JP2018505145A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018505145A5 JP2018505145A5 JP2017533501A JP2017533501A JP2018505145A5 JP 2018505145 A5 JP2018505145 A5 JP 2018505145A5 JP 2017533501 A JP2017533501 A JP 2017533501A JP 2017533501 A JP2017533501 A JP 2017533501A JP 2018505145 A5 JP2018505145 A5 JP 2018505145A5
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- fluoro
- indene
- ylidene
- amino
- 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.)
- Granted
Links
- -1 thiazepanyl Chemical group 0.000 claims description 201
- 125000000217 alkyl group Chemical group 0.000 claims description 98
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- 239000001257 hydrogen Substances 0.000 claims description 95
- 150000002431 hydrogen Chemical class 0.000 claims description 78
- 125000003545 alkoxy group Chemical group 0.000 claims description 70
- 125000001188 haloalkyl group Chemical group 0.000 claims description 69
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 56
- 125000000623 heterocyclic group Chemical group 0.000 claims description 54
- 150000001875 compounds Chemical class 0.000 claims description 43
- 150000003839 salts Chemical class 0.000 claims description 39
- 229940002612 prodrug Drugs 0.000 claims description 37
- 239000000651 prodrug Substances 0.000 claims description 37
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 36
- 125000003282 alkyl amino group Chemical group 0.000 claims description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 31
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 26
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 26
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 239000001301 oxygen Substances 0.000 claims description 26
- 125000004414 alkyl thio group Chemical group 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical class 0.000 claims description 25
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 22
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 22
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 21
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 229940124530 sulfonamide Drugs 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 150000003456 sulfonamides Chemical group 0.000 claims description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 15
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 13
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 13
- 239000004202 carbamide Substances 0.000 claims description 13
- 235000013877 carbamide Nutrition 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 239000011593 sulfur Chemical group 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 201000011510 cancer Diseases 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 11
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 11
- 229910019142 PO4 Inorganic materials 0.000 claims description 10
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 10
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims description 10
- 239000010452 phosphate Substances 0.000 claims description 10
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 claims description 8
- 150000003857 carboxamides Chemical class 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 7
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- RBCKJOAMDLCFEH-UHFFFAOYSA-N SN=[N+]=[N-] Chemical group SN=[N+]=[N-] RBCKJOAMDLCFEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003725 azepanyl group Chemical group 0.000 claims description 4
- 125000002785 azepinyl group Chemical group 0.000 claims description 4
- 125000002576 diazepinyl group Chemical group N1N=C(C=CC=C1)* 0.000 claims description 4
- 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 4
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 4
- 125000005411 dithiolanyl group Chemical group S1SC(CC1)* 0.000 claims description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000005961 oxazepanyl group Chemical group 0.000 claims description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 4
- 125000003585 oxepinyl group Chemical group 0.000 claims description 4
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 4
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 4
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
- 125000005458 thianyl group Chemical group 0.000 claims description 4
- 125000005308 thiazepinyl group Chemical group S1N=C(C=CC=C1)* 0.000 claims description 4
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000001583 thiepanyl group Chemical group 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- CJBUOVAXMPVXFB-UKWGHVSLSA-N 2-[(3Z)-6-fluoro-3-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-2-methylinden-1-yl]-N-(furan-2-ylmethyl)acetamide Chemical compound FC=1C=C2C(=C(/C(/C2=CC=1)=C/C1=CC(=C(C(=C1)OC)O)OC)C)CC(=O)NCC=1OC=CC=1 CJBUOVAXMPVXFB-UKWGHVSLSA-N 0.000 claims description 3
