BRPI0616663A2 - composto e uma base livre ou um sal, solvato ou solvato de um sal do mesmo farmaceuticamente aceitável, formulação farmacêutica, uso de um composto, e, processo para a preparação de um composto - Google Patents
composto e uma base livre ou um sal, solvato ou solvato de um sal do mesmo farmaceuticamente aceitável, formulação farmacêutica, uso de um composto, e, processo para a preparação de um composto Download PDFInfo
- Publication number
- BRPI0616663A2 BRPI0616663A2 BRPI0616663-6A BRPI0616663A BRPI0616663A2 BR PI0616663 A2 BRPI0616663 A2 BR PI0616663A2 BR PI0616663 A BRPI0616663 A BR PI0616663A BR PI0616663 A2 BRPI0616663 A2 BR PI0616663A2
- Authority
- BR
- Brazil
- Prior art keywords
- alkyl
- haloalkyl
- imidazo
- optionally substituted
- phenyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 183
- 150000003839 salts Chemical class 0.000 title claims abstract description 62
- 239000012453 solvate Substances 0.000 title claims abstract description 51
- 239000012458 free base Substances 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 230000008569 process Effects 0.000 title claims abstract description 14
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 4
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims description 119
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 112
- 239000001257 hydrogen Substances 0.000 claims description 89
- 229910052739 hydrogen Inorganic materials 0.000 claims description 89
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 86
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 68
- 125000005843 halogen group Chemical group 0.000 claims description 59
- 125000001072 heteroaryl group Chemical group 0.000 claims description 56
- -1 OR a Chemical group 0.000 claims description 55
- 125000001188 haloalkyl group Chemical group 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 229910052717 sulfur Inorganic materials 0.000 claims description 37
- 125000005842 heteroatom Chemical group 0.000 claims description 34
- 125000004429 atom Chemical group 0.000 claims description 31
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 29
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 27
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 27
- 229910052760 oxygen Inorganic materials 0.000 claims description 27
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 150000001412 amines Chemical class 0.000 claims description 18
- MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims description 18
- 206010012289 Dementia Diseases 0.000 claims description 17
- 208000024827 Alzheimer disease Diseases 0.000 claims description 16
- 208000010877 cognitive disease Diseases 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 238000001816 cooling Methods 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 12
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 208000020925 Bipolar disease Diseases 0.000 claims description 7
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
- 201000004384 Alopecia Diseases 0.000 claims description 6
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- QIIOUULEPKIONV-UHFFFAOYSA-N 4-[[4-(7-iodo-1h-imidazo[4,5-b]pyridin-2-yl)phenyl]methyl]morpholine Chemical compound N=1C=2C(I)=CC=NC=2NC=1C(C=C1)=CC=C1CN1CCOCC1 QIIOUULEPKIONV-UHFFFAOYSA-N 0.000 claims description 5
- 208000027061 mild cognitive impairment Diseases 0.000 claims description 5
- 230000004770 neurodegeneration Effects 0.000 claims description 5
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 5
- OWURUNJNKVMBQR-UHFFFAOYSA-N 7-chloro-2-[4-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=NC2=C(Cl)C=CN=C2N1 OWURUNJNKVMBQR-UHFFFAOYSA-N 0.000 claims description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 4
- 206010019196 Head injury Diseases 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 4
- 206010034010 Parkinsonism Diseases 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 210000000988 bone and bone Anatomy 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000006999 cognitive decline Effects 0.000 claims description 4
