JP5727946B2 - Ｋｃｎｑ２／３モジュレータとしての置換された２−メルカプトキノリン−３−カルボキサミド - Google Patents
Ｋｃｎｑ２／３モジュレータとしての置換された２−メルカプトキノリン−３−カルボキサミド Download PDFInfo
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- JP5727946B2 JP5727946B2 JP2011553352A JP2011553352A JP5727946B2 JP 5727946 B2 JP5727946 B2 JP 5727946B2 JP 2011553352 A JP2011553352 A JP 2011553352A JP 2011553352 A JP2011553352 A JP 2011553352A JP 5727946 B2 JP5727946 B2 JP 5727946B2
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- JP
- Japan
- Prior art keywords
- methyl
- carboxamide
- quinoline
- ethylsulfanyl
- trifluoromethyl
- 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.)
- Expired - Fee Related
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- CKWKREFECQVBBZ-UHFFFAOYSA-N 2-sulfanylidene-1h-quinoline-3-carboxamide Chemical class C1=CC=C2N=C(S)C(C(=O)N)=CC2=C1 CKWKREFECQVBBZ-UHFFFAOYSA-N 0.000 title claims description 22
- 108010006746 KCNQ2 Potassium Channel Proteins 0.000 title description 17
- 102000005453 KCNQ2 Potassium Channel Human genes 0.000 title description 17
- 125000001424 substituent group Chemical group 0.000 claims description 121
- 229920006395 saturated elastomer Polymers 0.000 claims description 82
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 125000001072 heteroaryl group Chemical group 0.000 claims description 65
- 125000000623 heterocyclic group Chemical group 0.000 claims description 59
- -1 heptanyl Chemical group 0.000 claims description 57
- 150000001875 compounds Chemical class 0.000 claims description 42
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
- 125000004076 pyridyl group Chemical group 0.000 claims description 32
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 30
- 208000002193 Pain Diseases 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000001544 thienyl group Chemical group 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 23
- 230000036407 pain Effects 0.000 claims description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- NBCYYXBLHMLNDK-UHFFFAOYSA-N methyl 3-[3-(thiophen-2-ylmethylcarbamoyl)quinolin-2-yl]sulfanylpropanoate Chemical compound COC(=O)CCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 NBCYYXBLHMLNDK-UHFFFAOYSA-N 0.000 claims description 15
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 206010015037 epilepsy Diseases 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- 239000000203 mixture Substances 0.000 claims description 9
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
- 206010046543 Urinary incontinence Diseases 0.000 claims description 8
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 150000003857 carboxamides Chemical class 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- QHSCXJURDJMJFF-UHFFFAOYSA-N 2-ethylsulfanyl-n-[(2-methoxyphenyl)methyl]-4-methyl-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=CC=C1OC QHSCXJURDJMJFF-UHFFFAOYSA-N 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- 206010003591 Ataxia Diseases 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000016285 Movement disease Diseases 0.000 claims description 5
- 230000036506 anxiety Effects 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 125000001624 naphthyl group Chemical class 0.000 claims description 5
- QSTRXYDQLKNNRG-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(thiophen-2-ylmethyl)-6-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C=1C=CSC=1CNC(=O)C1=CC2=CC(C(F)(F)F)=CC=C2N=C1SCCS(=O)(=O)C1=CC=CC=C1 QSTRXYDQLKNNRG-UHFFFAOYSA-N 0.000 claims description 4
- RBTMWCQEJUGFEI-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2N=C(SCCS(=O)(=O)C=2C=CC=CC=2)C=1C(=O)NCC1=CC=CS1 RBTMWCQEJUGFEI-UHFFFAOYSA-N 0.000 claims description 4
