ES2393741T3 - Ureas 1,3-diarilsustituidas como moduladores de la actividad quinasa - Google Patents
Ureas 1,3-diarilsustituidas como moduladores de la actividad quinasa Download PDFInfo
- Publication number
- ES2393741T3 ES2393741T3 ES06718359T ES06718359T ES2393741T3 ES 2393741 T3 ES2393741 T3 ES 2393741T3 ES 06718359 T ES06718359 T ES 06718359T ES 06718359 T ES06718359 T ES 06718359T ES 2393741 T3 ES2393741 T3 ES 2393741T3
- Authority
- ES
- Spain
- Prior art keywords
- phenyl
- pyridin
- ylmethyl
- optionally substituted
- urea
- 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.)
- Active
Links
- 108091000080 Phosphotransferase Proteins 0.000 title claims description 70
- 102000020233 phosphotransferase Human genes 0.000 title claims description 70
- 230000000694 effects Effects 0.000 title claims description 43
- 239000004202 carbamide Substances 0.000 title claims description 12
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 title description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 141
- -1 amino , aminocarbonyl Chemical group 0.000 claims abstract description 135
- 150000005829 chemical entities Chemical class 0.000 claims abstract description 133
- 150000001875 compounds Chemical class 0.000 claims abstract description 132
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 113
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 100
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 85
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims abstract description 76
- 239000000203 mixture Substances 0.000 claims abstract description 72
- 125000001424 substituent group Chemical group 0.000 claims abstract description 71
- 239000001257 hydrogen Substances 0.000 claims abstract description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 58
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 58
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 47
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims abstract description 45
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims abstract description 45
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 44
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 44
- 125000003118 aryl group Chemical group 0.000 claims abstract description 42
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 39
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 36
- 125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 31
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 29
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 25
- 125000002252 acyl group Chemical group 0.000 claims abstract description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 23
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 22
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 21
- 239000012453 solvate Substances 0.000 claims abstract description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 19
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 16
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 13
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 13
- 125000005415 substituted alkoxy group Chemical group 0.000 claims abstract description 13
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 13
- 229910006074 SO2NH2 Inorganic materials 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 7
- 239000002243 precursor Substances 0.000 claims abstract description 6
- 230000014509 gene expression Effects 0.000 claims abstract description 5
- HQLLTDZFHPPOMB-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-(1-pyridin-4-ylindol-5-yl)urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(N(C=C2)C=3C=CN=CC=3)C2=C1 HQLLTDZFHPPOMB-UHFFFAOYSA-N 0.000 claims abstract description 4
- LNPVNQWEALVSCD-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-(1-pyridin-4-ylindol-5-yl)urea Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC(=O)NC=2C=C3C=CN(C3=CC=2)C=2C=CN=CC=2)=C1 LNPVNQWEALVSCD-UHFFFAOYSA-N 0.000 claims abstract description 4
- VCEAIMUTAHEERT-UHFFFAOYSA-N 1-phenyl-3-[3-(2-pyridin-4-ylethyl)-1h-indol-5-yl]urea Chemical compound C=1C=C2NC=C(CCC=3C=CN=CC=3)C2=CC=1NC(=O)NC1=CC=CC=C1 VCEAIMUTAHEERT-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 4
- 239000000470 constituent Substances 0.000 claims abstract description 3
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims abstract description 3
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 33
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 68
- 238000000034 method Methods 0.000 claims description 46
- 201000010099 disease Diseases 0.000 claims description 45
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 34
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 32
- 102100031983 Ephrin type-B receptor 4 Human genes 0.000 claims description 29
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 claims description 28
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 claims description 28
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 claims description 26
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 claims description 26
- 230000033115 angiogenesis Effects 0.000 claims description 26
- 238000011282 treatment Methods 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 239000003981 vehicle Substances 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 230000005764 inhibitory process Effects 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 230000008859 change Effects 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 11
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 7
- 239000006188 syrup Substances 0.000 claims description 7
- 235000020357 syrup Nutrition 0.000 claims description 7
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 6
- ZXBFYBLSJMEBEP-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 ZXBFYBLSJMEBEP-UHFFFAOYSA-N 0.000 claims description 6
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 239000000499 gel Substances 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 6
- YKINCYOSYOLSFX-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indazol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=NN2CC1=CC=NC=C1 YKINCYOSYOLSFX-UHFFFAOYSA-N 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 230000001850 reproductive effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 125000006823 (C1-C6) acyl group Chemical group 0.000 claims description 4
- WWSTUNFETQEVAD-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[[2-(pyrazin-2-ylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2N=CC=NC=2)=C1 WWSTUNFETQEVAD-UHFFFAOYSA-N 0.000 claims description 4
- UKEXULSNZMFFQW-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(3-chloro-4-methylphenyl)urea Chemical compound C1=C(Cl)C(C)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 UKEXULSNZMFFQW-UHFFFAOYSA-N 0.000 claims description 4
- GPTRAPGXWSGCKJ-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(5-chloro-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 GPTRAPGXWSGCKJ-UHFFFAOYSA-N 0.000 claims description 4
- HLQVUGHYXJPWDB-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 HLQVUGHYXJPWDB-UHFFFAOYSA-N 0.000 claims description 4
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- UBERZPIAQDYONQ-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C=1C=C2OCOC2=CC=1NC(=O)NC(C=1C=C2)=CC=CC=1N2CC1=CC=NC=C1 UBERZPIAQDYONQ-UHFFFAOYSA-N 0.000 claims description 3
- XFERBKPZRBVADM-UHFFFAOYSA-N 1-(2-methoxy-5-phenylphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(C=2C=CC=CC=2)C=C1NC(=O)NC(C=1C=C2)=CC=CC=1N2CC1=CC=NC=C1 XFERBKPZRBVADM-UHFFFAOYSA-N 0.000 claims description 3
- FPWGFVUWXYCRQH-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(OC)C(OC)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 FPWGFVUWXYCRQH-UHFFFAOYSA-N 0.000 claims description 3
- VEKHFHMGKUQDCQ-UHFFFAOYSA-N 1-(3-bromo-4-fluorophenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Br)C(F)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 VEKHFHMGKUQDCQ-UHFFFAOYSA-N 0.000 claims description 3
- ZADWNBIFKQRSOU-UHFFFAOYSA-N 1-(3-bromo-4-methylphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Br)C(C)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 ZADWNBIFKQRSOU-UHFFFAOYSA-N 0.000 claims description 3
- DTHIVQGPJKVGPJ-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Cl)C(F)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 DTHIVQGPJKVGPJ-UHFFFAOYSA-N 0.000 claims description 3
- KTINNEIEHISFJF-UHFFFAOYSA-N 1-(3-chloro-4-methoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Cl)C(OC)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 KTINNEIEHISFJF-UHFFFAOYSA-N 0.000 claims description 3
- DHSXSHGHBPXOOY-UHFFFAOYSA-N 1-(3-chloro-4-methylphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Cl)C(C)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 DHSXSHGHBPXOOY-UHFFFAOYSA-N 0.000 claims description 3
- BBSJKVVUWIRQMG-UHFFFAOYSA-N 1-(5-bromo-2,4-difluorophenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Br)C(F)=CC(F)=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 BBSJKVVUWIRQMG-UHFFFAOYSA-N 0.000 claims description 3
- UZWMWXZSKSRTTA-UHFFFAOYSA-N 1-(5-bromo-2-ethoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound CCOC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 UZWMWXZSKSRTTA-UHFFFAOYSA-N 0.000 claims description 3
- SFATUYZETCDXJC-UHFFFAOYSA-N 1-(5-bromo-2-methoxy-4-methylphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(C)=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 SFATUYZETCDXJC-UHFFFAOYSA-N 0.000 claims description 3
- CPYKCKDISRLYRC-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-(pyridin-3-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=CN=C1 CPYKCKDISRLYRC-UHFFFAOYSA-N 0.000 claims description 3
