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
- 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 2
- CMYMIQFTYLXWST-UHFFFAOYSA-N 9-hydroxy-2-(2-hydroxy-3-phenylphenyl)-3H-benzo[e]benzimidazole-5-sulfonic acid hydrochloride Chemical compound Cl.N=1C2=C3C(O)=CC=CC3=C(S(O)(=O)=O)C=C2NC=1C(C=1O)=CC=CC=1C1=CC=CC=C1 CMYMIQFTYLXWST-UHFFFAOYSA-N 0.000 claims description 2
- WFDZKMZOMIEUGB-UHFFFAOYSA-N 9-hydroxy-2-(2-hydroxy-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(O)=CC=1C1=CC=CC=C1 WFDZKMZOMIEUGB-UHFFFAOYSA-N 0.000 claims description 2
- HAJCDJMVUFSIEJ-UHFFFAOYSA-N 9-hydroxy-2-(2-hydroxy-4-phenylphenyl)-3H-benzo[e]benzimidazole-7-sulfonic acid hydrochloride Chemical compound Cl.C=1C=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(O)(=O)=O)N=2)C(O)=CC=1C1=CC=CC=C1 HAJCDJMVUFSIEJ-UHFFFAOYSA-N 0.000 claims description 2
- QETVTIRTIXUXOQ-UHFFFAOYSA-N 9-hydroxy-2-(2-methoxy-3-phenylphenyl)-3h-benzo[e]benzimidazole-5-sulfonic acid;hydrochloride Chemical compound Cl.COC1=C(C=2NC3=C(C4=C(O)C=CC=C4C(=C3)S(O)(=O)=O)N=2)C=CC=C1C1=CC=CC=C1 QETVTIRTIXUXOQ-UHFFFAOYSA-N 0.000 claims description 2
- COUJBTBHGAIPTD-UHFFFAOYSA-N 9-hydroxy-2-(2-methoxy-4-phenylphenyl)-3h-benzo[e]benzimidazole-7-sulfonic acid;hydrochloride Chemical compound Cl.C=1C=C(C=2NC3=C(C4=C(O)C=C(C=C4C=C3)S(O)(=O)=O)N=2)C(OC)=CC=1C1=CC=CC=C1 COUJBTBHGAIPTD-UHFFFAOYSA-N 0.000 claims description 2
- VYZIIAYKVGFVLA-UHFFFAOYSA-N 9-hydroxy-2-(4-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=C1)=CC=C1C1=CC=CC=C1 VYZIIAYKVGFVLA-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003277 amino group Chemical group 0.000 claims description 2
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 229940124530 sulfonamide Drugs 0.000 claims description 2
- 150000003456 sulfonamides Chemical group 0.000 claims description 2
- MNOULQLXILYKNV-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenyl]-1h-pyrazole Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=NN1 MNOULQLXILYKNV-UHFFFAOYSA-N 0.000 claims 1
- 230000003213 activating effect Effects 0.000 claims 1
- HCCNHYWZYYIOFM-UHFFFAOYSA-N 3h-benzo[e]benzimidazole Chemical class C1=CC=C2C(N=CN3)=C3C=CC2=C1 HCCNHYWZYYIOFM-UHFFFAOYSA-N 0.000 abstract 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 94
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
- 239000007787 solid Substances 0.000 description 73
- 239000000243 solution Substances 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 47
- 238000005481 NMR spectroscopy Methods 0.000 description 42
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 31
- 239000011541 reaction mixture Substances 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 210000001772 blood platelet Anatomy 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 20
- CGYVZUDTONIBFP-UHFFFAOYSA-N 2-methoxy-3-(2-methylphenyl)benzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=CC=C1C CGYVZUDTONIBFP-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 19
- BSWRLRGCRDANNS-UHFFFAOYSA-N 3,4-diamino-5-hydroxynaphthalene-1-sulfonic acid;dihydrochloride Chemical compound Cl.Cl.C1=CC=C(O)C2=C(N)C(N)=CC(S(O)(=O)=O)=C21 BSWRLRGCRDANNS-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 210000003593 megakaryocyte Anatomy 0.000 description 17
- ZAMWWGYBPMCJPS-UHFFFAOYSA-N 5-(3,4-dimethylphenyl)furan-2-carbaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(C=O)O1 ZAMWWGYBPMCJPS-UHFFFAOYSA-N 0.000 description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- NSJVYHOPHZMZPN-UHFFFAOYSA-N (2-methylphenyl)boronic acid Chemical compound CC1=CC=CC=C1B(O)O NSJVYHOPHZMZPN-UHFFFAOYSA-N 0.000 description 14
- SZDPZQAPHXPVCN-UHFFFAOYSA-N 3-bromo-2-methoxybenzaldehyde Chemical compound COC1=C(Br)C=CC=C1C=O SZDPZQAPHXPVCN-UHFFFAOYSA-N 0.000 description 14
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 239000002244 precipitate Substances 0.000 description 14
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- KDVZJKOYSOFXRV-UHFFFAOYSA-N (3,4-dimethylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1C KDVZJKOYSOFXRV-UHFFFAOYSA-N 0.000 description 11
- AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- WJTFHWXMITZNHS-UHFFFAOYSA-N 5-bromofuran-2-carbaldehyde Chemical compound BrC1=CC=C(C=O)O1 WJTFHWXMITZNHS-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 108020003175 receptors Proteins 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 10
- 239000012043 crude product Substances 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 235000019198 oils Nutrition 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- HJBGZJMKTOMQRR-UHFFFAOYSA-N (3-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C=O)=C1 HJBGZJMKTOMQRR-UHFFFAOYSA-N 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- TVDYLKSDOVQCEL-UHFFFAOYSA-N 2-methoxy-3-phenylbenzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=CC=C1 TVDYLKSDOVQCEL-UHFFFAOYSA-N 0.000 description 6
- XQKYLOFAKXPMOM-UHFFFAOYSA-N 2-methoxy-4-(2-methylphenyl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C(=CC=CC=2)C)=C1 XQKYLOFAKXPMOM-UHFFFAOYSA-N 0.000 description 6
- MTZFHKMEJBHGJL-UHFFFAOYSA-N 5,6-diamino-4-hydroxynaphthalene-2-sulfonic acid;dihydrochloride Chemical compound Cl.Cl.C1=C(S(O)(=O)=O)C=C(O)C2=C(N)C(N)=CC=C21 MTZFHKMEJBHGJL-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 235000002639 sodium chloride Nutrition 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 5
- NVWHMKUNDKONSD-UHFFFAOYSA-N 2-hydroxy-3-(2-methylphenyl)benzaldehyde Chemical compound CC1=CC=CC=C1C1=CC=CC(C=O)=C1O NVWHMKUNDKONSD-UHFFFAOYSA-N 0.000 description 5
- IWIAAKKPAWSUSZ-UHFFFAOYSA-N 2-hydroxy-4-(2-methylphenyl)benzaldehyde Chemical compound CC1=CC=CC=C1C1=CC=C(C=O)C(O)=C1 IWIAAKKPAWSUSZ-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- USYCQABRSUEURP-UHFFFAOYSA-N 1h-benzo[f]benzimidazole Chemical class C1=CC=C2C=C(NC=N3)C3=CC2=C1 USYCQABRSUEURP-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 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 description 4
- OMANEIYEHZHHIZ-UHFFFAOYSA-N 2-methoxy-3-(3-methoxyphenyl)benzaldehyde Chemical compound COC1=CC=CC(C=2C(=C(C=O)C=CC=2)OC)=C1 OMANEIYEHZHHIZ-UHFFFAOYSA-N 0.000 description 4
- RUBOPGSPXSWTQX-UHFFFAOYSA-N 2-methoxy-3-(4-methylphenyl)benzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=C(C)C=C1 RUBOPGSPXSWTQX-UHFFFAOYSA-N 0.000 description 4
- OFCTWYWKBMXFAW-UHFFFAOYSA-N 2-methoxy-3-[3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=CC(C(F)(F)F)=C1 OFCTWYWKBMXFAW-UHFFFAOYSA-N 0.000 description 4
- DIJZOKBNXUPNLK-UHFFFAOYSA-N 2-methoxy-4-(3-methoxyphenyl)benzaldehyde Chemical compound COC1=CC=CC(C=2C=C(OC)C(C=O)=CC=2)=C1 DIJZOKBNXUPNLK-UHFFFAOYSA-N 0.000 description 4
- FXRGXRXMDXRNKT-UHFFFAOYSA-N 2-methoxy-4-(4-methylphenyl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=CC(C)=CC=2)=C1 FXRGXRXMDXRNKT-UHFFFAOYSA-N 0.000 description 4
- GAJMJRXLNNGTII-UHFFFAOYSA-N 2-methoxy-4-[3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=C(C=CC=2)C(F)(F)F)=C1 GAJMJRXLNNGTII-UHFFFAOYSA-N 0.000 description 4