- 230000027326 copulation Effects 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 230000003676 hair loss Effects 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 3
- 201000010374 Down Syndrome Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- 208000019022 Mood disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 239000003433 contraceptive agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 208000024963 hair loss Diseases 0.000 claims description 3
- 206010027175 memory impairment Diseases 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- ZZTJLLAGBYOSJR-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[4-(piperidin-1-ylmethyl)phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide;hydrochloride Chemical compound Cl.N=1C=2C(C(=O)NCCCOC)=CC=NC=2NC=1C(C=C1)=CC=C1CN1CCCCC1 ZZTJLLAGBYOSJR-UHFFFAOYSA-N 0.000 claims description 3
- XJAQDHHEMXUDCK-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[4-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide;hydrochloride Chemical compound Cl.N=1C=2C(C(=O)NCCCOC)=CC=NC=2NC=1C1=CC=C(C(F)(F)F)C=C1 XJAQDHHEMXUDCK-UHFFFAOYSA-N 0.000 claims description 3
- 230000007170 pathology Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 208000028698 Cognitive impairment Diseases 0.000 claims description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 2
- 201000002832 Lewy body dementia Diseases 0.000 claims description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 201000004810 Vascular dementia Diseases 0.000 claims description 2
- 206010068168 androgenetic alopecia Diseases 0.000 claims description 2
- 201000002996 androgenic alopecia Diseases 0.000 claims description 2
- 230000002254 contraceptive effect Effects 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- CNECMJPHWSKVJR-UHFFFAOYSA-N 2-[4-(dipropylsulfamoyl)phenyl]-n-(3-methoxypropyl)-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound C1=CC(S(=O)(=O)N(CCC)CCC)=CC=C1C1=NC2=NC=CC(C(=O)NCCCOC)=C2N1 CNECMJPHWSKVJR-UHFFFAOYSA-N 0.000 claims 1
- 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims 1
- 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 1
- 208000014060 Niemann-Pick disease Diseases 0.000 claims 1
- 206010033799 Paralysis Diseases 0.000 claims 1
- 208000006011 Stroke Diseases 0.000 claims 1
- 230000007000 age related cognitive decline Effects 0.000 claims 1
- 231100000876 cognitive deterioration Toxicity 0.000 claims 1
- 230000006866 deterioration Effects 0.000 claims 1
- 239000002184 metal Substances 0.000 claims 1
- ZBFLDYHJMSMQLD-UHFFFAOYSA-N n-(3-methoxypropyl)-2-(4-pyrrolidin-1-ylsulfonylphenyl)-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound N1C=2C(C(=O)NCCCOC)=CC=NC=2N=C1C(C=C1)=CC=C1S(=O)(=O)N1CCCC1 ZBFLDYHJMSMQLD-UHFFFAOYSA-N 0.000 claims 1
- WMFGWWXTAZTXLO-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[2-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound N1C=2C(C(=O)NCCCOC)=CC=NC=2N=C1C1=CC=CC=C1C(F)(F)F WMFGWWXTAZTXLO-UHFFFAOYSA-N 0.000 claims 1
- ZKNVGFSPLKOEJS-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[3-(2,2,3,3-tetrafluoropropoxymethyl)phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound N1C=2C(C(=O)NCCCOC)=CC=NC=2N=C1C1=CC=CC(COCC(F)(F)C(F)F)=C1 ZKNVGFSPLKOEJS-UHFFFAOYSA-N 0.000 claims 1
- WSKAOIFHJGEGBY-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[3-[(4-methylpiperazin-1-yl)methyl]phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound N1C=2C(C(=O)NCCCOC)=CC=NC=2N=C1C(C=1)=CC=CC=1CN1CCN(C)CC1 WSKAOIFHJGEGBY-UHFFFAOYSA-N 0.000 claims 1
- LCSWFDOJPKPHIU-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[4-(4-methylpiperazine-1-carbonyl)phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound N1C=2C(C(=O)NCCCOC)=CC=NC=2N=C1C(C=C1)=CC=C1C(=O)N1CCN(C)CC1 LCSWFDOJPKPHIU-UHFFFAOYSA-N 0.000 claims 1
- ZMAUONZYSAIZLF-UHFFFAOYSA-N n-(3-methoxypropyl)-2-[4-(morpholine-4-carbonyl)phenyl]-1h-imidazo[4,5-b]pyridine-7-carboxamide Chemical compound N1C=2C(C(=O)NCCCOC)=CC=NC=2N=C1C(C=C1)=CC=C1C(=O)N1CCOCC1 ZMAUONZYSAIZLF-UHFFFAOYSA-N 0.000 claims 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 10