- HULUDHUZWWWMRQ-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-(pyridin-3-ylmethyl)indol-5-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(N(CC=2C=NC=CC=2)C=C2)C2=C1 HULUDHUZWWWMRQ-UHFFFAOYSA-N 0.000 claims description 3
- ONIWGOKFYOBZSC-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 ONIWGOKFYOBZSC-UHFFFAOYSA-N 0.000 claims description 3
- QOVFTBYVBOLMHY-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-5-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(N(CC=2C=CN=CC=2)C=C2)C2=C1 QOVFTBYVBOLMHY-UHFFFAOYSA-N 0.000 claims description 3
- ZIFGHSVKFKSDPR-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(2-fluoropyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(F)=C1 ZIFGHSVKFKSDPR-UHFFFAOYSA-N 0.000 claims description 3
- QWBIUTWWXKGKBF-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(2-methoxypyridin-4-yl)methyl]indol-4-yl]urea Chemical compound C1=NC(OC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 QWBIUTWWXKGKBF-UHFFFAOYSA-N 0.000 claims description 3
- GMTLBHKLWRDJHH-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(2-methylpyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(C)=C1 GMTLBHKLWRDJHH-UHFFFAOYSA-N 0.000 claims description 3
- TXPNOGHKVNWPJQ-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(2-morpholin-4-ylpyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N2CCOCC2)=C1 TXPNOGHKVNWPJQ-UHFFFAOYSA-N 0.000 claims description 3
- FKFGITHAQSZFRF-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(2-oxo-1h-pyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(O)=C1 FKFGITHAQSZFRF-UHFFFAOYSA-N 0.000 claims description 3
- HVCRXOVVCFKXRR-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(3-chloropyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1Cl HVCRXOVVCFKXRR-UHFFFAOYSA-N 0.000 claims description 3
- SVQZZMXTVZCEGS-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[(3-fluoropyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1F SVQZZMXTVZCEGS-UHFFFAOYSA-N 0.000 claims description 3
- ZJJPGXDVXQEEOT-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[[2-(2-hydroxyethylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NCCO)=C1 ZJJPGXDVXQEEOT-UHFFFAOYSA-N 0.000 claims description 3
- YUJBRBUIEUFERZ-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[[2-(methanesulfonamido)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NS(C)(=O)=O)=C1 YUJBRBUIEUFERZ-UHFFFAOYSA-N 0.000 claims description 3
- GRSVWLJSKODNBT-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[[2-(methylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound C1=NC(NC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 GRSVWLJSKODNBT-UHFFFAOYSA-N 0.000 claims description 3
- YTGUWBBIBHACGN-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[3-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C(C)=CN2CC1=CC=NC=C1 YTGUWBBIBHACGN-UHFFFAOYSA-N 0.000 claims description 3
- LCDKPHAKDJIZGF-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[5-chloro-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=C(Cl)C=CC2=C1C=CN2CC1=CC=NC=C1 LCDKPHAKDJIZGF-UHFFFAOYSA-N 0.000 claims description 3
- HXINVQHQKKOWPT-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[5-fluoro-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=C(F)C=CC2=C1C=CN2CC1=CC=NC=C1 HXINVQHQKKOWPT-UHFFFAOYSA-N 0.000 claims description 3
- OGRXULSIWPKRED-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[5-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=C(C)C=CC2=C1C=CN2CC1=CC=NC=C1 OGRXULSIWPKRED-UHFFFAOYSA-N 0.000 claims description 3
- XVOUFMUKQDXRMM-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[6-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC(C)=CC2=C1C=CN2CC1=CC=NC=C1 XVOUFMUKQDXRMM-UHFFFAOYSA-N 0.000 claims description 3
- FNVMEZYUXHORRM-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[7-chloro-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(Cl)C2=C1C=CN2CC1=CC=NC=C1 FNVMEZYUXHORRM-UHFFFAOYSA-N 0.000 claims description 3
- KQAWHKKFZAQQNB-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[7-fluoro-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(F)C2=C1C=CN2CC1=CC=NC=C1 KQAWHKKFZAQQNB-UHFFFAOYSA-N 0.000 claims description 3
- FHEYVMONNUPHIK-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[7-methoxy-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(OC)C2=C1C=CN2CC1=CC=NC=C1 FHEYVMONNUPHIK-UHFFFAOYSA-N 0.000 claims description 3
- SCGXWQTZGPCZCE-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[7-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(C)C2=C1C=CN2CC1=CC=NC=C1 SCGXWQTZGPCZCE-UHFFFAOYSA-N 0.000 claims description 3
- BXRABKOISFMUKO-UHFFFAOYSA-N 1-(5-chloro-2-methoxy-4-methylphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(C)=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 BXRABKOISFMUKO-UHFFFAOYSA-N 0.000 claims description 3
- OCSHMIVAXMBEBS-UHFFFAOYSA-N 1-(5-chloro-2-methoxy-4-methylphenyl)-3-[7-fluoro-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(C)=C(Cl)C=C1NC(=O)NC1=CC=C(F)C2=C1C=CN2CC1=CC=NC=C1 OCSHMIVAXMBEBS-UHFFFAOYSA-N 0.000 claims description 3
- XNGOAKXUOZRXHP-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-5-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=C(N(CC=2C=CN=CC=2)C=C2)C2=C1 XNGOAKXUOZRXHP-UHFFFAOYSA-N 0.000 claims description 3
- CVUVYJZIEHGIFH-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[(3-methylpyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1C CVUVYJZIEHGIFH-UHFFFAOYSA-N 0.000 claims description 3
- ZRXMCSSZSIFTOK-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[[2-(methanesulfonamido)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NS(C)(=O)=O)=C1 ZRXMCSSZSIFTOK-UHFFFAOYSA-N 0.000 claims description 3
- MQQXYSGFMMMCSP-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[5-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=C(C)C=CC2=C1C=CN2CC1=CC=NC=C1 MQQXYSGFMMMCSP-UHFFFAOYSA-N 0.000 claims description 3
- ZMDVNXVEKYKBPA-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[7-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=C(C)C2=C1C=CN2CC1=CC=NC=C1 ZMDVNXVEKYKBPA-UHFFFAOYSA-N 0.000 claims description 3
- BRZYFPPCBGFDOM-UHFFFAOYSA-N 1-(5-fluoro-2,4-dimethoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(F)C(OC)=CC(OC)=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 BRZYFPPCBGFDOM-UHFFFAOYSA-N 0.000 claims description 3
- ILUDPKDIUKLTHL-UHFFFAOYSA-N 1-[1-[(2-amino-3-methylpyridin-4-yl)methyl]indol-4-yl]-3-(5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1C ILUDPKDIUKLTHL-UHFFFAOYSA-N 0.000 claims description 3
- BAMUBQUJNFQOMZ-UHFFFAOYSA-N 1-[1-[(2-amino-5-fluoropyridin-4-yl)methyl]indol-4-yl]-3-(5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC(N)=NC=C1F BAMUBQUJNFQOMZ-UHFFFAOYSA-N 0.000 claims description 3
- SBPJRUSUAMSHDY-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-5-chloroindol-4-yl]-3-(5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=C(Cl)C=CC2=C1C=CN2CC1=CC=NC(N)=C1 SBPJRUSUAMSHDY-UHFFFAOYSA-N 0.000 claims description 3
- HOHBFYQYTITGRT-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-5-fluoroindol-4-yl]-3-(2,5-dichlorophenyl)urea Chemical compound C1=NC(N)=CC(CN2C3=CC=C(F)C(NC(=O)NC=4C(=CC=C(Cl)C=4)Cl)=C3C=C2)=C1 HOHBFYQYTITGRT-UHFFFAOYSA-N 0.000 claims description 3
- NSEMYRFQGKPEKF-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-5-fluoroindol-4-yl]-3-(5-chloro-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=C(F)C=CC2=C1C=CN2CC1=CC=NC(N)=C1 NSEMYRFQGKPEKF-UHFFFAOYSA-N 0.000 claims description 3
- LCAAIHVTSQQSTK-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-5-fluoroindol-4-yl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(CN2C3=CC=C(F)C(NC(=O)NC=4C(=CC=C(C=4)C(F)(F)F)F)=C3C=C2)=C1 LCAAIHVTSQQSTK-UHFFFAOYSA-N 0.000 claims description 3
- DXZDSPXDYQWJNW-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-5-fluoroindol-4-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=C(F)C=CC2=C1C=CN2CC1=CC=NC(N)=C1 DXZDSPXDYQWJNW-UHFFFAOYSA-N 0.000 claims description 3
- GBIRJXOQVPDSOB-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-7-fluoroindol-4-yl]-3-(5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=C(F)C2=C1C=CN2CC1=CC=NC(N)=C1 GBIRJXOQVPDSOB-UHFFFAOYSA-N 0.000 claims description 3
- QLVDBFZSIMHZQC-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-7-fluoroindol-4-yl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(CN2C3=C(F)C=CC(NC(=O)NC=4C(=CC=C(C=4)C(F)(F)F)F)=C3C=C2)=C1 QLVDBFZSIMHZQC-UHFFFAOYSA-N 0.000 claims description 3
- QDUACQACRUCQLK-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(3-bromo-4-methoxyphenyl)urea Chemical compound C1=C(Br)C(OC)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 QDUACQACRUCQLK-UHFFFAOYSA-N 0.000 claims description 3
- LOMULLQYOJZHRS-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(5-bromo-2-methoxy-4-methylphenyl)urea Chemical compound COC1=CC(C)=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 LOMULLQYOJZHRS-UHFFFAOYSA-N 0.000 claims description 3
- QHDPRELNECVFMB-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(5-chloro-2,4-dimethoxyphenyl)urea Chemical compound C1=C(Cl)C(OC)=CC(OC)=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 QHDPRELNECVFMB-UHFFFAOYSA-N 0.000 claims description 3
- JFEFVVOHEOZTOL-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-(5-chloro-2-methoxy-4-methylphenyl)urea Chemical compound COC1=CC(C)=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 JFEFVVOHEOZTOL-UHFFFAOYSA-N 0.000 claims description 3
- HPHNINSVVJJJHJ-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-[2,4-dimethoxy-5-(trifluoromethyl)phenyl]urea Chemical compound COC1=CC(OC)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 HPHNINSVVJJJHJ-UHFFFAOYSA-N 0.000 claims description 3