- OSSPZRHEHZZDSX-UHFFFAOYSA-N 2-methoxy-4-phenylbenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=CC=CC=2)=C1 OSSPZRHEHZZDSX-UHFFFAOYSA-N 0.000 description 4
- HUBATZDQHYYLMX-UHFFFAOYSA-N 3-(3-chlorophenyl)-2-methoxybenzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=CC(Cl)=C1 HUBATZDQHYYLMX-UHFFFAOYSA-N 0.000 description 4
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 4
- GUKHHNJUACSVJA-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-methoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=C(Cl)C=CC=2)=C1 GUKHHNJUACSVJA-UHFFFAOYSA-N 0.000 description 4
- BVSTZODYKKJMKT-UHFFFAOYSA-N 5,6-diamino-4-hydroxynaphthalene-2-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.C1=C(C(O)=O)C=C(O)C2=C(N)C(N)=CC=C21 BVSTZODYKKJMKT-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 4
- 229910004298 SiO 2 Inorganic materials 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 210000001185 bone marrow Anatomy 0.000 description 4
- 210000002798 bone marrow cell Anatomy 0.000 description 4
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 238000003670 luciferase enzyme activity assay Methods 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- FDMCEXDXULPJPG-MERQFXBCSA-N tert-butyl (2s)-2-amino-3-phenylpropanoate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@@H](N)CC1=CC=CC=C1 FDMCEXDXULPJPG-MERQFXBCSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- MNJYZNVROSZZQC-UHFFFAOYSA-N (4-tert-butylphenyl)boronic acid Chemical compound CC(C)(C)C1=CC=C(B(O)O)C=C1 MNJYZNVROSZZQC-UHFFFAOYSA-N 0.000 description 3
- 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 description 3
- 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 description 3
- ORBBQTCGCRTVCF-UHFFFAOYSA-N 2-hydroxy-3-(3-nitrophenyl)benzaldehyde Chemical compound OC1=C(C=O)C=CC=C1C1=CC=CC([N+]([O-])=O)=C1 ORBBQTCGCRTVCF-UHFFFAOYSA-N 0.000 description 3
- UUNWUNNYZZWSDV-UHFFFAOYSA-N 2-hydroxy-3-(4-methylphenyl)benzaldehyde Chemical compound C1=CC(C)=CC=C1C1=CC=CC(C=O)=C1O UUNWUNNYZZWSDV-UHFFFAOYSA-N 0.000 description 3
- WHLVUYXBCNKSPV-UHFFFAOYSA-N 2-hydroxy-3-[3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound OC1=C(C=O)C=CC=C1C1=CC=CC(C(F)(F)F)=C1 WHLVUYXBCNKSPV-UHFFFAOYSA-N 0.000 description 3
- SGBJBHBIWXYUEZ-UHFFFAOYSA-N 2-hydroxy-4-(3-nitrophenyl)benzaldehyde Chemical compound C1=C(C=O)C(O)=CC(C=2C=C(C=CC=2)[N+]([O-])=O)=C1 SGBJBHBIWXYUEZ-UHFFFAOYSA-N 0.000 description 3
- XBVSMPXCQQMBOG-UHFFFAOYSA-N 3-(3,4-dimethylphenyl)benzaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=CC(C=O)=C1 XBVSMPXCQQMBOG-UHFFFAOYSA-N 0.000 description 3
- ZQDRIHGXANBKBA-UHFFFAOYSA-N 3-(3-chlorophenyl)-2-hydroxybenzaldehyde Chemical compound OC1=C(C=O)C=CC=C1C1=CC=CC(Cl)=C1 ZQDRIHGXANBKBA-UHFFFAOYSA-N 0.000 description 3
- ORESKBIFHBTXEM-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-hydroxybenzaldehyde Chemical compound OC1=C(C=O)C=CC=C1C1=CC=C(Cl)C=C1 ORESKBIFHBTXEM-UHFFFAOYSA-N 0.000 description 3
- LDUNCRPXHMORAC-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-hydroxybenzaldehyde Chemical compound OC1=C(C=O)C=CC=C1C1=CC=C(F)C=C1 LDUNCRPXHMORAC-UHFFFAOYSA-N 0.000 description 3
- FWBMHVOMCSIWCX-UHFFFAOYSA-N 4-(3,4-dimethylphenyl)benzaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(C=O)C=C1 FWBMHVOMCSIWCX-UHFFFAOYSA-N 0.000 description 3
- YAAQGONWJLEGRU-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-hydroxybenzaldehyde Chemical compound C1=C(C=O)C(O)=CC(C=2C=C(Cl)C=CC=2)=C1 YAAQGONWJLEGRU-UHFFFAOYSA-N 0.000 description 3
- QOGHRLGTXVMRLM-UHFFFAOYSA-N 4-bromo-1,2-dimethylbenzene Chemical compound CC1=CC=C(Br)C=C1C QOGHRLGTXVMRLM-UHFFFAOYSA-N 0.000 description 3
- QLPAVCRPZJSBET-UHFFFAOYSA-N 5,6-diamino-4-hydroxynaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=C(O)C2=C(N)C(N)=CC=C21 QLPAVCRPZJSBET-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- PQKAEOZLHFFFTD-UHFFFAOYSA-N COC1=C(C=O)C=CC(=C1)C1=CC=C(C=C1)Cl.COC1=C(C=O)C=CC(=C1)C1=CC=C(C=C1)F Chemical compound COC1=C(C=O)C=CC(=C1)C1=CC=C(C=C1)Cl.COC1=C(C=O)C=CC(=C1)C1=CC=C(C=C1)F PQKAEOZLHFFFTD-UHFFFAOYSA-N 0.000 description 3
- UBBUVBKLYDCAMA-UHFFFAOYSA-N COC1=C(C=O)C=CC=C1C1=CC=C(C=C1)Cl.COC1=C(C=O)C=CC=C1C1=CC=C(C=C1)F Chemical compound COC1=C(C=O)C=CC=C1C1=CC=C(C=C1)Cl.COC1=C(C=O)C=CC=C1C1=CC=C(C=C1)F UBBUVBKLYDCAMA-UHFFFAOYSA-N 0.000 description 3
- 241001529936 Murinae Species 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000010322 bone marrow transplantation Methods 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000011278 mitosis Effects 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 235000010288 sodium nitrite Nutrition 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- SDEAGACSNFSZCU-UHFFFAOYSA-N (3-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(Cl)=C1 SDEAGACSNFSZCU-UHFFFAOYSA-N 0.000 description 2
- NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 2
- BJQCPCFFYBKRLM-UHFFFAOYSA-N (3-methylphenyl)boronic acid Chemical group CC1=CC=CC(B(O)O)=C1 BJQCPCFFYBKRLM-UHFFFAOYSA-N 0.000 description 2
- CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 2
- YGGMQWSJXSNGDT-UHFFFAOYSA-N (4-fluorophenyl)boron Chemical compound [B]C1=CC=C(F)C=C1 YGGMQWSJXSNGDT-UHFFFAOYSA-N 0.000 description 2
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 2
- IEZUNJHXXNYRLM-UHFFFAOYSA-N 1,2-dimethyl-5-phenylcyclohexa-2,4-diene-1-carbaldehyde Chemical compound C1C(C=O)(C)C(C)=CC=C1C1=CC=CC=C1 IEZUNJHXXNYRLM-UHFFFAOYSA-N 0.000 description 2
- PLMQOYODRAYHJB-UHFFFAOYSA-N 1-(4-tert-butylphenyl)pyrazole-4-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1N1N=CC(C=O)=C1 PLMQOYODRAYHJB-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
- URFPRAHGGBYNPW-UHFFFAOYSA-N 1-bromo-4-ethylbenzene Chemical compound CCC1=CC=C(Br)C=C1 URFPRAHGGBYNPW-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- OHEBJKBKCRXZBW-UHFFFAOYSA-N 2,6-dimethyl-3-phenylbenzaldehyde Chemical compound CC1=C(C=O)C(C)=CC=C1C1=CC=CC=C1 OHEBJKBKCRXZBW-UHFFFAOYSA-N 0.000 description 2
- AWLAARNROPLFAH-UHFFFAOYSA-N 2-(1-benzothiophen-2-yl)-5-(dimethoxymethyl)furan Chemical compound O1C(C(OC)OC)=CC=C1C1=CC2=CC=CC=C2S1 AWLAARNROPLFAH-UHFFFAOYSA-N 0.000 description 2
- MCSFVTZBBKBUTQ-UHFFFAOYSA-N 2-(3,4-dichlorophenyl)-5-(dimethoxymethyl)furan Chemical compound O1C(C(OC)OC)=CC=C1C1=CC=C(Cl)C(Cl)=C1 MCSFVTZBBKBUTQ-UHFFFAOYSA-N 0.000 description 2
- WABBMXFNRFZTOX-UHFFFAOYSA-N 2-bromo-5-(dimethoxymethyl)furan Chemical compound COC(OC)C1=CC=C(Br)O1 WABBMXFNRFZTOX-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- JKRZNXWCYDKSBS-UHFFFAOYSA-N 2-hydroxy-4-(4-methylphenyl)benzaldehyde Chemical compound C1=CC(C)=CC=C1C1=CC=C(C=O)C(O)=C1 JKRZNXWCYDKSBS-UHFFFAOYSA-N 0.000 description 2
- PQPFIHPHEGDBQE-UHFFFAOYSA-N 2-hydroxy-4-phenylbenzaldehyde Chemical compound C1=C(C=O)C(O)=CC(C=2C=CC=CC=2)=C1 PQPFIHPHEGDBQE-UHFFFAOYSA-N 0.000 description 2
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 2
- AJHPGXZOIAYYDW-UHFFFAOYSA-N 3-(2-cyanophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CC1=CC=CC=C1C#N AJHPGXZOIAYYDW-UHFFFAOYSA-N 0.000 description 2
