KR20080059285A - 치매 및 신경변성 장애의 치료에 사용하기 위한 글리코겐신타제 키나제 3 억제제로서의 신규이미다조[4,5-ｂ]피리딘 유도체 - Google Patents

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Publication number

KR20080059285A

KR20080059285A KR1020087010753A KR20087010753A KR20080059285A KR 20080059285 A KR20080059285 A KR 20080059285A KR 1020087010753 A KR1020087010753 A KR 1020087010753A KR 20087010753 A KR20087010753 A KR 20087010753A KR 20080059285 A KR20080059285 A KR 20080059285A

Authority

KR

South Korea

Prior art keywords

alkyl

imidazo

phenyl

haloalkyl

optionally substituted

Prior art date

2005-10-03

Legal status (The legal status 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 status listed.)

Withdrawn

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• 238000011282 treatment Methods 0.000 title claims description 32
• 206010012289 Dementia Diseases 0.000 title claims description 24
• 208000015122 neurodegenerative disease Diseases 0.000 title claims description 7
• 239000003572 glycogen synthase kinase 3 inhibitor Substances 0.000 title 1
• 150000003222 pyridines Chemical class 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 308
• 150000003839 salts Chemical class 0.000 claims abstract description 60
• 238000000034 method Methods 0.000 claims abstract description 49
• 239000012453 solvate Substances 0.000 claims abstract description 49
• 239000012458 free base Substances 0.000 claims abstract description 22
• 238000002360 preparation method Methods 0.000 claims abstract description 8
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
• 125000000217 alkyl group Chemical group 0.000 claims description 349
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 136
• 229910052739 hydrogen Inorganic materials 0.000 claims description 130
• -1 OR a Chemical group 0.000 claims description 127
• 239000001257 hydrogen Substances 0.000 claims description 109
• 229910052799 carbon Inorganic materials 0.000 claims description 104
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 100
• 125000005843 halogen group Chemical group 0.000 claims description 99
• 150000002431 hydrogen Chemical class 0.000 claims description 94
• 125000001188 haloalkyl group Chemical group 0.000 claims description 79
• 125000000623 heterocyclic group Chemical group 0.000 claims description 70
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 64
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 60
• 125000001072 heteroaryl group Chemical group 0.000 claims description 55
• 125000003545 alkoxy group Chemical group 0.000 claims description 53
• 229910052717 sulfur Inorganic materials 0.000 claims description 51
• 125000005842 heteroatom Chemical group 0.000 claims description 50
• 125000004429 atom Chemical group 0.000 claims description 46
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 37
• 125000003118 aryl group Chemical group 0.000 claims description 36
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 36
• 229910052760 oxygen Inorganic materials 0.000 claims description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 238000006243 chemical reaction Methods 0.000 claims description 28
• 125000003821 2-(trimethylsilyl)ethoxymethyl group Chemical group [H]C([H])([H])[Si](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C(OC([H])([H])[*])([H])[H] 0.000 claims description 25
• KXLRANARIIPDBC-UHFFFAOYSA-N 4-(4-methoxyphenyl)pyridine-2,3-diamine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC(N)=C1N KXLRANARIIPDBC-UHFFFAOYSA-N 0.000 claims description 22
