JP2006524686A - ミエロペルオキシダーゼ酵素(mpo)の阻害剤としての2,4−ジヒドロ−[1,2,4]トリアゾール−3−チオン誘導体の使用 - Google Patents
ミエロペルオキシダーゼ酵素(mpo)の阻害剤としての2,4−ジヒドロ−[1,2,4]トリアゾール−3−チオン誘導体の使用 Download PDFInfo
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- JP2006524686A JP2006524686A JP2006508031A JP2006508031A JP2006524686A JP 2006524686 A JP2006524686 A JP 2006524686A JP 2006508031 A JP2006508031 A JP 2006508031A JP 2006508031 A JP2006508031 A JP 2006508031A JP 2006524686 A JP2006524686 A JP 2006524686A
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- JP
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- Prior art keywords
- dihydro
- triazole
- thione
- phenyl
- chlorobenzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 102000003896 Myeloperoxidases Human genes 0.000 title abstract description 9
- 108090000235 Myeloperoxidases Proteins 0.000 title abstract description 9
- 239000003112 inhibitor Substances 0.000 title abstract description 6
- AFBBKYQYNPNMAT-UHFFFAOYSA-N 1h-1,2,4-triazol-1-ium-3-thiolate Chemical class SC=1N=CNN=1 AFBBKYQYNPNMAT-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 234
- 238000000034 method Methods 0.000 claims abstract description 49
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 18
- 201000010099 disease Diseases 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims abstract description 7
- 230000005764 inhibitory process Effects 0.000 claims abstract description 6
- 230000002265 prevention Effects 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 53
- -1 NR 8 R 9 Chemical group 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 125000003545 alkoxy group Chemical group 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 239000000203 mixture Substances 0.000 claims description 25
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000001153 fluoro group Chemical group F* 0.000 claims description 14
- 102000004190 Enzymes Human genes 0.000 claims description 13
- 108090000790 Enzymes Proteins 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 12
- ILUVIMSFVCQFEJ-UHFFFAOYSA-N 3-[(2-chloro-6-fluoro-3-methylphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=C(F)C(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1Cl ILUVIMSFVCQFEJ-UHFFFAOYSA-N 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 11
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- LHIXMHUMAYGYCI-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-[3-(hydroxymethyl)phenyl]-1h-1,2,4-triazole-5-thione Chemical compound OCC1=CC=CC(N2C(NN=C2CC=2C(=CC=CC=2)Cl)=S)=C1 LHIXMHUMAYGYCI-UHFFFAOYSA-N 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 8
- FQLPBDOZNFNHGP-UHFFFAOYSA-N 1-[3-[3-[(2-chlorophenyl)methyl]-5-sulfanylidene-1h-1,2,4-triazol-4-yl]phenyl]ethanone Chemical compound CC(=O)C1=CC=CC(N2C(NN=C2CC=2C(=CC=CC=2)Cl)=S)=C1 FQLPBDOZNFNHGP-UHFFFAOYSA-N 0.000 claims description 7
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- SSVVTNOZSRBIKE-UHFFFAOYSA-N 3-[(2,3-dichlorophenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound ClC1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1Cl SSVVTNOZSRBIKE-UHFFFAOYSA-N 0.000 claims description 7
- NOPYAEFNZPMSJU-UHFFFAOYSA-N 3-[(2,3-dimethoxyphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1OC NOPYAEFNZPMSJU-UHFFFAOYSA-N 0.000 claims description 7