- RBHNASBMHJZBFY-MBTHVWNTSA-N 2-[4-[(Z)-[3-[2-(benzylamino)-2-oxoethyl]-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl]benzoic acid Chemical compound COc1cc(\C=C2\C(C)=C(CC(=O)NCc3ccccc3)c3cc(F)ccc23)cc(OC)c1-c1ccccc1C(O)=O RBHNASBMHJZBFY-MBTHVWNTSA-N 0.000 claims description 3
- WYGLMMWOUCXDKZ-MXAYSNPKSA-N 3-[4-[(Z)-[3-[2-(benzylamino)-2-oxoethyl]-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl]morpholine-4-carboxylic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4COCCN4C(=O)O)OC)C=CC(=C2)F)CC(=O)NCC5=CC=CC=C5 WYGLMMWOUCXDKZ-MXAYSNPKSA-N 0.000 claims description 3
- QCBZYUZGBWSIQZ-WGARJPEWSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NCC=1C=NC=CC=1)=O)C)OC QCBZYUZGBWSIQZ-WGARJPEWSA-N 0.000 claims description 3
- HLXZUQWXWHOMDV-UKWGHVSLSA-N [4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] dihydrogen phosphate Chemical compound P(=O)(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC=1OC=CC=1)C)OC)(O)O HLXZUQWXWHOMDV-UKWGHVSLSA-N 0.000 claims description 3
- ATZLDLKYKBLUMD-FBHDLOMBSA-N [4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] methanesulfonate Chemical compound FC=1C=C2C(=C(/C(/C2=CC=1)=C/C1=CC(=C(C(=C1)OC)OS(=O)(=O)C)OC)C)CC(=O)NCC=1OC=CC=1 ATZLDLKYKBLUMD-FBHDLOMBSA-N 0.000 claims description 3
- HLBRTVFVEZPFAK-ROTLSHHCSA-N [4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] pyridine-3-carboxylate Chemical compound C(C1=CN=CC=C1)(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC=1OC=CC=1)C)OC HLBRTVFVEZPFAK-ROTLSHHCSA-N 0.000 claims description 3
- 125000000532 dioxanyl group Chemical group 0.000 claims description 3
- 125000005883 dithianyl group Chemical group 0.000 claims description 3
- 125000005303 dithiazolyl group Chemical group S1SNC(=C1)* 0.000 claims description 3
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000002971 oxazolyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000005247 tetrazinyl group Chemical group N1=NN=NC(=C1)* 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 3
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 3
- 125000005455 trithianyl group Chemical group 0.000 claims description 3
- OJOZWNKVCAHSQU-NHDPSOOVSA-N 2-[(3Z)-6-fluoro-3-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-2-methylinden-1-yl]-N-phenoxyacetamide Chemical compound FC=1C=C2C(=C(/C(/C2=CC=1)=C/C1=CC(=C(C(=C1)OC)O)OC)C)CC(=O)NOC1=CC=CC=C1 OJOZWNKVCAHSQU-NHDPSOOVSA-N 0.000 claims description 2
- NBXUWTRRDXULPY-WGARJPEWSA-N 2-[4-[(Z)-[3-[2-(benzylamino)-2-oxoethyl]-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl]pyridine-3-carboxylic acid Chemical compound COc1cc(\C=C2\C(C)=C(CC(=O)NCc3ccccc3)c3cc(F)ccc23)cc(OC)c1-c1ncccc1C(O)=O NBXUWTRRDXULPY-WGARJPEWSA-N 0.000 claims description 2
- PYUFWOUZMIHHEN-VYYCAZPPSA-N 2-[4-[(Z)-[5-fluoro-2-methyl-3-[2-[(1-methylpyrrol-2-yl)methylamino]-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl]benzoic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4=CC=CC=C4C(=O)O)OC)C=CC(=C2)F)CC(=O)NCC5=CC=CN5C PYUFWOUZMIHHEN-VYYCAZPPSA-N 0.000 claims description 2
- LXMACKWPKQLWMC-MXAYSNPKSA-N 2-[4-[(Z)-[5-fluoro-2-methyl-3-[2-[(1-methylpyrrol-2-yl)methylamino]-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl]pyridine-3-carboxylic acid Chemical compound COc1cc(\C=C2\C(C)=C(CC(=O)NCc3cccn3C)c3cc(F)ccc23)cc(OC)c1-c1ncccc1C(O)=O LXMACKWPKQLWMC-MXAYSNPKSA-N 0.000 claims description 2
- NGMARNMVSIRBMW-WKIKZPBSSA-N 2-[4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl]benzoic acid Chemical compound COc1cc(\C=C2\C(C)=C(CC(=O)NCc3cccnc3)c3cc(F)ccc23)cc(OC)c1-c1ccccc1C(O)=O NGMARNMVSIRBMW-WKIKZPBSSA-N 0.000 claims description 2
- UXBOQICIICVKTQ-ROTLSHHCSA-N 2-[4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl]pyridine-3-carboxylic acid Chemical compound COc1cc(\C=C2\C(C)=C(CC(=O)NCc3cccnc3)c3cc(F)ccc23)cc(OC)c1-c1ncccc1C(O)=O UXBOQICIICVKTQ-ROTLSHHCSA-N 0.000 claims description 2
- NJLOBRKHYUKZOR-ZMFRSBBQSA-N 2-[4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl]benzoic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4=CC=CC=C4C(=O)O)OC)C=CC(=C2)F)CC(=O)NCC5=CC=CO5 NJLOBRKHYUKZOR-ZMFRSBBQSA-N 0.000 claims description 2
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- KYMCBVRBQQMBCN-MSXFZWOLSA-N 3-[4-[(Z)-[3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-5-methoxy-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl]morpholine-4-carboxylic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4COCCN4C(=O)O)OC)C=CC(=C2)OC)CC(=O)NCC5=CC=CO5 KYMCBVRBQQMBCN-MSXFZWOLSA-N 0.000 claims description 2
