CA2624649A1 - Novel imidazo [4,5 -b] pyridine derivatives as inhibitors of glycogen synthase kinase 3 for use in the treatment of dementia and neurodegenerative disorders - Google Patents

Info

Publication number

CA2624649A1

CA2624649A1 CA002624649A CA2624649A CA2624649A1 CA 2624649 A1 CA2624649 A1 CA 2624649A1 CA 002624649 A CA002624649 A CA 002624649A CA 2624649 A CA2624649 A CA 2624649A CA 2624649 A1 CA2624649 A1 CA 2624649A1

Authority

CA

Canada

Prior art keywords

imidazo

phenyl

3alkyl

pyridine

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.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 206010012289 Dementia Diseases 0.000 title claims description 14
• 208000015122 neurodegenerative disease Diseases 0.000 title claims description 7
• 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 title description 46
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical class C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 title description 7
• 239000003112 inhibitor Substances 0.000 title description 6
• 102000001267 GSK3 Human genes 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 315
• 150000003839 salts Chemical class 0.000 claims abstract description 74
• 239000012453 solvate Substances 0.000 claims abstract description 49
• 238000000034 method Methods 0.000 claims abstract description 31
• 239000012458 free base Substances 0.000 claims abstract description 26
• 230000008569 process Effects 0.000 claims abstract description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 115
• 239000001257 hydrogen Substances 0.000 claims description 109
• 229910052739 hydrogen Inorganic materials 0.000 claims description 109
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 102
• 125000005843 halogen group Chemical group 0.000 claims description 97
• 150000002431 hydrogen Chemical group 0.000 claims description 87
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 86
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 84
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 67
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 58
• 125000001072 heteroaryl group Chemical group 0.000 claims description 55
• 125000005842 heteroatom Chemical group 0.000 claims description 49
• 125000004429 atom Chemical group 0.000 claims description 46
• -1 OR a Chemical group 0.000 claims description 44
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 41
• 125000003118 aryl group Chemical group 0.000 claims description 41
• 229910052799 carbon Inorganic materials 0.000 claims description 41
• 125000000623 heterocyclic group Chemical group 0.000 claims description 41
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 39
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 38
• 238000006243 chemical reaction Methods 0.000 claims description 35
• 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 33
• 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 31
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 24
• 230000002265 prevention Effects 0.000 claims description 24
• 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
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 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 19
• 208000024827 Alzheimer disease Diseases 0.000 claims description 18
• 150000002367 halogens Chemical group 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 17
• 229910052717 sulfur Inorganic materials 0.000 claims description 17
• 238000001816 cooling Methods 0.000 claims description 16
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 150000001412 amines Chemical class 0.000 claims description 14
• 208000010877 cognitive disease Diseases 0.000 claims description 13
• DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 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 12
• 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 10
• 201000011240 Frontotemporal dementia Diseases 0.000 claims description 10
• 239000003054 catalyst Substances 0.000 claims description 10
• 239000003814 drug Substances 0.000 claims description 10
• 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
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• 238000006880 cross-coupling reaction Methods 0.000 claims description 9
• 238000010438 heat treatment Methods 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 206010027175 memory impairment Diseases 0.000 claims description 9
• 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 8
• 201000004384 Alopecia Diseases 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 8
• 230000015572 biosynthetic process Effects 0.000 claims description 8
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
• 201000010099 disease Diseases 0.000 claims description 8
• 208000035475 disorder Diseases 0.000 claims description 8
• 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 7
• 150000004985 diamines Chemical class 0.000 claims description 7
• 150000002148 esters Chemical class 0.000 claims description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
• 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 6
• 206010012601 diabetes mellitus Diseases 0.000 claims description 6
