DE60031714T2 - Thrombopoietin-mimetika - Google Patents
Thrombopoietin-mimetika Download PDFInfo
- Publication number
- DE60031714T2 DE60031714T2 DE60031714T DE60031714T DE60031714T2 DE 60031714 T2 DE60031714 T2 DE 60031714T2 DE 60031714 T DE60031714 T DE 60031714T DE 60031714 T DE60031714 T DE 60031714T DE 60031714 T2 DE60031714 T2 DE 60031714T2
- Authority
- DE
- Germany
- Prior art keywords
- hydroxy
- imidazole
- naphth
- sulfonic acid
- naphtho
- Prior art date
- 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.)
- Expired - Fee Related
Links
- 102000036693 Thrombopoietin Human genes 0.000 title description 35
- 108010041111 Thrombopoietin Proteins 0.000 title description 35
- 206010043554 thrombocytopenia Diseases 0.000 claims abstract description 18
- 241000124008 Mammalia Species 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims description 257
- -1 C 1-12 -aryl Chemical group 0.000 claims description 67
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 52
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- ZNWDDQLLGMFOEE-UHFFFAOYSA-N 1h-imidazole-5-sulfonic acid;hydrochloride Chemical compound Cl.OS(=O)(=O)C1=CN=CN1 ZNWDDQLLGMFOEE-UHFFFAOYSA-N 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 26
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 9
- 150000002148 esters Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- JRQVQXMCEHOMTD-UHFFFAOYSA-N 2-[4-(4-tert-butylphenyl)thiophen-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CSC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 JRQVQXMCEHOMTD-UHFFFAOYSA-N 0.000 claims description 8
- AFIXYXZIEDFJSQ-UHFFFAOYSA-N 2-[5-(4-tert-butylphenyl)furan-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)O1 AFIXYXZIEDFJSQ-UHFFFAOYSA-N 0.000 claims description 8
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 8
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 8
- RIXQDZPQQARWPF-UHFFFAOYSA-N 2-[3-(3,4-dimethylphenyl)-4-fluorophenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=CC=C1F RIXQDZPQQARWPF-UHFFFAOYSA-N 0.000 claims description 7
- UUCZHGTVNCOOGT-UHFFFAOYSA-N 2-[3-(4-tert-butylphenyl)-4-methoxyphenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound COC1=CC=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)C=C1C1=CC=C(C(C)(C)C)C=C1 UUCZHGTVNCOOGT-UHFFFAOYSA-N 0.000 claims description 7
- YUYKKHRGDBTSCO-UHFFFAOYSA-N 2-[4-(4-tert-butylphenyl)furan-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=COC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 YUYKKHRGDBTSCO-UHFFFAOYSA-N 0.000 claims description 7
- JGVUAKWZVVQDIZ-UHFFFAOYSA-N 2-[5-(1-benzothiophen-2-yl)furan-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC=C2SC(C3=CC=C(O3)C3=NC=4C5=C(O)C=C(C=C5C=CC=4N3)C(=O)O)=CC2=C1 JGVUAKWZVVQDIZ-UHFFFAOYSA-N 0.000 claims description 7
- BZFLTSNUYALYDP-UHFFFAOYSA-N 2-[5-(4-tert-butylphenyl)-2-fluorophenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(F)C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 BZFLTSNUYALYDP-UHFFFAOYSA-N 0.000 claims description 7
- IYUUWMOKXYWEKS-UHFFFAOYSA-N 2-[5-(4-tert-butylphenyl)thiophen-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)S1 IYUUWMOKXYWEKS-UHFFFAOYSA-N 0.000 claims description 7
- FZUAAPXAGQKWTR-UHFFFAOYSA-N 9-hydroxy-2-[3-[4-(trifluoromethyl)phenyl]phenyl]-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound N1C=2C=CC3=CC(C(=O)O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(C(F)(F)F)C=C1 FZUAAPXAGQKWTR-UHFFFAOYSA-N 0.000 claims description 7