- WNVZGVISWPFDOZ-MSXFZWOLSA-N 3-[4-[(Z)-[5-fluoro-2-methyl-3-[2-[(1-methylpyrrol-2-yl)methylamino]-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl]morpholine-4-carboxylic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4COCCN4C(=O)O)OC)C=CC(=C2)F)CC(=O)NCC5=CC=CN5C WNVZGVISWPFDOZ-MSXFZWOLSA-N 0.000 claims description 2
- WGGYEGZHAGOFAF-KSEXSDGBSA-N 3-[4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl]morpholine-4-carboxylic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4COCCN4C(=O)O)OC)C=CC(=C2)F)CC(=O)NCC5=CC=CO5 WGGYEGZHAGOFAF-KSEXSDGBSA-N 0.000 claims description 2
- LQHOJRNQESUSKS-VYYCAZPPSA-N C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NCC1=NC=CC=C1)=O)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NCC1=NC=CC=C1)=O)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O LQHOJRNQESUSKS-VYYCAZPPSA-N 0.000 claims description 2
- KXEXUVABFJRIBO-DICXZTSXSA-N [4-[(Z)-[3-(2-anilino-2-oxoethyl)-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NC1=CC=CC=C1)=O)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O KXEXUVABFJRIBO-DICXZTSXSA-N 0.000 claims description 2
- FATHYBVEMLAYOO-MBTHVWNTSA-N [4-[(Z)-[3-[2-(benzylamino)-2-oxoethyl]-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC1=CC=CC=C1)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O FATHYBVEMLAYOO-MBTHVWNTSA-N 0.000 claims description 2
- PSJOJUFEHGAVOJ-YUMHPJSZSA-N [4-[(Z)-[3-[2-(benzylamino)-2-oxoethyl]-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC1=CC=CC=C1)C)OC PSJOJUFEHGAVOJ-YUMHPJSZSA-N 0.000 claims description 2
- UNTJZMUWOQKHLZ-JJFYIABZSA-N [4-[(Z)-[3-[2-(benzylamino)-2-oxoethyl]-5-fluoro-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] dihydrogen phosphate Chemical compound P(=O)(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC1=CC=CC=C1)C)OC)(O)O UNTJZMUWOQKHLZ-JJFYIABZSA-N 0.000 claims description 2
- OMFYQWJDEIQIHD-VYYCAZPPSA-N [4-[(Z)-[3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-5-methoxy-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)OC)CC(=O)NCC=1OC=CC=1)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O OMFYQWJDEIQIHD-VYYCAZPPSA-N 0.000 claims description 2
- CFDRCFYPBKRYKB-YSMPRRRNSA-N [4-[(Z)-[3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-5-methoxy-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)OC)CC(=O)NCC=1OC=CC=1)C)OC CFDRCFYPBKRYKB-YSMPRRRNSA-N 0.000 claims description 2
- HUALWUQEEVDSOM-FBHDLOMBSA-N [4-[(Z)-[3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-5-methoxy-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] dihydrogen phosphate Chemical compound P(=O)(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)OC)CC(=O)NCC=1OC=CC=1)C)OC)(O)O HUALWUQEEVDSOM-FBHDLOMBSA-N 0.000 claims description 2
- WJKHZTNOLXOTPQ-VYYCAZPPSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-[(1-methylpyrrol-2-yl)methylamino]-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC=1N(C=CC=1)C)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O WJKHZTNOLXOTPQ-VYYCAZPPSA-N 0.000 claims description 2
- MZDCWJNGLQYYDL-FBHDLOMBSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-[(1-methylpyrrol-2-yl)methylamino]-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] dihydrogen phosphate Chemical compound COC1=CC(\C=C2\C(C)=C(CC(=O)NCC3=CC=CN3C)C3=C2C=CC(F)=C3)=CC(OC)=C1OP(O)(O)=O MZDCWJNGLQYYDL-FBHDLOMBSA-N 0.000 claims description 2
- MHQQLIAOAFTDTO-YSMPRRRNSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-2-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NCC1=NC=CC=C1)=O)C)OC MHQQLIAOAFTDTO-YSMPRRRNSA-N 0.000 claims description 2
- NILKUFLEDANGCI-WKIKZPBSSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NCC=1C=NC=CC=1)=O)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O NILKUFLEDANGCI-WKIKZPBSSA-N 0.000 claims description 2
- MTFAUHWAFJFHDY-NKVSQWTQSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] dihydrogen phosphate Chemical compound P(=O)(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(NCC=1C=NC=CC=1)=O)C)OC)(O)O MTFAUHWAFJFHDY-NKVSQWTQSA-N 0.000 claims description 2
- IFLZIGMFACDLEQ-MUXKCCDJSA-N [4-[(Z)-[5-fluoro-3-[2-(3-methoxyanilino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NC1=CC(=CC=C1)OC)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O IFLZIGMFACDLEQ-MUXKCCDJSA-N 0.000 claims description 2
- AVTSZWAGYNVUHA-DICXZTSXSA-N [4-[(Z)-[5-fluoro-3-[2-(3-methoxyanilino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NC1=CC(=CC=C1)OC)C)OC AVTSZWAGYNVUHA-DICXZTSXSA-N 0.000 claims description 2
- HJAHDOSMLFEBCH-ZMFRSBBQSA-N [4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] (4-nitrophenyl) carbonate Chemical compound C(OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC=1OC=CC=1)C)OC)(OC1=CC=C(C=C1)[N+](=O)[O-])=O HJAHDOSMLFEBCH-ZMFRSBBQSA-N 0.000 claims description 2
- BBDSBQYHFSLWGX-QFEZKATASA-N [4-[(Z)-[5-fluoro-3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC=1OC=CC=1)C)OC BBDSBQYHFSLWGX-QFEZKATASA-N 0.000 claims description 2