- ZTLQZLGRVVKUAU-UHFFFAOYSA-N 2-ethylsulfanyl-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 ZTLQZLGRVVKUAU-UHFFFAOYSA-N 0.000 claims description 4
- BREOLMRUUXYWDE-UHFFFAOYSA-N 2-pentylsulfanyl-n-(thiophen-2-ylmethyl)-6-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCCCCSC1=NC2=CC=C(C(F)(F)F)C=C2C=C1C(=O)NCC1=CC=CS1 BREOLMRUUXYWDE-UHFFFAOYSA-N 0.000 claims description 4
- YDGBZUQDDHAFFQ-UHFFFAOYSA-N 2-pentylsulfanyl-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound CCCCCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 YDGBZUQDDHAFFQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000020925 Bipolar disease Diseases 0.000 claims description 4
- 206010012335 Dependence Diseases 0.000 claims description 4
- 208000010877 cognitive disease Diseases 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- KSJCXIFGVXTUQS-UHFFFAOYSA-N methyl 3-[3-(thiophen-2-ylmethylcarbamoyl)-6-(trifluoromethyl)quinolin-2-yl]sulfanylpropanoate Chemical compound COC(=O)CCSC1=NC2=CC=C(C(F)(F)F)C=C2C=C1C(=O)NCC1=CC=CS1 KSJCXIFGVXTUQS-UHFFFAOYSA-N 0.000 claims description 4
- NTTDUJUDUWYVHA-UHFFFAOYSA-N n-(thiophen-2-ylmethyl)-2-[2-[3-(trifluoromethyl)phenyl]sulfonylethylsulfanyl]quinoline-3-carboxamide Chemical compound FC(F)(F)C1=CC=CC(S(=O)(=O)CCSC=2C(=CC3=CC=CC=C3N=2)C(=O)NCC=2SC=CC=2)=C1 NTTDUJUDUWYVHA-UHFFFAOYSA-N 0.000 claims description 4
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 208000028698 Cognitive impairment Diseases 0.000 claims description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 229940079593 drug Drugs 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- KXZSVYHFYHTNBI-UHFFFAOYSA-N 1h-quinoline-2-thione Chemical class C1=CC=CC2=NC(S)=CC=C21 KXZSVYHFYHTNBI-UHFFFAOYSA-N 0.000 claims description 2
- KGTWXLZUIRMNID-UHFFFAOYSA-N 2-(2-phenylsulfanylethylsulfanyl)-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2N=C(SCCSC=2C=CC=CC=2)C=1C(=O)NCC1=CC=CS1 KGTWXLZUIRMNID-UHFFFAOYSA-N 0.000 claims description 2
- BRDPCVBAVSHWJG-UHFFFAOYSA-N 2-(3-cyclohexylpropylsulfanyl)-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2N=C(SCCCC2CCCCC2)C=1C(=O)NCC1=CC=CS1 BRDPCVBAVSHWJG-UHFFFAOYSA-N 0.000 claims description 2
- DCPMSEUNUUZOKE-UHFFFAOYSA-N 2-(3-phenylpropylsulfanyl)-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2N=C(SCCCC=2C=CC=CC=2)C=1C(=O)NCC1=CC=CS1 DCPMSEUNUUZOKE-UHFFFAOYSA-N 0.000 claims description 2
- FIKGWBYHTKYKJN-UHFFFAOYSA-N 2-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C1=CC=C2N=C(C(F)(F)F)C(C(=O)N)=CC2=C1 FIKGWBYHTKYKJN-UHFFFAOYSA-N 0.000 claims description 2
- DKXNTGWJGKSAJN-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)sulfanylethylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C1=CC(F)=CC=C1SCCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 DKXNTGWJGKSAJN-UHFFFAOYSA-N 0.000 claims description 2
- LGLZFNXJLHWYLR-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)sulfonylethylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C1=CC(F)=CC=C1S(=O)(=O)CCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 LGLZFNXJLHWYLR-UHFFFAOYSA-N 0.000 claims description 2
- XNTODQLICDNQKF-UHFFFAOYSA-N 2-[2-(4-methylphenyl)sulfanylethylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C1=CC(C)=CC=C1SCCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 XNTODQLICDNQKF-UHFFFAOYSA-N 0.000 claims description 2
- VZFKPENHJUZZDW-UHFFFAOYSA-N 2-[2-(4-methylphenyl)sulfonylethylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)CCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 VZFKPENHJUZZDW-UHFFFAOYSA-N 0.000 claims description 2
- KNVVYVSPKSXKSE-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(2-cyclohexylethyl)quinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2N=C(SCCS(=O)(=O)C=2C=CC=CC=2)C=1C(=O)NCCC1CCCCC1 KNVVYVSPKSXKSE-UHFFFAOYSA-N 0.000 claims description 2