• 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 21
• 201000010099 disease Diseases 0.000 claims description 20
• 150000001412 amines Chemical class 0.000 claims description 18
• 239000000460 chlorine Substances 0.000 claims description 18
• 208000010877 cognitive disease Diseases 0.000 claims description 17
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 16
• 238000001816 cooling Methods 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 16
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 14
• 230000002265 prevention Effects 0.000 claims description 14
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
• IJXJGIWROCZHKS-UHFFFAOYSA-N 4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(O)=O)N2 IJXJGIWROCZHKS-UHFFFAOYSA-N 0.000 claims description 13
• 125000004076 pyridyl group Chemical group 0.000 claims description 12
• BALCZNSTFKAYEZ-UHFFFAOYSA-N 3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(C=CC=1)C(O)=O)N2 BALCZNSTFKAYEZ-UHFFFAOYSA-N 0.000 claims description 11
• 239000003054 catalyst Substances 0.000 claims description 11
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 11
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 238000004519 manufacturing process Methods 0.000 claims description 10
• PAAJESGBRNIYKE-UHFFFAOYSA-N 4-[[4-(7-chloro-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]methyl]morpholine Chemical compound N=1C=2C(Cl)=CC=NC=2NC=1C(C=C1)=CC=C1CN1CCOCC1 PAAJESGBRNIYKE-UHFFFAOYSA-N 0.000 claims description 9
• FXHZWSCNTVBMJZ-UHFFFAOYSA-N [4-(7-chloro-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(Cl)=C3N=2)C=C1 FXHZWSCNTVBMJZ-UHFFFAOYSA-N 0.000 claims description 9
• 239000008194 pharmaceutical composition Substances 0.000 claims description 9
• 201000004384 Alopecia Diseases 0.000 claims description 8
• 208000024827 Alzheimer disease Diseases 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
• 125000004122 cyclic group Chemical group 0.000 claims description 8
• 206010027175 memory impairment Diseases 0.000 claims description 8
• 208000028698 Cognitive impairment Diseases 0.000 claims description 7
• PYDQOBHBRGWVIL-UHFFFAOYSA-N [4-(7-chloro-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]-morpholin-4-ylmethanone Chemical compound N=1C=2C(Cl)=CC=NC=2NC=1C(C=C1)=CC=C1C(=O)N1CCOCC1 PYDQOBHBRGWVIL-UHFFFAOYSA-N 0.000 claims description 7
• 230000006999 cognitive decline Effects 0.000 claims description 7
• 150000004985 diamines Chemical class 0.000 claims description 7
• 150000002148 esters Chemical class 0.000 claims description 7
• 230000008569 process Effects 0.000 claims description 7
• 201000000980 schizophrenia Diseases 0.000 claims description 7
• 241000894007 species Species 0.000 claims description 7
• XNQXCKZRTQGHQV-UHFFFAOYSA-N 7-chloro-2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound C1CN(C)CCN1CC1=CC=C(C=2NC3=NC=CC(Cl)=C3N=2)C=C1 XNQXCKZRTQGHQV-UHFFFAOYSA-N 0.000 claims description 6
• 208000020925 Bipolar disease Diseases 0.000 claims description 6
• 208000018737 Parkinson disease Diseases 0.000 claims description 6
• 210000000988 bone and bone Anatomy 0.000 claims description 6
• 238000006880 cross-coupling reaction Methods 0.000 claims description 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 210000002682 neurofibrillary tangle Anatomy 0.000 claims description 6