- 125000003838 furazanyl group Chemical group 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims description 2
- 125000003965 isoxazolidinyl group Chemical group 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 3
- 125000000597 dioxinyl group Chemical group 0.000 claims 3
- 239000005711 Benzoic acid Substances 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 235000010233 benzoic acid Nutrition 0.000 claims 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims 2
- 229910052799 carbon Inorganic materials 0.000 claims 2
- MTBULSBBUNXIPE-MYKKPKGFSA-N 3-[4-[(Z)-[5-fluoro-2-methyl-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl]morpholine-4-carboxylic acid Chemical compound CC\1=C(C2=C(/C1=C\C3=CC(=C(C(=C3)OC)C4COCCN4C(=O)O)OC)C=CC(=C2)F)CC(=O)NCC5=CN=CC=C5 MTBULSBBUNXIPE-MYKKPKGFSA-N 0.000 claims 1
- DJHGAFSJWGLOIV-UHFFFAOYSA-N Arsenic acid Chemical compound O[As](O)(O)=O DJHGAFSJWGLOIV-UHFFFAOYSA-N 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims 1
- ITFWPLSEBIPKKX-ZMFRSBBQSA-N [4-[(Z)-[3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-5-methoxy-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] pyridine-3-carboxylate Chemical compound C(C1=CN=CC=C1)(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)OC)CC(=O)NCC=1OC=CC=1)C)OC ITFWPLSEBIPKKX-ZMFRSBBQSA-N 0.000 claims 1
- JMWVPRFDGGKSSY-YSMPRRRNSA-N [4-[(Z)-[5-fluoro-2-methyl-3-[2-[(1-methylpyrrol-2-yl)methylamino]-2-oxoethyl]inden-1-ylidene]methyl]-2,6-dimethoxyphenyl] 4-methylpiperazine-1-carboxylate Chemical compound CN1CCN(CC1)C(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)F)CC(=O)NCC=1N(C=CC=1)C)C)OC JMWVPRFDGGKSSY-YSMPRRRNSA-N 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 17
- 125000003396 thiol group Chemical class [H]S* 0.000 description 17
- 125000003341 7 membered heterocyclic group Chemical group 0.000 description 13
- 125000005843 halogen group Chemical group 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 11
- 125000000304 alkynyl group Chemical group 0.000 description 11
- 125000002837 carbocyclic group Chemical group 0.000 description 11
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 10
- 0 CCC*(C(C)(*)C(C)(C)C(*)(*)*)C1=C(*)C(*)(C(*)(*)*)c2c(*)c(*)c(*)c(*)c12 Chemical compound CCC*(C(C)(*)C(C)(C)C(*)(*)*)C1=C(*)C(*)(C(*)(*)*)c2c(*)c(*)c(*)c(*)c12 0.000 description 10
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 9
- 125000001627 3 membered heterocyclic group Chemical group 0.000 description 8
- 125000001963 4 membered heterocyclic group Chemical group 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
- 125000004350 aryl cycloalkyl group Chemical group 0.000 description 6
- 125000004452 carbocyclyl group Chemical group 0.000 description 6
- 125000005884 carbocyclylalkyl group Chemical group 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000001613 neoplastic effect Effects 0.000 description 5
- 230000005855 radiation Effects 0.000 description 5
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 4
- 125000001960 7 membered carbocyclic group Chemical group 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 208000001333 Colorectal Neoplasms Diseases 0.000 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 4
- 125000004946 alkenylalkyl group Chemical group 0.000 description 4
- 125000005093 alkyl carbonyl alkyl group Chemical group 0.000 description 4
- 125000005038 alkynylalkyl group Chemical group 0.000 description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 4
- 150000001540 azides Chemical class 0.000 description 4
- 230000000711 cancerogenic effect Effects 0.000 description 4
- 231100000315 carcinogenic Toxicity 0.000 description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 4
- 201000007270 liver cancer Diseases 0.000 description 4
- 208000014018 liver neoplasm Diseases 0.000 description 4
- 201000005202 lung cancer Diseases 0.000 description 4
- 208000020816 lung neoplasm Diseases 0.000 description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 4
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 description 4
- 201000002528 pancreatic cancer Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 3
- 125000005018 aryl alkenyl group Chemical group 0.000 description 3
- 125000001072 heteroaryl group Chemical group 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 125000005415 substituted alkoxy group Chemical group 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 125000001845 4 membered carbocyclic group Chemical group 0.000 description 2
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 2
- 208000003174 Brain Neoplasms Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 206010059866 Drug resistance Diseases 0.000 description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- 206010025323 Lymphomas Diseases 0.000 description 2
