JP2003515560A - トロンボポイエチン模倣物 - Google Patents
トロンボポイエチン模倣物Info
- Publication number
- JP2003515560A JP2003515560A JP2001541505A JP2001541505A JP2003515560A JP 2003515560 A JP2003515560 A JP 2003515560A JP 2001541505 A JP2001541505 A JP 2001541505A JP 2001541505 A JP2001541505 A JP 2001541505A JP 2003515560 A JP2003515560 A JP 2003515560A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- naphtho
- imidazole
- imidazol
- carboxylic acid
- 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.)
- Pending
Links
- 102000036693 Thrombopoietin Human genes 0.000 title description 40
- 108010041111 Thrombopoietin Proteins 0.000 title description 40
- 230000003278 mimic effect Effects 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 100
- 206010043554 thrombocytopenia Diseases 0.000 claims abstract description 18
- 241000124008 Mammalia Species 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 256
- -1 N-sulfonylamino Chemical group 0.000 claims description 128
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 49
- 125000000217 alkyl group Chemical group 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 25
- 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 23
- 150000002431 hydrogen Chemical class 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 238000004519 manufacturing process Methods 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
- 125000001424 substituent group Chemical group 0.000 claims description 15
- 125000000449 nitro group Chemical class [O-][N+](*)=O 0.000 claims description 14
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 12
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 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
- 125000004043 oxo group Chemical group O=* 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
- 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 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
- 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
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 150000002148 esters Chemical class 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- BONRIQWDXHCVOH-UHFFFAOYSA-N 1h-imidazole-5-sulfonic acid Chemical compound OS(=O)(=O)C1=CN=CN1 BONRIQWDXHCVOH-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
- 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 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
- 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 6
- 239000003814 drug Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
- 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
- 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 5
- 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 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
- 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
- 239000005973 Carvone Substances 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 230000002708 enhancing effect Effects 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 125000003367 polycyclic group Chemical group 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- 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 4
- 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
- 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 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
- 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 4
- CEWMMRRJLMXMNM-UHFFFAOYSA-N 2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.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 CEWMMRRJLMXMNM-UHFFFAOYSA-N 0.000 claims description 4
- YFYUMMQGLANYIX-UHFFFAOYSA-N 2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-sulfonic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(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 YFYUMMQGLANYIX-UHFFFAOYSA-N 0.000 claims description 4
- 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 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
