HRP20020328A2 - Heteroalkylamino-substited bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase - Google Patents

Heteroalkylamino-substited bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase Download PDF

Info

Publication number: HRP20020328A2
Authority: HR; Croatia
Prior art keywords: optionally substituted; dihydropyrimido; chlorophenyl; mmol; pyrimidin
Prior art date: 1999-10-21

Application number

HR20020328A

Other languages

English (en)

Croatian (hr)

Inventor

James Patrick Dunn

Lawrence Emerson Fisher

David Michael Goldstein

Harris William

Christopher Huw Hill

Ian Edward David Smith

Teresa Rosanne Welch

Original Assignee

Hoffmann La Roche

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.)

1999-10-21

Filing date

2002-04-12

Publication date

2004-02-29

2002-04-12 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2004-02-29 Publication of HRP20020328A2 publication Critical patent/HRP20020328A2/hr

Links

102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 title description 22
108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 title description 22
229910052757 nitrogen Inorganic materials 0.000 title description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title description 12
239000003112 inhibitor Substances 0.000 title 1
-1 amino, monosubstituted amino Chemical group 0.000 claims description 273
150000001875 compounds Chemical class 0.000 claims description 259
239000000203 mixture Substances 0.000 claims description 138
125000000217 alkyl group Chemical group 0.000 claims description 85
239000001257 hydrogen Substances 0.000 claims description 60
229910052739 hydrogen Inorganic materials 0.000 claims description 60
150000003839 salts Chemical class 0.000 claims description 57
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 42
125000004404 heteroalkyl group Chemical group 0.000 claims description 39
125000000753 cycloalkyl group Chemical group 0.000 claims description 37
125000000623 heterocyclic group Chemical group 0.000 claims description 37
125000001188 haloalkyl group Chemical group 0.000 claims description 34
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
238000000034 method Methods 0.000 claims description 31
125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 30
238000011282 treatment Methods 0.000 claims description 30
125000003710 aryl alkyl group Chemical group 0.000 claims description 22
125000001072 heteroaryl group Chemical group 0.000 claims description 22
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 21
125000003107 substituted aryl group Chemical group 0.000 claims description 20
125000004475 heteroaralkyl group Chemical group 0.000 claims description 19
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 16
150000001412 amines Chemical class 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 15
125000003118 aryl group Chemical group 0.000 claims description 10
239000003814 drug Substances 0.000 claims description 10
125000001475 halogen functional group Chemical group 0.000 claims description 8
229940079593 drug Drugs 0.000 claims description 7
239000000825 pharmaceutical preparation Substances 0.000 claims description 7
125000002252 acyl group Chemical group 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
125000004966 cyanoalkyl group Chemical group 0.000 claims description 6
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
208000024827 Alzheimer disease Diseases 0.000 claims description 5
208000011231 Crohn disease Diseases 0.000 claims description 5
208000001132 Osteoporosis Diseases 0.000 claims description 5
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 5
125000005356 cycloalkylalkenyl group Chemical group 0.000 claims description 5
125000005357 cycloalkylalkynyl group Chemical group 0.000 claims description 5
239000000543 intermediate Substances 0.000 claims description 5
FDBVYXJFOHVTSQ-UHFFFAOYSA-N 3-(2-chlorophenyl)-1-methyl-7-[(4-oxocyclohexyl)amino]-4h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C)C(=O)N(C=3C(=CC=CC=3)Cl)CC2=CN=C1NC1CCC(=O)CC1 FDBVYXJFOHVTSQ-UHFFFAOYSA-N 0.000 claims description 4
XFBDYRNRMRJJBD-UHFFFAOYSA-N 6-(2-chlorophenyl)-2-(oxan-4-ylamino)-5,8-dihydropyrimido[4,5-d]pyrimidin-7-one Chemical compound ClC1=CC=CC=C1N1C(=O)NC2=NC(NC3CCOCC3)=NC=C2C1 XFBDYRNRMRJJBD-UHFFFAOYSA-N 0.000 claims description 4
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
230000002452 interceptive effect Effects 0.000 claims description 4
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239000007800 oxidant agent Substances 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
HQHXVEZJBBPLII-UHFFFAOYSA-N 7-[[1-(2-hydroxyethyl)piperidin-4-yl]amino]-1-methyl-3-(2-methylphenyl)-4h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=C2N(C)C(=O)N(C=3C(=CC=CC=3)C)CC2=CN=C1NC1CCN(CCO)CC1 HQHXVEZJBBPLII-UHFFFAOYSA-N 0.000 claims description 3
IPDRIFQWRUIZSL-KOMQPUFPSA-N C1C[C@@H](OC)CC[C@@H]1CNC1=NC=C(CN(C(=O)N2C)C=3C(=CC=CC=3)Cl)C2=N1 Chemical compound C1C[C@@H](OC)CC[C@@H]1CNC1=NC=C(CN(C(=O)N2C)C=3C(=CC=CC=3)Cl)C2=N1 IPDRIFQWRUIZSL-KOMQPUFPSA-N 0.000 claims description 3
NSHBSERFNQQOCC-JOCQHMNTSA-N chembl1235713 Chemical compound C1C[C@@H](O)CC[C@@H]1NC1=NC=C(CN(C(=O)N2)C=3C(=CC=CC=3)Cl)C2=N1 NSHBSERFNQQOCC-JOCQHMNTSA-N 0.000 claims description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
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 claims description 3
229920002554 vinyl polymer Polymers 0.000 claims description 3
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
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238000010511 deprotection reaction Methods 0.000 claims 1