- 206010027476 Metastases Diseases 0.000 description 2
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 206010039491 Sarcoma Diseases 0.000 description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 description 2
- 208000002495 Uterine Neoplasms Diseases 0.000 description 2
- NQGLTAZYNRAYMY-DICXZTSXSA-N [4-[(Z)-[3-[2-(furan-2-ylmethylamino)-2-oxoethyl]-5-methoxy-2-methylinden-1-ylidene]methyl]-2,6-dimethoxyphenyl] benzoate Chemical compound C(C1=CC=CC=C1)(=O)OC1=C(C=C(C=C1OC)\C=C/1\C(=C(C2=CC(=CC=C\12)OC)CC(=O)NCC=1OC=CC=1)C)OC NQGLTAZYNRAYMY-DICXZTSXSA-N 0.000 description 2
- 201000007455 central nervous system cancer Diseases 0.000 description 2
- 125000006317 cyclopropyl amino group Chemical group 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- 206010017758 gastric cancer Diseases 0.000 description 2
- 201000003115 germ cell cancer Diseases 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 208000032839 leukemia Diseases 0.000 description 2
- 208000029559 malignant endocrine neoplasm Diseases 0.000 description 2
- 201000001441 melanoma Diseases 0.000 description 2
- 230000009401 metastasis Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 201000011549 stomach cancer Diseases 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 230000004565 tumor cell growth Effects 0.000 description 2
- 206010046766 uterine cancer Diseases 0.000 description 2
- HIQSEEGADGSFCJ-XZWPQECSSA-N 1-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-2-[(3Z)-2,6-dimethyl-3-[(3,4,5-trimethoxyphenyl)methylidene]inden-1-yl]ethanone hydrochloride Chemical compound Cl.COc1cc(\C=C2\C(C)=C(CC(=O)N3CC[C@H](C3)N(C)C)c3cc(C)ccc23)cc(OC)c1OC HIQSEEGADGSFCJ-XZWPQECSSA-N 0.000 description 1
- VLQSJJJCPYXDHH-DUSZCDDOSA-N 1-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]-2-[(3Z)-6-methoxy-2-methyl-3-[(3,4,5-trimethoxyphenyl)methylidene]inden-1-yl]ethanone hydrochloride Chemical compound Cl.COc1ccc2\C(=C/c3cc(OC)c(OC)c(OC)c3)C(C)=C(CC(=O)N3CC[C@H](C3)N(C)C)c2c1 VLQSJJJCPYXDHH-DUSZCDDOSA-N 0.000 description 1
- VLQSJJJCPYXDHH-PWRRSTETSA-N 1-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-2-[(3Z)-6-methoxy-2-methyl-3-[(3,4,5-trimethoxyphenyl)methylidene]inden-1-yl]ethanone hydrochloride Chemical compound Cl.COc1ccc2\C(=C/c3cc(OC)c(OC)c(OC)c3)C(C)=C(CC(=O)N3CC[C@@H](C3)N(C)C)c2c1 VLQSJJJCPYXDHH-PWRRSTETSA-N 0.000 description 1
- CLUXRNJXRVBVPS-UCQKPKSFSA-N 2-(dimethylamino)-2-[(3Z)-3-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-6-methoxy-2-methylinden-1-yl]-N-phenylacetamide Chemical compound CN(C(C(=O)NC1=CC=CC=C1)C1=C(/C(/C2=CC=C(C=C12)OC)=C/C1=CC(=C(C(=C1)OC)O)OC)C)C CLUXRNJXRVBVPS-UCQKPKSFSA-N 0.000 description 1
- LIEKZWFJRMHIAH-BWLGBDCWSA-N 2-[(3Z)-6-methoxy-2-methyl-3-[(3,4,5-trimethoxyphenyl)methylidene]inden-1-yl]-1-(4-methylpiperazin-1-yl)ethanone hydrochloride Chemical compound Cl.COc1ccc2\C(=C/c3cc(OC)c(OC)c(OC)c3)C(C)=C(CC(=O)N3CCN(C)CC3)c2c1 LIEKZWFJRMHIAH-BWLGBDCWSA-N 0.000 description 1
- RVFQTZYFYOKLOH-MTJSOVHGSA-N 2-azido-2-[(3Z)-3-[(4-hydroxy-3,5-dimethoxyphenyl)methylidene]-6-methoxy-2-methylinden-1-yl]-N-phenylacetamide Chemical compound N(=[N+]=[N-])C(C(=O)NC1=CC=CC=C1)C1=C(/C(/C2=CC=C(C=C12)OC)=C/C1=CC(=C(C(=C1)OC)O)OC)C RVFQTZYFYOKLOH-MTJSOVHGSA-N 0.000 description 1
- 125000004011 3 membered carbocyclic group Chemical group 0.000 description 1
- JIPPWJVJUJVGQC-UHFFFAOYSA-N C(C)(=O)NC1=C(C(C2=CC=C(C=C12)OC)=CC1=CC(=C(C(=C1)OC)C(=O)OCC)OC)C Chemical compound C(C)(=O)NC1=C(C(C2=CC=C(C=C12)OC)=CC1=CC(=C(C(=C1)OC)C(=O)OCC)OC)C JIPPWJVJUJVGQC-UHFFFAOYSA-N 0.000 description 1
- GJWUFAZBHYTYPJ-FMCGGJTJSA-N N-(furan-2-ylmethyl)-2-[(3Z)-6-methoxy-2-methyl-3-[(3,4,5-trimethoxyphenyl)methylidene]inden-1-yl]-N-methylacetamide Chemical compound O1C(=CC=C1)CN(C(CC1=C(/C(/C2=CC=C(C=C12)OC)=C/C1=CC(=C(C(=C1)OC)OC)OC)C)=O)C GJWUFAZBHYTYPJ-FMCGGJTJSA-N 0.000 description 1
- DNMIDQZPRUGNOE-JLPGSUDCSA-N N-[2-(dimethylamino)ethyl]-2-[(3Z)-3-[[4-(dimethylamino)phenyl]methylidene]-6-methoxy-2-methylinden-1-yl]-N-methylacetamide Chemical compound CN(C1=CC=C(\C=C/2\C(=C(C3=CC(=CC=C\23)OC)CC(=O)N(C)CCN(C)C)C)C=C1)C DNMIDQZPRUGNOE-JLPGSUDCSA-N 0.000 description 1
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000002188 cycloheptatrienyl group Chemical group C1(=CC=CC=CC1)* 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000058 cyclopentadienyl group Chemical group C1(=CC=CC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- ZSWFCLXCOIISFI-UHFFFAOYSA-N endo-cyclopentadiene Chemical group C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000005059 halophenyl group Chemical group 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14/571,647 | 2014-12-16 | ||
| US14/571,647 US9862698B2 (en) | 2014-12-16 | 2014-12-16 | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