- IXAZYBWMTOQTNB-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(3,3-dimethylbutyl)quinoline-3-carboxamide Chemical compound CC(C)(C)CCNC(=O)C1=CC2=CC=CC=C2N=C1SCCS(=O)(=O)C1=CC=CC=C1 IXAZYBWMTOQTNB-UHFFFAOYSA-N 0.000 claims description 2
- ICECDKYGZLCPCK-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(cyclohexylmethyl)quinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2N=C(SCCS(=O)(=O)C=2C=CC=CC=2)C=1C(=O)NCC1CCCCC1 ICECDKYGZLCPCK-UHFFFAOYSA-N 0.000 claims description 2
- WAUDLZDKCYBPFH-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(thiophen-2-ylmethyl)-5-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C=1C=CSC=1CNC(=O)C=1C=C2C(C(F)(F)F)=CC=CC2=NC=1SCCS(=O)(=O)C1=CC=CC=C1 WAUDLZDKCYBPFH-UHFFFAOYSA-N 0.000 claims description 2
- IDAUDNJJPNYANF-UHFFFAOYSA-N 2-[2-(benzenesulfonyl)ethylsulfanyl]-n-(thiophen-2-ylmethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C=1C=CC=CC=1S(=O)(=O)CCSC1=NC2=CC(C(F)(F)F)=CC=C2C=C1C(=O)NCC1=CC=CS1 IDAUDNJJPNYANF-UHFFFAOYSA-N 0.000 claims description 2
- SVTHLGYCZILPPE-UHFFFAOYSA-N 2-[3-(4-fluorophenyl)propylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C1=CC(F)=CC=C1CCCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 SVTHLGYCZILPPE-UHFFFAOYSA-N 0.000 claims description 2
- CAMGJASCBPTCFP-UHFFFAOYSA-N 2-[3-(4-methylphenyl)propylsulfanyl]-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound C1=CC(C)=CC=C1CCCSC1=NC2=CC=CC=C2C=C1C(=O)NCC1=CC=CS1 CAMGJASCBPTCFP-UHFFFAOYSA-N 0.000 claims description 2
- VRQWABCZGRMEQJ-UHFFFAOYSA-N 2-butan-2-ylsulfanyl-n-[(3-fluorophenyl)methyl]-4-methyl-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCC(C)SC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=CC(F)=C1 VRQWABCZGRMEQJ-UHFFFAOYSA-N 0.000 claims description 2
- DJHVPBBAOXXVAQ-UHFFFAOYSA-N 2-cyclohexylsulfanyl-n-[(3-fluorophenyl)methyl]-4-methyl-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C1CCCCC1SC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=CC(F)=C1 DJHVPBBAOXXVAQ-UHFFFAOYSA-N 0.000 claims description 2
- HRZPDVLZIHPYIZ-UHFFFAOYSA-N 2-cyclopentylsulfanyl-n-[(3-fluorophenyl)methyl]-4-methyl-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C1CCCC1SC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=CC(F)=C1 HRZPDVLZIHPYIZ-UHFFFAOYSA-N 0.000 claims description 2
- TWWCMRROISPVRQ-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-7-(trifluoromethyl)-n-[(2,4,5-trifluorophenyl)methyl]quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC(F)=C(F)C=C1F TWWCMRROISPVRQ-UHFFFAOYSA-N 0.000 claims description 2
- RGAFQVDDHODCOV-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-7-(trifluoromethyl)-n-[[4-(trifluoromethyl)phenyl]methyl]quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=C(C(F)(F)F)C=C1 RGAFQVDDHODCOV-UHFFFAOYSA-N 0.000 claims description 2
- FBCCCXHQDZEHAC-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(1,3-thiazol-2-ylmethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=NC=CS1 FBCCCXHQDZEHAC-UHFFFAOYSA-N 0.000 claims description 2
- XUGHLZBAJAZKQZ-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(2-phenylethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCCC1=CC=CC=C1 XUGHLZBAJAZKQZ-UHFFFAOYSA-N 0.000 claims description 2
- CSFVPXMKBCZQBY-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(3-methylbutyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound FC(F)(F)C1=CC=C2C(C)=C(C(=O)NCCC(C)C)C(SCC)=NC2=C1 CSFVPXMKBCZQBY-UHFFFAOYSA-N 0.000 claims description 2
- KZGVSMQUEAHERR-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(3-phenylpropyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCCCC1=CC=CC=C1 KZGVSMQUEAHERR-UHFFFAOYSA-N 0.000 claims description 2
- MWGVUZKBKRYEKP-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(4-methylpentyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound FC(F)(F)C1=CC=C2C(C)=C(C(=O)NCCCC(C)C)C(SCC)=NC2=C1 MWGVUZKBKRYEKP-UHFFFAOYSA-N 0.000 claims description 2
- YZELSMCHGJYNQE-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(naphthalen-2-ylmethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C1=CC=CC2=CC(CNC(=O)C3=C(C)C4=CC=C(C=C4N=C3SCC)C(F)(F)F)=CC=C21 YZELSMCHGJYNQE-UHFFFAOYSA-N 0.000 claims description 2
- JVVRXTXGGYVPAJ-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(oxan-2-ylmethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1CCCCO1 JVVRXTXGGYVPAJ-UHFFFAOYSA-N 0.000 claims description 2
- ZXWBBKUQWALZRY-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(pyridin-3-ylmethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=CN=C1 ZXWBBKUQWALZRY-UHFFFAOYSA-N 0.000 claims description 2
- WJVVKGGHLHKRFE-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(pyridin-4-ylmethyl)-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=NC=C1 WJVVKGGHLHKRFE-UHFFFAOYSA-N 0.000 claims description 2
- AYYXMMBTPXLNMB-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-(thiophen-2-ylmethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC=CC=C2C(C)=C1C(=O)NCC1=CC=CS1 AYYXMMBTPXLNMB-UHFFFAOYSA-N 0.000 claims description 2
- SFNWNEULSOKQDG-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-[(2-methylphenyl)methyl]-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=CC=C1C SFNWNEULSOKQDG-UHFFFAOYSA-N 0.000 claims description 2
- NCTJTIHXQVHHTQ-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-[(4-methylphenyl)methyl]-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=C(C)C=C1 NCTJTIHXQVHHTQ-UHFFFAOYSA-N 0.000 claims description 2
- FVLUNDJABKIFLB-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-[(4-methylthiophen-2-yl)methyl]-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC(C)=CS1 FVLUNDJABKIFLB-UHFFFAOYSA-N 0.000 claims description 2
- BPZASLDQFMWJDE-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-[(5-methylfuran-2-yl)methyl]-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=C(C)O1 BPZASLDQFMWJDE-UHFFFAOYSA-N 0.000 claims description 2
- MESBCMXZDOPINP-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-[(5-methylthiophen-2-yl)methyl]-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(C(F)(F)F)=CC=C2C(C)=C1C(=O)NCC1=CC=C(C)S1 MESBCMXZDOPINP-UHFFFAOYSA-N 0.000 claims description 2
- BQUSIWROFGNJHZ-UHFFFAOYSA-N 2-ethylsulfanyl-4-methyl-n-propyl-7-(trifluoromethyl)quinoline-3-carboxamide Chemical compound C1=C(C(F)(F)F)C=C2N=C(SCC)C(C(=O)NCCC)=C(C)C2=C1 BQUSIWROFGNJHZ-UHFFFAOYSA-N 0.000 claims description 2
- FVZVRJDBPYZXNJ-UHFFFAOYSA-N 2-ethylsulfanyl-5-fluoro-n-[(3-fluorophenyl)methyl]-4-methylquinoline-3-carboxamide Chemical compound CCSC1=NC2=CC=CC(F)=C2C(C)=C1C(=O)NCC1=CC=CC(F)=C1 FVZVRJDBPYZXNJ-UHFFFAOYSA-N 0.000 claims description 2
- INILATDIIGNRRP-UHFFFAOYSA-N 2-ethylsulfanyl-5-fluoro-n-[(4-fluorophenyl)methyl]-4-methylquinoline-3-carboxamide Chemical compound CCSC1=NC2=CC=CC(F)=C2C(C)=C1C(=O)NCC1=CC=C(F)C=C1 INILATDIIGNRRP-UHFFFAOYSA-N 0.000 claims description 2
- XAJZZLZZOGAEOE-UHFFFAOYSA-N 2-ethylsulfanyl-6,7-difluoro-n-[(3-fluorophenyl)methyl]-4-methylquinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(F)=C(F)C=C2C(C)=C1C(=O)NCC1=CC=CC(F)=C1 XAJZZLZZOGAEOE-UHFFFAOYSA-N 0.000 claims description 2
- KDYVECDQZBNVNN-UHFFFAOYSA-N 2-ethylsulfanyl-6,7-difluoro-n-[(4-fluorophenyl)methyl]-4-methylquinoline-3-carboxamide Chemical compound CCSC1=NC2=CC(F)=C(F)C=C2C(C)=C1C(=O)NCC1=CC=C(F)C=C1 KDYVECDQZBNVNN-UHFFFAOYSA-N 0.000 claims description 2
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- HNUSZIQSLZBZTO-UHFFFAOYSA-N quinoline-3-carbonyl chloride Chemical compound C1=CC=CC2=CC(C(=O)Cl)=CN=C21 HNUSZIQSLZBZTO-UHFFFAOYSA-N 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
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- 239000011780 sodium chloride Substances 0.000 description 1
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- 125000000547 substituted alkyl group Chemical group 0.000 description 1
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- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
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- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
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Classifications
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/06—Anti-spasmodics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Quinoline Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP09003597 | 2009-03-12 | ||
| EP09003597.3 | 2009-03-12 | ||
| PCT/EP2010/001509 WO2010102811A1 (de) | 2009-03-12 | 2010-03-11 | Substituierte 2-mercaptochinolin-3-carboxamide als kcnq2/3 modulatoren |
Publications (3)
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| JP2012520249A JP2012520249A (ja) | 2012-09-06 |
| JP2012520249A5 JP2012520249A5 (https=) | 2014-10-16 |
| JP5727946B2 true JP5727946B2 (ja) | 2015-06-03 |
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| EP (1) | EP2406229A1 (https=) |
| JP (1) | JP5727946B2 (https=) |
| KR (1) | KR20110132590A (https=) |
| CN (1) | CN102348692A (https=) |
| AR (1) | AR075824A1 (https=) |
| AU (1) | AU2010223513B2 (https=) |
| BR (1) | BRPI1008939A2 (https=) |
| CA (1) | CA2755004A1 (https=) |
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| IL (1) | IL214945A0 (https=) |
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| TW (1) | TWI461197B (https=) |
| WO (1) | WO2010102811A1 (https=) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3178067B2 (ja) | 1991-02-26 | 2001-06-18 | ぺんてる株式会社 | スズ−ニッケル二元合金電気めっき液組成物 |
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| TWI504395B (zh) * | 2009-03-10 | 2015-10-21 | Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier | |
| BRPI1009428A2 (pt) * | 2009-03-10 | 2016-03-01 | Gruenenthal Gmbh | 3-aminoisoxazolopiridina substituída como moduladores de kcnq2/3 |
| TWI475020B (zh) | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier | |
| TW201038565A (en) | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| SI2609086T1 (sl) | 2010-08-27 | 2015-04-30 | Gruenenthal Gmbh | Substituirani 2-okso in 2-tiokso-dihidrokinolin-3-karboksamidi kot KCNQ2/3 modulatorji |
| DK2609083T3 (da) * | 2010-08-27 | 2015-03-30 | Gruenenthal Gmbh | Substituerede 2-oxy-quinolin-3-carboxamider som KCNQ2/3 modulatorer |
| MX2013002295A (es) | 2010-09-01 | 2013-05-09 | Gruenenthal Gmbh | 1-oxo-dihidroisoquinolin-3-carboxamidas sustituidas como moduladores de kcnq2/3. |
| US9775843B2 (en) | 2012-10-11 | 2017-10-03 | Grünenthal GmbH | Treatment and/or prophylaxis of TSPO mediated diseases and/or disorders |
| US9248122B2 (en) | 2012-11-28 | 2016-02-02 | Grünenthal GmbH | Heteroquinoline-3-carboxamides as KCNQ2/3 modulators |
| AU2013351551A1 (en) | 2012-11-28 | 2015-07-16 | Grunenthal Gmbh | Heteroquinoline-3-carboxamides as KCNQ2/3 modulators |
| BR112015012418A2 (pt) * | 2012-11-28 | 2017-07-11 | Gruenenthal Gmbh | carboxamidas específicas como moduladores de kcnq2/3 |
| CN105073738B (zh) * | 2013-01-31 | 2018-01-05 | 沃泰克斯药物股份有限公司 | 作为钠通道调节剂的喹啉及喹喔啉酰胺类 |
| US9139583B2 (en) | 2013-02-01 | 2015-09-22 | Acetylon Pharmaceuticals, Inc. | Selective HDAC3 inhibitors |