• 230000004770 neurodegeneration Effects 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
• JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 5
• 208000027089 Parkinsonian disease Diseases 0.000 claims description 5
• 206010034010 Parkinsonism Diseases 0.000 claims description 5
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
• 210000000988 bone and bone Anatomy 0.000 claims description 5
• 230000001684 chronic effect Effects 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 230000003676 hair loss Effects 0.000 claims description 5
• SSTZONWYPGYLEG-UHFFFAOYSA-N methyl 4-[7-iodo-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(I)C=CN=C2N1COCC[Si](C)(C)C SSTZONWYPGYLEG-UHFFFAOYSA-N 0.000 claims description 5
• 230000009467 reduction Effects 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
• 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
• 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 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
• 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 4
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 4
• 208000020925 Bipolar disease Diseases 0.000 claims description 4
• 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 4
• 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 4
• 201000010374 Down Syndrome Diseases 0.000 claims description 4
• 208000023105 Huntington disease Diseases 0.000 claims description 4
• 208000019022 Mood disease Diseases 0.000 claims description 4
• 208000014060 Niemann-Pick disease Diseases 0.000 claims description 4
• 208000018737 Parkinson disease Diseases 0.000 claims description 4
• 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
• 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 4
• 239000004480 active ingredient Substances 0.000 claims description 4
• 150000001408 amides Chemical class 0.000 claims description 4
• 230000006999 cognitive decline Effects 0.000 claims description 4
• 238000009833 condensation Methods 0.000 claims description 4
• 230000005494 condensation Effects 0.000 claims description 4
• 239000003433 contraceptive agent Substances 0.000 claims description 4
• 208000017004 dementia pugilistica Diseases 0.000 claims description 4
• 208000024963 hair loss Diseases 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
• WYFUKOPEMTUKDY-UHFFFAOYSA-N methyl 6-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]pyridine-3-carboxylate Chemical compound N1=CC(C(=O)OC)=CC=C1C1=NC2=C(C=3C=CC(OC)=CC=3)C=CN=C2N1 WYFUKOPEMTUKDY-UHFFFAOYSA-N 0.000 claims description 4
• 230000007170 pathology Effects 0.000 claims description 4
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 4
• 230000009466 transformation Effects 0.000 claims description 4
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
• 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 3
• 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 3
• 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 3
• 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 3
• 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 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
• 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 3
• 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 3
• 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 3
• HNIFHMSPACDFRS-UHFFFAOYSA-N 3-[7-(4-carbamoylphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]-n-(3-methoxypropyl)benzamide;hydrochloride Chemical compound Cl.COCCCNC(=O)C1=CC=CC(C=2NC3=NC=CC(=C3N=2)C=2C=CC(=CC=2)C(N)=O)=C1 HNIFHMSPACDFRS-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• 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 3
• 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 3
• 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 3
• 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 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
• 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 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
• 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 3
• 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 3
• 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 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
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• KIMGDDXRMVKAPK-UHFFFAOYSA-N [4-[7-(3-fluoro-4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1=C(F)C(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CCN(C)CC1)N2 KIMGDDXRMVKAPK-UHFFFAOYSA-N 0.000 claims description 3
• CVDNBZXGWVGYPR-UHFFFAOYSA-N [4-[7-(3-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.COC1=CC=CC(C=2C=3N=C(NC=3N=CC=2)C=2C=CC(=CC=2)C(=O)N2CCN(C)CC2)=C1 CVDNBZXGWVGYPR-UHFFFAOYSA-N 0.000 claims description 3
• UABNBNVPWOZNRB-UHFFFAOYSA-N [4-[7-(4-chlorophenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.C1CN(C)CCN1C(=O)C1=CC=C(C=2NC3=NC=CC(=C3N=2)C=2C=CC(Cl)=CC=2)C=C1 UABNBNVPWOZNRB-UHFFFAOYSA-N 0.000 claims description 3
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• HIWOHIQSVOSTAP-UHFFFAOYSA-N [4-[7-(4-methoxy-2-methylphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone;hydrochloride Chemical compound Cl.CC1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CCN(C)CC1)N2 HIWOHIQSVOSTAP-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