| PCT/US2015/066146 WO2016100542A1 (en) | 2014-12-16 | 2015-12-16 | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020029699A Division JP2020079307A (ja) | 2014-12-16 | 2020-02-25 | インデニル化合物、医薬組成物、およびその医学的使用 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018505145A JP2018505145A (ja) | 2018-02-22 |
| JP2018505145A5 true JP2018505145A5 (enExample) | 2019-01-24 |
| JP6698089B2 JP6698089B2 (ja) | 2020-05-27 |
Family
ID=55085918
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017533501A Active JP6698089B2 (ja) | 2014-12-16 | 2015-12-16 | インデニル化合物、医薬組成物、およびその医学的使用 |
| JP2020029699A Withdrawn JP2020079307A (ja) | 2014-12-16 | 2020-02-25 | インデニル化合物、医薬組成物、およびその医学的使用 |
| JP2021145211A Withdrawn JP2021185193A (ja) | 2014-12-16 | 2021-09-07 | インデニル化合物、医薬組成物、およびその医学的使用 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020029699A Withdrawn JP2020079307A (ja) | 2014-12-16 | 2020-02-25 | インデニル化合物、医薬組成物、およびその医学的使用 |
| JP2021145211A Withdrawn JP2021185193A (ja) | 2014-12-16 | 2021-09-07 | インデニル化合物、医薬組成物、およびその医学的使用 |
Country Status (16)
| Country | Link |
|---|---|
| US (7) | US9862698B2 (enExample) |
| EP (2) | EP4053105A1 (enExample) |
| JP (3) | JP6698089B2 (enExample) |
| KR (1) | KR20170135820A (enExample) |
| CN (2) | CN112047909A (enExample) |
| AU (1) | AU2015364696B2 (enExample) |
| BR (1) | BR112017013012A2 (enExample) |
| CA (1) | CA2970803A1 (enExample) |
| CL (1) | CL2017001539A1 (enExample) |
| CO (1) | CO2017007076A2 (enExample) |
| IL (1) | IL252897A0 (enExample) |
| MX (2) | MX2021012096A (enExample) |
| PH (1) | PH12017501130A1 (enExample) |
| RU (1) | RU2017125024A (enExample) |
| SG (1) | SG11201704934YA (enExample) |
| WO (1) | WO2016100542A1 (enExample) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9862698B2 (en) | 2014-12-16 | 2018-01-09 | Adt Pharmaceuticals, Inc. | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
| US20160168108A1 (en) | 2014-12-16 | 2016-06-16 | Adt Pharmaceuticals, Inc. | Method of treating or preventing ras-mediated diseases |
| CN110291089B (zh) | 2017-01-17 | 2022-05-27 | 海帕瑞吉尼克斯股份有限公司 | 用于促进肝再生或者减少或预防肝细胞死亡的蛋白激酶抑制剂 |
| US11186534B2 (en) * | 2017-03-17 | 2021-11-30 | University Of South Alabama | Derivatives of sulindac can protect normal cells against oxidative damage |
| CA3072616A1 (en) | 2017-08-31 | 2019-03-07 | Musc Foundation For Research Development | Indene derivatives and uses thereof |
| CN112020354A (zh) * | 2018-04-26 | 2020-12-01 | Adt制药有限责任公司 | 抗癌茚类、茚满类、氮杂茚类、氮杂茚满类、药物组合物和用途 |
| CN113289020B (zh) * | 2021-05-17 | 2023-04-18 | 福州大学 | 蛋白质二硫键异构酶小分子抑制剂及其应用 |
| TW202504599A (zh) | 2023-06-30 | 2025-02-01 | 美商必治妥美雅史谷比公司 | Kras抑制劑 |
Family Cites Families (61)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3325358A (en) * | 1962-06-06 | 1967-06-13 | Merck & Co Inc | Method of treating inflammation |
| NL7005270A (enExample) | 1969-04-29 | 1970-11-02 | ||
| US3888902A (en) | 1972-10-30 | 1975-06-10 | Merck & Co Inc | Cyano-indenyl acetic acids |
| US3642785A (en) | 1969-08-11 | 1972-02-15 | Merck & Co Inc | Indenyl-3-aliphatic amines |
| NL7200058A (enExample) | 1971-01-21 | 1972-07-25 | ||
| SE7501517L (enExample) * | 1974-02-28 | 1975-08-29 | Merck & Co Inc | |
| ATE40561T1 (de) | 1983-07-21 | 1989-02-15 | Troponwerke Gmbh & Co Kg | Antiphlogistika enthaltende thermoplastische kunststoffe. |
| US4656190A (en) | 1983-11-14 | 1987-04-07 | Merck & Co., Inc. | Indene derivatives and their use as PAF-antagonists |
| US5093356A (en) | 1990-01-16 | 1992-03-03 | Merck Frosst Canada, Inc. | Indenyl hydroxamic acids and hydroxy ureas as inhibitors of 5-lipoxygenase |
| US5401774A (en) | 1991-03-08 | 1995-03-28 | University Of Arizona | Method for treating patients with precancerous lesions by administering substituted sulfonyl idenyl acetic and propionic acids and esters to patients with lesions sensitive to such compounds |
| AU650720B2 (en) * | 1991-03-08 | 1994-06-30 | Fgn, Inc. | Method for treating patients with precancerous lesions by administering substituted sulfonyl indenyl acetic and propionic acids and esters thereof |
| AU3162695A (en) | 1994-08-03 | 1996-03-04 | Asta Medica Aktiengesellschaft | Indol, indazol, pyridopyrrol and pyridopyrazol derivatives with anti-asthmatic, anti-allergic, anti-inflammatory and immunomodulating effects |
| US5965619A (en) | 1996-06-13 | 1999-10-12 | Cell Pathways Inc. | Method for treating patients having precancerous lesions with substituted indene derivatives |
| US6063818A (en) * | 1996-06-13 | 2000-05-16 | Cell Pathways Inc. | Substituted benzylidene indenyl formamides, acetamides and propionamides |
| US6121321A (en) | 1996-06-13 | 2000-09-19 | Cell Pathways, Inc. | Substituted methoxy benzylidene indenyl acetic and propionic acids for treating patients with precancerous lesions |