• 125000003107 substituted aryl group Chemical group 0.000 claims description 6
• FACBSERRRVDKFO-UHFFFAOYSA-N 4-(3-methoxyphenyl)pyridine-2,3-diamine Chemical compound COC1=CC=CC(C=2C(=C(N)N=CC=2)N)=C1 FACBSERRRVDKFO-UHFFFAOYSA-N 0.000 claims description 5
• 206010019196 Head injury Diseases 0.000 claims description 5
• 241000282412 Homo Species 0.000 claims description 5
• 230000032683 aging Effects 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 230000007423 decrease Effects 0.000 claims description 5
• 230000003676 hair loss Effects 0.000 claims description 5
• 238000011321 prophylaxis Methods 0.000 claims description 5
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 230000009467 reduction Effects 0.000 claims description 5
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
• HMLRBRPZIQSPBV-UHFFFAOYSA-N 3-[7-(4-carbamoylphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound C1=CC(C(=O)N)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(C=CC=1)C(O)=O)N2 HMLRBRPZIQSPBV-UHFFFAOYSA-N 0.000 claims description 4
• PQLCSWPDNRIYPJ-UHFFFAOYSA-N 4-(3-methoxyphenyl)-3-nitro-2-phenylmethoxypyridine Chemical compound COC1=CC=CC(C=2C(=C(OCC=3C=CC=CC=3)N=CC=2)[N+]([O-])=O)=C1 PQLCSWPDNRIYPJ-UHFFFAOYSA-N 0.000 claims description 4
• WGFCHNWKFQLGTG-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3-nitro-2-phenylmethoxypyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O WGFCHNWKFQLGTG-UHFFFAOYSA-N 0.000 claims description 4
• JGUVOZHBKZAPNL-UHFFFAOYSA-N 4-(4-methoxyphenyl)-3-nitropyridin-2-amine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC(N)=C1[N+]([O-])=O JGUVOZHBKZAPNL-UHFFFAOYSA-N 0.000 claims description 4
• XGBAZKBVSNNKJF-UHFFFAOYSA-N 4-(7-iodo-1h-imidazo[4,5-b]pyridin-2-yl)benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=NC2=C(I)C=CN=C2N1 XGBAZKBVSNNKJF-UHFFFAOYSA-N 0.000 claims description 4
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
• XYJNNGCPTPXGBG-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-(1h-pyrrol-2-yl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1NC=CC=1)N2 XYJNNGCPTPXGBG-UHFFFAOYSA-N 0.000 claims description 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
• 201000010374 Down Syndrome Diseases 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• 206010033799 Paralysis Diseases 0.000 claims description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 238000009833 condensation Methods 0.000 claims description 4
• 230000005494 condensation Effects 0.000 claims description 4
• 208000017004 dementia pugilistica Diseases 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 206010014599 encephalitis Diseases 0.000 claims description 4
• 210000001652 frontal lobe Anatomy 0.000 claims description 4
• 208000024963 hair loss Diseases 0.000 claims description 4
• XIPIZLYYOZWNEX-UHFFFAOYSA-N methyl 4-(7-iodo-1h-imidazo[4,5-b]pyridin-2-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(I)C=CN=C2N1 XIPIZLYYOZWNEX-UHFFFAOYSA-N 0.000 claims description 4
• LXDBMNQRJJHDTA-UHFFFAOYSA-N methyl 4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 LXDBMNQRJJHDTA-UHFFFAOYSA-N 0.000 claims description 4
• FVAZSNNBIWFQHL-UHFFFAOYSA-N methyl 4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(C=3C=CC(OC)=CC=3)C=CN=C2N1 FVAZSNNBIWFQHL-UHFFFAOYSA-N 0.000 claims description 4
• 230000004770 neurodegeneration Effects 0.000 claims description 4
• 208000021090 palsy Diseases 0.000 claims description 4