- TXUOGPCEAWQFGI-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-[2,4-dimethyl-5-(trifluoromethyl)phenyl]urea Chemical compound CC1=CC(C)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 TXUOGPCEAWQFGI-UHFFFAOYSA-N 0.000 claims description 3
- WGTRZNZQPKYHAZ-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-[5-bromo-2-(difluoromethoxy)phenyl]urea Chemical compound C1=NC(N)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC(F)F)=C3C=C2)=C1 WGTRZNZQPKYHAZ-UHFFFAOYSA-N 0.000 claims description 3
- BXDKAUPSHZCHEO-UHFFFAOYSA-N 1-[1-[(2-bromopyridin-4-yl)methyl]indol-4-yl]-3-(5-chloro-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(Br)=C1 BXDKAUPSHZCHEO-UHFFFAOYSA-N 0.000 claims description 3
- DIPZWTGIYFHUSH-UHFFFAOYSA-N 1-[1-[(2-cyanopyridin-4-yl)methyl]indol-4-yl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(C#N)=C1 DIPZWTGIYFHUSH-UHFFFAOYSA-N 0.000 claims description 3
- ZCLBJZPFJVOOHS-UHFFFAOYSA-N 1-[2,4-dimethoxy-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(OC)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 ZCLBJZPFJVOOHS-UHFFFAOYSA-N 0.000 claims description 3
- NMSZLMIKYUOFBH-UHFFFAOYSA-N 1-[2,4-dimethyl-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound CC1=CC(C)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 NMSZLMIKYUOFBH-UHFFFAOYSA-N 0.000 claims description 3
- BODINVSOSLSUTP-UHFFFAOYSA-N 1-[2-chloro-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-5-yl]urea Chemical compound FC(F)(F)C1=CC=C(Cl)C(NC(=O)NC=2C=C3C=CN(CC=4C=CN=CC=4)C3=CC=2)=C1 BODINVSOSLSUTP-UHFFFAOYSA-N 0.000 claims description 3
- SRGKGPPRCFDTPT-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 SRGKGPPRCFDTPT-UHFFFAOYSA-N 0.000 claims description 3
- BETHWIXRWGMBOS-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-5-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(N(CC=2C=CN=CC=2)C=C2)C2=C1 BETHWIXRWGMBOS-UHFFFAOYSA-N 0.000 claims description 3
- VPYMVOHUSKAVPZ-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-[[2-(1h-imidazol-2-yl)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(C=2NC=CN=2)=C1 VPYMVOHUSKAVPZ-UHFFFAOYSA-N 0.000 claims description 3
- LZFNCHIOCYXQTO-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-[[2-(pyridin-3-ylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2C=NC=CC=2)=C1 LZFNCHIOCYXQTO-UHFFFAOYSA-N 0.000 claims description 3
- XHMNDDYGEZUICY-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[3-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C12=CC=CC(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)F)=C2C(C)=CN1CC1=CC=NC=C1 XHMNDDYGEZUICY-UHFFFAOYSA-N 0.000 claims description 3
- IAKQWBMHEQMUKB-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[5-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=CC2=C(NC(=O)NC=3C(=CC=C(C=3)C(F)(F)F)F)C(C)=CC=C2N1CC1=CC=NC=C1 IAKQWBMHEQMUKB-UHFFFAOYSA-N 0.000 claims description 3
- JOXIUEJQYIGAPO-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[7-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=2C=CN(CC=3C=CN=CC=3)C=2C(C)=CC=C1NC(=O)NC1=CC(C(F)(F)F)=CC=C1F JOXIUEJQYIGAPO-UHFFFAOYSA-N 0.000 claims description 3
- IHDFIWGWTMLLNG-UHFFFAOYSA-N 1-[2-methoxy-4-methyl-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(C)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 IHDFIWGWTMLLNG-UHFFFAOYSA-N 0.000 claims description 3
- FUNLKXXAJNDCRT-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 FUNLKXXAJNDCRT-UHFFFAOYSA-N 0.000 claims description 3
- GFLYNPUQZKWJAQ-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-5-yl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(N(CC=2C=CN=CC=2)C=C2)C2=C1 GFLYNPUQZKWJAQ-UHFFFAOYSA-N 0.000 claims description 3
- PCVZIYRGVDCFQW-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-6-yl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(C=CN2CC=3C=CN=CC=3)C2=C1 PCVZIYRGVDCFQW-UHFFFAOYSA-N 0.000 claims description 3
- DPTPSBUQLXSYMM-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-[3-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C(C)=CN2CC1=CC=NC=C1 DPTPSBUQLXSYMM-UHFFFAOYSA-N 0.000 claims description 3
- AYAVIONWAGJVKH-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-[5-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=C(C)C=CC2=C1C=CN2CC1=CC=NC=C1 AYAVIONWAGJVKH-UHFFFAOYSA-N 0.000 claims description 3
- APOFDZYKVUXEMG-UHFFFAOYSA-N 1-[2-methoxy-5-(trifluoromethyl)phenyl]-3-[7-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(C)C2=C1C=CN2CC1=CC=NC=C1 APOFDZYKVUXEMG-UHFFFAOYSA-N 0.000 claims description 3
- NREUFTRUVSLGJN-UHFFFAOYSA-N 1-[4-chloro-2-methoxy-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(Cl)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 NREUFTRUVSLGJN-UHFFFAOYSA-N 0.000 claims description 3
- RJAUIFUJMCXRMJ-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-5-yl]urea Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC(=O)NC=2C=C3C=CN(CC=4C=CN=CC=4)C3=CC=2)=C1 RJAUIFUJMCXRMJ-UHFFFAOYSA-N 0.000 claims description 3
- VNBHBBDWWITXBR-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[7-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=2C=CN(CC=3C=CN=CC=3)C=2C(C)=CC=C1NC(=O)NC1=CC=C(Cl)C(C(F)(F)F)=C1 VNBHBBDWWITXBR-UHFFFAOYSA-N 0.000 claims description 3
- IBPAJVKFBVLGRR-UHFFFAOYSA-N 1-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(C(F)(F)F)C(F)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 IBPAJVKFBVLGRR-UHFFFAOYSA-N 0.000 claims description 3
- KOJOSWZDSHVBDS-UHFFFAOYSA-N 1-[4-methoxy-3-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(C(F)(F)F)C(OC)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 KOJOSWZDSHVBDS-UHFFFAOYSA-N 0.000 claims description 3
- RLEUGRKSIDGIDO-UHFFFAOYSA-N 1-[5-chloro-2-(1,3-dioxolan-2-ylmethoxy)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C=1C=CC=2N(CC=3C=CN=CC=3)C=CC=2C=1NC(=O)NC1=CC(Cl)=CC=C1OCC1OCCO1 RLEUGRKSIDGIDO-UHFFFAOYSA-N 0.000 claims description 3
- AZNHIOJCPXYZIQ-UHFFFAOYSA-N 1-[7-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]-3-[4-methyl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC(=O)NC1=CC=C(C)C2=C1C=CN2CC1=CC=NC=C1 AZNHIOJCPXYZIQ-UHFFFAOYSA-N 0.000 claims description 3
- PEHYSXZDOXLVOD-UHFFFAOYSA-N 2-amino-n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CN)=C1 PEHYSXZDOXLVOD-UHFFFAOYSA-N 0.000 claims description 3
- ISONNBWXPQPYIZ-UHFFFAOYSA-N 3-[acetyl(methyl)amino]-n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]propanamide Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CCN(C)C(C)=O)=C1 ISONNBWXPQPYIZ-UHFFFAOYSA-N 0.000 claims description 3
- ALEHLBBPJSTXOZ-UHFFFAOYSA-N 3-amino-n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]propanamide Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CCN)=C1 ALEHLBBPJSTXOZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001204 N-oxides Chemical class 0.000 claims description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 3
- 239000006071 cream Substances 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- AJAJPCNOPZDPIZ-UHFFFAOYSA-N methyl n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 AJAJPCNOPZDPIZ-UHFFFAOYSA-N 0.000 claims description 3
- MQSZGGUEGKYKRC-UHFFFAOYSA-N n-[4-[[4-[(3-chloro-4-methylphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(CN2C3=CC=CC(NC(=O)NC=4C=C(Cl)C(C)=CC=4)=C3C=C2)=C1 MQSZGGUEGKYKRC-UHFFFAOYSA-N 0.000 claims description 3
- UISMOGMDAKUXCE-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-(dimethylamino)acetamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CN(C)C)=C1 UISMOGMDAKUXCE-UHFFFAOYSA-N 0.000 claims description 3
- SIROTSYUCGCPTK-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-hydroxyacetamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CO)=C1 SIROTSYUCGCPTK-UHFFFAOYSA-N 0.000 claims description 3
- FUSABTAFEIOLFH-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-methylpropanamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C(C)C)=C1 FUSABTAFEIOLFH-UHFFFAOYSA-N 0.000 claims description 3
- PHHNMTKUGSBZQV-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-morpholin-4-ylacetamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CN2CCOCC2)=C1 PHHNMTKUGSBZQV-UHFFFAOYSA-N 0.000 claims description 3
- UBCKVZJPRAKVDU-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-pyrrolidin-1-ylacetamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CN2CCCC2)=C1 UBCKVZJPRAKVDU-UHFFFAOYSA-N 0.000 claims description 3
- UOKPGGOJVXZTOM-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-3-(diethylamino)propanamide Chemical compound C1=NC(NC(=O)CCN(CC)CC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 UOKPGGOJVXZTOM-UHFFFAOYSA-N 0.000 claims description 3
- BUVVREQLRRRLQF-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(C)=O)=C1 BUVVREQLRRRLQF-UHFFFAOYSA-N 0.000 claims description 3
- FCDLTRRRVZNJAR-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]formamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=O)=C1 FCDLTRRRVZNJAR-UHFFFAOYSA-N 0.000 claims description 3
- CVPZGGJMRTYSRL-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]propanamide Chemical compound C1=NC(NC(=O)CC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 CVPZGGJMRTYSRL-UHFFFAOYSA-N 0.000 claims description 3
- FAKLPVXVBMSKPQ-UHFFFAOYSA-N n-[4-[[4-[(5-chloro-2-methoxy-4-methylphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound COC1=CC(C)=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(C)=O)=C1 FAKLPVXVBMSKPQ-UHFFFAOYSA-N 0.000 claims description 3
- SINNDLBFBMOQRE-UHFFFAOYSA-N n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-morpholin-4-ylacetamide Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)CN2CCOCC2)=C1 SINNDLBFBMOQRE-UHFFFAOYSA-N 0.000 claims description 3
- VVYVEDFYSRXISP-UHFFFAOYSA-N n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-3-(diethylamino)propanamide Chemical compound C1=NC(NC(=O)CCN(CC)CC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Cl)C=4)OC)=C3C=C2)=C1 VVYVEDFYSRXISP-UHFFFAOYSA-N 0.000 claims description 3