- 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
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 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
- 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
- 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 3
- 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 3
- KUOCSFZNWSSKNQ-UHFFFAOYSA-N 2-[4-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.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)C=C1 KUOCSFZNWSSKNQ-UHFFFAOYSA-N 0.000 claims description 3
- BFCKDCLYXKVZNH-UHFFFAOYSA-N 9-hydroxy-2-(2-hydroxy-3-phenylphenyl)-3H-benzo[e]benzimidazole-7-sulfonic acid hydrochloride Chemical compound Cl.N=1C2=C3C(O)=CC(S(O)(=O)=O)=CC3=CC=C2NC=1C(C=1O)=CC=CC=1C1=CC=CC=C1 BFCKDCLYXKVZNH-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- FQBOPVPAANYUNP-UHFFFAOYSA-N 9-hydroxy-2-(2-methoxy-3-phenylphenyl)-3h-benzo[e]benzimidazole-7-sulfonic acid;hydrochloride Chemical compound Cl.COC1=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(O)(=O)=O)N=2)C=CC=C1C1=CC=CC=C1 FQBOPVPAANYUNP-UHFFFAOYSA-N 0.000 claims description 3
- RGXVDSGUPSHCBU-UHFFFAOYSA-N 9-hydroxy-2-(2-methoxy-4-phenylphenyl)-3h-benzo[e]benzimidazole-5-sulfonic acid;hydrochloride Chemical compound Cl.C=1C=C(C=2NC3=C(C4=C(O)C=CC=C4C(=C3)S(O)(=O)=O)N=2)C(OC)=CC=1C1=CC=CC=C1 RGXVDSGUPSHCBU-UHFFFAOYSA-N 0.000 claims description 3
- DXSQQJMOMUMDRZ-UHFFFAOYSA-N 9-hydroxy-2-(3-phenoxyphenyl)-3h-benzo[e]benzimidazole-7-carboxylic acid;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1C=2C=CC3=CC(C(=O)O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1OC1=CC=CC=C1 DXSQQJMOMUMDRZ-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- SCEWJWDMGYCDCP-UHFFFAOYSA-N 9-hydroxy-2-pyridin-2-yl-3H-benzo[e]benzimidazole-7-carboxylic acid 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.N1=C(C=CC=C1)C=1NC2=C(N1)C1=C(C=C(C=C1C=C2)C(=O)O)O SCEWJWDMGYCDCP-UHFFFAOYSA-N 0.000 claims description 3
- SIXHDXGTAOCFKD-UHFFFAOYSA-N C1=CC2=C(C=CC3=C2N=CN3)C=C1C(=O)O Chemical compound C1=CC2=C(C=CC3=C2N=CN3)C=C1C(=O)O SIXHDXGTAOCFKD-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 239000011593 sulfur Substances 0.000 claims description 3
- 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 2
- 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 2
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- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 108091007466 transmembrane glycoproteins Proteins 0.000 description 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 description 1
- 229930195735 unsaturated hydrocarbon Natural products 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
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (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 | |
| US60/169,130 | 1999-12-06 | ||
| PCT/US2000/033432 WO2001039773A1 (en) | 1999-12-06 | 2000-12-06 | Thrombopoietin mimetics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003515560A true JP2003515560A (ja) | 2003-05-07 |
| JP2003515560A5 JP2003515560A5 (enExample) | 2008-01-31 |
Family
ID=22614367
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001541505A Pending JP2003515560A (ja) | 1999-12-06 | 2000-12-06 | トロンボポイエチン模倣物 |
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) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007528362A (ja) * | 2003-08-14 | 2007-10-11 | 旭化成ファーマ株式会社 | 置換アリールアルカン酸誘導体及びその用途 |
| JP2009504758A (ja) * | 2005-08-15 | 2009-02-05 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｔｐｏ模倣剤としての化合物および組成物 |
| US8436022B2 (en) | 2006-07-11 | 2013-05-07 | Daewoong Pharmaceutical Co., Ltd. | Biaryl benzolmidazole derivatives and pharmaceutical composition comprising the same |
Families Citing this family (23)
| 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 |