- FYCMTWIYPPCFMC-UHFFFAOYSA-N 3-(3,4-dimethylphenyl)-2-hydroxybenzaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=CC(C=O)=C1O FYCMTWIYPPCFMC-UHFFFAOYSA-N 0.000 description 2
- OJURTZDANNAQAR-UHFFFAOYSA-N 3-(3,4-dimethylphenyl)-2-methoxybenzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=C(C)C(C)=C1 OJURTZDANNAQAR-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- AWMIXZIEZZSXFQ-UHFFFAOYSA-N 3-[(3,4-dimethylphenyl)methoxy]benzaldehyde Chemical compound C1=C(C)C(C)=CC=C1COC1=CC=CC(C=O)=C1 AWMIXZIEZZSXFQ-UHFFFAOYSA-N 0.000 description 2
- QXLDRBGJFJMTIW-UHFFFAOYSA-N 3-[(4-tert-butylphenyl)methoxy]benzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1COC1=CC=CC(C=O)=C1 QXLDRBGJFJMTIW-UHFFFAOYSA-N 0.000 description 2
- JLQBHCYLEQJWCE-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]benzaldehyde Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=CC(C=O)=C1 JLQBHCYLEQJWCE-UHFFFAOYSA-N 0.000 description 2
- OXBDHTPFAFXIEA-UHFFFAOYSA-N 3-[[3-(trifluoromethyl)phenyl]methoxy]benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(COC=2C=C(C=O)C=CC=2)=C1 OXBDHTPFAFXIEA-UHFFFAOYSA-N 0.000 description 2
- FAHZIKXYYRGSHF-UHFFFAOYSA-N 3-bromo-4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1Br FAHZIKXYYRGSHF-UHFFFAOYSA-N 0.000 description 2
- ZNRGSYUVFVNSAW-UHFFFAOYSA-N 3-nitrophenylboronic acid Chemical compound OB(O)C1=CC=CC([N+]([O-])=O)=C1 ZNRGSYUVFVNSAW-UHFFFAOYSA-N 0.000 description 2
- BFPBBTBMPZFBAJ-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-hydroxybenzaldehyde Chemical compound C1=C(C=O)C(O)=CC(C=2C=CC(Cl)=CC=2)=C1 BFPBBTBMPZFBAJ-UHFFFAOYSA-N 0.000 description 2
- RWWHTWAJPSSXGO-UHFFFAOYSA-N 4-(4-tert-butylphenyl)furan-2-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=COC(C=O)=C1 RWWHTWAJPSSXGO-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- MRGBBKQOSUHKPF-UHFFFAOYSA-N 4-bromofuran-2-carbaldehyde Chemical compound BrC1=COC(C=O)=C1 MRGBBKQOSUHKPF-UHFFFAOYSA-N 0.000 description 2
- PSQLTDROSWBPGT-UHFFFAOYSA-N 5-(3,4-dichlorophenyl)furan-2-carbaldehyde Chemical compound C1=C(Cl)C(Cl)=CC=C1C1=CC=C(C=O)O1 PSQLTDROSWBPGT-UHFFFAOYSA-N 0.000 description 2
- YTOKXAQEJOFNOU-UHFFFAOYSA-N 5-(4-tert-butylphenyl)furan-2-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(C=O)O1 YTOKXAQEJOFNOU-UHFFFAOYSA-N 0.000 description 2
- RNHZYYPGXJEDGG-UHFFFAOYSA-N 6-amino-4-hydroxynaphthalene-2-carboxylic acid Chemical compound C1=C(C(O)=O)C=C(O)C2=CC(N)=CC=C21 RNHZYYPGXJEDGG-UHFFFAOYSA-N 0.000 description 2
- AIWKIEDXXJDPLU-UHFFFAOYSA-N 7,8-diaminonaphthalen-1-ol Chemical compound C1=CC=C(O)C2=C(N)C(N)=CC=C21 AIWKIEDXXJDPLU-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 102100031573 Hematopoietic progenitor cell antigen CD34 Human genes 0.000 description 2
- 101000777663 Homo sapiens Hematopoietic progenitor cell antigen CD34 Proteins 0.000 description 2
- 101001078143 Homo sapiens Integrin alpha-IIb Proteins 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- 102100025306 Integrin alpha-IIb Human genes 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- AJFYPLFBIIYJJB-UHFFFAOYSA-N OC1=C(C=O)C(C)=NN1C1=CC=C(C)C(C)=C1 Chemical compound OC1=C(C=O)C(C)=NN1C1=CC=C(C)C(C)=C1 AJFYPLFBIIYJJB-UHFFFAOYSA-N 0.000 description 2
- 208000020584 Polyploidy Diseases 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 235000021355 Stearic acid Nutrition 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 102100034196 Thrombopoietin receptor Human genes 0.000 description 2
- 101710148535 Thrombopoietin receptor Proteins 0.000 description 2
- WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000011149 active material Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 239000004305 biphenyl Substances 0.000 description 2
- 235000010290 biphenyl Nutrition 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- PASHVRUKOFIRIK-UHFFFAOYSA-L calcium sulfate dihydrate Chemical compound O.O.[Ca+2].[O-]S([O-])(=O)=O PASHVRUKOFIRIK-UHFFFAOYSA-L 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940126142 compound 16 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 150000004985 diamines Chemical class 0.000 description 2
- JOFBTOVNZIUWPX-UHFFFAOYSA-N dibenzofuran-1-ylboronic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2B(O)O JOFBTOVNZIUWPX-UHFFFAOYSA-N 0.000 description 2
- GVLZIMQSYQDAHB-QRPNPIFTSA-N ditert-butyl (2s)-2-aminobutanedioate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)C[C@H](N)C(=O)OC(C)(C)C GVLZIMQSYQDAHB-QRPNPIFTSA-N 0.000 description 2
- NTUGPDFKMVHCCJ-VIFPVBQESA-N ditert-butyl (2s)-2-aminopentanedioate Chemical compound CC(C)(C)OC(=O)CC[C@H](N)C(=O)OC(C)(C)C NTUGPDFKMVHCCJ-VIFPVBQESA-N 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000035800 maturation Effects 0.000 description 2
- 230000003343 megakaryocytopoietic effect Effects 0.000 description 2
- 230000000394 mitotic effect Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- HUMMCEUVDBVXTQ-UHFFFAOYSA-N naphthalen-1-ylboronic acid Chemical compound C1=CC=C2C(B(O)O)=CC=CC2=C1 HUMMCEUVDBVXTQ-UHFFFAOYSA-N 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- HXOFRBVHQQOXNL-UHFFFAOYSA-N phenyl(trifluoromethoxy)borinic acid Chemical compound FC(F)(F)OB(O)C1=CC=CC=C1 HXOFRBVHQQOXNL-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000008117 stearic acid Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- CBYKTKOQAVJTOU-PPHPATTJSA-N tert-butyl (2s)-2-amino-2-phenylacetate;hydrochloride Chemical compound Cl.CC(C)(C)OC(=O)[C@@H](N)C1=CC=CC=C1 CBYKTKOQAVJTOU-PPHPATTJSA-N 0.000 description 2
- BCIXAFNTAKZNCN-LBPRGKRZSA-N tert-butyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate Chemical compound C1=CC=C2C(C[C@H](N)C(=O)OC(C)(C)C)=CNC2=C1 BCIXAFNTAKZNCN-LBPRGKRZSA-N 0.000 description 2
- DIGHFXIWRPMGSA-NSHDSACASA-N tert-butyl (2s)-2-amino-3-(4-hydroxyphenyl)propanoate Chemical compound CC(C)(C)OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 DIGHFXIWRPMGSA-NSHDSACASA-N 0.000 description 2
- HBEJJYHFTZDAHZ-QMMMGPOBSA-N tert-butyl (2s)-2-amino-4-methylpentanoate Chemical compound CC(C)C[C@H](N)C(=O)OC(C)(C)C HBEJJYHFTZDAHZ-QMMMGPOBSA-N 0.000 description 2
- XJJBXZIKXFOMLP-ZETCQYMHSA-N tert-butyl (2s)-pyrrolidine-2-carboxylate Chemical compound CC(C)(C)OC(=O)[C@@H]1CCCN1 XJJBXZIKXFOMLP-ZETCQYMHSA-N 0.000 description 2
- IFRYMHOZFAPYPJ-WSZWBAFRSA-N tert-butyl (2s,3s)-2-amino-3-methylpentanoate;hydron;chloride Chemical compound Cl.CC[C@H](C)[C@H](N)C(=O)OC(C)(C)C IFRYMHOZFAPYPJ-WSZWBAFRSA-N 0.000 description 2
- AUIVQIHTTVPKFS-UHFFFAOYSA-N tert-butyl 2-amino-3-methylbutanoate;hydron;chloride Chemical compound Cl.CC(C)C(N)C(=O)OC(C)(C)C AUIVQIHTTVPKFS-UHFFFAOYSA-N 0.000 description 2
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- YPFFIMMNZIALME-UHFFFAOYSA-N tributyl-[5-(dimethoxymethyl)furan-2-yl]stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C(OC)OC)O1 YPFFIMMNZIALME-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 description 1
- UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 1
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 1