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SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 72
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 54
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
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 50
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230000002829 reductive effect Effects 0.000 description 46
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 45
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 33
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HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 30
150000002431 hydrogen Chemical group 0.000 description 30
239000010410 layer Substances 0.000 description 27
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235000019341 magnesium sulphate Nutrition 0.000 description 27
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102100040247 Tumor necrosis factor Human genes 0.000 description 25
239000000706 filtrate Substances 0.000 description 24
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
238000003756 stirring Methods 0.000 description 21
238000003818 flash chromatography Methods 0.000 description 20
239000012044 organic layer Substances 0.000 description 20
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 19
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
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239000006260 foam Substances 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
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IMLXLGZJLAOKJN-UHFFFAOYSA-N 4-aminocyclohexan-1-ol Chemical compound NC1CCC(O)CC1 IMLXLGZJLAOKJN-UHFFFAOYSA-N 0.000 description 16
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RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 15
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FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
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DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical class O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
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UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
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239000010452 phosphate Substances 0.000 description 1
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UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
239000003880 polar aprotic solvent Substances 0.000 description 1
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229920002223 polystyrene Polymers 0.000 description 1
NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical compound [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
238000012545 processing Methods 0.000 description 1
VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
239000003909 protein kinase inhibitor Substances 0.000 description 1
208000009305 pseudorabies Diseases 0.000 description 1
201000003651 pulmonary sarcoidosis Diseases 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
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229940107700 pyruvic acid Drugs 0.000 description 1
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239000012066 reaction slurry Substances 0.000 description 1
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230000036573 scar formation Effects 0.000 description 1
150000003333 secondary alcohols Chemical class 0.000 description 1
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238000013207 serial dilution Methods 0.000 description 1
239000010802 sludge Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000011006 sodium potassium tartrate Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
238000000935 solvent evaporation Methods 0.000 description 1
201000005671 spondyloarthropathy Diseases 0.000 description 1
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125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-N sulfurothioic S-acid Chemical compound OS(O)(=O)=S DHCDFWKWKRSZHF-UHFFFAOYSA-N 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
KLKBCNDBOVRQIJ-UHFFFAOYSA-N tert-butyl 4-(aminomethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CN)CC1 KLKBCNDBOVRQIJ-UHFFFAOYSA-N 0.000 description 1
SFTFWJVRAUOAAN-UHFFFAOYSA-N tert-butyl 4-[[[6-(2-chlorophenyl)-7-oxo-5,8-dihydropyrimido[4,5-d]pyrimidin-2-yl]amino]methyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1CNC1=NC=C(CN(C(=O)N2)C=3C(=CC=CC=3)Cl)C2=N1 SFTFWJVRAUOAAN-UHFFFAOYSA-N 0.000 description 1
PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 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
239000012085 test solution Substances 0.000 description 1
125000005887 tetrahydrobenzofuranyl group Chemical group 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
208000037816 tissue injury Diseases 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-N trans-cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-N 0.000 description 1
238000012546 transfer Methods 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
QXJQHYBHAIHNGG-UHFFFAOYSA-N trimethylolethane Chemical compound OCC(C)(CO)CO QXJQHYBHAIHNGG-UHFFFAOYSA-N 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
241000712461 unidentified influenza virus Species 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
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230000009385 viral infection Effects 0.000 description 1
230000003612 virological effect Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
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Classifications