• WGAMUFDJOHTHRC-UHFFFAOYSA-N (2-methylpiperazin-1-yl)-[4-[7-(3-phenylmethoxyphenyl)-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]phenyl]methanone Chemical compound CC1CNCCN1C(=O)C1=CC=C(C=2N(C3=NC=CC(=C3N=2)C=2C=C(OCC=3C=CC=CC=3)C=CC=2)COCC[Si](C)(C)C)C=C1 WGAMUFDJOHTHRC-UHFFFAOYSA-N 0.000 claims description 3
• GLSSLQQFUSWGCO-UHFFFAOYSA-N 2-(butoxymethyl)-7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CN=C2NC(COCCCC)=NC2=C1C1=CC=C(OC)C=C1 GLSSLQQFUSWGCO-UHFFFAOYSA-N 0.000 claims description 3
• MIORAZJRJQHQHZ-UHFFFAOYSA-N 2-(furan-2-ylmethyl)-7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(CC=1OC=CC=1)N2 MIORAZJRJQHQHZ-UHFFFAOYSA-N 0.000 claims description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
• ZALZZNHYZCGVKO-UHFFFAOYSA-N 4-(7-chloro-1h-imidazo[4,5-b]pyridin-2-yl)-n-(2-morpholin-4-ylethyl)benzamide Chemical compound N=1C=2C(Cl)=CC=NC=2NC=1C(C=C1)=CC=C1C(=O)NCCN1CCOCC1 ZALZZNHYZCGVKO-UHFFFAOYSA-N 0.000 claims description 3
• JLLKIKHUTZDFCG-UHFFFAOYSA-N 4-[2-(4-carboxyphenyl)-1h-imidazo[4,5-b]pyridin-7-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=NC2=C(C=3C=CC(=CC=3)C(O)=O)C=CN=C2N1 JLLKIKHUTZDFCG-UHFFFAOYSA-N 0.000 claims description 3
• YXJDTECHHFCYKK-UHFFFAOYSA-N 4-[3-(morpholin-4-ylmethyl)phenyl]pyridine-2,3-diamine Chemical compound NC1=NC=CC(C=2C=C(CN3CCOCC3)C=CC=2)=C1N YXJDTECHHFCYKK-UHFFFAOYSA-N 0.000 claims description 3
• LMWYVGFPAOYHGP-UHFFFAOYSA-N 4-[7-[3-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=NC2=NC=CC(C=3C=C(CN4CCOCC4)C=CC=3)=C2N1 LMWYVGFPAOYHGP-UHFFFAOYSA-N 0.000 claims description 3
• GKRRBTNYWQUJMS-UHFFFAOYSA-N 5-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]pyridine-3-carboxylic acid Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(C=NC=1)C(O)=O)N2 GKRRBTNYWQUJMS-UHFFFAOYSA-N 0.000 claims description 3
• ZQHYVHUGNIVYES-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-(1-methylcyclopropyl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C1(C)CC1)N2 ZQHYVHUGNIVYES-UHFFFAOYSA-N 0.000 claims description 3
• NZTKENWPOBUUHP-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-(3-methylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(C=CC=1)S(C)(=O)=O)N2 NZTKENWPOBUUHP-UHFFFAOYSA-N 0.000 claims description 3
• PFZVYMQANHMFIV-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-(4-methylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)S(C)(=O)=O)N2 PFZVYMQANHMFIV-UHFFFAOYSA-N 0.000 claims description 3
• DHDKTDJNVQASCH-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-phenyl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC=CC=1)N2 DHDKTDJNVQASCH-UHFFFAOYSA-N 0.000 claims description 3
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 3
• 201000002832 Lewy body dementia Diseases 0.000 claims description 3
• 208000019022 Mood disease Diseases 0.000 claims description 3
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• 206010044688 Trisomy 21 Diseases 0.000 claims description 3
• 201000004810 Vascular dementia Diseases 0.000 claims description 3
• BEWLGIZSXTVJMR-UHFFFAOYSA-N [3-(2,3-diaminopyridin-4-yl)phenyl]-morpholin-4-ylmethanone Chemical compound NC1=NC=CC(C=2C=C(C=CC=2)C(=O)N2CCOCC2)=C1N BEWLGIZSXTVJMR-UHFFFAOYSA-N 0.000 claims description 3
• PJWTUHZITJAHDB-UHFFFAOYSA-N [3-(2-amino-3-nitropyridin-4-yl)phenyl]-morpholin-4-ylmethanone Chemical compound NC1=NC=CC(C=2C=C(C=CC=2)C(=O)N2CCOCC2)=C1[N+]([O-])=O PJWTUHZITJAHDB-UHFFFAOYSA-N 0.000 claims description 3