• NHECRIZPDJYOLQ-UHFFFAOYSA-N [4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]phenyl]-piperidin-1-ylmethanone Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)N1CCCCC1)N2 NHECRIZPDJYOLQ-UHFFFAOYSA-N 0.000 claims description 3
• OETXCWHFFRQIEN-UHFFFAOYSA-N [4-[7-[3-(3-hydroxypropoxy)phenyl]-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(OCCCO)C=CC=2)COCC[Si](C)(C)C)C=C1 OETXCWHFFRQIEN-UHFFFAOYSA-N 0.000 claims description 3
• ACBCYZPAISGQKJ-UHFFFAOYSA-N [4-[7-[3-(3-methoxypropoxy)phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]phenyl]-(4-methylpiperazin-1-yl)methanone Chemical compound COCCCOC1=CC=CC(C=2C=3N=C(N(COCC[Si](C)(C)C)C=3N=CC=2)C=2C=CC(=CC=2)C(=O)N2CCN(C)CC2)=C1 ACBCYZPAISGQKJ-UHFFFAOYSA-N 0.000 claims description 3
• HLVDXDQDRNTZDL-UHFFFAOYSA-N [5-[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=C1N=C(C=1C=C(C=NC=1)C(=O)N1CCN(C)CC1)N2 HLVDXDQDRNTZDL-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
• 230000007000 age related cognitive decline Effects 0.000 claims description 3
• 206010068168 androgenetic alopecia Diseases 0.000 claims description 3
• 201000002996 androgenic alopecia Diseases 0.000 claims description 3
• YDCDUQPXQNWFEL-UHFFFAOYSA-N azetidin-1-yl-[4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]phenyl]methanone;hydrochloride Chemical compound Cl.C=1C=C(C=2C=3N=C(NC=3N=CC=2)C=2C=CC(CN3CCOCC3)=CC=2)C=CC=1C(=O)N1CCC1 YDCDUQPXQNWFEL-UHFFFAOYSA-N 0.000 claims description 3
• 230000001149 cognitive effect Effects 0.000 claims description 3
• 230000002254 contraceptive effect Effects 0.000 claims description 3
• 230000007423 decrease Effects 0.000 claims description 3
• 229940079593 drug Drugs 0.000 claims description 3
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
• BUURIHMBJYACFK-UHFFFAOYSA-N methyl 3-(1h-imidazo[4,5-b]pyridin-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2NC3=NC=CC=C3N=2)=C1 BUURIHMBJYACFK-UHFFFAOYSA-N 0.000 claims description 3
• HSUXPKGWFKGHSX-UHFFFAOYSA-N methyl 3-(7-chloro-1h-imidazo[4,5-b]pyridin-2-yl)benzoate Chemical compound COC(=O)C1=CC=CC(C=2NC3=NC=CC(Cl)=C3N=2)=C1 HSUXPKGWFKGHSX-UHFFFAOYSA-N 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
• 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 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
• RWXXZUMEMMCJJJ-UHFFFAOYSA-N methyl 4-[7-(3-phenylmethoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(C=3C=C(OCC=4C=CC=CC=4)C=CC=3)C=CN=C2N1 RWXXZUMEMMCJJJ-UHFFFAOYSA-N 0.000 claims description 3
• NCKKFDNUOSKORE-UHFFFAOYSA-N methyl 4-[7-(4-cyanophenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(C=3C=CC(=CC=3)C#N)C=CN=C2N1 NCKKFDNUOSKORE-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
• RFTQTIVAYYCZLB-UHFFFAOYSA-N methyl 4-[7-[3-(3-hydroxypropyl)phenyl]-3-(2-trimethylsilylethoxymethyl)imidazo[4,5-b]pyridin-2-yl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=NC2=C(C=3C=C(CCCO)C=CC=3)C=CN=C2N1COCC[Si](C)(C)C RFTQTIVAYYCZLB-UHFFFAOYSA-N 0.000 claims description 3
• 208000027061 mild cognitive impairment Diseases 0.000 claims description 3
• UPRXTQAJDYJXNI-UHFFFAOYSA-N n-(2-methoxyethyl)-3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]benzamide;hydrochloride Chemical compound Cl.COCCNC(=O)C1=CC=CC(C=2NC3=NC=CC(=C3N=2)C=2C=CC(OC)=CC=2)=C1 UPRXTQAJDYJXNI-UHFFFAOYSA-N 0.000 claims description 3
• JLUVYUKBEDVRHA-UHFFFAOYSA-N n-(3-methoxypropyl)-4-(7-pyridin-4-yl-1h-imidazo[4,5-b]pyridin-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)NCCCOC)=CC=C1C1=NC2=C(C=3C=CN=CC=3)C=CN=C2N1 JLUVYUKBEDVRHA-UHFFFAOYSA-N 0.000 claims description 3
• QDTSCWMFJGFENP-UHFFFAOYSA-N n-methyl-4-[2-[4-(morpholin-4-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridin-7-yl]benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)NC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(CN3CCOCC3)=CC=1)N2 QDTSCWMFJGFENP-UHFFFAOYSA-N 0.000 claims description 3
• 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 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
• 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
• 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 2
• MBFMBSHGZDKLGD-UHFFFAOYSA-N 3-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]-n-(3-methoxypropyl)benzamide;hydrochloride Chemical compound Cl.COCCCNC(=O)C1=CC=CC(C=2NC3=NC=CC(=C3N=2)C=2C=CC(OC)=CC=2)=C1 MBFMBSHGZDKLGD-UHFFFAOYSA-N 0.000 claims description 2
• JBJOMWZBRVNAPF-UHFFFAOYSA-N 4-[2-[3-(morpholine-4-carbonyl)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=C(C=CC=1)C(=O)N1CCOCC1)N2 JBJOMWZBRVNAPF-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
• 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
• WTIILCXQIXXIJL-UHFFFAOYSA-N 4-[7-(4-methoxyphenyl)-1h-imidazo[4,5-b]pyridin-2-yl]-n-(2-piperidin-1-ylethyl)benzamide Chemical compound C1=CC(OC)=CC=C1C1=CC=NC2=C1N=C(C=1C=CC(=CC=1)C(=O)NCCN1CCCCC1)N2 WTIILCXQIXXIJL-UHFFFAOYSA-N 0.000 claims description 2
• PVOZVSDWDTVFIO-UHFFFAOYSA-N 4-[7-[3-(2-cyanoethylcarbamoyl)phenyl]-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=C1C1=CC=CC(C(=O)NCCC#N)=C1 PVOZVSDWDTVFIO-UHFFFAOYSA-N 0.000 claims description 2
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