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 1
- CFJUXEAYSIGXTF-UHFFFAOYSA-N (2-methylpropan-2-yl)oxy-phenylborinic acid Chemical compound CC(C)(C)OB(O)C1=CC=CC=C1 CFJUXEAYSIGXTF-UHFFFAOYSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- GCTFTMWXZFLTRR-GFCCVEGCSA-N (2r)-2-amino-n-[3-(difluoromethoxy)-4-(1,3-oxazol-5-yl)phenyl]-4-methylpentanamide Chemical compound FC(F)OC1=CC(NC(=O)[C@H](N)CC(C)C)=CC=C1C1=CN=CO1 GCTFTMWXZFLTRR-GFCCVEGCSA-N 0.000 description 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 description 1
- ITOFPJRDSCGOSA-KZLRUDJFSA-N (2s)-2-[[(4r)-4-[(3r,5r,8r,9s,10s,13r,14s,17r)-3-hydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H](CC[C@]13C)[C@@H]2[C@@H]3CC[C@@H]1[C@H](C)CCC(=O)N[C@H](C(O)=O)CC1=CNC2=CC=CC=C12 ITOFPJRDSCGOSA-KZLRUDJFSA-N 0.000 description 1
- QCVYWXAFZVEYLR-PMERELPUSA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-2-phenylacetic 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)N[C@H](C(O)=O)C=3C=CC=CC=3)N=2)=C1 QCVYWXAFZVEYLR-PMERELPUSA-N 0.000 description 1
- QEIGDJCALREJSP-HKBQPEDESA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-(1h-indol-3-yl)propanoic 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)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(O)=O)N=2)=C1 QEIGDJCALREJSP-HKBQPEDESA-N 0.000 description 1
- ZUEMKLIGDAXJOU-LJAQVGFWSA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic 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)N[C@@H](CC=3C=CC(O)=CC=3)C(O)=O)N=2)=C1 ZUEMKLIGDAXJOU-LJAQVGFWSA-N 0.000 description 1
- RAOLBHDJEIKNBZ-SNCIIYAQSA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-methylpentanoic acid Chemical compound N1C=2C=CC3=CC(C(=O)N[C@@H](C(C)CC)C(O)=O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(C)C(C)=C1 RAOLBHDJEIKNBZ-SNCIIYAQSA-N 0.000 description 1
- JDOGYUXGSPRATD-SANMLTNESA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-4-methylpentanoic acid Chemical compound N1C=2C=CC3=CC(C(=O)N[C@@H](CC(C)C)C(O)=O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(C)C(C)=C1 JDOGYUXGSPRATD-SANMLTNESA-N 0.000 description 1
- CURKMTDDRAFSNQ-QHCPKHFHSA-N (2s)-2-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]butanedioic 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)N[C@@H](CC(O)=O)C(O)=O)N=2)=C1 CURKMTDDRAFSNQ-QHCPKHFHSA-N 0.000 description 1
- BTGKFAQDNUYLDQ-HKBQPEDESA-N (2s)-2-[[2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-2-phenylacetic 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)N[C@H](C(O)=O)C=3C=CC=CC=3)N=2)=C1 BTGKFAQDNUYLDQ-HKBQPEDESA-N 0.000 description 1
- OYIBYAZBEWZFHO-YTTGMZPUSA-N (2s)-2-[[2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-(1h-indol-3-yl)propanoic 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)N[C@@H](CC=3C4=CC=CC=C4NC=3)C(O)=O)N=2)=C1 OYIBYAZBEWZFHO-YTTGMZPUSA-N 0.000 description 1
- RUXMUZURGZVXTF-PMERELPUSA-N (2s)-2-[[2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-(4-hydroxyphenyl)propanoic 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)N[C@@H](CC=3C=CC(O)=CC=3)C(O)=O)N=2)=C1 RUXMUZURGZVXTF-PMERELPUSA-N 0.000 description 1
- XYJNTPPWPWAXBP-NDEPHWFRSA-N (2s)-2-[[2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-methylbutanoic acid Chemical compound N1C=2C=CC3=CC(C(=O)N[C@@H](C(C)C)C(O)=O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(C(C)(C)C)C=C1 XYJNTPPWPWAXBP-NDEPHWFRSA-N 0.000 description 1
- LMODDGCPQKRFIX-NEFVBLPJSA-N (2s)-2-[[2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]-3-methylpentanoic acid Chemical compound N1C=2C=CC3=CC(C(=O)N[C@@H](C(C)CC)C(O)=O)=CC(O)=C3C=2N=C1C(C=1)=CC=CC=1C1=CC=C(C(C)(C)C)C=C1 LMODDGCPQKRFIX-NEFVBLPJSA-N 0.000 description 1
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 1
- RMGYQBHKEWWTOY-UHFFFAOYSA-N (3,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(F)=C1 RMGYQBHKEWWTOY-UHFFFAOYSA-N 0.000 description 1
- OKGZCXPDJKKZAP-UHFFFAOYSA-N (3,4-dimethylphenyl)methanol Chemical compound CC1=CC=C(CO)C=C1C OKGZCXPDJKKZAP-UHFFFAOYSA-N 0.000 description 1
- QSWLFBMVIGQONC-UHFFFAOYSA-N (3-propan-2-ylphenyl)boronic acid Chemical compound CC(C)C1=CC=CC(B(O)O)=C1 QSWLFBMVIGQONC-UHFFFAOYSA-N 0.000 description 1
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
- UDQTXCHQKHIQMH-KYGLGHNPSA-N (3ar,5s,6s,7r,7ar)-5-(difluoromethyl)-2-(ethylamino)-5,6,7,7a-tetrahydro-3ah-pyrano[3,2-d][1,3]thiazole-6,7-diol Chemical compound S1C(NCC)=N[C@H]2[C@@H]1O[C@H](C(F)F)[C@@H](O)[C@@H]2O UDQTXCHQKHIQMH-KYGLGHNPSA-N 0.000 description 1
- OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 description 1
- STPKWKPURVSAJF-LJEWAXOPSA-N (4r,5r)-5-[4-[[4-(1-aza-4-azoniabicyclo[2.2.2]octan-4-ylmethyl)phenyl]methoxy]phenyl]-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-4,5-dihydro-2h-1$l^{6}-benzothiepin-4-ol Chemical compound O[C@H]1C(CCCC)(CCCC)CS(=O)(=O)C2=CC=C(N(C)C)C=C2[C@H]1C(C=C1)=CC=C1OCC(C=C1)=CC=C1C[N+]1(CC2)CCN2CC1 STPKWKPURVSAJF-LJEWAXOPSA-N 0.000 description 1
- NKKNXLPHCRLBDY-UHFFFAOYSA-N (5-formyl-2-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(C=O)C=C1B(O)O NKKNXLPHCRLBDY-UHFFFAOYSA-N 0.000 description 1
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 description 1
- DEVSOMFAQLZNKR-RJRFIUFISA-N (z)-3-[3-[3,5-bis(trifluoromethyl)phenyl]-1,2,4-triazol-1-yl]-n'-pyrazin-2-ylprop-2-enehydrazide Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(C2=NN(\C=C/C(=O)NNC=3N=CC=NC=3)C=N2)=C1 DEVSOMFAQLZNKR-RJRFIUFISA-N 0.000 description 1
- KKHFRAFPESRGGD-UHFFFAOYSA-N 1,3-dimethyl-7-[3-(n-methylanilino)propyl]purine-2,6-dione Chemical compound C1=NC=2N(C)C(=O)N(C)C(=O)C=2N1CCCN(C)C1=CC=CC=C1 KKHFRAFPESRGGD-UHFFFAOYSA-N 0.000 description 1
- UFHMXIZTTKKUOU-UHFFFAOYSA-N 1-(4-tert-butylphenyl)pyrazole Chemical compound C1=CC(C(C)(C)C)=CC=C1N1N=CC=C1 UFHMXIZTTKKUOU-UHFFFAOYSA-N 0.000 description 1
- MHSLDASSAFCCDO-UHFFFAOYSA-N 1-(5-tert-butyl-2-methylpyrazol-3-yl)-3-(4-pyridin-4-yloxyphenyl)urea Chemical compound CN1N=C(C(C)(C)C)C=C1NC(=O)NC(C=C1)=CC=C1OC1=CC=NC=C1 MHSLDASSAFCCDO-UHFFFAOYSA-N 0.000 description 1
- MYYYZNVAUZVXBO-UHFFFAOYSA-N 1-(bromomethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CBr)=C1 MYYYZNVAUZVXBO-UHFFFAOYSA-N 0.000 description 1
- QZNQSIHCDAGZIA-UHFFFAOYSA-N 1-(bromomethyl)-4-tert-butylbenzene Chemical compound CC(C)(C)C1=CC=C(CBr)C=C1 QZNQSIHCDAGZIA-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- KQZLRWGGWXJPOS-NLFPWZOASA-N 1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(4S,5R)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrile Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)C1=CC[C@@H]([C@@H](C1)C)N1[C@@H](CCC1)CO)C#N KQZLRWGGWXJPOS-NLFPWZOASA-N 0.000 description 1
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
- FRNCYVHNJMSHKX-UHFFFAOYSA-N 1-bromo-2,5-difluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC(C(F)(F)F)=C(F)C=C1Br FRNCYVHNJMSHKX-UHFFFAOYSA-N 0.000 description 1
- XCTQZIUCYJVRLJ-UHFFFAOYSA-N 1-bromo-2-fluoro-4-(trifluoromethyl)benzene Chemical compound FC1=CC(C(F)(F)F)=CC=C1Br XCTQZIUCYJVRLJ-UHFFFAOYSA-N 0.000 description 1