- AFZQCRNXYKOEAR-UHFFFAOYSA-N 3-[(2,5-dimethoxyphenyl)methyl]-4-(3,4,5-trimethoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(OC)C(CC=2N(C(=S)NN=2)C=2C=C(OC)C(OC)=C(OC)C=2)=C1 AFZQCRNXYKOEAR-UHFFFAOYSA-N 0.000 claims description 7
- IRDZYSFFLNUIHF-UHFFFAOYSA-N 3-[(2,5-dimethoxyphenyl)methyl]-4-(3-methylsulfanylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(OC)C(CC=2N(C(=S)NN=2)C=2C=C(SC)C=CC=2)=C1 IRDZYSFFLNUIHF-UHFFFAOYSA-N 0.000 claims description 7
- QPSZUCMUTAIOAF-UHFFFAOYSA-N 3-[(2,5-dimethoxyphenyl)methyl]-4-(4-iodophenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(OC)C(CC=2N(C(=S)NN=2)C=2C=CC(I)=CC=2)=C1 QPSZUCMUTAIOAF-UHFFFAOYSA-N 0.000 claims description 7
- XKKGDLHIDGBDPF-UHFFFAOYSA-N 3-[(2,5-dimethoxyphenyl)methyl]-4-(4-piperidin-1-ylsulfonylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(OC)C(CC=2N(C(=S)NN=2)C=2C=CC(=CC=2)S(=O)(=O)N2CCCCC2)=C1 XKKGDLHIDGBDPF-UHFFFAOYSA-N 0.000 claims description 7
- PFBXTQRUUAMZBT-UHFFFAOYSA-N 3-[(2,6-dimethylphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=CC(C)=C1CC1=NNC(=S)N1C1=CC=CC=C1 PFBXTQRUUAMZBT-UHFFFAOYSA-N 0.000 claims description 7
- PFJUYXTUUIGGDO-UHFFFAOYSA-N 3-[(2-bromo-5-methylphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=C(Br)C(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 PFJUYXTUUIGGDO-UHFFFAOYSA-N 0.000 claims description 7
- DOPNNIJPDROHOB-UHFFFAOYSA-N 3-[(2-bromophenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound BrC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 DOPNNIJPDROHOB-UHFFFAOYSA-N 0.000 claims description 7
- LCVYZHJOKKFBDH-UHFFFAOYSA-N 3-[(2-butoxyphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCOC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 LCVYZHJOKKFBDH-UHFFFAOYSA-N 0.000 claims description 7
- XUXKLLUPTARGCC-UHFFFAOYSA-N 3-[(2-chloro-5-methoxyphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(Cl)C(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 XUXKLLUPTARGCC-UHFFFAOYSA-N 0.000 claims description 7
- RDUOCWCXSJWWQI-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(2-ethoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound CCOC1=CC=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl RDUOCWCXSJWWQI-UHFFFAOYSA-N 0.000 claims description 7
- ARVGOXXQWHHIEV-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(2-methoxy-5-methylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(C)C=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl ARVGOXXQWHHIEV-UHFFFAOYSA-N 0.000 claims description 7
- BZAXXDFKWPOPKQ-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(2-methoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl BZAXXDFKWPOPKQ-UHFFFAOYSA-N 0.000 claims description 7
- ARAGFPWJUWXPFP-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(2-methylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl ARAGFPWJUWXPFP-UHFFFAOYSA-N 0.000 claims description 7
- ZUXPBKANVDWKKY-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(3-methoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC(N2C(NN=C2CC=2C(=CC=CC=2)Cl)=S)=C1 ZUXPBKANVDWKKY-UHFFFAOYSA-N 0.000 claims description 7
- ILECFXMUJYCDAH-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(3-methylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=CC(N2C(NN=C2CC=2C(=CC=CC=2)Cl)=S)=C1 ILECFXMUJYCDAH-UHFFFAOYSA-N 0.000 claims description 7
- RHJSVFTUOAWVHH-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(4-fluorophenyl)-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(F)=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl RHJSVFTUOAWVHH-UHFFFAOYSA-N 0.000 claims description 7
- FGBWZHZMDZYANY-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound ClC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 FGBWZHZMDZYANY-UHFFFAOYSA-N 0.000 claims description 7
- GISGOKKFTWBOHA-UHFFFAOYSA-N 3-[(2-fluorophenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound FC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 GISGOKKFTWBOHA-UHFFFAOYSA-N 0.000 claims description 7
- RIICDYWUQHGKID-UHFFFAOYSA-N 3-[(2-methoxyphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 RIICDYWUQHGKID-UHFFFAOYSA-N 0.000 claims description 7
- HHFBHYFKFCXLPI-UHFFFAOYSA-N 3-[(2-methylphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 HHFBHYFKFCXLPI-UHFFFAOYSA-N 0.000 claims description 7
- GZODEUOARIIRIG-UHFFFAOYSA-N 3-[(3-butoxyphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCOC1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 GZODEUOARIIRIG-UHFFFAOYSA-N 0.000 claims description 7
- BWOFOFNNUSUDDC-UHFFFAOYSA-N 4-(2-chlorophenyl)-3-[(2-chlorophenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound ClC1=CC=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1Cl BWOFOFNNUSUDDC-UHFFFAOYSA-N 0.000 claims description 7
- KQRYTFGTIWXPQL-UHFFFAOYSA-N 4-(2-methoxyphenyl)-3-[(2-methylphenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1C KQRYTFGTIWXPQL-UHFFFAOYSA-N 0.000 claims description 7
- MUOPEVOOHPTDEF-UHFFFAOYSA-N 4-(3-chlorophenyl)-3-[(2-chlorophenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound ClC1=CC=CC(N2C(NN=C2CC=2C(=CC=CC=2)Cl)=S)=C1 MUOPEVOOHPTDEF-UHFFFAOYSA-N 0.000 claims description 7
- BSVQOJXDBTVQCN-UHFFFAOYSA-N 4-(4-chlorophenyl)-3-[(2-chlorophenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(Cl)=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl BSVQOJXDBTVQCN-UHFFFAOYSA-N 0.000 claims description 7
- DIYYMZBMFGPMFP-UHFFFAOYSA-N 4-[2-chloro-5-(trifluoromethyl)phenyl]-3-[(2,5-dimethoxyphenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=C(OC)C(CC=2N(C(=S)NN=2)C=2C(=CC=C(C=2)C(F)(F)F)Cl)=C1 DIYYMZBMFGPMFP-UHFFFAOYSA-N 0.000 claims description 7
- ZHJHEODCLCILNC-UHFFFAOYSA-N 4-[3-[(2-bromophenyl)methyl]-5-sulfanylidene-1h-1,2,4-triazol-4-yl]benzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Br ZHJHEODCLCILNC-UHFFFAOYSA-N 0.000 claims description 7
- KOGIVIWZHBKZEE-UHFFFAOYSA-N 4-[5-sulfanylidene-3-[(2,4,6-trimethylphenyl)methyl]-1h-1,2,4-triazol-4-yl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1CC1=NNC(=S)N1C1=CC=C(S(N)(=O)=O)C=C1 KOGIVIWZHBKZEE-UHFFFAOYSA-N 0.000 claims description 7
- JLDQLIPWNVYSKM-UHFFFAOYSA-N 4-phenyl-3-[(2,3,4-trimethoxyphenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound COC1=C(OC)C(OC)=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 JLDQLIPWNVYSKM-UHFFFAOYSA-N 0.000 claims description 7
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- AIFHYGAIPROJHU-UHFFFAOYSA-N n-methyl-3-[(4-phenyl-5-sulfanylidene-1h-1,2,4-triazol-3-yl)methyl]benzamide Chemical compound CNC(=O)C1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 AIFHYGAIPROJHU-UHFFFAOYSA-N 0.000 claims description 7