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 150000004677 hydrates Chemical class 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 7
- DHDPRFWMBZYBHQ-UHFFFAOYSA-N 2-[3-(4-tert-butylphenyl)-4-fluorophenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=CC=C1F DHDPRFWMBZYBHQ-UHFFFAOYSA-N 0.000 claims description 6
- JUTHBNVXQXOKAW-UHFFFAOYSA-N 2-[4-(3,4-dimethylphenyl)thiophen-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CSC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 JUTHBNVXQXOKAW-UHFFFAOYSA-N 0.000 claims description 6
- BVFJXHBESHGUAG-UHFFFAOYSA-N 2-[5-(3,4-dichlorophenyl)furan-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound N1C=2C=CC3=CC(C(=O)O)=CC(O)=C3C=2N=C1C(O1)=CC=C1C1=CC=C(Cl)C(Cl)=C1 BVFJXHBESHGUAG-UHFFFAOYSA-N 0.000 claims description 6
- NBZHPHMNNFTTGT-UHFFFAOYSA-N 2-[5-(3,4-dimethylphenyl)thiophen-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)S1 NBZHPHMNNFTTGT-UHFFFAOYSA-N 0.000 claims description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- HMYQKSCWAIVMPA-UHFFFAOYSA-N 2-[1-(4-tert-butylphenyl)pyrazol-4-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1N1N=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 HMYQKSCWAIVMPA-UHFFFAOYSA-N 0.000 claims description 5
- CCDYVLRMODKYBN-UHFFFAOYSA-N 2-[3-(3,4-difluorophenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound N1C=2C=CC3=CC(C(=O)O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(F)C(F)=C1 CCDYVLRMODKYBN-UHFFFAOYSA-N 0.000 claims description 5
- UHQHZVOLONUFDA-UHFFFAOYSA-N 2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-sulfonic acid;hydrochloride Chemical compound Cl.C1=C(C)C(C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(O)(=O)=O)N=2)=C1 UHQHZVOLONUFDA-UHFFFAOYSA-N 0.000 claims description 5
- ZSVLXFZCIUIOQN-UHFFFAOYSA-N 2-[3-(4-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(CCCC)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 ZSVLXFZCIUIOQN-UHFFFAOYSA-N 0.000 claims description 5
- YIGCYXIJBYEWHG-UHFFFAOYSA-N 2-[3-(4-carboxy-3-methylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C(O)=O)C(C)=CC(C=2C=C(C=CC=2)C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 YIGCYXIJBYEWHG-UHFFFAOYSA-N 0.000 claims description 5
- MJOUJSVVDLUTNU-UHFFFAOYSA-N 2-[3-(4-cyano-3-methylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C#N)C(C)=CC(C=2C=C(C=CC=2)C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 MJOUJSVVDLUTNU-UHFFFAOYSA-N 0.000 claims description 5
- WDPVPCHFYXVZBH-UHFFFAOYSA-N 2-[3-(4-fluoro-3-methylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(F)C(C)=CC(C=2C=C(C=CC=2)C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 WDPVPCHFYXVZBH-UHFFFAOYSA-N 0.000 claims description 5
- NLMFQHLOROEZBE-UHFFFAOYSA-N 2-[3-(9h-fluoren-2-yl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C2CC3=CC=CC=C3C2=CC=C1C1=CC(C2=NC=3C4=C(O)C=C(C=C4C=CC=3N2)C(=O)O)=CC=C1 NLMFQHLOROEZBE-UHFFFAOYSA-N 0.000 claims description 5
- MRINVXQHKAFPJM-UHFFFAOYSA-N 2-[5-(3,4-dimethylphenyl)-2-fluorophenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(F)C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 MRINVXQHKAFPJM-UHFFFAOYSA-N 0.000 claims description 5
- URPRRKYQUKYLLB-UHFFFAOYSA-N 2-[5-(3,4-dimethylphenyl)furan-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)O1 URPRRKYQUKYLLB-UHFFFAOYSA-N 0.000 claims description 5
- AGWRYRHIQJXNLW-UHFFFAOYSA-N 2-[5-(4-tert-butylphenyl)pyridin-3-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CN=CC(C=2NC3=C4C(O)=CC(=CC4=CC=C3N=2)C(O)=O)=C1 AGWRYRHIQJXNLW-UHFFFAOYSA-N 0.000 claims description 5