- BRGVKVZXDWGJBX-UHFFFAOYSA-N 1-bromo-4-butylbenzene Chemical compound CCCCC1=CC=C(Br)C=C1 BRGVKVZXDWGJBX-UHFFFAOYSA-N 0.000 description 1
- NUPWGLKBGVNSJX-UHFFFAOYSA-N 1-bromo-4-propylbenzene Chemical compound CCCC1=CC=C(Br)C=C1 NUPWGLKBGVNSJX-UHFFFAOYSA-N 0.000 description 1
- XHCAGOVGSDHHNP-UHFFFAOYSA-N 1-bromo-4-tert-butylbenzene Chemical compound CC(C)(C)C1=CC=C(Br)C=C1 XHCAGOVGSDHHNP-UHFFFAOYSA-N 0.000 description 1
- RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 description 1
- OITQDWKMIPXGFL-UHFFFAOYSA-N 1-hydroxy-2-naphthaldehyde Chemical compound C1=CC=C2C(O)=C(C=O)C=CC2=C1 OITQDWKMIPXGFL-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- WGFNXGPBPIJYLI-UHFFFAOYSA-N 2,6-difluoro-3-[(3-fluorophenyl)sulfonylamino]-n-(3-methoxy-1h-pyrazolo[3,4-b]pyridin-5-yl)benzamide Chemical compound C1=C2C(OC)=NNC2=NC=C1NC(=O)C(C=1F)=C(F)C=CC=1NS(=O)(=O)C1=CC=CC(F)=C1 WGFNXGPBPIJYLI-UHFFFAOYSA-N 0.000 description 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 description 1
- VCUXVXLUOHDHKK-UHFFFAOYSA-N 2-(2-aminopyrimidin-4-yl)-4-(2-chloro-4-methoxyphenyl)-1,3-thiazole-5-carboxamide Chemical compound ClC1=CC(OC)=CC=C1C1=C(C(N)=O)SC(C=2N=C(N)N=CC=2)=N1 VCUXVXLUOHDHKK-UHFFFAOYSA-N 0.000 description 1
- QEBYEVQKHRUYPE-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-[(1-methylpyrazol-3-yl)methyl]-4-[[methyl(pyridin-3-ylmethyl)amino]methyl]-1h-pyrazolo[4,3-c]pyridine-3,6-dione Chemical compound C1=CN(C)N=C1CN1C(=O)C=C2NN(C=3C(=CC=CC=3)Cl)C(=O)C2=C1CN(C)CC1=CC=CN=C1 QEBYEVQKHRUYPE-UHFFFAOYSA-N 0.000 description 1
- GJBBAPXESBCGRU-UHFFFAOYSA-N 2-(3,4-dimethylphenyl)-5-methyl-4h-pyrazol-3-one Chemical compound O=C1CC(C)=NN1C1=CC=C(C)C(C)=C1 GJBBAPXESBCGRU-UHFFFAOYSA-N 0.000 description 1
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 1
- ROTDDZDFTAPDEY-UHFFFAOYSA-N 2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-sulfonic 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)=O)N=2)=C1 ROTDDZDFTAPDEY-UHFFFAOYSA-N 0.000 description 1
- CANPVTDMCNTPJI-UHFFFAOYSA-N 2-[4-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-sulfonic 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)S(O)(=O)=O)N=2)C=C1 CANPVTDMCNTPJI-UHFFFAOYSA-N 0.000 description 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
- FMKGJQHNYMWDFJ-CVEARBPZSA-N 2-[[4-(2,2-difluoropropoxy)pyrimidin-5-yl]methylamino]-4-[[(1R,4S)-4-hydroxy-3,3-dimethylcyclohexyl]amino]pyrimidine-5-carbonitrile Chemical compound FC(COC1=NC=NC=C1CNC1=NC=C(C(=N1)N[C@H]1CC([C@H](CC1)O)(C)C)C#N)(C)F FMKGJQHNYMWDFJ-CVEARBPZSA-N 0.000 description 1
- PAYROHWFGZADBR-UHFFFAOYSA-N 2-[[4-amino-5-(5-iodo-4-methoxy-2-propan-2-ylphenoxy)pyrimidin-2-yl]amino]propane-1,3-diol Chemical compound C1=C(I)C(OC)=CC(C(C)C)=C1OC1=CN=C(NC(CO)CO)N=C1N PAYROHWFGZADBR-UHFFFAOYSA-N 0.000 description 1
- VVCMGAUPZIKYTH-VGHSCWAPSA-N 2-acetyloxybenzoic acid;[(2s,3r)-4-(dimethylamino)-3-methyl-1,2-diphenylbutan-2-yl] propanoate;1,3,7-trimethylpurine-2,6-dione Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C.C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 VVCMGAUPZIKYTH-VGHSCWAPSA-N 0.000 description 1
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
- HXUMDXIKPVFXIP-UHFFFAOYSA-N 2-bromo-3h-thiophene-2-carbaldehyde Chemical compound O=CC1(Br)CC=CS1 HXUMDXIKPVFXIP-UHFFFAOYSA-N 0.000 description 1
- FXZRJSNPRWVFQX-UHFFFAOYSA-N 2-fluoro-5-[4-(trifluoromethyl)phenyl]benzaldehyde Chemical compound C1=C(C=O)C(F)=CC=C1C1=CC=C(C(F)(F)F)C=C1 FXZRJSNPRWVFQX-UHFFFAOYSA-N 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- WIESUMHGNDSKRB-UHFFFAOYSA-N 2-hydroxy-1h-naphthalene-2-carbaldehyde Chemical compound C1=CC=C2C=CC(O)(C=O)CC2=C1 WIESUMHGNDSKRB-UHFFFAOYSA-N 0.000 description 1
- IKYDTCFKUJZPPO-UHFFFAOYSA-N 2-hydroxy-3-phenylbenzaldehyde Chemical compound OC1=C(C=O)C=CC=C1C1=CC=CC=C1 IKYDTCFKUJZPPO-UHFFFAOYSA-N 0.000 description 1
- CZXFNLAJTMZELR-UHFFFAOYSA-N 2-hydroxy-4-(3-hydroxyphenyl)benzaldehyde Chemical compound OC1=CC=CC(C=2C=C(O)C(C=O)=CC=2)=C1 CZXFNLAJTMZELR-UHFFFAOYSA-N 0.000 description 1
- RTYVNQSKWNUSCM-UHFFFAOYSA-N 2-methoxy-3-(3-nitrophenyl)benzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=CC([N+]([O-])=O)=C1 RTYVNQSKWNUSCM-UHFFFAOYSA-N 0.000 description 1
- XICUARVCKBJWGD-UHFFFAOYSA-N 2-methoxy-4-(3-nitrophenyl)benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=C(C=CC=2)[N+]([O-])=O)=C1 XICUARVCKBJWGD-UHFFFAOYSA-N 0.000 description 1
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
- LCRCBXLHWTVPEQ-UHFFFAOYSA-N 2-phenylbenzaldehyde Chemical compound O=CC1=CC=CC=C1C1=CC=CC=C1 LCRCBXLHWTVPEQ-UHFFFAOYSA-N 0.000 description 1
- GATQWOACFTWRQU-UHFFFAOYSA-N 2-tert-butyl-5-phenylbenzaldehyde Chemical compound C1=C(C=O)C(C(C)(C)C)=CC=C1C1=CC=CC=C1 GATQWOACFTWRQU-UHFFFAOYSA-N 0.000 description 1
- DYLTZDSMIKPQDQ-UHFFFAOYSA-N 3,4-diamino-2-hydroxynaphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(O)(=O)=O)=C(O)C(N)=C(N)C2=C1 DYLTZDSMIKPQDQ-UHFFFAOYSA-N 0.000 description 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
- DFRAKBCRUYUFNT-UHFFFAOYSA-N 3,8-dicyclohexyl-2,4,7,9-tetrahydro-[1,3]oxazino[5,6-h][1,3]benzoxazine Chemical compound C1CCCCC1N1CC(C=CC2=C3OCN(C2)C2CCCCC2)=C3OC1 DFRAKBCRUYUFNT-UHFFFAOYSA-N 0.000 description 1
- CMMCIJBGFQYEMA-UHFFFAOYSA-N 3-(3,4-difluorophenyl)benzaldehyde Chemical compound C1=C(F)C(F)=CC=C1C1=CC=CC(C=O)=C1 CMMCIJBGFQYEMA-UHFFFAOYSA-N 0.000 description 1
- TZNXFZYSTXCXKN-UHFFFAOYSA-N 3-(3,4-dimethylphenyl)-4-fluorobenzaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC(C=O)=CC=C1F TZNXFZYSTXCXKN-UHFFFAOYSA-N 0.000 description 1
- XLRKOYCECSXNRN-UHFFFAOYSA-N 3-(4-butylphenyl)benzaldehyde Chemical compound C1=CC(CCCC)=CC=C1C1=CC=CC(C=O)=C1 XLRKOYCECSXNRN-UHFFFAOYSA-N 0.000 description 1
- RWHZQMRUKDMAPQ-UHFFFAOYSA-N 3-(4-chlorophenyl)-2-methoxybenzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=C(Cl)C=C1 RWHZQMRUKDMAPQ-UHFFFAOYSA-N 0.000 description 1
- HKOXWDGKDQJANT-UHFFFAOYSA-N 3-(4-ethylphenyl)benzaldehyde Chemical compound C1=CC(CC)=CC=C1C1=CC=CC(C=O)=C1 HKOXWDGKDQJANT-UHFFFAOYSA-N 0.000 description 1
- IFMWARRXRDWXBH-UHFFFAOYSA-N 3-(4-fluoro-3-methylphenyl)benzaldehyde Chemical compound C1=C(F)C(C)=CC(C=2C=C(C=O)C=CC=2)=C1 IFMWARRXRDWXBH-UHFFFAOYSA-N 0.000 description 1
- BGANZGOIIYTUOB-UHFFFAOYSA-N 3-(4-fluorophenyl)-2-methoxybenzaldehyde Chemical compound COC1=C(C=O)C=CC=C1C1=CC=C(F)C=C1 BGANZGOIIYTUOB-UHFFFAOYSA-N 0.000 description 1
- KCBAXUJWKGKCTG-UHFFFAOYSA-N 3-(4-propylphenyl)benzaldehyde Chemical compound C1=CC(CCC)=CC=C1C1=CC=CC(C=O)=C1 KCBAXUJWKGKCTG-UHFFFAOYSA-N 0.000 description 1
- JVNKGZFUCJQKSH-UHFFFAOYSA-N 3-(4-tert-butylphenyl)-4-fluorobenzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC(C=O)=CC=C1F JVNKGZFUCJQKSH-UHFFFAOYSA-N 0.000 description 1
- JGDTVFIYBMWTIE-UHFFFAOYSA-N 3-(4-tert-butylphenyl)-4-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1C1=CC=C(C(C)(C)C)C=C1 JGDTVFIYBMWTIE-UHFFFAOYSA-N 0.000 description 1
- LGCFXYBKJMFGJC-UHFFFAOYSA-N 3-(4-tert-butylphenyl)benzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=CC(C=O)=C1 LGCFXYBKJMFGJC-UHFFFAOYSA-N 0.000 description 1