• HBFNRIYXMFRSEJ-UHFFFAOYSA-N [4-(7-chloro-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]-piperidin-1-ylmethanone Chemical compound N=1C=2C(Cl)=CC=NC=2NC=1C(C=C1)=CC=C1C(=O)N1CCCCC1 HBFNRIYXMFRSEJ-UHFFFAOYSA-N 0.000 claims description 3
• FXZWIBJICOEWKH-UHFFFAOYSA-N [4-[7-(3-hydroxyphenyl)-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N(C3=NC=CC(=C3N=2)C=2C=C(O)C=CC=2)COCC[Si](C)(C)C)C=C1 FXZWIBJICOEWKH-UHFFFAOYSA-N 0.000 claims description 3
• IPICHSBCZSQZJV-UHFFFAOYSA-N [4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methyl-1,4-diazepan-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CCN(C)CCC1)N2 IPICHSBCZSQZJV-UHFFFAOYSA-N 0.000 claims description 3
• YOOOBTGZFFDDAN-UHFFFAOYSA-N [4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-morpholin-4-ylmethanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CCOCC1)N2 YOOOBTGZFFDDAN-UHFFFAOYSA-N 0.000 claims description 3
• FKKKXIVHZIEUTC-UHFFFAOYSA-N [4-[7-[3-(3-methoxypropoxy)phenyl]-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound COCCCOC1=CC=CC(C=2C=3N=C(NC=3N=CC=2)C=2C=CC(=CC=2)C(=O)N2CCN(C)CC2)=C1 FKKKXIVHZIEUTC-UHFFFAOYSA-N 0.000 claims description 3
• WRYBAXIMARUDLZ-UHFFFAOYSA-N [6-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]pyridin-3-yl]-(4-methylpiperazin-1-yl)methanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1NC(C=1N=CC(=CC=1)C(=O)N1CCN(C)CC1)=N2 WRYBAXIMARUDLZ-UHFFFAOYSA-N 0.000 claims description 3
• 150000001408 amides Chemical class 0.000 claims description 3
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• 230000002254 contraceptive effect Effects 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• FVFKDCKCUZPDHW-UHFFFAOYSA-N methyl 3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound COC(=O)C1=CC=CC(C=2NC3=NC=CC(=C3N=2)C=2C=CC(OC)=CC=2)=C1 FVFKDCKCUZPDHW-UHFFFAOYSA-N 0.000 claims description 3
• HZEOQABBGYBGSX-UHFFFAOYSA-N methyl 4-[7-(3-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(C=3C=C(OC)C=CC=3)C=CN=C2N1 HZEOQABBGYBGSX-UHFFFAOYSA-N 0.000 claims description 3
• XCLZKTYDTPVQIK-UHFFFAOYSA-N methyl 4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OC)=CC(C=2NC3=NC=CC(=C3N=2)C=2C=CC(OC)=CC=2)=C1 XCLZKTYDTPVQIK-UHFFFAOYSA-N 0.000 claims description 3
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• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• CBCIAUMJVNQJRQ-UHFFFAOYSA-N (3,3-difluoropyrrolidin-1-yl)-[4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CC(F)(F)CC1)N2 CBCIAUMJVNQJRQ-UHFFFAOYSA-N 0.000 claims description 2
• WMMGLBJEZYMFLR-UHFFFAOYSA-N (3-hydroxypyrrolidin-1-yl)-[4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CC(O)CC1)N2 WMMGLBJEZYMFLR-UHFFFAOYSA-N 0.000 claims description 2
• XDSKFFHHNMPIQI-UHFFFAOYSA-N (4-ethylpiperazin-1-yl)-[4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone Chemical compound C1CN(CC)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CC(OC)=CC=2)C=C1 XDSKFFHHNMPIQI-UHFFFAOYSA-N 0.000 claims description 2
• LYSLFYAVVPQHDU-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-(7-pyridin-3-yl-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=NC=CC=2)C=C1 LYSLFYAVVPQHDU-UHFFFAOYSA-N 0.000 claims description 2
• CTGLAMQPUCKHHS-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-(7-pyridin-4-yl-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CN=CC=2)C=C1 CTGLAMQPUCKHHS-UHFFFAOYSA-N 0.000 claims description 2