- UFTVNMRVQIUXPU-UHFFFAOYSA-N 2-[6-(4-tert-butylphenyl)pyridin-2-yl]-9-hydroxy-3H-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=N1 UFTVNMRVQIUXPU-UHFFFAOYSA-N 0.000 claims description 5
- UDKWCHCYYXBFLF-UHFFFAOYSA-N 9-hydroxy-2-[3-(4-propylphenyl)phenyl]-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(CCC)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 UDKWCHCYYXBFLF-UHFFFAOYSA-N 0.000 claims description 5
- OFGYBOHAQNSGKW-UHFFFAOYSA-N 9-hydroxy-2-[4-[4-(trifluoromethyl)phenyl]thiophen-2-yl]-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound N1C=2C=CC3=CC(C(=O)O)=CC(O)=C3C=2N=C1C(SC=1)=CC=1C1=CC=C(C(F)(F)F)C=C1 OFGYBOHAQNSGKW-UHFFFAOYSA-N 0.000 claims description 5
- VHVGKHMMCSHNKO-UHFFFAOYSA-N 9-hydroxy-2-[5-[4-(trifluoromethyl)phenyl]furan-2-yl]-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound N1C=2C=CC3=CC(C(=O)O)=CC(O)=C3C=2N=C1C(O1)=CC=C1C1=CC=C(C(F)(F)F)C=C1 VHVGKHMMCSHNKO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229930195734 saturated hydrocarbon Natural products 0.000 claims description 5
- 238000002560 therapeutic procedure Methods 0.000 claims description 5
- 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 5
- VBYPCJIAVPFBDO-UHFFFAOYSA-N 1-fluoro-4-[4-(trifluoromethyl)phenyl]benzene Chemical group C1=CC(F)=CC=C1C1=CC=C(C(F)(F)F)C=C1 VBYPCJIAVPFBDO-UHFFFAOYSA-N 0.000 claims description 4
- LWERZCYTAOCHIQ-UHFFFAOYSA-N 2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid;hydrochloride Chemical compound Cl.C1=C(C)C(C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 LWERZCYTAOCHIQ-UHFFFAOYSA-N 0.000 claims description 4
- FMMBNUOLITXBJH-UHFFFAOYSA-N 2-[3-(4-ethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(CC)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 FMMBNUOLITXBJH-UHFFFAOYSA-N 0.000 claims description 4
- PIEPXWFWRZNOOU-UHFFFAOYSA-N 2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 PIEPXWFWRZNOOU-UHFFFAOYSA-N 0.000 claims description 4
- OTZGPXBQZJFLQX-UHFFFAOYSA-N 2-[4-(3,4-dimethylphenyl)furan-2-yl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=COC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 OTZGPXBQZJFLQX-UHFFFAOYSA-N 0.000 claims description 4
- ITRBTOXCUXWGGG-UHFFFAOYSA-N 2-fluoro-1-phenyl-4-(trifluoromethyl)benzene Chemical group FC1=CC(C(F)(F)F)=CC=C1C1=CC=CC=C1 ITRBTOXCUXWGGG-UHFFFAOYSA-N 0.000 claims description 4
- YDDZHDBISXIDKD-UHFFFAOYSA-N 3-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazol-7-yl]sulfonylamino]benzoic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(=O)(=O)NC=3C=C(C=CC=3)C(O)=O)N=2)=C1 YDDZHDBISXIDKD-UHFFFAOYSA-N 0.000 claims description 4
- VWIYXNRAXFAPGX-UHFFFAOYSA-N 9-hydroxy-2-(2-methoxy-3-phenylphenyl)-3h-benzo[e]benzimidazole-7-carboxylic acid;hydrochloride Chemical compound Cl.COC1=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)C=CC=C1C1=CC=CC=C1 VWIYXNRAXFAPGX-UHFFFAOYSA-N 0.000 claims description 4
- PRRDCKYEDGCCLO-UHFFFAOYSA-N 9-hydroxy-2-[5-(3-propan-2-ylphenyl)furan-2-yl]-3h-benzo[e]benzimidazole-7-carboxylic acid Chemical compound CC(C)C1=CC=CC(C=2OC(=CC=2)C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(O)=O)N=2)=C1 PRRDCKYEDGCCLO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004423 acyloxy group Chemical group 0.000 claims description 4
- 125000004104 aryloxy group Chemical group 0.000 claims description 4
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000003367 polycyclic group Chemical group 0.000 claims description 4