- 238000007429 general method Methods 0.000 description 43
- 239000002904 solvent Substances 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 35
- 239000000203 mixture Substances 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 29
- 102000001267 GSK3 Human genes 0.000 description 28
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 238000005160 1H NMR spectroscopy Methods 0.000 description 25
- 239000000047 product Substances 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 16
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical compound C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 13
- 101000823051 Homo sapiens Amyloid-beta precursor protein Proteins 0.000 description 13
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- 238000000746 purification Methods 0.000 description 13
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 238000002953 preparative HPLC Methods 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 239000000460 chlorine Substances 0.000 description 11
- 238000001914 filtration Methods 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 239000003643 water by type Substances 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- FAXDZWQIWUSWJH-UHFFFAOYSA-N 3-methoxypropan-1-amine Chemical compound COCCCN FAXDZWQIWUSWJH-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 150000002500 ions Chemical class 0.000 description 8
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 7
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 239000003112 inhibitor Substances 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- 102000015735 Beta-catenin Human genes 0.000 description 6
- 108060000903 Beta-catenin Proteins 0.000 description 6
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- BLPAOIRJAAEMPC-UHFFFAOYSA-N 2-iodo-1h-imidazo[4,5-b]pyridine Chemical compound C1=CC=C2NC(I)=NC2=N1 BLPAOIRJAAEMPC-UHFFFAOYSA-N 0.000 description 5
- 108010001483 Glycogen Synthase Proteins 0.000 description 5
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 229910002091 carbon monoxide Inorganic materials 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 235000009518 sodium iodide Nutrition 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 4
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 4
- NVVZAKSOQZCEKH-UHFFFAOYSA-N 7-chloro-2-[2-(trifluoromethyl)phenyl]-1h-imidazo[4,5-b]pyridine Chemical compound FC(F)(F)C1=CC=CC=C1C1=NC2=C(Cl)C=CN=C2N1 NVVZAKSOQZCEKH-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P3/00—Drugs for disorders of the metabolism
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
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| SE0502173-8 | 2005-10-03 | ||
| SE0502173 | 2005-10-03 | ||
| PCT/SE2006/001115 WO2007040439A1 (en) | 2005-10-03 | 2006-10-02 | New compounds ii |
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| BRPI0616663A2 true BRPI0616663A2 (pt) | 2011-06-28 |
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| Country | Link |
|---|---|
| US (1) | US20080255106A1 (enExample) |
| EP (1) | EP1934217A4 (enExample) |
| JP (1) | JP2009510162A (enExample) |
| KR (1) | KR20080057334A (enExample) |
| CN (1) | CN101321754A (enExample) |
| AR (1) | AR057525A1 (enExample) |
| AU (1) | AU2006297889A1 (enExample) |
| BR (1) | BRPI0616663A2 (enExample) |
| CA (1) | CA2624869A1 (enExample) |
| IL (1) | IL189945A0 (enExample) |
| NO (1) | NO20082054L (enExample) |
| SA (1) | SA06270365B1 (enExample) |
| TW (1) | TW200800984A (enExample) |
| UY (1) | UY29823A1 (enExample) |
| WO (1) | WO2007040439A1 (enExample) |
| ZA (1) | ZA200802637B (enExample) |
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| UY29825A1 (es) * | 2005-10-03 | 2007-05-31 | Astrazeneca Ab | Derivados sustituidos de 3h-imidazol-(4,5 b (beta))piridina-2-il benzoatos y benzamidas, composiciones farmacéuticas que los contienen y aplicaciones |
| JP2009523845A (ja) * | 2006-01-23 | 2009-06-25 | クリスタルゲノミクス インコーポレーテッド | たんぱく質キナーゼの活性を阻害するイミダゾピリジン誘導体、これの製造方法およびこれを含む薬学組成物 |