| CN100513398C (zh) | 2002-12-03 | 2009-07-15 | Axys药物公司 | 作为因子viia抑制剂的2-(2-羟基联苯-3-基)-1h-苯并咪唑-5-甲脒衍生物 |
| JP4896518B2 (ja) * | 2002-12-13 | 2012-03-14 | ワイエム・バイオサイエンシズ・オーストラリア・ピーティーワイ・リミテッド | ニコチンアミド系キナーゼ阻害薬 |
| US20060084682A1 (en) * | 2002-12-13 | 2006-04-20 | Heerding Dirk A | Thrombopoietin mimetics |
| TW200418791A (en) * | 2003-01-23 | 2004-10-01 | Bristol Myers Squibb Co | Pharmaceutical compositions for inhibiting proteasome |
| US8729117B2 (en) | 2004-06-02 | 2014-05-20 | Pharmacyclics, Inc. | Factor VIIa inhibitor |
| WO2006062240A1 (en) | 2004-12-08 | 2006-06-15 | Nissan Chemical Industries, Ltd. | 3-ethylidenehydrazino substituted heterocyclic compounds as thrombopoietin receptor activators |
| KR101215207B1 (ko) | 2004-12-14 | 2012-12-26 | 닛산 가가쿠 고교 가부시키 가이샤 | 아미드 화합물 및 트롬보포이에틴 리셉터 활성화제 |
| EP1910338B1 (en) * | 2005-07-14 | 2010-08-25 | Irm, Llc | Heterotetracyclic compounds as tpo mimetics |
| JP5071375B2 (ja) | 2005-07-15 | 2012-11-14 | 日産化学工業株式会社 | チオフェン化合物及びトロンボポエチンレセプター活性化剤 |
| JP5104752B2 (ja) | 2005-07-20 | 2012-12-19 | 日産化学工業株式会社 | ピラゾール化合物及びトロンボポエチンレセプター活性化剤 |
| US8026368B2 (en) | 2005-11-07 | 2011-09-27 | Nissan Chemical Industries, Ltd. | Hydrazide compounds and thrombopoietin receptor activators |
| US8093251B2 (en) | 2006-06-07 | 2012-01-10 | Nissan Chemical Industries, Ltd. | Nitrogen-containing heterocyclic compounds and thrombopoietin receptor activators |
| NZ580662A (en) | 2007-04-30 | 2012-01-12 | Abbott Lab | Inhibitors of diacylglycerol o-acyltransferase type 1 enzyme used in manufacture of medicament for treatment of diabetes or lipid associated disorders |
| 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 |
| WO2013086436A1 (en) | 2011-12-08 | 2013-06-13 | Fred Hutchinson Cancer Research Center | Compositions and methods for enhanced generation of hematopoietic stem/progenitor cells |
| SI2807165T1 (sl) | 2012-01-27 | 2019-08-30 | Universite De Montreal | Pirimido(4,5-B)indol derivati in njihova uporaba pri ekspanziji hematopoetskih matičnih celic |
| CA2946446C (en) | 2014-04-22 | 2020-11-03 | Universite De Montreal | Pyrido-pyrrolo-pyrimidine and pyrido-indole compounds, pharmaceutical compositions containing same and their 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 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JPH06500316A (ja) * | 1990-08-15 | 1994-01-13 | ブリティッシュ バイオ―テクノロジー リミテッド | 化合物 |
Family Cites Families (2)
| 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. |
-
2000
- 2000-12-06 DE DE60031714T patent/DE60031714T2/de not_active Expired - Fee Related
- 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 EP EP00984123A patent/EP1244446B1/en 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 ES ES00984123T patent/ES2275567T3/es not_active Expired - Lifetime
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| JPH06500316A (ja) * | 1990-08-15 | 1994-01-13 | ブリティッシュ バイオ―テクノロジー リミテッド | 化合物 |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007528362A (ja) * | 2003-08-14 | 2007-10-11 | 旭化成ファーマ株式会社 | 置換アリールアルカン酸誘導体及びその用途 |
| JP2009504758A (ja) * | 2005-08-15 | 2009-02-05 | アイアールエム・リミテッド・ライアビリティ・カンパニー | Ｔｐｏ模倣剤としての化合物および組成物 |
| US8436022B2 (en) | 2006-07-11 | 2013-05-07 | Daewoong Pharmaceutical Co., Ltd. | Biaryl benzolmidazole derivatives and pharmaceutical composition comprising the same |
| US8940769B2 (en) | 2006-07-11 | 2015-01-27 | Daewoong Pharmaceutical Co., Ltd. | Biaryl benzoimidazole derivatives and pharmaceutical composition comprising the same |
Also Published As
| Publication number | Publication date |
|---|---|
| ES2275567T3 (es) | 2007-06-16 |
| EP1244446A4 (en) | 2003-01-08 |
| WO2001039773A1 (en) | 2001-06-07 |
| DE60031714T2 (de) | 2007-09-06 |
| AU2079901A (en) | 2001-06-12 |
| EP1244446A1 (en) | 2002-10-02 |
| ATE344031T1 (de) | 2006-11-15 |
| EP1244446B1 (en) | 2006-11-02 |
| DE60031714D1 (de) | 2006-12-14 |
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