- GFVJZXBMFOFSQG-VWLOTQADSA-N (2s)-1-[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)C(=O)N3[C@@H](CCC3)C(O)=O)N=2)=C1 GFVJZXBMFOFSQG-VWLOTQADSA-N 0.000 claims description 3
- IDFUAIXQXIJJAT-VWLOTQADSA-N (2s)-1-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazol-7-yl]sulfonyl]pyrrolidine-2-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(=O)(=O)N3[C@@H](CCC3)C(O)=O)N=2)=C1 IDFUAIXQXIJJAT-VWLOTQADSA-N 0.000 claims description 3
- OYPYAUDYSUKVSI-KRWDZBQOSA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]propanoic acid Chemical compound N1C=2C=CC3=CC(C(=O)N[C@@H](C)C(O)=O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(C)C(C)=C1 OYPYAUDYSUKVSI-KRWDZBQOSA-N 0.000 claims description 3
- WJRLZGRPVWMNFM-UHFFFAOYSA-N 1,4-difluoro-2-phenyl-5-(trifluoromethyl)benzene Chemical group FC1=CC(=C(F)C=C1C(F)(F)F)C1=CC=CC=C1 WJRLZGRPVWMNFM-UHFFFAOYSA-N 0.000 claims description 3
- FVEFQOZRXHWTHO-UHFFFAOYSA-N 1-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazol-7-yl]sulfonyl]piperidine-3-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1C1=CC=CC(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(=O)(=O)N3CC(CCC3)C(O)=O)N=2)=C1 FVEFQOZRXHWTHO-UHFFFAOYSA-N 0.000 claims description 3
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16913099P | 1999-12-06 | 1999-12-06 | |
| US169130P | 1999-12-06 | ||
| PCT/US2000/033432 WO2001039773A1 (en) | 1999-12-06 | 2000-12-06 | Thrombopoietin mimetics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60031714D1 DE60031714D1 (de) | 2006-12-14 |
| DE60031714T2 true DE60031714T2 (de) | 2007-09-06 |
Family
ID=22614367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60031714T Expired - Fee Related DE60031714T2 (de) | 1999-12-06 | 2000-12-06 | Thrombopoietin-mimetika |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1244446B1 (enExample) |
| JP (1) | JP2003515560A (enExample) |
| AT (1) | ATE344031T1 (enExample) |
| AU (1) | AU2079901A (enExample) |
| DE (1) | DE60031714T2 (enExample) |
| ES (1) | ES2275567T3 (enExample) |
| WO (1) | WO2001039773A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7851503B2 (en) | 2002-08-14 | 2010-12-14 | Nissan Chemical Industries, Ltd. | Thrombopoetin receptor activator and process for producing the same |
| TWI324593B (en) | 2002-10-09 | 2010-05-11 | Nissan Chemical Ind Ltd | Pyrazolone compounds and thrombopoietin receptor activator |
| SI1569912T1 (sl) | 2002-12-03 | 2015-09-30 | Pharmacyclics Llc | Derivati 2-(2-hidroksibifenil-3-il)-1h-benzoimidazol-5-karboksamidina kot inhibitorji faktorja viia |
| ES2571779T3 (es) * | 2002-12-13 | 2016-05-26 | Ym Biosciences Australia Pty | Inhibidores de cinasa a base de nicotinamida |
| EP1581527A4 (en) * | 2002-12-13 | 2006-11-22 | Smithkline Beecham Corp | MIMETICS OF THROMBOPOIETINE |
| TW200418791A (en) * | 2003-01-23 | 2004-10-01 | Bristol Myers Squibb Co | Pharmaceutical compositions for inhibiting proteasome |
| EP1660427A4 (en) * | 2003-08-14 | 2006-12-20 | Asahi Kasei Pharma Corp | SUBSTITUTED ARYLALKANIC DERIVATIVE AND ITS USE |
| US8729117B2 (en) | 2004-06-02 | 2014-05-20 | Pharmacyclics, Inc. | Factor VIIa inhibitor |
| KR101215225B1 (ko) | 2004-12-08 | 2012-12-26 | 닛산 가가쿠 고교 가부시키 가이샤 | 트롬보포이에틴 수용체 활성화제로서의3-에틸리덴히드라지노 치환 헤테로시클릭 화합물 |
| WO2006064957A1 (ja) | 2004-12-14 | 2006-06-22 | Nissan Chemical Industries, Ltd. | アミド化合物及びトロンボポエチンレセプター活性化剤 |
| PL1910338T3 (pl) | 2005-07-14 | 2011-02-28 | Irm Llc | Związki heterotetracykliczne jako mimetyki TPO |