| US6071934A (en) | 1997-03-25 | 2000-06-06 | Cell Pathways, Inc. | Indenyl hydroxamic acids, (hydroxy) ureas and urethanes for treating patients with precancerous lesions |
| HUP9903620A3 (en) | 1997-06-12 | 2001-03-28 | Univ Arizona Tucson | Pharmaceutical compositions containing substituted benzylidene indenyl formamides, acetamide and propionamide derivatives and use of these compounds |
| CA2314339C (en) * | 1997-12-12 | 2009-09-08 | Cell Pathways, Inc. | N-benzyl-3-indenylacetamide derivatives for treating neoplasia |
| US6028116A (en) * | 1998-04-03 | 2000-02-22 | Cell Pathways, Inc. | Substituted condensation products of 1H-indenyl-hydroxyalkanes with aldehydes for neoplasia |
| US6025394A (en) * | 1999-01-29 | 2000-02-15 | Cell Pathways, Inc. | Method for treating patients with acne by administering substituted sulfonyl indenyl acetic acids, amides and alcohols |
| US6649629B2 (en) | 1999-12-23 | 2003-11-18 | Nitromed, Inc. | Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use |
| EP1854804B1 (en) | 1999-12-28 | 2011-05-04 | Basell Polyolefine GmbH | Heterocyclic metallocene compounds and use thereof in catalyst systems for producing olefin polymers |
| CA2424222A1 (en) | 2000-10-02 | 2002-04-11 | Merck & Co., Inc. | Inhibitors of prenyl-protein transferase |
| US20030176316A1 (en) * | 2001-08-24 | 2003-09-18 | Whitehead Clark M. | Methods for treatment of rheumatoid arthritis |
| DE10163426A1 (de) * | 2001-12-21 | 2003-07-03 | Max Planck Gesellschaft | Pharmakologisch wirksame Inden-Derivate |
| US20030194750A1 (en) | 2002-04-05 | 2003-10-16 | Han Li | Methods for treatment of diseases where GSK 3-beta is desired, and methods to identify compounds usefule for that |
| US6538029B1 (en) | 2002-05-29 | 2003-03-25 | Cell Pathways | Methods for treatment of renal cell carcinoma |
| US7211598B2 (en) | 2002-06-28 | 2007-05-01 | Nitromed, Inc. | Oxime and/or hydrozone containing nitrosated and/or nitrosylated cyclooxygenase-2 selective inhibitors, compositions and methods of use |
| JP2007534702A (ja) * | 2004-04-26 | 2007-11-29 | バンダービルト・ユニバーシティ | 胃腸毒性の低い治療薬としてのインドール酢酸、及びインデン酢酸誘導体 |
| WO2006124874A2 (en) | 2005-05-12 | 2006-11-23 | Kalypsys, Inc. | Inhibitors of b-raf kinase |
| US8217041B2 (en) * | 2005-11-08 | 2012-07-10 | Laboratories del Sr. Esteve, S.A. | Indene derivatives, their preparation and use as medicaments |
| GB0525143D0 (en) | 2005-12-09 | 2006-01-18 | Novartis Ag | Organic compounds |
| CN101365461B (zh) | 2006-01-04 | 2013-07-24 | 南方研究所 | 舒林酸衍生物、其用途和其制备 |
| AU2016219617B2 (en) | 2006-07-09 | 2018-05-17 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of aspirin |
| US20090221703A1 (en) | 2006-07-09 | 2009-09-03 | Chongxi Yu | High penetration composition and uses thereof |
| AU2013206215C9 (en) | 2006-07-09 | 2018-03-08 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of aspirin |
| WO2008012603A1 (en) | 2006-07-26 | 2008-01-31 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of diflunisal and related compounds with very fast skin penetration rate |
| JP5759672B2 (ja) | 2006-07-09 | 2015-08-05 | テックフィールズ バイオケム カンパニー リミテッド | アスピリンの正荷電水溶性プロドラッグ |
| AU2013231152B2 (en) | 2006-07-18 | 2016-06-09 | Techfields Biochem Co. Ltd | Positively charged water-soluble pro-drugs of ibuprofen |
| CA2657636C (en) | 2006-07-18 | 2021-11-09 | Techfields Biochem Co. Ltd | Positively charged water soluble prodrugs of ibuprofen with very fast skin penetration rate |
| CN101500982A (zh) | 2006-07-25 | 2009-08-05 | 于崇曦 | 具有快速皮肤穿透速度的带正电荷的水溶性双氯芬酸前药 |
| CN108250090B (zh) | 2006-07-27 | 2021-08-20 | 于崇曦 | 具有快速皮肤穿透速度的带正电荷的水溶性酮洛芬及相关化合物的前药 |
| EP2049520A4 (en) | 2006-08-07 | 2011-01-05 | Ironwood Pharmaceuticals Inc | indole compounds |
| PL2049482T3 (pl) | 2006-08-08 | 2016-04-29 | Techfields Biochem Co Ltd | Dodatnio naładowane rozpuszczalne w wodzie proleki kwasów arylo- i heteroarylooctowych o bardzo dużej szybkości przenikania przez skórę |
| AU2013206218B2 (en) | 2006-08-15 | 2016-06-30 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of aryl- and heteroarylpropionic acids with very fast skin penetration rate |
| CN101506161B (zh) | 2006-08-15 | 2013-11-13 | 于崇曦 | 具有快速皮肤穿透速度的带正电荷的水溶性的芳基和杂芳基丙酸类前药 |
| JP5466006B2 (ja) | 2006-09-03 | 2014-04-09 | テックフィールズ バイオケム カンパニー リミテッド | 非常に速い皮膚浸透率を有するアセトアミノフェン及び関連化合物の正荷電水溶性プロドラッグ |
| AU2014201024B2 (en) | 2006-09-03 | 2016-05-05 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of acetaminophen and related compounds with very fast skin penetration rate |
| EP2084132B1 (en) | 2006-09-03 | 2018-08-08 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of n-arylanthranilic acids with very fast skin penetration rate |
| CN101522692A (zh) | 2006-10-11 | 2009-09-02 | 于崇曦 | 具有快速皮肤穿透速度的带正电荷的水溶性的昔康及其相关化合物的前药 |