- LRPMOUJSDVQWBZ-UHFFFAOYSA-N n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(C)=O)=C1 LRPMOUJSDVQWBZ-UHFFFAOYSA-N 0.000 claims description 3
- MIRIZLBZGQKGKX-UHFFFAOYSA-N n-[4-[[4-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-(methylamino)acetamide Chemical compound C1=NC(NC(=O)CNC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(C=4)C(F)(F)F)F)=C3C=C2)=C1 MIRIZLBZGQKGKX-UHFFFAOYSA-N 0.000 claims description 3
- INGQXNFQBHSVDC-UHFFFAOYSA-N n-[4-[[4-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(C=4)C(F)(F)F)F)=C3C=C2)=C1 INGQXNFQBHSVDC-UHFFFAOYSA-N 0.000 claims description 3
- FHVCLBVTZRQYRN-UHFFFAOYSA-N n-[4-[[4-[[5-bromo-2-(difluoromethoxy)phenyl]carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]acetamide Chemical compound C1=NC(NC(=O)C)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC(F)F)=C3C=C2)=C1 FHVCLBVTZRQYRN-UHFFFAOYSA-N 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 239000003826 tablet Substances 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- LDTAAGFKEVACHC-UHFFFAOYSA-N 1-(3-bromo-4-methoxyphenyl)-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Br)C(OC)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 LDTAAGFKEVACHC-UHFFFAOYSA-N 0.000 claims description 2
- PZZKGCZXTTVKIO-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[[2-(2-methoxyethylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound C1=NC(NCCOC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 PZZKGCZXTTVKIO-UHFFFAOYSA-N 0.000 claims description 2
- ARTUJNNYCCINHT-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[1-[[2-(propan-2-ylcarbamoylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)NC(C)C)=C1 ARTUJNNYCCINHT-UHFFFAOYSA-N 0.000 claims description 2
- BDNSJPXQXSEINJ-UHFFFAOYSA-N 1-(5-bromo-2-methoxyphenyl)-3-[5-methoxy-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=C(OC)C=CC2=C1C=CN2CC1=CC=NC=C1 BDNSJPXQXSEINJ-UHFFFAOYSA-N 0.000 claims description 2
- UFZABACKBCHKPB-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[[2-(1,3-thiazol-2-ylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2SC=CN=2)=C1 UFZABACKBCHKPB-UHFFFAOYSA-N 0.000 claims description 2
- XTJPXQSREYFVEG-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[[2-[(6-cyanopyridin-3-yl)amino]pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2C=NC(=CC=2)C#N)=C1 XTJPXQSREYFVEG-UHFFFAOYSA-N 0.000 claims description 2
- URBOIBWNZLNFKT-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound C1=NC(N)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(C=4)C(F)(F)F)F)=C3C=C2)=C1 URBOIBWNZLNFKT-UHFFFAOYSA-N 0.000 claims description 2
- XHIODSXMABORLF-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]indol-4-yl]-3-[2-methoxy-4-methyl-5-(trifluoromethyl)phenyl]urea Chemical compound COC1=CC(C)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(N)=C1 XHIODSXMABORLF-UHFFFAOYSA-N 0.000 claims description 2
- MTBAGZVMIBHZJT-UHFFFAOYSA-N 1-[1-[(2-bromopyridin-4-yl)methyl]indol-4-yl]-3-[2-fluoro-5-(trifluoromethyl)phenyl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(Br)=C1 MTBAGZVMIBHZJT-UHFFFAOYSA-N 0.000 claims description 2
- DVYBGFOYCKJSOB-UHFFFAOYSA-N 1-[1-[(3-fluoropyridin-4-yl)methyl]indol-4-yl]-3-[4-methyl-3-(trifluoromethyl)phenyl]urea Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1F DVYBGFOYCKJSOB-UHFFFAOYSA-N 0.000 claims description 2
- ADMWECYINHHTHO-UHFFFAOYSA-N 1-[2,4-dimethoxy-5-(trifluoromethyl)phenyl]-3-[7-methoxy-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound COC1=CC(OC)=C(C(F)(F)F)C=C1NC(=O)NC1=CC=C(OC)C2=C1C=CN2CC1=CC=NC=C1 ADMWECYINHHTHO-UHFFFAOYSA-N 0.000 claims description 2
- KOURTBIKKKOPAN-UHFFFAOYSA-N 1-[2-ethoxy-5-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound CCOC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 KOURTBIKKKOPAN-UHFFFAOYSA-N 0.000 claims description 2
- LOAMWSUGNVHLDO-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-[[2-(pyridin-2-ylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2N=CC=CC=2)=C1 LOAMWSUGNVHLDO-UHFFFAOYSA-N 0.000 claims description 2
- OTJVAGGOOFFPEA-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-[[2-(pyrimidin-2-ylamino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2N=CC=CN=2)=C1 OTJVAGGOOFFPEA-UHFFFAOYSA-N 0.000 claims description 2
- OZEYRVHPKXQCPT-UHFFFAOYSA-N 1-[4-methyl-3-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(C(F)(F)F)C(C)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC=C1 OZEYRVHPKXQCPT-UHFFFAOYSA-N 0.000 claims description 2
- AGSHUPSOVOLTLL-UHFFFAOYSA-N 1-[5-chloro-2-(3-hydroxypropoxy)phenyl]-3-[5-methyl-1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=CC2=C(NC(=O)NC=3C(=CC=C(Cl)C=3)OCCCO)C(C)=CC=C2N1CC1=CC=NC=C1 AGSHUPSOVOLTLL-UHFFFAOYSA-N 0.000 claims description 2
- RZGUIXACFQACLU-UHFFFAOYSA-N 4-[[4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]-5-methylindol-1-yl]methyl]-n-methylpyridine-2-carboxamide Chemical compound C1=NC(C(=O)NC)=CC(CN2C3=CC=C(C)C(NC(=O)NC=4C(=CC=C(C=4)C(F)(F)F)OC)=C3C=C2)=C1 RZGUIXACFQACLU-UHFFFAOYSA-N 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 201000009273 Endometriosis Diseases 0.000 claims description 2
- 206010027339 Menstruation irregular Diseases 0.000 claims description 2
- 239000000443 aerosol Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 2
- 208000031169 hemorrhagic disease Diseases 0.000 claims description 2
- OKEICWSSZYJJDD-UHFFFAOYSA-N n-[4-[[4-[(3-chloro-4-methylphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound C1=C(Cl)C(C)=CC=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C2CC2)=C1 OKEICWSSZYJJDD-UHFFFAOYSA-N 0.000 claims description 2
- PVYUFDMJTULNPU-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-(methylamino)acetamide Chemical compound C1=NC(NC(=O)CNC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 PVYUFDMJTULNPU-UHFFFAOYSA-N 0.000 claims description 2
- IRZZMUCPCJTYRL-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-methoxyacetamide Chemical compound C1=NC(NC(=O)COC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Br)C=4)OC)=C3C=C2)=C1 IRZZMUCPCJTYRL-UHFFFAOYSA-N 0.000 claims description 2
- DESZFQQRSWTNKO-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C2CC2)=C1 DESZFQQRSWTNKO-UHFFFAOYSA-N 0.000 claims description 2
- FGLAISSCRCJXHN-UHFFFAOYSA-N n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-2-(methylamino)acetamide Chemical compound C1=NC(NC(=O)CNC)=CC(CN2C3=CC=CC(NC(=O)NC=4C(=CC=C(Cl)C=4)OC)=C3C=C2)=C1 FGLAISSCRCJXHN-UHFFFAOYSA-N 0.000 claims description 2
- NSOJCRGBVPOADB-UHFFFAOYSA-N n-[4-[[4-[(5-chloro-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C2CC2)=C1 NSOJCRGBVPOADB-UHFFFAOYSA-N 0.000 claims description 2
- IZELTQQMSQVHNI-UHFFFAOYSA-N n-[4-[[4-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C2CC2)=C1 IZELTQQMSQVHNI-UHFFFAOYSA-N 0.000 claims description 2
- PQKJVXXAJNEJFE-UHFFFAOYSA-N n-[4-[[4-[[2-methoxy-5-(trifluoromethyl)phenyl]carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]cyclopropanecarboxamide Chemical compound COC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C2CC2)=C1 PQKJVXXAJNEJFE-UHFFFAOYSA-N 0.000 claims description 2
- 239000002997 ophthalmic solution Substances 0.000 claims description 2
- 230000016087 ovulation Effects 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 8
- DVHIKTXYEJAOSR-UHFFFAOYSA-N (5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(N)=O DVHIKTXYEJAOSR-UHFFFAOYSA-N 0.000 claims 1
- BBRVGUAGUUBENF-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[[2-(4-cyanoanilino)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC=2C=CC(=CC=2)C#N)=C1 BBRVGUAGUUBENF-UHFFFAOYSA-N 0.000 claims 1
- 239000012530 fluid Substances 0.000 claims 1
- IEPMMODFAXICIE-UHFFFAOYSA-N n-[4-[[4-[(5-bromo-2-methoxyphenyl)carbamoylamino]indol-1-yl]methyl]pyridin-2-yl]-1-methylimidazole-2-carboxamide Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(NC(=O)C=2N(C=CN=2)C)=C1 IEPMMODFAXICIE-UHFFFAOYSA-N 0.000 claims 1
- 125000003277 amino group Chemical group 0.000 abstract description 7
- 125000004426 substituted alkynyl group Chemical group 0.000 abstract description 6
- 125000001188 haloalkyl group Chemical group 0.000 abstract description 3
- 125000005843 halogen group Chemical group 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 239000000243 solution Substances 0.000 description 30
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 125000004432 carbon atom Chemical group C* 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 20
- 238000003556 assay Methods 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- 239000013543 active substance Substances 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 14
- 229940127093 camptothecin Drugs 0.000 description 13
- 239000000651 prodrug Substances 0.000 description 13
- 229940002612 prodrug Drugs 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000003755 preservative agent Substances 0.000 description 8
- 102000001253 Protein Kinase Human genes 0.000 description 7
- 235000013877 carbamide Nutrition 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000839 emulsion Substances 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 235000013772 propylene glycol Nutrition 0.000 description 7
- 229960004063 propylene glycol Drugs 0.000 description 7
- 108060006633 protein kinase Proteins 0.000 description 7
- 235000010356 sorbitol Nutrition 0.000 description 7
- 239000000600 sorbitol Substances 0.000 description 7
- 239000000375 suspending agent Substances 0.000 description 7
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 6
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 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 6