- UVFJHYIFPZHLGT-UHFFFAOYSA-N 3-(9h-fluoren-2-yl)benzaldehyde Chemical compound O=CC1=CC=CC(C=2C=C3C(C4=CC=CC=C4C3)=CC=2)=C1 UVFJHYIFPZHLGT-UHFFFAOYSA-N 0.000 description 1
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 1
- CHTIYJRLQSZOAC-UHFFFAOYSA-N 3-[2,5-difluoro-3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound FC(F)(F)C1=CC(F)=CC(C=2C=C(C=O)C=CC=2)=C1F CHTIYJRLQSZOAC-UHFFFAOYSA-N 0.000 description 1
- XJCCQMWFBZSHBH-UHFFFAOYSA-N 3-[2-fluoro-3-(trifluoromethyl)phenyl]benzaldehyde Chemical compound C1=CC=C(C(F)(F)F)C(F)=C1C1=CC=CC(C=O)=C1 XJCCQMWFBZSHBH-UHFFFAOYSA-N 0.000 description 1
- SOGDVUKDBJMXEX-UHFFFAOYSA-N 3-[4-(trifluoromethyl)phenyl]thiophene-2-carbaldehyde Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=C(C=O)SC=C1 SOGDVUKDBJMXEX-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- QKJVCASTYBUZNJ-UHFFFAOYSA-N 3-[[2-[3-(4-tert-butylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazole-7-carbonyl]amino]propanoic 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)NCCC(O)=O)N=2)=C1 QKJVCASTYBUZNJ-UHFFFAOYSA-N 0.000 description 1
- CLBQHDAKOPHNQI-UHFFFAOYSA-N 3-amino-2-hydroxynaphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(O)(=O)=O)=C(O)C(N)=CC2=C1 CLBQHDAKOPHNQI-UHFFFAOYSA-N 0.000 description 1
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
- MRLGCTNJRREZHZ-UHFFFAOYSA-N 3-phenoxybenzaldehyde Chemical compound O=CC1=CC=CC(OC=2C=CC=CC=2)=C1 MRLGCTNJRREZHZ-UHFFFAOYSA-N 0.000 description 1
- FACHGQGXNLXBEQ-UHFFFAOYSA-N 4-(3,4-dimethylphenyl)-2-hydroxybenzaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(C=O)C(O)=C1 FACHGQGXNLXBEQ-UHFFFAOYSA-N 0.000 description 1
- XPMYNDMKLHDSEK-UHFFFAOYSA-N 4-(3,4-dimethylphenyl)-2-methoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=C(C)C(C)=CC=2)=C1 XPMYNDMKLHDSEK-UHFFFAOYSA-N 0.000 description 1
- FZAMUBZKCYNWQL-UHFFFAOYSA-N 4-(3,4-dimethylphenyl)thiophene-2-carbaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CSC(C=O)=C1 FZAMUBZKCYNWQL-UHFFFAOYSA-N 0.000 description 1
- AFGZUKJHVNNVQA-UHFFFAOYSA-N 4-(3-formylphenyl)-2-methylbenzoic acid Chemical compound C1=C(C(O)=O)C(C)=CC(C=2C=C(C=O)C=CC=2)=C1 AFGZUKJHVNNVQA-UHFFFAOYSA-N 0.000 description 1
- NGDAPFNOCHARIT-UHFFFAOYSA-N 4-(3-formylphenyl)-2-methylbenzonitrile Chemical compound C1=C(C#N)C(C)=CC(C=2C=C(C=O)C=CC=2)=C1 NGDAPFNOCHARIT-UHFFFAOYSA-N 0.000 description 1
- WGWKHRBHJPBGPS-UHFFFAOYSA-N 4-(4-chlorophenyl)-2-methoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=CC(Cl)=CC=2)=C1 WGWKHRBHJPBGPS-UHFFFAOYSA-N 0.000 description 1
- MMASPRKSNDDQHU-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-hydroxybenzaldehyde Chemical compound C1=C(C=O)C(O)=CC(C=2C=CC(F)=CC=2)=C1 MMASPRKSNDDQHU-UHFFFAOYSA-N 0.000 description 1
- KMECEUDGEBTNKR-UHFFFAOYSA-N 4-(4-fluorophenyl)-2-methoxybenzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(C=2C=CC(F)=CC=2)=C1 KMECEUDGEBTNKR-UHFFFAOYSA-N 0.000 description 1
- NQJLDUNCTHXCSW-UHFFFAOYSA-N 4-(4-tert-butylphenyl)thiophene-2-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CSC(C=O)=C1 NQJLDUNCTHXCSW-UHFFFAOYSA-N 0.000 description 1
- MXZAFJVBFPQBGO-UHFFFAOYSA-N 4-[4-(1,3-dihydroisoindol-2-yl)phenyl]-3-ethoxycarbonylbut-3-enoic acid Chemical compound C1=CC(C=C(CC(O)=O)C(=O)OCC)=CC=C1N1CC2=CC=CC=C2C1 MXZAFJVBFPQBGO-UHFFFAOYSA-N 0.000 description 1
- KEJFPCAETPDXQR-UHFFFAOYSA-N 4-[4-(trifluoromethyl)phenyl]thiophene-2-carbaldehyde Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CSC(C=O)=C1 KEJFPCAETPDXQR-UHFFFAOYSA-N 0.000 description 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 1
- MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 1
- LRDIEHDJWYRVPT-UHFFFAOYSA-N 4-amino-5-hydroxynaphthalene-1-sulfonic acid Chemical compound C1=CC(O)=C2C(N)=CC=C(S(O)(=O)=O)C2=C1 LRDIEHDJWYRVPT-UHFFFAOYSA-N 0.000 description 1
- CFPZDVAZISWERM-UHFFFAOYSA-N 4-bromo-1,2-dichlorobenzene Chemical compound ClC1=CC=C(Br)C=C1Cl CFPZDVAZISWERM-UHFFFAOYSA-N 0.000 description 1
- YMXQYZABFWVXEK-UHFFFAOYSA-N 4-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC(Br)=CC=C1C=O YMXQYZABFWVXEK-UHFFFAOYSA-N 0.000 description 1
- RVCJOGNLYVNRDN-UHFFFAOYSA-N 4-bromo-2-methylbenzoic acid Chemical compound CC1=CC(Br)=CC=C1C(O)=O RVCJOGNLYVNRDN-UHFFFAOYSA-N 0.000 description 1
- LPEBMDFRIKYFCF-UHFFFAOYSA-N 4-bromo-2-methylbenzonitrile Chemical compound CC1=CC(Br)=CC=C1C#N LPEBMDFRIKYFCF-UHFFFAOYSA-N 0.000 description 1
- GSDQYSSLIKJJOG-UHFFFAOYSA-N 4-chloro-2-(3-chloroanilino)benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1NC1=CC=CC(Cl)=C1 GSDQYSSLIKJJOG-UHFFFAOYSA-N 0.000 description 1
- NIOAVQYSSKOCQP-UHFFFAOYSA-N 4-hydroxynaphthalene-2-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC(O)=C21 NIOAVQYSSKOCQP-UHFFFAOYSA-N 0.000 description 1
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 1
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
- IPBRDLJFHQZKFQ-UHFFFAOYSA-N 5-(1-benzothiophen-2-yl)furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C1=CC2=CC=CC=C2S1 IPBRDLJFHQZKFQ-UHFFFAOYSA-N 0.000 description 1
- OCGIMHGHNOVCPV-UHFFFAOYSA-N 5-(3,4-dimethylphenyl)-2-fluorobenzaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(F)C(C=O)=C1 OCGIMHGHNOVCPV-UHFFFAOYSA-N 0.000 description 1
- QLOARUWVOFKQSU-UHFFFAOYSA-N 5-(3,4-dimethylphenyl)thiophene-2-carbaldehyde Chemical compound C1=C(C)C(C)=CC=C1C1=CC=C(C=O)S1 QLOARUWVOFKQSU-UHFFFAOYSA-N 0.000 description 1
- KJYMUHACPKJYHY-UHFFFAOYSA-N 5-(3-propan-2-ylphenyl)furan-2-carbaldehyde Chemical compound CC(C)C1=CC=CC(C=2OC(C=O)=CC=2)=C1 KJYMUHACPKJYHY-UHFFFAOYSA-N 0.000 description 1
- MKCCAXAWKVVCRY-UHFFFAOYSA-N 5-(4-butylphenyl)pyridine-3-carbaldehyde Chemical compound C1=CC(CCCC)=CC=C1C1=CN=CC(C=O)=C1 MKCCAXAWKVVCRY-UHFFFAOYSA-N 0.000 description 1
- CKGNNCMNADJRDY-UHFFFAOYSA-N 5-(4-tert-butylphenyl)-2-fluorobenzaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(F)C(C=O)=C1 CKGNNCMNADJRDY-UHFFFAOYSA-N 0.000 description 1
- DDEVJQDGKYYOKK-UHFFFAOYSA-N 5-(4-tert-butylphenyl)thiophene-2-carbaldehyde Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=C(C=O)S1 DDEVJQDGKYYOKK-UHFFFAOYSA-N 0.000 description 1
- VPYRAXYANHWDHL-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenyl]furan-2-carbaldehyde Chemical compound C1=CC(C(F)(F)F)=CC=C1C1=CC=C(C=O)O1 VPYRAXYANHWDHL-UHFFFAOYSA-N 0.000 description 1
- VKLKXFOZNHEBSW-UHFFFAOYSA-N 5-[[3-[(4-morpholin-4-ylbenzoyl)amino]phenyl]methoxy]pyridine-3-carboxamide Chemical compound O1CCN(CC1)C1=CC=C(C(=O)NC=2C=C(COC=3C=NC=C(C(=O)N)C=3)C=CC=2)C=C1 VKLKXFOZNHEBSW-UHFFFAOYSA-N 0.000 description 1
- MMFGGDVQLQQQRX-UHFFFAOYSA-N 5-bromo-2-fluorobenzaldehyde Chemical compound FC1=CC=C(Br)C=C1C=O MMFGGDVQLQQQRX-UHFFFAOYSA-N 0.000 description 1
- XFJBGINZIMNZBW-CRAIPNDOSA-N 5-chloro-2-[4-[(1r,2s)-2-[2-(5-methylsulfonylpyridin-2-yl)oxyethyl]cyclopropyl]piperidin-1-yl]pyrimidine Chemical compound N1=CC(S(=O)(=O)C)=CC=C1OCC[C@H]1[C@@H](C2CCN(CC2)C=2N=CC(Cl)=CN=2)C1 XFJBGINZIMNZBW-CRAIPNDOSA-N 0.000 description 1
- IJRKLHTZAIFUTB-UHFFFAOYSA-N 5-nitro-2-(2-phenylethylamino)benzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NCCC1=CC=CC=C1 IJRKLHTZAIFUTB-UHFFFAOYSA-N 0.000 description 1
