CZ293863B6 (cs)	2004-08-18
EP0946512A1 (en)	1999-10-06
WO1998024766A1 (en)	1998-06-11
EA199900448A1 (ru)	2000-02-28
AR010331A1 (es)	2000-06-07
IL130111A0 (en)	2000-06-01
JP2005170924A (ja)	2005-06-30
DZ2361A1 (fr)	2002-12-28
JP3604399B2 (ja)	2004-12-22
TNSN97198A1 (fr)	2005-03-15
DK0946512T3 (da)	2004-01-12
MA26453A1 (fr)	2004-12-20
HN1997000027A (es)	1997-06-05
NO992725D0 (no)	1999-06-04
HUP0001848A2 (hu)	2001-04-28
US20020032191A1 (en)	2002-03-14
NO313517B1 (no)	2002-10-14
CZ201799A3 (cs)	2000-07-12
HUP0001848A3 (en)	2002-03-28
NZ335733A (en)	2001-01-26
BG103540A (bg)	2000-12-29
ZA9710906B (en)	1999-06-09
ES2206691T3 (es)	2004-05-16
KR100360633B1 (ko)	2002-11-13
CN1117077C (zh)	2003-08-06
CN1239952A (zh)	1999-12-29
US20020103227A1 (en)	2002-08-01
ATE251612T1 (de)	2003-10-15
TW491840B (en)	2002-06-21
EP0946512B1 (en)	2003-10-08
UA59379C2 (uk)	2003-09-15
JP2000505814A (ja)	2000-05-16
AU4791797A (en)	1998-06-29

Publication	Publication Date	Title
SK70899A3 (en)	2002-04-04	6-phenylpyridyl-2-amine derivatives useful as nos inhibitors
JP3411271B2 (ja)	2003-05-26	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
CZ261498A3 (cs)	1999-08-11	6-fenylpyridyl-2-aminové deriváty, farmaceutické kompozice na jejich bázi a způsoby léčení
HRP980476A2 (en)	1999-06-30	Branched alkoxy-substituted 2-aminopyridines
JP3825636B2 (ja)	2006-09-27	縮合環置換基を含む２−アミノピリジン
JP3444495B2 (ja)	2003-09-08	酸化窒素合成酵素阻害剤として縮合環置換基を含有する２−アミノピリジン
US20010049379A1 (en)	2001-12-06	2-aminopyridines containing fused ring substituents
US20040142924A1 (en)	2004-07-22	6-Phenylpyridyl-2-amine derivatives useful as NOS inhibitors
KR20040053157A (ko)	2004-06-23	산화질소 합성효소 억제제로서 사용하기 위한2-아미노-6-(2,4,5-치환된-페닐)-피리딘
MXPA00002030A (en)	2001-05-17	2-aminopyridines containing fused ring substituents as nos inhibitors