- 229930006000 Sucrose Natural products 0.000 description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 description 6
- 239000002260 anti-inflammatory agent Substances 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 235000013355 food flavoring agent Nutrition 0.000 description 6
- 235000003599 food sweetener Nutrition 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 5
- 235000019483 Peanut oil Nutrition 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 5
- 230000002491 angiogenic effect Effects 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000002837 carbocyclic group Chemical group 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 5
- 230000005754 cellular signaling Effects 0.000 description 5
- 239000003086 colorant Substances 0.000 description 5
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 5
- 230000007423 decrease Effects 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 239000003623 enhancer Substances 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 229960005150 glycerol Drugs 0.000 description 5
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 5
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 5
- 239000003906 humectant Substances 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 238000003674 kinase activity assay Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 229960000485 methotrexate Drugs 0.000 description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000000312 peanut oil Substances 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 4
- 244000215068 Acacia senegal Species 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 229920000084 Gum arabic Polymers 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 239000000205 acacia gum Substances 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 239000007859 condensation product Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 230000012010 growth Effects 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 235000010445 lecithin Nutrition 0.000 description 4
- 239000000787 lecithin Substances 0.000 description 4
- 229940067606 lecithin Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 239000002480 mineral oil Substances 0.000 description 4
- 235000010446 mineral oil Nutrition 0.000 description 4
- 229940042472 mineral oil Drugs 0.000 description 4
- 239000004006 olive oil Substances 0.000 description 4
- 235000008390 olive oil Nutrition 0.000 description 4
- 230000002246 oncogenic effect Effects 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 125000006413 ring segment Chemical group 0.000 description 4
- 239000008159 sesame oil Substances 0.000 description 4
- 235000011803 sesame oil Nutrition 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- HGVAAXOOGHJCEL-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)indazol-4-amine Chemical compound N1=CC=2C(N)=CC=CC=2N1CC1=CC=NC=C1 HGVAAXOOGHJCEL-UHFFFAOYSA-N 0.000 description 3
- QNXRLMIFYVMGGO-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)indol-4-amine Chemical compound C1=CC=2C(N)=CC=CC=2N1CC1=CC=NC=C1 QNXRLMIFYVMGGO-UHFFFAOYSA-N 0.000 description 3
- XFXPJZKPLFXVKP-UHFFFAOYSA-N 4-nitro-1-(pyridin-4-ylmethyl)indazole Chemical compound N1=CC=2C([N+](=O)[O-])=CC=CC=2N1CC1=CC=NC=C1 XFXPJZKPLFXVKP-UHFFFAOYSA-N 0.000 description 3
- VVVDETQOLBGSDI-UHFFFAOYSA-N 4-nitro-1-(pyridin-4-ylmethyl)indole Chemical compound C1=CC=2C([N+](=O)[O-])=CC=CC=2N1CC1=CC=NC=C1 VVVDETQOLBGSDI-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 235000021355 Stearic acid Nutrition 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000003240 coconut oil Substances 0.000 description 3
- 235000019864 coconut oil Nutrition 0.000 description 3
- 239000003246 corticosteroid Substances 0.000 description 3
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical class NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 239000003974 emollient agent Substances 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 229940088598 enzyme Drugs 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 3
- 239000010931 gold Substances 0.000 description 3
- 229910052737 gold Inorganic materials 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 235000010981 methylcellulose Nutrition 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 3
- NCBIJCNTNRCYHW-UHFFFAOYSA-N n-[4-[(4-nitroindol-1-yl)methyl]pyridin-2-yl]pyrazin-2-amine Chemical compound C1=CC=2C([N+](=O)[O-])=CC=CC=2N1CC(C=1)=CC=NC=1NC1=CN=CC=N1 NCBIJCNTNRCYHW-UHFFFAOYSA-N 0.000 description 3
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 3
- 229940060184 oil ingredients Drugs 0.000 description 3
- 231100000590 oncogenic Toxicity 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 3
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000008117 stearic acid Substances 0.000 description 3
- 229960004274 stearic acid Drugs 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 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
- 102000003390 tumor necrosis factor Human genes 0.000 description 3
- 150000003672 ureas Chemical class 0.000 description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 description 3
- 239000008158 vegetable oil Substances 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- VDCAEBCHUGSNJK-UHFFFAOYSA-N 1-(5-chloro-2-methoxyphenyl)-3-[1-[(2-cyanopyridin-4-yl)methyl]indol-4-yl]urea Chemical compound COC1=CC=C(Cl)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(C#N)=C1 VDCAEBCHUGSNJK-UHFFFAOYSA-N 0.000 description 2
- LQCGUOBZMOSNRK-UHFFFAOYSA-N 1-[1-[(2-aminopyridin-4-yl)methyl]-5-fluoroindol-4-yl]-3-(5-bromo-2-methoxyphenyl)urea Chemical compound COC1=CC=C(Br)C=C1NC(=O)NC1=C(F)C=CC2=C1C=CN2CC1=CC=NC(N)=C1 LQCGUOBZMOSNRK-UHFFFAOYSA-N 0.000 description 2
- OONGKRSRLXHIQU-UHFFFAOYSA-N 1-[4-chloro-3-(trifluoromethyl)phenyl]-3-[1-(pyridin-4-ylmethyl)indol-4-yl]urea Chemical compound C1=C(Cl)C(C(F)(F)F)=CC(NC(=O)NC=2C=3C=CN(CC=4C=CN=CC=4)C=3C=CC=2)=C1 OONGKRSRLXHIQU-UHFFFAOYSA-N 0.000 description 2
- DWAKGLZEDYTPJV-UHFFFAOYSA-N 1-[[2-(pyrazin-2-ylamino)pyridin-4-yl]methyl]indol-4-amine Chemical compound C1=CC=2C(N)=CC=CC=2N1CC(C=1)=CC=NC=1NC1=CN=CC=N1 DWAKGLZEDYTPJV-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-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
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- VAJUUDUWDNCECT-UHFFFAOYSA-N 4-(bromomethyl)pyridine;hydron;bromide Chemical compound Br.BrCC1=CC=NC=C1 VAJUUDUWDNCECT-UHFFFAOYSA-N 0.000 description 2
- LAVZKLJDKGRZJG-UHFFFAOYSA-N 4-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=CC2=C1C=CN2 LAVZKLJDKGRZJG-UHFFFAOYSA-N 0.000 description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
- 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 2
- 239000005995 Aluminium silicate Substances 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 102100034608 Angiopoietin-2 Human genes 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 2
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102000050554 Eph Family Receptors Human genes 0.000 description 2
- 108091008815 Eph receptors Proteins 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 108091008794 FGF receptors Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 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 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 102000029749 Microtubule Human genes 0.000 description 2
- 108091022875 Microtubule Proteins 0.000 description 2
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 2
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 239000000783 alginic acid Substances 0.000 description 2
- 229960001126 alginic acid Drugs 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 description 2
- 235000012211 aluminium silicate Nutrition 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 238000010256 biochemical assay Methods 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical class N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 235000019437 butane-1,3-diol Nutrition 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000012045 crude solution Substances 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- SASYSVUEVMOWPL-NXVVXOECSA-N decyl oleate Chemical compound CCCCCCCCCCOC(=O)CCCCCCC\C=C/CCCCCCCC SASYSVUEVMOWPL-NXVVXOECSA-N 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- DOIRQSBPFJWKBE-UHFFFAOYSA-N dibutyl phthalate Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 2
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical compound C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 102000052178 fibroblast growth factor receptor activity proteins Human genes 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 2
- 229960000681 leflunomide Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000006166 lysate Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 229960001924 melphalan Drugs 0.000 description 2
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 210000004688 microtubule Anatomy 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 125000006574 non-aromatic ring group Chemical group 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 229910052701 rubidium Inorganic materials 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 229960001860 salicylate Drugs 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 229940114926 stearate Drugs 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 235000000346 sugar 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
- NRUKOCRGYNPUPR-QBPJDGROSA-N teniposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@@H](OC[C@H]4O3)C=3SC=CC=3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 NRUKOCRGYNPUPR-QBPJDGROSA-N 0.000 description 2
- NAMYUHIQKPOVFW-UHFFFAOYSA-N tert-butyl n-[4-[(4-nitroindol-1-yl)methyl]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC(CN2C3=CC=CC(=C3C=C2)[N+]([O-])=O)=C1 NAMYUHIQKPOVFW-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 235000010487 tragacanth Nutrition 0.000 description 2
- 239000000196 tragacanth Substances 0.000 description 2
- 229940116362 tragacanth Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- MCEHFIXEKNKSRW-LBPRGKRZSA-N (2s)-2-[[3,5-dichloro-4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=C(Cl)C=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1Cl MCEHFIXEKNKSRW-LBPRGKRZSA-N 0.000 description 1
- ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- QMMJWQMCMRUYTG-UHFFFAOYSA-N 1,2,4,5-tetrachloro-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=C(Cl)C(Cl)=CC(Cl)=C1Cl QMMJWQMCMRUYTG-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WJKZNACFWGUOAP-UHFFFAOYSA-N 1-[(2-bromopyridin-4-yl)methyl]-4-nitroindole Chemical compound C1=CC=2C([N+](=O)[O-])=CC=CC=2N1CC1=CC=NC(Br)=C1 WJKZNACFWGUOAP-UHFFFAOYSA-N 0.000 description 1
- DHLDLTUJNDDTCK-UHFFFAOYSA-N 1-[2-fluoro-5-(trifluoromethyl)phenyl]-3-[1-[[2-(2h-tetrazol-5-yl)pyridin-4-yl]methyl]indol-4-yl]urea Chemical compound FC1=CC=C(C(F)(F)F)C=C1NC(=O)NC1=CC=CC2=C1C=CN2CC1=CC=NC(C=2NN=NN=2)=C1 DHLDLTUJNDDTCK-UHFFFAOYSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- WLDPWZQYAVZTTP-UHFFFAOYSA-N 1-methyl-imidazole-2-carboxylic acid Chemical compound CN1C=CN=C1C(O)=O WLDPWZQYAVZTTP-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- LGEZTMRIZWCDLW-UHFFFAOYSA-N 14-methylpentadecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC(C)C LGEZTMRIZWCDLW-UHFFFAOYSA-N 0.000 description 1
- SXFWKZNLYYRHMK-UHFFFAOYSA-N 1h-indolo[7,6-f]quinoline Chemical class C1=CC=C2C3=C(NC=C4)C4=CC=C3C=CC2=N1 SXFWKZNLYYRHMK-UHFFFAOYSA-N 0.000 description 1
- HDIFHQMREAYYJW-FMIVXFBMSA-N 2,3-dihydroxypropyl (e)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C\CCCCCCCC(=O)OCC(O)CO HDIFHQMREAYYJW-FMIVXFBMSA-N 0.000 description 1
- FLPJVCMIKUWSDR-UHFFFAOYSA-N 2-(4-formylphenoxy)acetamide Chemical compound NC(=O)COC1=CC=C(C=O)C=C1 FLPJVCMIKUWSDR-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- OJIBJRXMHVZPLV-UHFFFAOYSA-N 2-methylpropyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(C)C OJIBJRXMHVZPLV-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- 125000001137 3-hydroxypropoxy group Chemical group [H]OC([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000005917 3-methylpentyl group Chemical group 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- JETIPBCSRYCACD-UHFFFAOYSA-N 4-bromo-2-isocyanato-1-methoxybenzene Chemical compound COC1=CC=C(Br)C=C1N=C=O JETIPBCSRYCACD-UHFFFAOYSA-N 0.000 description 1
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 description 1
- WBTVZVUYPVQEIF-UHFFFAOYSA-N 4-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=CC2=C1C=NN2 WBTVZVUYPVQEIF-UHFFFAOYSA-N 0.000 description 1
- HTMGQIXFZMZZKD-UHFFFAOYSA-N 5,6,7,8-tetrahydroisoquinoline Chemical compound N1=CC=C2CCCCC2=C1 HTMGQIXFZMZZKD-UHFFFAOYSA-N 0.000 description 1
- AMEMLELAMQEAIA-UHFFFAOYSA-N 6-(tert-butyl)thieno[3,2-d]pyrimidin-4(3H)-one Chemical compound N1C=NC(=O)C2=C1C=C(C(C)(C)C)S2 AMEMLELAMQEAIA-UHFFFAOYSA-N 0.000 description 1
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- OYHQOLUKZRVURQ-HZJYTTRNSA-M 9-cis,12-cis-Octadecadienoate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC([O-])=O OYHQOLUKZRVURQ-HZJYTTRNSA-M 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 244000144927 Aloe barbadensis Species 0.000 description 1
- 235000002961 Aloe barbadensis Nutrition 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 102000009088 Angiopoietin-1 Human genes 0.000 description 1
- 108010048154 Angiopoietin-1 Proteins 0.000 description 1
- 108010048036 Angiopoietin-2 Proteins 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 239000004358 Butane-1, 3-diol Substances 0.000 description 1
- 240000001546 Byrsonima crassifolia Species 0.000 description 1
- 101100275473 Caenorhabditis elegans ctc-3 gene Proteins 0.000 description 1
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 229940117937 Dihydrofolate reductase inhibitor Drugs 0.000 description 1
- 229940083266 Dihydroorotate dehydrogenase inhibitor Drugs 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- QXRSDHAAWVKZLJ-OXZHEXMSSA-N Epothilone B Natural products O=C1[C@H](C)[C@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C QXRSDHAAWVKZLJ-OXZHEXMSSA-N 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 101150021185 FGF gene Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 206010051066 Gastrointestinal stromal tumour Diseases 0.000 description 1
- CMBYOWLFQAFZCP-UHFFFAOYSA-N Hexyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCCCCC CMBYOWLFQAFZCP-UHFFFAOYSA-N 0.000 description 1
- 108010093488 His-His-His-His-His-His Proteins 0.000 description 1
- 101000924533 Homo sapiens Angiopoietin-2 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000008839 Kidney Neoplasms Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- JXLYSJRDGCGARV-PJXZDTQASA-N Leurosidine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-PJXZDTQASA-N 0.000 description 1
- LPGWZGMPDKDHEP-HLTPFJCJSA-N Leurosine Chemical compound C([C@]1([C@@H]2O1)CC)N(CCC=1C3=CC=CC=C3NC=11)C[C@H]2C[C@]1(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC LPGWZGMPDKDHEP-HLTPFJCJSA-N 0.000 description 1
- LPGWZGMPDKDHEP-GKWAKPNHSA-N Leurosine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@]6(CC)O[C@@H]6[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C LPGWZGMPDKDHEP-GKWAKPNHSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical class [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 1
- 235000006679 Mentha X verticillata Nutrition 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 229910003827 NRaRb Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 241000772415 Neovison vison Species 0.000 description 1
- 101100168274 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cox-3 gene Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- HRHKSTOGXBBQCB-UHFFFAOYSA-N Porfiromycine Chemical compound O=C1C(N)=C(C)C(=O)C2=C1C(COC(N)=O)C1(OC)C3N(C)C3CN12 HRHKSTOGXBBQCB-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 239000004146 Propane-1,2-diol Substances 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 206010038389 Renal cancer Diseases 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 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
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 229940123237 Taxane Drugs 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 241000863480 Vinca Species 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- GANNOFFDYMSBSZ-UHFFFAOYSA-N [AlH3].[Mg] Chemical class [AlH3].[Mg] GANNOFFDYMSBSZ-UHFFFAOYSA-N 0.000 description 1
- JXLYSJRDGCGARV-KSNABSRWSA-N ac1l29ym Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-KSNABSRWSA-N 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229940048299 acetylated lanolin alcohols Drugs 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 229960000458 allantoin Drugs 0.000 description 1
- 230000003281 allosteric effect Effects 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000011399 aloe vera Nutrition 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229960000473 altretamine Drugs 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
- 229940063655 aluminum stearate Drugs 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 238000011122 anti-angiogenic therapy Methods 0.000 description 1
- 230000003388 anti-hormonal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940045988 antineoplastic drug protein kinase inhibitors Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 235000019568 aromas Nutrition 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- AUJRCFUBUPVWSZ-XTZHGVARSA-M auranofin Chemical compound CCP(CC)(CC)=[Au]S[C@@H]1O[C@H](COC(C)=O)[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O AUJRCFUBUPVWSZ-XTZHGVARSA-M 0.000 description 1
- 229960005207 auranofin Drugs 0.000 description 1
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 229940050390 benzoate Drugs 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000005510 but-1-en-2-yl group Chemical group 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- DHAZIUXMHRHVMP-UHFFFAOYSA-N butyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OCCCC DHAZIUXMHRHVMP-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- XREUEWVEMYWFFA-CSKJXFQVSA-N carminomycin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XREUEWVEMYWFFA-CSKJXFQVSA-N 0.000 description 1
- 229930188550 carminomycin Natural products 0.000 description 1
- XREUEWVEMYWFFA-UHFFFAOYSA-N carminomycin I Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=C(O)C=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XREUEWVEMYWFFA-UHFFFAOYSA-N 0.000 description 1
- 229950001725 carubicin Drugs 0.000 description 1
- 229960001777 castor oil Drugs 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229940074979 cetyl palmitate Drugs 0.000 description 1
- 239000013522 chelant Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000002153 concerted effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 229960005168 croscarmellose Drugs 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 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
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 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
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229960000684 cytarabine Drugs 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000005432 dialkylcarboxamide group Chemical group 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical class O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical group OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 229940028356 diethylene glycol monobutyl ether Drugs 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 239000003166 dihydrofolate reductase inhibitor Substances 0.000 description 1
- 239000003363 dihydroorotate dehydrogenase inhibitor Substances 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000004205 dimethyl polysiloxane Substances 0.000 description 1
- 235000013870 dimethyl polysiloxane Nutrition 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- VZFDRQUWHOVFCA-UHFFFAOYSA-L disodium;2-sulfanylbutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(S)C([O-])=O VZFDRQUWHOVFCA-UHFFFAOYSA-L 0.000 description 1
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- QQQMUBLXDAFBRH-UHFFFAOYSA-N dodecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCOC(=O)C(C)O QQQMUBLXDAFBRH-UHFFFAOYSA-N 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 229960002224 eculizumab Drugs 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 230000009881 electrostatic interaction Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- YJGVMLPVUAXIQN-UHFFFAOYSA-N epipodophyllotoxin Natural products COC1=C(OC)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YJGVMLPVUAXIQN-UHFFFAOYSA-N 0.000 description 1
- 229930013356 epothilone Natural products 0.000 description 1
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 229960004667 ethyl cellulose Drugs 0.000 description 1
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 1
- 239000001761 ethyl methyl cellulose Substances 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 description 1
- 229960000752 etoposide phosphate Drugs 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- RMBPEFMHABBEKP-UHFFFAOYSA-N fluorene Chemical compound C1=CC=C2C3=C[CH]C=CC3=CC2=C1 RMBPEFMHABBEKP-UHFFFAOYSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 201000011243 gastrointestinal stromal tumor Diseases 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 1
- 229960005277 gemcitabine Drugs 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940022353 herceptin Drugs 0.000 description 1
- 125000005844 heterocyclyloxy group Chemical group 0.000 description 1
- PXDJXZJSCPSGGI-UHFFFAOYSA-N hexadecanoic acid hexadecyl ester Natural products CCCCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCCCC PXDJXZJSCPSGGI-UHFFFAOYSA-N 0.000 description 1
- UUVWYPNAQBNQJQ-UHFFFAOYSA-N hexamethylmelamine Chemical compound CN(C)C1=NC(N(C)C)=NC(N(C)C)=N1 UUVWYPNAQBNQJQ-UHFFFAOYSA-N 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940100463 hexyl laurate Drugs 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 description 1
- 229960001101 ifosfamide Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229940078545 isocetyl stearate Drugs 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 229940093629 isopropyl isostearate Drugs 0.000 description 1
- 229940033357 isopropyl laurate Drugs 0.000 description 1
- 229940074928 isopropyl myristate Drugs 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 229940075495 isopropyl palmitate Drugs 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 125000003971 isoxazolinyl group Chemical group 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 201000010982 kidney cancer Diseases 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940049918 linoleate Drugs 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 229960000994 lumiracoxib Drugs 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 229960005249 misoprostol Drugs 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229960001156 mitoxantrone Drugs 0.000 description 1
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000004312 morpholin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])OC([H])(*)C1([H])[H] 0.000 description 1
- 125000004572 morpholin-3-yl group Chemical group N1C(COCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 229940078812 myristyl myristate Drugs 0.000 description 1
- 229940078555 myristyl propionate Drugs 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229960003940 naproxen sodium Drugs 0.000 description 1
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940055577 oleyl alcohol Drugs 0.000 description 1
- XMLQWXUVTXCDDL-UHFFFAOYSA-N oleyl alcohol Natural products CCCCCCC=CCCCCCCCCCCO XMLQWXUVTXCDDL-UHFFFAOYSA-N 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- JCGNDDUYTRNOFT-UHFFFAOYSA-N oxolane-2,4-dione Chemical compound O=C1COC(=O)C1 JCGNDDUYTRNOFT-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 229950003203 pexelizumab Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229960001237 podophyllotoxin Drugs 0.000 description 1
- YJGVMLPVUAXIQN-XVVDYKMHSA-N podophyllotoxin Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@H](O)[C@@H]3[C@@H]2C(OC3)=O)=C1 YJGVMLPVUAXIQN-XVVDYKMHSA-N 0.000 description 1
- YVCVYCSAAZQOJI-UHFFFAOYSA-N podophyllotoxin Natural products COC1=C(O)C(OC)=CC(C2C3=CC=4OCOC=4C=C3C(O)C3C2C(OC3)=O)=C1 YVCVYCSAAZQOJI-UHFFFAOYSA-N 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- JDOZJEUDSLGTLU-VWUMJDOOSA-N prednisolone phosphate Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 JDOZJEUDSLGTLU-VWUMJDOOSA-N 0.000 description 1
- 229960002943 prednisolone sodium phosphate Drugs 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 1
- NEOZOXKVMDBOSG-UHFFFAOYSA-N propan-2-yl 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC(C)C NEOZOXKVMDBOSG-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 238000002731 protein assay Methods 0.000 description 1
- 239000003909 protein kinase inhibitor Substances 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- XFTQRUTUGRCSGO-UHFFFAOYSA-N pyrazin-2-amine Chemical compound NC1=CN=CC=N1 XFTQRUTUGRCSGO-UHFFFAOYSA-N 0.000 description 1
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000003439 radiotherapeutic effect Effects 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 239000010979 ruby Substances 0.000 description 1
- 229910001750 ruby Inorganic materials 0.000 description 1
- 150000003873 salicylate salts Chemical class 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- CRPCXAMJWCDHFM-UHFFFAOYSA-M sodium;5-oxopyrrolidine-2-carboxylate Chemical compound [Na+].[O-]C(=O)C1CCC(=O)N1 CRPCXAMJWCDHFM-UHFFFAOYSA-M 0.000 description 1
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 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
- 230000009885 systemic effect Effects 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 229960001603 tamoxifen Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000006068 taste-masking agent Substances 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 229960001278 teniposide Drugs 0.000 description 1
- TWFAMEOZPYPOIV-UHFFFAOYSA-N tert-butyl n-[4-(bromomethyl)pyridin-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC(CBr)=CC=N1 TWFAMEOZPYPOIV-UHFFFAOYSA-N 0.000 description 1
- FDKPZEOWSCALKP-UHFFFAOYSA-N tert-butyl n-[4-[(4-aminoindol-1-yl)methyl]pyridin-2-yl]carbamate Chemical compound C1=NC(NC(=O)OC(C)(C)C)=CC(CN2C3=CC=CC(N)=C3C=C2)=C1 FDKPZEOWSCALKP-UHFFFAOYSA-N 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- BORJONZPSTVSFP-UHFFFAOYSA-N tetradecyl 2-hydroxypropanoate Chemical compound CCCCCCCCCCCCCCOC(=O)C(C)O BORJONZPSTVSFP-UHFFFAOYSA-N 0.000 description 1
- YRZGMTHQPGNLEK-UHFFFAOYSA-N tetradecyl propionate Chemical compound CCCCCCCCCCCCCCOC(=O)CC YRZGMTHQPGNLEK-UHFFFAOYSA-N 0.000 description 1
- DZKXJUASMGQEMA-UHFFFAOYSA-N tetradecyl tetradecanoate Chemical compound CCCCCCCCCCCCCCOC(=O)CCCCCCCCCCCCC DZKXJUASMGQEMA-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000009210 therapy by ultrasound Methods 0.000 description 1
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/12—Drugs for genital or sexual disorders; Contraceptives for climacteric disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Reproductive Health (AREA)
- Endocrinology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Rheumatology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychiatry (AREA)
- Gynecology & Obstetrics (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Obesity (AREA)
- Transplantation (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Pregnancy & Childbirth (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US64388605P | 2005-01-14 | 2005-01-14 | |
| US643886P | 2005-01-14 | ||
| US73299905P | 2005-11-02 | 2005-11-02 | |
| US732999P | 2005-11-02 | ||
| PCT/US2006/001272 WO2006076593A1 (en) | 2005-01-14 | 2006-01-13 | 1,3-diaryl substituted ureas as modulators of kinase activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2393741T3 true ES2393741T3 (es) | 2012-12-27 |
Family
ID=36250833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES06718359T Active ES2393741T3 (es) | 2005-01-14 | 2006-01-13 | Ureas 1,3-diarilsustituidas como moduladores de la actividad quinasa |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20060199846A1 (enExample) |
| EP (2) | EP2397478A1 (enExample) |
| JP (2) | JP2008526988A (enExample) |
| KR (1) | KR101292598B1 (enExample) |
| CN (1) | CN102267978A (enExample) |
| AU (1) | AU2006204790B2 (enExample) |
| CA (1) | CA2594449A1 (enExample) |
| ES (1) | ES2393741T3 (enExample) |
| IL (1) | IL184494A (enExample) |
| NZ (1) | NZ556433A (enExample) |
| RU (1) | RU2402544C2 (enExample) |
| TW (1) | TWI378925B (enExample) |
| WO (1) | WO2006076593A1 (enExample) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ556433A (en) * | 2005-01-14 | 2010-10-29 | Cgi Pharmaceuticals Inc | 1, 3-diaryl substituted ureas as modulators of kinase activity |
| WO2007024294A2 (en) * | 2005-05-03 | 2007-03-01 | Cgi Pharmaceuticals, Inc. | Certain substituted ureas, as modulators of kinase activity |
| JP5236499B2 (ja) * | 2006-01-27 | 2013-07-17 | アレイ バイオファーマ、インコーポレイテッド | グルコキナーゼ活性化剤 |