| WO2008149181A1 (en) | 2007-06-04 | 2008-12-11 | Techfields Inc | Pro-drugs of nsaias with very high skin and membranes penetration rates and their new medicinal uses |
| CN102843909A (zh) | 2010-01-25 | 2012-12-26 | 埃南塔制药公司 | 丙型肝炎病毒抑制剂 |
| US9365528B2 (en) * | 2011-04-01 | 2016-06-14 | Southern Research Institute | Derivatives of sulindac, use thereof and preparation thereof |
| KR20150085509A (ko) | 2012-09-21 | 2015-07-23 | 바질 리가스 | 염증-관련 장애, 통증 및 열, 피부 장애, 암 및 이의 전암성 질환의 치료용 조성물 |
| WO2015126462A1 (en) | 2014-02-19 | 2015-08-27 | Materia, Inc. | Preparation of surfactants via cross-metathesis |
| CA2908383A1 (en) | 2013-04-09 | 2014-10-16 | Materia, Inc. | Preparation of surfactants via cross-metathesis |
| US20160168108A1 (en) | 2014-12-16 | 2016-06-16 | Adt Pharmaceuticals, Inc. | Method of treating or preventing ras-mediated diseases |
| EP3233070A4 (en) | 2014-12-16 | 2018-08-08 | ADT Pharmaceuticals, LLC | Ras-inhibiting indenyl acetamide compounds, compositions, and uses |
| US9862698B2 (en) | 2014-12-16 | 2018-01-09 | Adt Pharmaceuticals, Inc. | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
| WO2017106520A1 (en) | 2015-12-16 | 2017-06-22 | Adt Pharmaceuticals, Inc. | Compounds, compositions and methods of treating cancer |
| CN112020354A (zh) | 2018-04-26 | 2020-12-01 | Adt制药有限责任公司 | 抗癌茚类、茚满类、氮杂茚类、氮杂茚满类、药物组合物和用途 |
-
2014
- 2014-12-16 US US14/571,647 patent/US9862698B2/en active Active
-
2015
- 2015-12-16 SG SG11201704934YA patent/SG11201704934YA/en unknown
- 2015-12-16 CN CN202010795274.XA patent/CN112047909A/zh active Pending
- 2015-12-16 CA CA2970803A patent/CA2970803A1/en active Pending
- 2015-12-16 US US15/537,292 patent/US10526307B2/en active Active
- 2015-12-16 MX MX2021012096A patent/MX2021012096A/es unknown
- 2015-12-16 EP EP22157443.7A patent/EP4053105A1/en not_active Withdrawn
- 2015-12-16 KR KR1020177019639A patent/KR20170135820A/ko not_active Withdrawn
- 2015-12-16 CN CN201580076108.1A patent/CN107531615B/zh not_active Expired - Fee Related
- 2015-12-16 EP EP15823453.4A patent/EP3233794B1/en active Active
- 2015-12-16 RU RU2017125024A patent/RU2017125024A/ru not_active Application Discontinuation
- 2015-12-16 WO PCT/US2015/066146 patent/WO2016100542A1/en not_active Ceased
- 2015-12-16 AU AU2015364696A patent/AU2015364696B2/en not_active Ceased
- 2015-12-16 BR BR112017013012-2A patent/BR112017013012A2/pt not_active Application Discontinuation
- 2015-12-16 JP JP2017533501A patent/JP6698089B2/ja active Active
- 2015-12-16 MX MX2017007840A patent/MX386761B/es unknown
-
2017
- 2017-06-14 CL CL2017001539A patent/CL2017001539A1/es unknown
- 2017-06-14 IL IL252897A patent/IL252897A0/en unknown
- 2017-06-16 PH PH12017501130A patent/PH12017501130A1/en unknown
- 2017-07-14 CO CONC2017/0007076A patent/CO2017007076A2/es unknown
-
2019
- 2019-10-04 US US16/593,776 patent/US10975054B2/en active Active
- 2019-10-04 US US16/593,806 patent/US10981886B2/en active Active
-
2020
- 2020-02-25 JP JP2020029699A patent/JP2020079307A/ja not_active Withdrawn
- 2020-03-30 US US16/834,348 patent/US11130744B2/en not_active Expired - Fee Related
- 2020-03-30 US US16/834,267 patent/US11407727B2/en active Active
-
2021
- 2021-09-07 JP JP2021145211A patent/JP2021185193A/ja not_active Withdrawn
-
2022
- 2022-06-08 US US17/835,551 patent/US12479813B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2017125024A (ru) | Инденилсодержащие соединения, фармацевтические композиции и их применения в медицине | |
| JP2021107415A (ja) | 統合ストレス経路のモジュレーター | |
| CN109641844B (zh) | 整合应激通路的调节剂 | |
| JP2017530999A5 (enExample) | ||
| CN1902196B (zh) | 噻唑衍生物 | |
| JP2023518722A (ja) | Ｙａｐ／ｔａｚ－ｔｅａｄタンパク質－タンパク質相互作用阻害剤としてのビアリール誘導体 | |
| JP5667684B2 (ja) | 関節炎の治療方法 | |
| RU2017116598A (ru) | Соединения и композиции для модуляции киназной активности мутантов egfr | |
| JP2019517596A5 (enExample) | ||
| CN107531679B (zh) | 芳香酰胺类衍生物、其制备方法及其在医药上的应用 | |
| JP2016503009A5 (enExample) | ||
| RU2015127822A (ru) | Ингибиторы энхансера гомолога 2 белка zeste | |
| JP2016517878A5 (enExample) | ||
| EA036942B1 (ru) | Применение amg232 в комбинации с цитарабином или децитабином для лечения острого миелогенного лейкоза | |
| EA032754B1 (ru) | Аминогетероарил бензамиды в качестве ингибиторов киназы | |
| RU2008126391A (ru) | Производные 1,5-замещенного индол-2-иламида | |
| JP2020079307A5 (enExample) | ||
| JP2018522929A5 (enExample) | ||
| WO2023147531A1 (en) | Inhibitors of protein tyrosine phosphatase, compositions, and methods of use | |
| JP2017538772A5 (enExample) | ||
| JP2019521167A5 (enExample) | ||
| JP2012531456A5 (enExample) | ||
| HRP20241015T1 (hr) | Derivati aminopiridina i njihova uporaba kao selektivnih alk-2 inhibitora | |
| US8420810B2 (en) | Bicyclic heterocyclic compound | |
| WO2020262603A1 (ja) | Ｅｐ２アンタゴニスト |