- RSIWALKZYXPAGW-NSHDSACASA-N 6-(3-fluorophenyl)-3-methyl-7-[(1s)-1-(7h-purin-6-ylamino)ethyl]-[1,3]thiazolo[3,2-a]pyrimidin-5-one Chemical compound C=1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)N=C2SC=C(C)N2C(=O)C=1C1=CC=CC(F)=C1 RSIWALKZYXPAGW-NSHDSACASA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- HBZVNWNSRNTWPS-UHFFFAOYSA-N 6-amino-4-hydroxynaphthalene-2-sulfonic acid Chemical compound C1=C(S(O)(=O)=O)C=C(O)C2=CC(N)=CC=C21 HBZVNWNSRNTWPS-UHFFFAOYSA-N 0.000 description 1
- GDUANFXPOZTYKS-UHFFFAOYSA-N 6-bromo-8-[(2,6-difluoro-4-methoxybenzoyl)amino]-4-oxochromene-2-carboxylic acid Chemical compound FC1=CC(OC)=CC(F)=C1C(=O)NC1=CC(Br)=CC2=C1OC(C(O)=O)=CC2=O GDUANFXPOZTYKS-UHFFFAOYSA-N 0.000 description 1
- XURXQNUIGWHWHU-UHFFFAOYSA-N 6-bromopyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=CC(Br)=N1 XURXQNUIGWHWHU-UHFFFAOYSA-N 0.000 description 1
- XASOHFCUIQARJT-UHFFFAOYSA-N 8-methoxy-6-[7-(2-morpholin-4-ylethoxy)imidazo[1,2-a]pyridin-3-yl]-2-(2,2,2-trifluoroethyl)-3,4-dihydroisoquinolin-1-one Chemical compound C(N1C(=O)C2=C(OC)C=C(C=3N4C(=NC=3)C=C(C=C4)OCCN3CCOCC3)C=C2CC1)C(F)(F)F XASOHFCUIQARJT-UHFFFAOYSA-N 0.000 description 1
- IRBAWVGZNJIROV-SFHVURJKSA-N 9-(2-cyclopropylethynyl)-2-[[(2s)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=C2C3=CC=C(C#CC4CC4)C=C3CCN2C(=O)N=C1OC[C@@H]1COCCO1 IRBAWVGZNJIROV-SFHVURJKSA-N 0.000 description 1
- AOWUASXGYDUMKM-UHFFFAOYSA-N 9-hydroxy-2-(1-hydroxynaphthalen-2-yl)-3H-benzo[e]benzimidazole-7-carboxylic acid 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.OC1=C(C=CC2=CC=CC=C12)C=1NC2=C(N1)C1=C(C=C(C=C1C=C2)C(=O)O)O AOWUASXGYDUMKM-UHFFFAOYSA-N 0.000 description 1
- QYNWXCCSDNIZNH-UHFFFAOYSA-N 9-hydroxy-2-(2-hydroxynaphthalen-1-yl)-3H-benzo[e]benzimidazole-7-carboxylic acid 2,2,2-trifluoroacetic acid Chemical compound FC(C(=O)O)(F)F.OC1=C(C2=CC=CC=C2C=C1)C=1NC2=C(N1)C1=C(C=C(C=C1C=C2)C(=O)O)O QYNWXCCSDNIZNH-UHFFFAOYSA-N 0.000 description 1
- OIWAWOJRRRBLPH-UHFFFAOYSA-N 9-hydroxy-2-[3-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]-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=1)=CC=CC=1OCC1=CC=CC(C(F)(F)F)=C1 OIWAWOJRRRBLPH-UHFFFAOYSA-N 0.000 description 1
- 102000012440 Acetylcholinesterase Human genes 0.000 description 1
- 108010022752 Acetylcholinesterase Proteins 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241001553178 Arachis glabrata Species 0.000 description 1
- OMLWNBVRVJYMBQ-YUMQZZPRSA-N Arg-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N[C@@H](CCCN=C(N)N)C(O)=O OMLWNBVRVJYMBQ-YUMQZZPRSA-N 0.000 description 1
- IYHHRZBKXXKDDY-UHFFFAOYSA-N BI-605906 Chemical compound N=1C=2SC(C(N)=O)=C(N)C=2C(C(F)(F)CC)=CC=1N1CCC(S(C)(=O)=O)CC1 IYHHRZBKXXKDDY-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- JQUCWIWWWKZNCS-LESHARBVSA-N C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F Chemical compound C(C1=CC=CC=C1)(=O)NC=1SC[C@H]2[C@@](N1)(CO[C@H](C2)C)C=2SC=C(N2)NC(=O)C2=NC=C(C=C2)OC(F)F JQUCWIWWWKZNCS-LESHARBVSA-N 0.000 description 1
- BGGALFIXXQOTPY-NRFANRHFSA-N C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC Chemical compound C1(=C(C2=C(C=C1)N(C(C#N)=C2)C[C@@H](N1CCN(CC1)S(=O)(=O)C)C)C)CN1CCC(CC1)NC1=NC(=NC2=C1C=C(S2)CC(F)(F)F)NC BGGALFIXXQOTPY-NRFANRHFSA-N 0.000 description 1
- KCBAMQOKOLXLOX-BSZYMOERSA-N CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O Chemical compound CC1=C(SC=N1)C2=CC=C(C=C2)[C@H](C)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](C(C)(C)C)NC(=O)CCCCCCCCCCNCCCONC(=O)C4=C(C(=C(C=C4)F)F)NC5=C(C=C(C=C5)I)F)O KCBAMQOKOLXLOX-BSZYMOERSA-N 0.000 description 1
- UHNRLQRZRNKOKU-UHFFFAOYSA-N CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O Chemical compound CCN(CC1=NC2=C(N1)C1=CC=C(C=C1N=C2N)C1=NNC=C1)C(C)=O UHNRLQRZRNKOKU-UHFFFAOYSA-N 0.000 description 1
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 1
- PKMUHQIDVVOXHQ-HXUWFJFHSA-N C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O Chemical compound C[C@H](C1=CC(C2=CC=C(CNC3CCCC3)S2)=CC=C1)NC(C1=C(C)C=CC(NC2CNC2)=C1)=O PKMUHQIDVVOXHQ-HXUWFJFHSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229940126657 Compound 17 Drugs 0.000 description 1
- 229940126639 Compound 33 Drugs 0.000 description 1
- 229940127007 Compound 39 Drugs 0.000 description 1
- DKMROQRQHGEIOW-UHFFFAOYSA-N Diethyl succinate Chemical compound CCOC(=O)CCC(=O)OCC DKMROQRQHGEIOW-UHFFFAOYSA-N 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 108010075944 Erythropoietin Receptors Proteins 0.000 description 1
- 102100036509 Erythropoietin receptor Human genes 0.000 description 1
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 101100220044 Homo sapiens CD34 gene Proteins 0.000 description 1
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 1
- 101000617830 Homo sapiens Sterol O-acyltransferase 1 Proteins 0.000 description 1
- 101000799461 Homo sapiens Thrombopoietin Proteins 0.000 description 1
- 101000694103 Homo sapiens Thyroid peroxidase Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101000783705 Myxoma virus (strain Uriarra) Envelope protein A28 homolog Proteins 0.000 description 1
- LIMFPAAAIVQRRD-BCGVJQADSA-N N-[2-[(3S,4R)-3-fluoro-4-methoxypiperidin-1-yl]pyrimidin-4-yl]-8-[(2R,3S)-2-methyl-3-(methylsulfonylmethyl)azetidin-1-yl]-5-propan-2-ylisoquinolin-3-amine Chemical compound F[C@H]1CN(CC[C@H]1OC)C1=NC=CC(=N1)NC=1N=CC2=C(C=CC(=C2C=1)C(C)C)N1[C@@H]([C@H](C1)CS(=O)(=O)C)C LIMFPAAAIVQRRD-BCGVJQADSA-N 0.000 description 1
- AVYVHIKSFXVDBG-UHFFFAOYSA-N N-benzyl-N-hydroxy-2,2-dimethylbutanamide Chemical compound C(C1=CC=CC=C1)N(C(C(CC)(C)C)=O)O AVYVHIKSFXVDBG-UHFFFAOYSA-N 0.000 description 1
- POFVJRKJJBFPII-UHFFFAOYSA-N N-cyclopentyl-5-[2-[[5-[(4-ethylpiperazin-1-yl)methyl]pyridin-2-yl]amino]-5-fluoropyrimidin-4-yl]-4-methyl-1,3-thiazol-2-amine Chemical compound C1(CCCC1)NC=1SC(=C(N=1)C)C1=NC(=NC=C1F)NC1=NC=C(C=C1)CN1CCN(CC1)CC POFVJRKJJBFPII-UHFFFAOYSA-N 0.000 description 1
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 description 1
- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 206010033661 Pancytopenia Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 1
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 102100021993 Sterol O-acyltransferase 1 Human genes 0.000 description 1
- 101000697584 Streptomyces lavendulae Streptothricin acetyltransferase Proteins 0.000 description 1
- 238000006069 Suzuki reaction reaction Methods 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 241000283907 Tragelaphus oryx Species 0.000 description 1
- 102100023935 Transmembrane glycoprotein NMB Human genes 0.000 description 1
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 description 1
- ALMFIOZYDASRRC-UHFFFAOYSA-N [4-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=C(C(F)(F)F)C=C1 ALMFIOZYDASRRC-UHFFFAOYSA-N 0.000 description 1
- RCZCFMPNFYUHFD-UHFFFAOYSA-N [6-(4-tert-butylphenyl)pyridin-2-yl]methanol Chemical compound C1=CC(C(C)(C)C)=CC=C1C1=CC=CC(CO)=N1 RCZCFMPNFYUHFD-UHFFFAOYSA-N 0.000 description 1