| TWI368617B (en) | 2005-07-15 | 2012-07-21 | Nissan Chemical Ind Ltd | Thiophene compounds and thrombopoietin receptor activators |
| EP1904488B1 (en) | 2005-07-20 | 2013-03-06 | Nissan Chemical Industries, Ltd. | Pyrazole compounds and thrombopoietin receptor activators |
| WO2007022269A2 (en) * | 2005-08-15 | 2007-02-22 | Irm Llc | Compounds and compositions as tpo mimetics |
| US8026368B2 (en) | 2005-11-07 | 2011-09-27 | Nissan Chemical Industries, Ltd. | Hydrazide compounds and thrombopoietin receptor activators |
| JP5157900B2 (ja) | 2006-06-07 | 2013-03-06 | 日産化学工業株式会社 | 含窒素ヘテロ環化合物及びトロンボポエチンレセプター活性化剤 |
| PT2054405E (pt) | 2006-07-11 | 2013-12-24 | Dae Woong Pharma | Novos derivados de biaril benzoimidazol e composição farmacêutica que compreende os mesmos |
| JP5383661B2 (ja) | 2007-04-30 | 2014-01-08 | アッヴィ・インコーポレイテッド | ジアシルグリセロールｏ−アシル転移酵素１型酵素の阻害剤 |
| CN101481352A (zh) | 2008-01-10 | 2009-07-15 | 上海恒瑞医药有限公司 | 双环取代吡唑酮偶氮类衍生物、其制备方法及其在医药上的应用 |
| PE20100362A1 (es) | 2008-10-30 | 2010-05-27 | Irm Llc | Derivados de purina que expanden las celulas madre hematopoyeticas |
| CN101921232A (zh) | 2009-06-11 | 2010-12-22 | 上海恒瑞医药有限公司 | 双环取代吡唑酮偶氮类衍生物的盐,其制备方法及其在医药上的应用 |
| WO2012102937A2 (en) | 2011-01-25 | 2012-08-02 | Irm Llc | Compounds that expand hematopoietic stem cells |
| HK1203081A1 (en) | 2011-12-08 | 2015-10-16 | Fred Hutchinson Cancer Research Center | Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells |
| CA2862140C (en) | 2012-01-27 | 2020-04-21 | Universite De Montreal | Pyrimido[4,5-b]indole derivatives and use thereof in the expansion of hematopoietic stem cells |
| WO2015161373A1 (en) | 2014-04-22 | 2015-10-29 | Université de Montréal | Compounds and use thereof in the expansion of hematopoietic stem cells and/or hematopoietic progenitor cells |
| SG11201703407UA (en) | 2014-10-31 | 2017-05-30 | Nissan Chemical Ind Ltd | Ligand-binding fiber and cell culture substrate using said fiber |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE193350C (enExample) * | ||||
| US851444A (en) * | 1905-11-13 | 1907-04-23 | Agfa Ag | Amido-oxy-sulfonic acid of phenylnaphthimidazol and process of making same. |
| US4435417A (en) * | 1981-02-20 | 1984-03-06 | Gruppo Lepetit S.P.A. | Antiinflammatory 3H-naphtho[1,2-d]imidazoles |
| DE4126612A1 (de) * | 1990-08-14 | 1992-02-20 | Ciba Geigy Ag | Reaktivfarbstoffe, deren herstellung und verwendung |
| IE70217B1 (en) * | 1990-08-15 | 1996-10-30 | British Bio Technology | Benzimidazole derivatives process for their preparation and application |
-
2000
- 2000-12-06 JP JP2001541505A patent/JP2003515560A/ja active Pending
- 2000-12-06 AU AU20799/01A patent/AU2079901A/en not_active Abandoned
- 2000-12-06 DE DE60031714T patent/DE60031714T2/de not_active Expired - Fee Related
- 2000-12-06 ES ES00984123T patent/ES2275567T3/es not_active Expired - Lifetime
- 2000-12-06 WO PCT/US2000/033432 patent/WO2001039773A1/en not_active Ceased
- 2000-12-06 AT AT00984123T patent/ATE344031T1/de not_active IP Right Cessation
- 2000-12-06 EP EP00984123A patent/EP1244446B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| AU2079901A (en) | 2001-06-12 |
| EP1244446A4 (en) | 2003-01-08 |
| EP1244446B1 (en) | 2006-11-02 |
| EP1244446A1 (en) | 2002-10-02 |
| DE60031714D1 (de) | 2006-12-14 |
| JP2003515560A (ja) | 2003-05-07 |
| ES2275567T3 (es) | 2007-06-16 |
| WO2001039773A1 (en) | 2001-06-07 |
| ATE344031T1 (de) | 2006-11-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |