JP2018505145A5 - - Google Patents
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- 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
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- -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
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| US20160168108A1 (en) | 2014-12-16 | 2016-06-16 | Adt Pharmaceuticals, Inc. | Method of treating or preventing ras-mediated diseases |
| US9862698B2 (en) * | 2014-12-16 | 2018-01-09 | Adt Pharmaceuticals, Inc. | Indenyl compounds, pharmaceutical compositions, and medical uses thereof |
| AU2018209164B2 (en) | 2017-01-17 | 2021-11-04 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
| WO2018170410A1 (en) * | 2017-03-17 | 2018-09-20 | University Of South Alabama | Derivatives of sulindac can protect normal cells against oxidative damage |
| US10329269B2 (en) | 2017-08-31 | 2019-06-25 | Leukogene Therapeutics Incorporated | Indene derivatives and uses thereof |
| US11186596B2 (en) | 2018-04-26 | 2021-11-30 | Adt Pharmaceuticals, Llc | Anticancer indenes, indanes, azaindenes, azaindanes, pharmaceutical compositions and uses |
| 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 |
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 | ||
| FI750366A7 (enExample) * | 1974-02-28 | 1975-08-29 | Merck & Co Inc | |
| DE3476550D1 (en) | 1983-07-21 | 1989-03-09 | Troponwerke Gmbh & Co Kg | Thermoplastics containing antiphlogistics |
| 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 |
| EP0508586B1 (en) | 1991-03-08 | 1995-05-31 | Fgn, Inc. | Substituted indenyl compounds |
| US5965582A (en) | 1994-08-03 | 1999-10-12 | Asta Medica Aktiengesellschaft | N-benzylindole and benzopyrazole derivatives with anti-asthmatic, anti-allergic, anti-inflammatory and immunemodulating effect |
| 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 |
| ATE257152T1 (de) | 1997-12-12 | 2004-01-15 | Osi Pharm Inc | N-benzyl-3-indenylaceamidderivative zur behandlung von 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 |
| JP2003523958A (ja) | 1999-12-23 | 2003-08-12 | ニトロメド インコーポレーテッド | ニトロソ化およびニトロシル化されたシクロオキシゲナーゼ−２の阻害剤、組成物ならびに使用法 |
| EP1157027B1 (en) | 1999-12-28 | 2007-09-19 | Basell Polyolefine GmbH | Heterocyclic metallocene compounds and use thereof in catalyst systems for producing olefin polymers |
| AU2002211828A1 (en) | 2000-10-02 | 2002-04-15 | 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 |
| WO2004002420A2 (en) | 2002-06-28 | 2004-01-08 | Nitromed, Inc. | Oxime and/or hydrazone containing nitrosated and/or nitrosylated cyclooxigenase-2 selective inhibitors, compositions and methods of use |
| CN101031289A (zh) * | 2004-04-26 | 2007-09-05 | 范德比尔特大学 | 作为具有降低胃肠毒性的治疗剂的吲哚乙酸和茚乙酸衍生物 |
| WO2006124874A2 (en) | 2005-05-12 | 2006-11-23 | Kalypsys, Inc. | Inhibitors of b-raf kinase |
| EP2202222A3 (en) * | 2005-11-08 | 2010-09-15 | Laboratorios Del Dr. Esteve, S.A. | Indene derivatives, their preparation and use as medicaments |
| GB0525143D0 (en) | 2005-12-09 | 2006-01-18 | Novartis Ag | Organic compounds |
| JP5337491B2 (ja) * | 2006-01-04 | 2013-11-06 | サザン リサーチ インスティテュート | スリンダクの誘導体類、その使用及びその調製 |
| AU2016219617B2 (en) | 2006-07-09 | 2018-05-17 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of aspirin |
| 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 |
| 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 |
| 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 |
| AU2013231152B2 (en) | 2006-07-18 | 2016-06-09 | Techfields Biochem Co. Ltd | Positively charged water-soluble pro-drugs of ibuprofen |
| ES2616315T3 (es) | 2006-07-18 | 2017-06-12 | Techfields Biochem Co. Ltd | Profármacos de ibuprofeno solubles en agua cargados positivamente con una velocidad de penetración en la piel muy rápida |
| 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 |
| WO2008019357A2 (en) | 2006-08-07 | 2008-02-14 | 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 |
| EP2054384A4 (en) | 2006-08-15 | 2010-11-03 | Techfields Biochem Co Ltd | POSITIVELY LOADED WATER-SOLUBLE PRODRUGS OF ARYL AND HETEROARYLPROPIONIC ACIDS WITH A VERY FAST SKIN PUNCHING RATE |
| 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 |
| CN101506168B (zh) | 2006-09-03 | 2014-12-10 | 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邻氨基苯甲酸的前药 |
| EP2061749B1 (en) | 2006-09-03 | 2018-02-21 | Techfields Biochem Co. Ltd | Positively charged water-soluble prodrugs of acetaminophen and related compounds 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 |
| KR20220107078A (ko) | 2007-06-04 | 2022-08-01 | 테크필즈 인크 | 매우 높은 피부 및 막 침투율을 가지는 비스테로이드성 소염제(ｎｓａｉａ) 약물전구체 및 이들의 새로운 의약적 용도 |
| MX2012008658A (es) | 2010-01-25 | 2012-12-05 | Enanta Pharm Inc | Inhibidores del virus de la hepatitis c. |
| JP2014517813A (ja) * | 2011-04-01 | 2014-07-24 | サザン リサーチ インスティテュート | スリンダク誘導体、その使用及びその調製 |
| WO2014047592A2 (en) | 2012-09-21 | 2014-03-27 | Basil Rigas | Compounds and compositions for use in the prevention and treatment of inflammation-related disorders, pain and fever, skin disorders, cancer and precancerous conditions thereof |
| 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 |
| 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 |
| WO2016099452A1 (en) | 2014-12-16 | 2016-06-23 | Adt Pharmaceuticals, Inc. | Ras-inhibiting indenyl acetamide compounds, compositions, and uses |
| WO2017106520A1 (en) | 2015-12-16 | 2017-06-22 | Adt Pharmaceuticals, Inc. | Compounds, compositions and methods of treating cancer |
| US11186596B2 (en) | 2018-04-26 | 2021-11-30 | Adt Pharmaceuticals, Llc | Anticancer indenes, indanes, azaindenes, azaindanes, pharmaceutical compositions and uses |
-
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- 2015-12-16 EP EP15823453.4A patent/EP3233794B1/en active Active
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- 2015-12-16 KR KR1020177019639A patent/KR20170135820A/ko not_active Withdrawn
- 2015-12-16 MX MX2021012096A patent/MX2021012096A/es unknown
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- 2015-12-16 EP EP22157443.7A patent/EP4053105A1/en not_active Withdrawn
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