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HR20020328A 1999-10-21 2002-04-12 Heteroalkylamino-substited bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase HRP20020328A2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US16080399P	1999-10-21	1999-10-21
US21374300P	2000-06-22	2000-06-22
PCT/EP2000/010088 WO2001029042A1 (en)	1999-10-21	2000-10-13	Heteroalkylamino-substituted bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase

Publications (1)

Publication Number	Publication Date
HRP20020328A2 true HRP20020328A2 (en)	2004-02-29

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ID=26857240

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HR20020328A HRP20020328A2 (en)	1999-10-21	2002-04-12	Heteroalkylamino-substited bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase

Country Status (27)

Country	Link
US (1)	US6451804B1 (zh)
EP (1)	EP1228070B1 (zh)
JP (1)	JP3961830B2 (zh)
KR (1)	KR100523120B1 (zh)
CN (1)	CN1171889C (zh)
AR (1)	AR026084A1 (zh)
AT (1)	ATE353329T1 (zh)
AU (1)	AU776250B2 (zh)
BR (1)	BR0015243A (zh)
CA (1)	CA2388142C (zh)
CZ (1)	CZ20021744A3 (zh)
DE (1)	DE60033307T2 (zh)
ES (1)	ES2280247T3 (zh)
HK (1)	HK1051039A1 (zh)
HR (1)	HRP20020328A2 (zh)
HU (1)	HUP0203564A3 (zh)
IL (1)	IL149100A0 (zh)
MA (1)	MA26837A1 (zh)
MX (1)	MXPA02003950A (zh)
NO (1)	NO20021781L (zh)
NZ (1)	NZ518119A (zh)
PE (1)	PE20010758A1 (zh)
PL (1)	PL357502A1 (zh)
RU (1)	RU2265606C2 (zh)
TR (1)	TR200201057T2 (zh)
WO (1)	WO2001029042A1 (zh)
YU (1)	YU29102A (zh)

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- 2000-10-13 CZ CZ20021744A patent/CZ20021744A3/cs unknown
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- 2000-10-13 AU AU77873/00A patent/AU776250B2/en not_active Ceased
- 2000-10-13 KR KR10-2002-7005031A patent/KR100523120B1/ko not_active IP Right Cessation
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- 2000-10-13 WO PCT/EP2000/010088 patent/WO2001029042A1/en active Search and Examination
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Also Published As

Publication number	Publication date
KR20020038963A (ko)	2002-05-24
EP1228070B1 (en)	2007-02-07
AR026084A1 (es)	2002-12-26
CA2388142C (en)	2008-12-09
MXPA02003950A (es)	2002-10-23
RU2002112753A (ru)	2004-01-20
RU2265606C2 (ru)	2005-12-10
NZ518119A (en)	2004-02-27
AU776250B2 (en)	2004-09-02
NO20021781D0 (no)	2002-04-16
CA2388142A1 (en)	2001-04-26
HK1051039A1 (en)	2003-07-18
PE20010758A1 (es)	2001-07-21
WO2001029042A1 (en)	2001-04-26
PL357502A1 (en)	2004-07-26
JP3961830B2 (ja)	2007-08-22
DE60033307D1 (en)	2007-03-22
JP2003512378A (ja)	2003-04-02
EP1228070A1 (en)	2002-08-07
AU7787300A (en)	2001-04-30
MA26837A1 (fr)	2004-12-20
BR0015243A (pt)	2002-07-16
CN1382144A (zh)	2002-11-27
CN1171889C (zh)	2004-10-20
DE60033307T2 (de)	2007-07-12
NO20021781L (no)	2002-04-18
ES2280247T3 (es)	2007-09-16
YU29102A (sh)	2004-12-31
KR100523120B1 (ko)	2005-10-20
IL149100A0 (en)	2002-11-10
US6451804B1 (en)	2002-09-17
HUP0203564A3 (en)	2004-07-28
TR200201057T2 (tr)	2002-09-23
HUP0203564A2 (hu)	2003-02-28
CZ20021744A3 (cs)	2002-08-14
ATE353329T1 (de)	2007-02-15

Publication	Publication Date	Title
HRP20020328A2 (en)	2004-02-29	Heteroalkylamino-substited bicyclic nitrogen heterocycles as inhibitors of p38 protein kinase
US6642241B1 (en)	2003-11-04	Alkylamino-substituted bicyclic nitrogen heterocycles
RU2310657C2 (ru)	2007-11-20	Имидазоконденсированные соединения и фармацевтическая композиция, содержащая их
JP4141830B2 (ja)	2008-08-27	細胞増殖の阻害剤としての７−オキソ−ピリドピリミジン類
ES2314224T3 (es)	2009-03-16	Inhibidores pirimidina y piridina biciclicos de p38 quinasa.
US7608603B2 (en)	2009-10-27	Substituted pyrazolo[3,4-D]pyrimidines as p38 MAP kinase inhibitors
SK11322003A3 (en)	2004-10-05	6-Substituted pyrido-pyrimidines
AU2006283941A1 (en)	2007-03-01	P38 MAP kinase inhibitors and methods for using the same
CA2875990A1 (en)	2013-11-28	Heterocyclyl pyrimidine analogues as tyk2 inhibitors
AU2004289428B2 (en)	2010-06-03	Hydroxyalkyl substituted pyrido-7-pyrimidin-7-ones
WO2010072823A1 (en)	2010-07-01	PYRAZOLE[1,5a]PYRIDINE DERIVATIVES
US7563800B2 (en)	2009-07-21	Substituted pyrazolo[3,4-D]pyrimidines as p38 map kinase inhibitors
JP4028236B6 (ja)	2008-03-12	ｐ３８プロテインキナーゼのインヒビターとしてのアルキルアミノ置換二環式窒素複素環
RU2264404C2 (ru)	2005-11-20	Алкиламинозамещенные бициклические азотсодержащие гетероциклы и фармацевтическая композиция на их основе

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2004-02-29	A1OB	Publication of a patent application
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2008-12-10	OBST	Application withdrawn