| JP2010523490A (ja) * | 2007-03-30 | 2010-07-15 | アストラゼネカ・アクチエボラーグ | 新規イミダゾ［４，５−ｂ］ピリジン−７−カルボキサミド７０４ |
| CN102127070A (zh) * | 2010-01-15 | 2011-07-20 | 山东轩竹医药科技有限公司 | 吡啶并环衍生物 |
| KR101889993B1 (ko) * | 2010-09-10 | 2018-08-20 | 시오노기세야쿠 가부시키가이샤 | Ａｍｐｋ 활성화 작용을 갖는 헤테로환 축합 이미다졸 유도체 |
| JP2017524739A (ja) | 2014-07-17 | 2017-08-31 | アンセルムＩｎｓｅｒｍ | 神経筋接合部関連疾患の処置方法 |
| WO2016207366A1 (en) | 2015-06-26 | 2016-12-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of viral infections |
| GB201519573D0 (en) | 2015-11-05 | 2015-12-23 | King S College London | Combination |
| CN107151235B (zh) * | 2016-03-04 | 2019-12-13 | 上海市计划生育科学研究所 | 噻二唑烷二酮基gsk3抑制剂在调节精子运动能力中的用途 |
| ES2896938T3 (es) * | 2016-11-28 | 2022-02-28 | Bristol Myers Squibb Co | Inhibidores de GSK-3 |
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| US6187777B1 (en) * | 1998-02-06 | 2001-02-13 | Amgen Inc. | Compounds and methods which modulate feeding behavior and related diseases |
| KR20040084896A (ko) * | 2002-02-06 | 2004-10-06 | 버텍스 파마슈티칼스 인코포레이티드 | Ｇｓｋ-3의 억제제로서 유용한 헤테로아릴 화합물 |
| BR0308785A (pt) * | 2002-03-27 | 2005-01-11 | Altana Pharma Ag | Derivados de alcoxipiridina |
| SE0202462D0 (sv) * | 2002-08-14 | 2002-08-14 | Astrazeneca Ab | Novel use |
| WO2004065370A1 (en) * | 2003-01-23 | 2004-08-05 | Crystalgenomics, Inc. | Glycogen synthase kinase 3beta inhibitor, composition and process for the preparation thereof |
| NZ546437A (en) * | 2003-10-01 | 2009-09-25 | Altana Pharma Ag | Imidazopyridine-derivatives as inducible NO-synthase inhibitors |
| ATE399168T1 (de) * | 2003-10-01 | 2008-07-15 | Nycomed Gmbh | Imidazopyridin-derivate und ihre verwendung als induzierbare no-synthase inhibitoren |
| UY29825A1 (es) * | 2005-10-03 | 2007-05-31 | Astrazeneca Ab | Derivados sustituidos de 3h-imidazol-(4,5 b (beta))piridina-2-il benzoatos y benzamidas, composiciones farmacéuticas que los contienen y aplicaciones |
| JP2009523845A (ja) * | 2006-01-23 | 2009-06-25 | クリスタルゲノミクス インコーポレーテッド | たんぱく質キナーゼの活性を阻害するイミダゾピリジン誘導体、これの製造方法およびこれを含む薬学組成物 |
-
2006
- 2006-09-29 AR ARP060104309A patent/AR057525A1/es not_active Application Discontinuation
- 2006-09-29 UY UY29823A patent/UY29823A1/es not_active Application Discontinuation
- 2006-10-02 EP EP06799715A patent/EP1934217A4/en not_active Withdrawn
- 2006-10-02 BR BRPI0616663-6A patent/BRPI0616663A2/pt not_active IP Right Cessation
- 2006-10-02 KR KR1020087010754A patent/KR20080057334A/ko not_active Withdrawn
- 2006-10-02 CA CA002624869A patent/CA2624869A1/en not_active Abandoned
- 2006-10-02 WO PCT/SE2006/001115 patent/WO2007040439A1/en not_active Ceased
- 2006-10-02 CN CNA2006800453255A patent/CN101321754A/zh active Pending
- 2006-10-02 US US12/088,897 patent/US20080255106A1/en not_active Abandoned
- 2006-10-02 JP JP2008534485A patent/JP2009510162A/ja active Pending
- 2006-10-02 AU AU2006297889A patent/AU2006297889A1/en not_active Abandoned
- 2006-10-03 SA SA06270365A patent/SA06270365B1/ar unknown
- 2006-10-03 TW TW095136782A patent/TW200800984A/zh unknown
-
2008
- 2008-03-04 IL IL189945A patent/IL189945A0/en unknown
- 2008-03-25 ZA ZA200802637A patent/ZA200802637B/xx unknown
- 2008-04-30 NO NO20082054A patent/NO20082054L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL189945A0 (en) | 2008-08-07 |
| ZA200802637B (en) | 2008-12-31 |
| US20080255106A1 (en) | 2008-10-16 |
| CN101321754A (zh) | 2008-12-10 |
| AU2006297889A1 (en) | 2007-04-12 |
| UY29823A1 (es) | 2007-05-31 |
| WO2007040439A1 (en) | 2007-04-12 |
| TW200800984A (en) | 2008-01-01 |
| KR20080057334A (ko) | 2008-06-24 |
| NO20082054L (no) | 2008-06-02 |
| EP1934217A4 (en) | 2010-08-04 |
| SA06270365B1 (ar) | 2009-12-22 |
| AR057525A1 (es) | 2007-12-05 |
| CA2624869A1 (en) | 2007-04-12 |
| JP2009510162A (ja) | 2009-03-12 |
| EP1934217A1 (en) | 2008-06-25 |
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| B08K | Patent lapsed as no evidence of payment of the annual fee has been furnished to inpi [chapter 8.11 patent gazette] |
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