• CFTZTWRIOMKBFT-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-[7-(4-propan-2-yloxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone;hydrochloride Chemical compound Cl.C1=CC(OC(C)C)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CCN(C)CC1)N2 CFTZTWRIOMKBFT-UHFFFAOYSA-N 0.000 claims description 2
• MXGZVMBBTXDMGO-UHFFFAOYSA-N (4-methylpiperazin-1-yl)-[4-[7-[4-(trifluoromethoxy)phenyl]-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CC(OC(F)(F)F)=CC=2)C=C1 MXGZVMBBTXDMGO-UHFFFAOYSA-N 0.000 claims description 2
• UOKUQFDSZLDBOH-UHFFFAOYSA-N 1-[4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]phenyl]ethanone;hydrochloride Chemical compound Cl.C1=CC(C(=O)C)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 UOKUQFDSZLDBOH-UHFFFAOYSA-N 0.000 claims description 2
• RLIVPPAEIIRNMH-UHFFFAOYSA-N 2-(methoxymethyl)-7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CN=C2NC(COC)=NC2=C1C1=CC=C(OC)C=C1 RLIVPPAEIIRNMH-UHFFFAOYSA-N 0.000 claims description 2
• RXMUTEXQWNOBOA-UHFFFAOYSA-N 2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-7-pyridin-4-yl-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.C1CN(C)CCN1CC1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CN=CC=2)C=C1 RXMUTEXQWNOBOA-UHFFFAOYSA-N 0.000 claims description 2
• AVUCVRZLKJBJNI-UHFFFAOYSA-N 2-[4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]phenyl]acetonitrile;hydrochloride Chemical compound Cl.C1=CC(CC#N)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 AVUCVRZLKJBJNI-UHFFFAOYSA-N 0.000 claims description 2
• LKPAFARFQDZNGR-UHFFFAOYSA-N 3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]-n-pyridin-3-ylbenzamide;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(C=CC=1)C(=O)NC=1C=NC=CC=1)N2 LKPAFARFQDZNGR-UHFFFAOYSA-N 0.000 claims description 2
• DRJFKMUKYAQPQR-UHFFFAOYSA-N 4-[2-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]benzonitrile;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CC(=CC=2)C#N)C=C1 DRJFKMUKYAQPQR-UHFFFAOYSA-N 0.000 claims description 2
• SIIHBPHCRUCPOR-UHFFFAOYSA-N 4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)N)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 SIIHBPHCRUCPOR-UHFFFAOYSA-N 0.000 claims description 2
• QJOUUBUMERTVNV-UHFFFAOYSA-N 4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]benzoic acid;hydrochloride Chemical compound Cl.C1=CC(C(=O)O)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 QJOUUBUMERTVNV-UHFFFAOYSA-N 0.000 claims description 2
• NXNDYFZIEBKHSO-UHFFFAOYSA-N 4-[2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]benzamide;hydrochloride Chemical compound Cl.C1CN(C)CCN1CC1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CC(=CC=2)C(N)=O)C=C1 NXNDYFZIEBKHSO-UHFFFAOYSA-N 0.000 claims description 2
• VDQQMFGWBDEXDV-UHFFFAOYSA-N 4-[3-[2-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]phenoxy]butanenitrile Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=C(OCCCC#N)C=CC=2)C=C1 VDQQMFGWBDEXDV-UHFFFAOYSA-N 0.000 claims description 2
• MWRHGSOULIQURG-UHFFFAOYSA-N 4-[3-[2-[4-(4-methylpiperazine-1-carbonyl)phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-7-yl]phenoxy]butanenitrile Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(C=2N(C3=NC=CC(=C3N=2)C=2C=C(OCCCC#N)C=CC=2)COCC[Si](C)(C)C)C=C1 MWRHGSOULIQURG-UHFFFAOYSA-N 0.000 claims description 2
