JP2005539000A

JP2005539000A - Ａｌｋ５阻害剤としての２−フェニルピリジン−４−イル誘導体

Ａｌｋ５阻害剤としての２−フェニルピリジン−４−イル誘導体 Download PDF

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Publication number: JP2005539000A
Authority: JP; Japan
Prior art keywords: mmol; pyridin; alkyl; compound; hydrogen
Prior art date: 2002-07-31
Legal status : Pending

Application number

JP2004525405A

Other languages

English (en)

Japanese (ja)

Other versions

JP2005539000A5 (enExample

Inventor

ネリナ・ドディック

フランソワーズ・ジャンヌ・ジェリベール

Current Assignee

SmithKline Beecham Corp

Original Assignee

SmithKline Beecham Corp

Priority date

2002-07-31

Filing date

2003-07-29

Publication date

2005-12-22

2002-07-31 Priority claimed from GB0217751A external-priority patent/GB0217751D0/en

2003-06-24 Priority claimed from GB0314698A external-priority patent/GB0314698D0/en

2003-07-29 Application filed by SmithKline Beecham Corp filed Critical SmithKline Beecham Corp

2005-12-22 Publication of JP2005539000A publication Critical patent/JP2005539000A/ja

2006-09-14 Publication of JP2005539000A5 publication Critical patent/JP2005539000A5/ja

Status Pending legal-status Critical Current

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-1 2-Phenylpyridin-4-yl Chemical class 0.000 title claims description 49
239000003112 inhibitor Substances 0.000 title abstract description 5
238000011282 treatment Methods 0.000 claims abstract description 20
239000003814 drug Substances 0.000 claims abstract description 8
230000001404 mediated effect Effects 0.000 claims abstract description 6
230000002265 prevention Effects 0.000 claims abstract description 5
150000001875 compounds Chemical class 0.000 claims description 365
125000000217 alkyl group Chemical group 0.000 claims description 73
229910052739 hydrogen Inorganic materials 0.000 claims description 65
239000001257 hydrogen Substances 0.000 claims description 59
125000005843 halogen group Chemical group 0.000 claims description 41
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 40
125000003545 alkoxy group Chemical group 0.000 claims description 36
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 33
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 33
150000002431 hydrogen Chemical class 0.000 claims description 31
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
125000004093 cyano group Chemical group *C#N 0.000 claims description 27
229910052757 nitrogen Inorganic materials 0.000 claims description 22
229920006395 saturated elastomer Polymers 0.000 claims description 22
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 20
FXXJRBVEYNARBS-UHFFFAOYSA-N 4-[[4-[4-[5-(6-methylpyridin-2-yl)-2-propan-2-yl-1h-imidazol-4-yl]pyridin-2-yl]phenyl]methyl]morpholine Chemical compound N1C(C(C)C)=NC(C=2C=C(N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)=C1C1=CC=CC(C)=N1 FXXJRBVEYNARBS-UHFFFAOYSA-N 0.000 claims description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 11
150000003839 salts Chemical class 0.000 claims description 10
239000012453 solvate Substances 0.000 claims description 10
ZNEWDLYYLKDPRH-UHFFFAOYSA-N 4-[4-[5-(6-methylpyridin-2-yl)-2-propan-2-yl-1h-imidazol-4-yl]pyridin-2-yl]-n-(oxan-4-yl)benzamide Chemical compound N1C(C(C)C)=NC(C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)NC2CCOCC2)=C1C1=CC=CC(C)=N1 ZNEWDLYYLKDPRH-UHFFFAOYSA-N 0.000 claims description 9
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
125000001309 chloro group Chemical group Cl* 0.000 claims description 9
IVTGNDUCNRHJET-UHFFFAOYSA-N 4-[4-[2-tert-butyl-5-(6-methylpyridin-2-yl)-1h-imidazol-4-yl]pyridin-2-yl]-n-(oxan-4-yl)benzamide Chemical compound CC1=CC=CC(C2=C(N=C(N2)C(C)(C)C)C=2C=C(N=CC=2)C=2C=CC(=CC=2)C(=O)NC2CCOCC2)=N1 IVTGNDUCNRHJET-UHFFFAOYSA-N 0.000 claims description 8
GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 8
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 8
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YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
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125000005842 heteroatom Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
229910052760 oxygen Inorganic materials 0.000 claims description 8
150000003852 triazoles Chemical class 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
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125000004429 atom Chemical group 0.000 claims description 6
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125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
125000004193 piperazinyl group Chemical group 0.000 claims description 6
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ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
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VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 4
229930192474 thiophene Natural products 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 3
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 3
IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 claims description 3
VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 claims description 3
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 claims description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
208000024827 Alzheimer disease Diseases 0.000 claims description 3
208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 3
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208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
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208000018565 Hemochromatosis Diseases 0.000 claims description 3
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JTBSSXWFYSSVJP-UHFFFAOYSA-N [S].C1=CSC=N1 Chemical compound [S].C1=CSC=N1 JTBSSXWFYSSVJP-UHFFFAOYSA-N 0.000 claims description 3
230000001154 acute effect Effects 0.000 claims description 3
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RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 3
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HEEWFRYQSLPADJ-UHFFFAOYSA-N 2-[2-tert-butyl-4-[2-[4-(pyrrolidin-1-ylmethyl)phenyl]pyridin-4-yl]-1h-imidazol-5-yl]-6-methylpyridine Chemical compound CC1=CC=CC(C2=C(N=C(N2)C(C)(C)C)C=2C=C(N=CC=2)C=2C=CC(CN3CCCC3)=CC=2)=N1 HEEWFRYQSLPADJ-UHFFFAOYSA-N 0.000 claims description 2
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