| CN101058561B (zh) * | 2006-04-19 | 2011-01-26 | 苏州爱斯鹏药物研发有限责任公司 | 用于抑制蛋白激酶的二苯脲衍生物及其组合物和用途 |
| JP2011520809A (ja) * | 2008-05-05 | 2011-07-21 | アムジエン・インコーポレーテツド | γセクレターゼモジュレーターとしての尿素化合物 |
| GB0812969D0 (en) | 2008-07-15 | 2008-08-20 | Sentinel Oncology Ltd | Pharmaceutical compounds |
| WO2010036316A1 (en) * | 2008-09-24 | 2010-04-01 | Yangbo Feng | Urea and carbamate compounds and analogs as kinase inhibitors |
| EP2470533A4 (en) | 2009-08-24 | 2013-01-23 | Ascepion Pharmaceuticals Inc | UREA COMPOUNDS CONTAINING A 5,6-BICYCLIC HETEROARYL GROUP |
| CN103288684B (zh) * | 2013-05-03 | 2014-12-10 | 西安交通大学 | 一种具有抗肿瘤活性的联苯脲化合物及其制备方法 |
| PL3149001T3 (pl) * | 2014-05-28 | 2019-10-31 | Novartis Ag | Nowe pochodne pirazolopirymidyny i ich zastosowanie jako inhibitory MALT1 |
| CN104725319A (zh) * | 2015-03-11 | 2015-06-24 | 西安交通大学 | 一种具有抗肿瘤活性的1h-吲唑-3-氨基联苯脲类化合物及其制备方法和应用 |
| JP2022536755A (ja) * | 2019-06-14 | 2022-08-18 | アイエフエム デュー インコーポレイテッド | Ｓｔｉｎｇ活性に関連する状態を治療するための化合物および組成物 |
| CN113527254B (zh) * | 2021-07-07 | 2022-05-03 | 北京华氏信华科生物科技有限公司 | 7-甲氧基-1h-吲哚类化合物、制备方法、药物组合物及应用 |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4301169A (en) * | 1978-11-14 | 1981-11-17 | Eisai Co., Ltd. | Novel imidazole compound and anti-depressing agent containing the same |
| US5395817A (en) * | 1992-01-22 | 1995-03-07 | Imperial Chemical Industries Plc | N-arylindoles and their use as herbicides |
| EP0630373A1 (en) * | 1992-03-12 | 1994-12-28 | Smithkline Beecham Plc | Indole derivatives as 5ht1c antagonists |
| DE4327027A1 (de) * | 1993-02-15 | 1994-08-18 | Bayer Ag | Imidazoazine |
| DE4337611A1 (de) * | 1993-11-04 | 1995-05-11 | Boehringer Ingelheim Kg | Neue Benzoylguanidine, ihre Herstellung und ihre Verwendung in Arzneimitteln |
| US5593997A (en) * | 1995-05-23 | 1997-01-14 | Pfizer Inc. | 4-aminopyrazolo(3-,4-D)pyrimidine and 4-aminopyrazolo-(3,4-D)pyridine tyrosine kinase inhibitors |
| US5773459A (en) * | 1995-06-07 | 1998-06-30 | Sugen, Inc. | Urea- and thiourea-type compounds |
| US5807876A (en) * | 1996-04-23 | 1998-09-15 | Vertex Pharmaceuticals Incorporated | Inhibitors of IMPDH enzyme |
| WO1997040028A1 (en) * | 1996-04-23 | 1997-10-30 | Vertex Pharmaceuticals Incorporated | Urea derivatives as inhibitors of impdh enzyme |
| WO1997048697A1 (en) * | 1996-06-19 | 1997-12-24 | Rhone-Poulenc Rorer Limited | Substituted azabicylic compounds and their use as inhibitors of the production of tnf and cyclic amp phosphodiesterase |
| PL205321B1 (pl) * | 1997-12-22 | 2010-04-30 | Bayer Corp | Zastosowanie podstawionych heterocyklicznych moczników do wytwarzania leku do hamowania kinazy raf, podstawione heterocykliczne moczniki oraz kompozycja farmaceutyczna je zawierająca |
| CA2315646C (en) * | 1997-12-22 | 2010-02-09 | Bayer Corporation | Inhibition of raf kinase using symmetrical and unsymmetrical substituted diphenyl ureas |
| US6858577B1 (en) * | 1999-06-29 | 2005-02-22 | Ortho-Mcneil Pharmaceutical, Inc. | Indole peptidomimetics as thrombin receptor antagonists |
| US6627647B1 (en) * | 2000-03-23 | 2003-09-30 | Boehringer Ingelheim Pharmaceuticals, Inc. | Substituted 1-(4-aminophenyl)imidazoles and their use as anti-inflammatory agents |
| US6645990B2 (en) * | 2000-08-15 | 2003-11-11 | Amgen Inc. | Thiazolyl urea compounds and methods of uses |
| US20030073692A1 (en) * | 2001-08-07 | 2003-04-17 | Pharmacia & Upjohn S.P.A. | Amino-phthalazinone derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions containing them |
| DE10139416A1 (de) * | 2001-08-17 | 2003-03-06 | Aventis Pharma Gmbh | Aminoalkyl substituierte aromatische Bicyclen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US7307097B2 (en) * | 2001-09-27 | 2007-12-11 | Smithkline Beechman Corporation | Chemical compounds |
| TWI323658B (en) * | 2001-12-06 | 2010-04-21 | Nat Health Research Institutes | Novel compounds of indol-3-yl-2-oxyacetylamide derivatives, pharmaceutical composition thereof, and method for manufacturing the same |
| US7528165B2 (en) * | 2001-12-13 | 2009-05-05 | National Health Research Institutes | Indole compounds |
| US6933316B2 (en) * | 2001-12-13 | 2005-08-23 | National Health Research Institutes | Indole compounds |
| AU2003209116A1 (en) * | 2002-02-11 | 2003-09-04 | Bayer Pharmaceuticals Corporation | Aryl ureas with angiogenesis inhibiting activity |
| EP1495016A2 (en) * | 2002-04-09 | 2005-01-12 | Astex Technology Limited | Heterocyclic compounds and their use as modulators of p38 map kinase |
| US20050124620A1 (en) * | 2002-04-09 | 2005-06-09 | Martyn Frederickson | Pharmaceutical compounds |
| US6919340B2 (en) * | 2002-04-19 | 2005-07-19 | Cellular Genomics, Inc. | Imidazo[1,2-a]pyrazin-8-ylamines, method of making, and method of use thereof |
| WO2004022562A1 (en) * | 2002-09-09 | 2004-03-18 | Cellular Genomics, Inc. | 6-ARYL-IMIDAZO[1,2-a]PYRAZIN-8-YLAMINES, METHOD OF MAKING, AND METHOD OF USE THEREOF |
| TW200413378A (en) * | 2002-09-23 | 2004-08-01 | Schering Corp | Novel imidazopyrazines as cyclin dependent kinase inhibitors |
| AU2003275031B2 (en) * | 2002-09-23 | 2006-08-17 | Schering Corporation | Novel imidazopyrazines as cyclin dependent kinase inhibitors |
| US7189723B2 (en) * | 2003-02-10 | 2007-03-13 | Cgi Pharmaceuticals, Inc. | Certain 8-heteroaryl-6-phenyl-imidazo[1,2-a]pyrazines as modulators of kinase activity |
| US7186832B2 (en) * | 2003-02-20 | 2007-03-06 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US7157460B2 (en) * | 2003-02-20 | 2007-01-02 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US20040235892A1 (en) * | 2003-05-22 | 2004-11-25 | Yujia Dai | Indazole and benzisoxazole kinase inhibitors |
| US20060183746A1 (en) * | 2003-06-04 | 2006-08-17 | Currie Kevin S | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
| WO2005014599A1 (en) * | 2003-06-04 | 2005-02-17 | Cellular Genomics, Inc. | Imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of bruton’s tyrosine kinase by such compounds |
| WO2005005429A1 (en) * | 2003-06-30 | 2005-01-20 | Cellular Genomics, Inc. | Certain heterocyclic substituted imidazo[1,2-a]pyrazin-8-ylamines and methods of inhibition of bruton’s tyrosine kinase by such compounds |
| US7259164B2 (en) * | 2003-08-11 | 2007-08-21 | Cgi Pharmaceuticals, Inc. | Certain substituted imidazo[1,2-a]pyrazines, as modulators of kinase activity |
| WO2005047290A2 (en) * | 2003-11-11 | 2005-05-26 | Cellular Genomics Inc. | Imidazo[1,2-a] pyrazin-8-ylamines as kinase inhibitors |
| EP1858877B1 (en) * | 2005-01-14 | 2014-03-12 | Gilead Connecticut, Inc. | 1,3 substituted diaryl ureas as modulators of kinase activity |
| NZ556433A (en) * | 2005-01-14 | 2010-10-29 | Cgi Pharmaceuticals Inc | 1, 3-diaryl substituted ureas as modulators of kinase activity |
| WO2007024294A2 (en) * | 2005-05-03 | 2007-03-01 | Cgi Pharmaceuticals, Inc. | Certain substituted ureas, as modulators of kinase activity |
-
2006
- 2006-01-13 NZ NZ556433A patent/NZ556433A/en not_active IP Right Cessation
- 2006-01-13 EP EP11181551A patent/EP2397478A1/en not_active Withdrawn
- 2006-01-13 AU AU2006204790A patent/AU2006204790B2/en not_active Ceased
- 2006-01-13 KR KR1020077018205A patent/KR101292598B1/ko not_active Expired - Fee Related
- 2006-01-13 TW TW095101448A patent/TWI378925B/zh not_active IP Right Cessation
- 2006-01-13 US US11/331,346 patent/US20060199846A1/en not_active Abandoned
- 2006-01-13 RU RU2007130895/04A patent/RU2402544C2/ru not_active IP Right Cessation
- 2006-01-13 EP EP06718359A patent/EP1858879B1/en not_active Not-in-force
- 2006-01-13 CN CN2011101127260A patent/CN102267978A/zh active Pending
- 2006-01-13 CA CA002594449A patent/CA2594449A1/en not_active Abandoned
- 2006-01-13 ES ES06718359T patent/ES2393741T3/es active Active
- 2006-01-13 WO PCT/US2006/001272 patent/WO2006076593A1/en not_active Ceased
- 2006-01-13 JP JP2007551409A patent/JP2008526988A/ja active Pending
-
2007
- 2007-07-09 IL IL184494A patent/IL184494A/en not_active IP Right Cessation
-
2012
- 2012-09-21 JP JP2012208429A patent/JP2013028628A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| JP2013028628A (ja) | 2013-02-07 |
| KR20070113200A (ko) | 2007-11-28 |
| TWI378925B (en) | 2012-12-11 |
| KR101292598B1 (ko) | 2013-08-05 |
| CN102267978A (zh) | 2011-12-07 |
| IL184494A0 (en) | 2007-10-31 |
| US20060199846A1 (en) | 2006-09-07 |
| WO2006076593A1 (en) | 2006-07-20 |
| JP2008526988A (ja) | 2008-07-24 |
| TW200639165A (en) | 2006-11-16 |
| NZ556433A (en) | 2010-10-29 |
| AU2006204790B2 (en) | 2012-08-23 |
| AU2006204790A1 (en) | 2006-07-20 |
| RU2007130895A (ru) | 2009-02-20 |
| EP2397478A1 (en) | 2011-12-21 |
| RU2402544C2 (ru) | 2010-10-27 |
| EP1858879A1 (en) | 2007-11-28 |
| CA2594449A1 (en) | 2006-07-20 |
| EP1858879B1 (en) | 2012-06-06 |
| IL184494A (en) | 2013-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2465469T3 (es) | Diaril ureas 1,3-sustituidas como moduladores de la actividad quinasa | |
| US8222421B2 (en) | Certain substituted ureas, as modulators of kinase activity | |
| TWI426908B (zh) | 特定化學品、組成物及方法 | |
| JP2013028628A (ja) | キナーゼ活性モジュレーターとしての１，３−ジアリール置換尿素 | |
| EP1233769B1 (en) | Imidazole derivatives | |
| ES2363269T3 (es) | Amidas sustituidas, procedimiento de preparación y procedimiento de utlización de las mismas. | |
| HUE029370T2 (hu) | Rákellenes aktivitású vegyületek | |
| KR102834593B1 (ko) | 면역조절 화합물 | |
| KR20210025061A (ko) | 세레블론(crbn)에 대한 리간드 | |
| JP4217480B2 (ja) | 新規化合物 | |
| JP2018524367A (ja) | 癌の処置のためのｄｕｂ阻害剤としてのシアノピロリジン | |
| WO2017167182A1 (zh) | 一种选择性的c-kit激酶抑制剂 | |
| WO2011046991A2 (en) | Certain substituted ureas as modulators of kinase activity | |
| CN107501279B (zh) | 呋喃并喹啉二酮类化合物及其医药用途 | |
| CN101163691A (zh) | 作为激酶活性调节剂的1,3-二芳基取代的脲 | |
| HK1114392A (en) | 1,3-diaryl substituted ureas as modulators of kinase activity |