- SMNRFWMNPDABKZ-WVALLCKVSA-N [[(2R,3S,4R,5S)-5-(2,6-dioxo-3H-pyridin-3-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [[[(2R,3S,4S,5R,6R)-4-fluoro-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-hydroxyphosphoryl]oxy-hydroxyphosphoryl] hydrogen phosphate Chemical compound OC[C@H]1O[C@H](OP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)C2C=CC(=O)NC2=O)[C@H](O)[C@@H](F)[C@@H]1O SMNRFWMNPDABKZ-WVALLCKVSA-N 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- QBYJBZPUGVGKQQ-SJJAEHHWSA-N aldrin Chemical compound C1[C@H]2C=C[C@@H]1[C@H]1[C@@](C3(Cl)Cl)(Cl)C(Cl)=C(Cl)[C@@]3(Cl)[C@H]12 QBYJBZPUGVGKQQ-SJJAEHHWSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 108010068380 arginylarginine Proteins 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 1
- 238000006149 azo coupling reaction Methods 0.000 description 1
- RRRODXJHANJPEB-UHFFFAOYSA-L benzenediazonium;sulfate Chemical compound [O-]S([O-])(=O)=O.N#[N+]C1=CC=CC=C1.N#[N+]C1=CC=CC=C1 RRRODXJHANJPEB-UHFFFAOYSA-L 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000007963 capsule composition Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000005757 colony formation Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125758 compound 15 Drugs 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 229940126086 compound 21 Drugs 0.000 description 1
- 229940126208 compound 22 Drugs 0.000 description 1
- 229940125833 compound 23 Drugs 0.000 description 1
- 229940125961 compound 24 Drugs 0.000 description 1
- 229940125846 compound 25 Drugs 0.000 description 1
- 229940125851 compound 27 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125877 compound 31 Drugs 0.000 description 1
- 229940125878 compound 36 Drugs 0.000 description 1
- 229940125807 compound 37 Drugs 0.000 description 1
- 229940127573 compound 38 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 229940125936 compound 42 Drugs 0.000 description 1
- 229940125844 compound 46 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 229940126545 compound 53 Drugs 0.000 description 1
- 229940127113 compound 57 Drugs 0.000 description 1
- 229940125900 compound 59 Drugs 0.000 description 1
- 229940126179 compound 72 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 238000004163 cytometry Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000017858 demethylation Effects 0.000 description 1
- 238000010520 demethylation reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 150000008049 diazo compounds Chemical class 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- BJXYHBKEQFQVES-NWDGAFQWSA-N enpatoran Chemical compound N[C@H]1CN(C[C@H](C1)C(F)(F)F)C1=C2C=CC=NC2=C(C=C1)C#N BJXYHBKEQFQVES-NWDGAFQWSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 150000002168 ethanoic acid esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- GWNFQAKCJYEJEW-UHFFFAOYSA-N ethyl 3-[8-[[4-methyl-5-[(3-methyl-4-oxophthalazin-1-yl)methyl]-1,2,4-triazol-3-yl]sulfanyl]octanoylamino]benzoate Chemical compound CCOC(=O)C1=CC(NC(=O)CCCCCCCSC2=NN=C(CC3=NN(C)C(=O)C4=CC=CC=C34)N2C)=CC=C1 GWNFQAKCJYEJEW-UHFFFAOYSA-N 0.000 description 1
- PJRWALWPLXMCTB-UHFFFAOYSA-N ethyl 4-acetyloxy-6-aminonaphthalene-2-carboxylate Chemical compound C1=C(N)C=CC2=CC(C(=O)OCC)=CC(OC(C)=O)=C21 PJRWALWPLXMCTB-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000013265 extended release Methods 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000011132 hemopoiesis Effects 0.000 description 1
- 102000053400 human TPO Human genes 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229960001388 interferon-beta Drugs 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- LBBMOAOCCQOIAQ-UHFFFAOYSA-N methoxy(phenyl)borinic acid Chemical compound COB(O)C1=CC=CC=C1 LBBMOAOCCQOIAQ-UHFFFAOYSA-N 0.000 description 1
- ZBELDPMWYXDLNY-UHFFFAOYSA-N methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate Chemical compound C12=C3SC(C(=N)OC)=NC3=CC=C2N=CN=C1NC1=CC=C(Br)C=C1F ZBELDPMWYXDLNY-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- YGBMCLDVRUGXOV-UHFFFAOYSA-N n-[6-[6-chloro-5-[(4-fluorophenyl)sulfonylamino]pyridin-3-yl]-1,3-benzothiazol-2-yl]acetamide Chemical compound C1=C2SC(NC(=O)C)=NC2=CC=C1C(C=1)=CN=C(Cl)C=1NS(=O)(=O)C1=CC=C(F)C=C1 YGBMCLDVRUGXOV-UHFFFAOYSA-N 0.000 description 1
- JHPVDNDKBOVZHR-UHFFFAOYSA-N naphthalene-1-carboxylic acid dihydrochloride Chemical compound C1=CC=C2C(=C1)C=CC=C2C(=O)O.Cl.Cl JHPVDNDKBOVZHR-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000005416 organic matter Substances 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 210000001850 polyploid cell Anatomy 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- KSVSZLXDULFGDQ-UHFFFAOYSA-M sodium;4-aminobenzenesulfonate Chemical compound [Na+].NC1=CC=C(S([O-])(=O)=O)C=C1 KSVSZLXDULFGDQ-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- MFYSDHXZECYPNR-NDEPHWFRSA-N tert-butyl (2s)-1-[[2-[3-(3,4-dimethylphenyl)phenyl]-9-hydroxy-3h-benzo[e]benzimidazol-7-yl]sulfonyl]pyrrolidine-2-carboxylate 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)OC(C)(C)C)N=2)=C1 MFYSDHXZECYPNR-NDEPHWFRSA-N 0.000 description 1
- TZHVYFBSLOMRCU-YFKPBYRVSA-N tert-butyl (2s)-2-aminopropanoate Chemical compound C[C@H](N)C(=O)OC(C)(C)C TZHVYFBSLOMRCU-YFKPBYRVSA-N 0.000 description 1
- MYKMOIQAHCMLIR-UHFFFAOYSA-N tert-butyl 2-(methylamino)acetate Chemical compound CNCC(=O)OC(C)(C)C MYKMOIQAHCMLIR-UHFFFAOYSA-N 0.000 description 1
- ZJXHVYSDMUKUCA-UHFFFAOYSA-N tert-butyl 3-aminopropanoate Chemical compound CC(C)(C)OC(=O)CCN ZJXHVYSDMUKUCA-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 208000014754 thrombocytosis disease Diseases 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 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
- 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 | |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
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 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
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 |
|---|---|
| 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 |
| DE60031714T2 (de) | 2007-09-06 |
| ES2275567T3 (es) | 2007-06-16 |
| WO2001039773A1 (en) | 2001-06-07 |
| ATE344031T1 (de) | 2006-11-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2003515560A (ja) | トロンボポイエチン模倣物 | |
| JP3813875B2 (ja) | トロンボポエチン摸倣物 | |
| JP4488663B2 (ja) | トロンボポイエチン模倣物 | |
| ES2279769T3 (es) | Mimeticos de trombopoyetina. | |
| JP2006514951A (ja) | トロンボポエチン模倣物 | |
| AU2001274938A1 (en) | Thrombopoietin mimetics | |
| JP2003513965A (ja) | セミカルバゾン誘導体およびそれらのトロンボポエチン模倣物としての使用 | |
| US6858630B2 (en) | Naphthimidazole derivatives and their use as thrombopoietin mimetics | |
| JP2004527541A (ja) | トロンボポエチン模倣物 | |
| US20130078213A1 (en) | Thrombopoietin mimetics | |
| HK1117825B (en) | Thrombopoietin mimetics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20071204 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20071204 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20110607 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20111101 |