• XFWPVDFHFGIYEJ-UHFFFAOYSA-N 4-[7-(3-phenylmethoxyphenyl)-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]benzoic acid Chemical compound C1=CN=C2N(COCC[Si](C)(C)C)C(C=3C=CC(=CC=3)C(O)=O)=NC2=C1C(C=1)=CC=CC=1OCC1=CC=CC=C1 XFWPVDFHFGIYEJ-UHFFFAOYSA-N 0.000 claims description 2
• VBVGVQSWIKMKJZ-UHFFFAOYSA-N 4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]-n-(2-morpholin-4-ylethyl)benzamide;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)NCCN1CCOCC1)N2 VBVGVQSWIKMKJZ-UHFFFAOYSA-N 0.000 claims description 2
• YELUXWWGBHRGGM-UHFFFAOYSA-N 4-[[3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methyl]morpholine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(CN3CCOCC3)C=CC=1)N2 YELUXWWGBHRGGM-UHFFFAOYSA-N 0.000 claims description 2
• QGUVPBFAOYXJKS-UHFFFAOYSA-N 4-[[4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methyl]morpholine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 QGUVPBFAOYXJKS-UHFFFAOYSA-N 0.000 claims description 2
• YEJNEAKCGBRFBM-UHFFFAOYSA-N 5-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]pyridine-2-carbonitrile Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=NC(=CC=1)C#N)N2 YEJNEAKCGBRFBM-UHFFFAOYSA-N 0.000 claims description 2
• DGUACQWNOOVTBK-UHFFFAOYSA-N 7-(3-methoxyphenyl)-2-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=3N=C(NC=3N=CC=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCN(C)CC2)=C1 DGUACQWNOOVTBK-UHFFFAOYSA-N 0.000 claims description 2
• WSRPZUAKUXIARM-UHFFFAOYSA-N 7-(4-ethoxyphenyl)-2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.C1=CC(OCC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCN(C)CC3)=CC=1)N2 WSRPZUAKUXIARM-UHFFFAOYSA-N 0.000 claims description 2
• ANVNDQRXXNEAQZ-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-(6-methylpyridin-3-yl)-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=NC(C)=CC=1)N2 ANVNDQRXXNEAQZ-UHFFFAOYSA-N 0.000 claims description 2
• HYYMWEKOLMNRIM-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(CN3CCN(C)CC3)C=CC=1)N2 HYYMWEKOLMNRIM-UHFFFAOYSA-N 0.000 claims description 2
• LUFOXOGQGFQGKD-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)S(=O)(=O)N1CCN(C)CC1)N2 LUFOXOGQGFQGKD-UHFFFAOYSA-N 0.000 claims description 2
• ABRSGLVDQLXKBF-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-[4-(piperidin-1-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCCCC3)=CC=1)N2 ABRSGLVDQLXKBF-UHFFFAOYSA-N 0.000 claims description 2
• CPHCSCBDAUTLQS-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-imidazo[4,5-b]pyridine;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCN(C)CC3)=CC=1)N2 CPHCSCBDAUTLQS-UHFFFAOYSA-N 0.000 claims description 2
• AEXZTLNXKLHAAS-UHFFFAOYSA-N 7-(4-methoxyphenyl)-2-pyridazin-4-yl-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=NN=CC=1)N2 AEXZTLNXKLHAAS-UHFFFAOYSA-N 0.000 claims description 2
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• YLUGSARWSQZSGI-SFHVURJKSA-N [(3s)-3-fluoropyrrolidin-1-yl]-[4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1C[C@@H](F)CC1)N2 YLUGSARWSQZSGI-SFHVURJKSA-N 0.000 claims description 2
• OWSDVSPPIDUVND-UHFFFAOYSA-N [3-(dimethylamino)pyrrolidin-1-yl]-[4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]methanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CC(CC1)N(C)C)N2 OWSDVSPPIDUVND-UHFFFAOYSA-N 0.000 claims description 2
• DZULTYVDZXLWOA-UHFFFAOYSA-N [3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=C(C=CC=1)C(=O)N1CCN(C)CC1)N2 DZULTYVDZXLWOA-UHFFFAOYSA-N 0.000 claims description 2
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