| JP2016511237A (ja) | 2013-02-01 | 2016-04-14 | アセチロン ファーマシューティカルズ インコーポレイテッドＡｃｅｔｙｌｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ，Ｉｎｃ． | 選択的ｈｄａｃ３阻害剤 |
| JP6669499B2 (ja) | 2013-02-15 | 2020-03-18 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物 |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| JP2016510000A (ja) | 2013-02-20 | 2016-04-04 | カラ ファーマシューティカルズ インコーポレイテッド | 治療用化合物およびその使用 |
| NZ719185A (en) | 2013-11-01 | 2017-11-24 | Kala Pharmaceuticals Inc | Crystalline forms of therapeutic compounds and uses thereof |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
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| AU2017324713B2 (en) | 2016-09-08 | 2020-08-13 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| KR20190051010A (ko) | 2016-09-08 | 2019-05-14 | 칼라 파마슈티컬스, 인크. | 치료 화합물의 결정형 및 그의 용도 |
| EP3509423A4 (en) | 2016-09-08 | 2020-05-13 | Kala Pharmaceuticals, Inc. | CRYSTALLINE FORMS OF THERAPEUTIC COMPOUNDS AND USES THEREOF |
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| DE102018212006B3 (de) * | 2018-07-18 | 2019-10-31 | Universität Greifswald | Thioether als Modulatoren von Kv7.2/Kv7.3-Kanälen |
| JP2025529185A (ja) * | 2022-08-30 | 2025-09-04 | パンネックス セラピューティクス インコーポレイテッド | パネキシン－１調節剤及びパネキシン－１が関与する疾患の治療方法 |
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| CA2702469A1 (en) | 2007-10-19 | 2009-04-23 | Boehringer Ingelheim International Gmbh | Ccr10 antagonists |
| TWI504395B (zh) * | 2009-03-10 | 2015-10-21 | Substituted 3-amino-2-mercaptoquinoline as a KCNQ2 / 3 modifier | |
| BRPI1009428A2 (pt) * | 2009-03-10 | 2016-03-01 | Gruenenthal Gmbh | 3-aminoisoxazolopiridina substituída como moduladores de kcnq2/3 |
| TW201038565A (en) * | 2009-03-12 | 2010-11-01 | Gruenenthal Gmbh | Substituted 2-mercapto-3-aminopyridines as KCNQ2/3 modulators |
| TWI475020B (zh) * | 2009-03-12 | 2015-03-01 | The substituted nicotine amide as a KCNQ2 / 3 modifier |
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2010
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- 2010-03-10 US US12/720,864 patent/US20100234372A1/en not_active Abandoned
- 2010-03-11 CN CN2010800112967A patent/CN102348692A/zh active Pending
- 2010-03-11 CA CA2755004A patent/CA2755004A1/en not_active Abandoned
- 2010-03-11 EP EP10708726A patent/EP2406229A1/de not_active Withdrawn
- 2010-03-11 PE PE2011001567A patent/PE20120790A1/es not_active Application Discontinuation
- 2010-03-11 BR BRPI1008939A patent/BRPI1008939A2/pt not_active IP Right Cessation
- 2010-03-11 KR KR1020117023788A patent/KR20110132590A/ko not_active Withdrawn
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- 2011-09-23 EC EC2011011348A patent/ECSP11011348A/es unknown
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3178067B2 (ja) | 1991-02-26 | 2001-06-18 | ぺんてる株式会社 | スズ−ニッケル二元合金電気めっき液組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| AR075824A1 (es) | 2011-04-27 |
| ECSP11011348A (es) | 2011-10-31 |
| US20120252841A1 (en) | 2012-10-04 |
| CO6410292A2 (es) | 2012-03-30 |
| KR20110132590A (ko) | 2011-12-08 |
| TWI461197B (zh) | 2014-11-21 |
| CN102348692A (zh) | 2012-02-08 |
| AU2010223513B2 (en) | 2014-12-04 |
| MX2011009369A (es) | 2011-09-27 |
| TW201034670A (en) | 2010-10-01 |
| RU2011141188A (ru) | 2013-04-20 |
| WO2010102811A1 (de) | 2010-09-16 |
| EP2406229A1 (de) | 2012-01-18 |
| BRPI1008939A2 (pt) | 2016-03-15 |
| CA2755004A1 (en) | 2010-09-16 |
| PE20120790A1 (es) | 2012-07-08 |
| ZA201107444B (en) | 2012-06-27 |
| NZ595625A (en) | 2012-10-26 |
| CL2011002209A1 (es) | 2012-02-10 |
| US20100234372A1 (en) | 2010-09-16 |
| JP2012520249A (ja) | 2012-09-06 |
| AU2010223513A1 (en) | 2011-11-03 |
| US8399673B2 (en) | 2013-03-19 |
| IL214945A0 (en) | 2011-11-30 |
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