- MWGQAMNHTMXRBR-UHFFFAOYSA-N 3-[(2-butoxyphenoxy)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCOC1=CC=CC=C1OCC1=NNC(=S)N1C1=CC=CC=C1 MWGQAMNHTMXRBR-UHFFFAOYSA-N 0.000 claims description 6
- XKZKTFSXESQQNG-UHFFFAOYSA-N 3-[(2-chlorophenyl)methyl]-4-(4-methylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(C)=CC=C1N1C(=S)NN=C1CC1=CC=CC=C1Cl XKZKTFSXESQQNG-UHFFFAOYSA-N 0.000 claims description 6
- PTGCVRCZBFUXJJ-UHFFFAOYSA-N 3-[(3,5-dimethylphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC(C)=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 PTGCVRCZBFUXJJ-UHFFFAOYSA-N 0.000 claims description 6
- PGDUNEOUCOKJAL-UHFFFAOYSA-N 3-[(3-chlorophenyl)methyl]-4-(2-methoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC=C1N1C(=S)NN=C1CC1=CC=CC(Cl)=C1 PGDUNEOUCOKJAL-UHFFFAOYSA-N 0.000 claims description 6
- QVCQUURNLKSLDL-UHFFFAOYSA-N 3-[(3-chlorophenyl)methyl]-4-(2-methylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=CC=C1N1C(=S)NN=C1CC1=CC=CC(Cl)=C1 QVCQUURNLKSLDL-UHFFFAOYSA-N 0.000 claims description 6
- YHWNRQSWAVIQNU-UHFFFAOYSA-N 3-[(3-methoxyphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound COC1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 YHWNRQSWAVIQNU-UHFFFAOYSA-N 0.000 claims description 6
- XQZAUEBTIPOWJP-UHFFFAOYSA-N 3-[(3-methylphenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CC1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 XQZAUEBTIPOWJP-UHFFFAOYSA-N 0.000 claims description 6
- QYQDJHHVPACBNV-UHFFFAOYSA-N 3-[(4-chlorophenyl)methyl]-4-(4-methylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(C)=CC=C1N1C(=S)NN=C1CC1=CC=C(Cl)C=C1 QYQDJHHVPACBNV-UHFFFAOYSA-N 0.000 claims description 6
- WVVBLYUXAYHNRM-UHFFFAOYSA-N 3-[(4-chlorophenyl)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(Cl)=CC=C1CC1=NNC(=S)N1C1=CC=CC=C1 WVVBLYUXAYHNRM-UHFFFAOYSA-N 0.000 claims description 6
- MYBBWSOOXWBPHV-UHFFFAOYSA-N 3-[(4-hydroxyphenyl)methyl]-4-(2,4,6-trichlorophenyl)-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(O)=CC=C1CC1=NNC(=S)N1C1=C(Cl)C=C(Cl)C=C1Cl MYBBWSOOXWBPHV-UHFFFAOYSA-N 0.000 claims description 6
- ORYDSUNJINDVOY-UHFFFAOYSA-N 3-[(4-hydroxyphenyl)methyl]-4-(3,4,5-trimethoxyphenyl)-1h-1,2,4-triazole-5-thione Chemical compound COC1=C(OC)C(OC)=CC(N2C(NN=C2CC=2C=CC(O)=CC=2)=S)=C1 ORYDSUNJINDVOY-UHFFFAOYSA-N 0.000 claims description 6
- MRCZUSHYNCEZAK-UHFFFAOYSA-N 3-[(4-hydroxyphenyl)methyl]-4-(3-methylsulfanylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound CSC1=CC=CC(N2C(NN=C2CC=2C=CC(O)=CC=2)=S)=C1 MRCZUSHYNCEZAK-UHFFFAOYSA-N 0.000 claims description 6
- SJWXTTHJTAWUFY-UHFFFAOYSA-N 3-[(4-hydroxyphenyl)methyl]-4-(4-iodophenyl)-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(O)=CC=C1CC1=NNC(=S)N1C1=CC=C(I)C=C1 SJWXTTHJTAWUFY-UHFFFAOYSA-N 0.000 claims description 6
- UIWJPXQEUUJZFB-UHFFFAOYSA-N 3-[(4-hydroxyphenyl)methyl]-4-(4-piperidin-1-ylsulfonylphenyl)-1h-1,2,4-triazole-5-thione Chemical compound C1=CC(O)=CC=C1CC1=NNC(=S)N1C1=CC=C(S(=O)(=O)N2CCCCC2)C=C1 UIWJPXQEUUJZFB-UHFFFAOYSA-N 0.000 claims description 6
- JJCBLKIDNIUEEQ-UHFFFAOYSA-N 4-(2,6-dibromo-4-methylphenyl)-3-[(4-hydroxyphenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound BrC1=CC(C)=CC(Br)=C1N1C(=S)NN=C1CC1=CC=C(O)C=C1 JJCBLKIDNIUEEQ-UHFFFAOYSA-N 0.000 claims description 6
- PPLVOPZFVJSNHO-UHFFFAOYSA-N 4-[5-sulfanylidene-3-[(2,4,6-trimethylphenyl)methyl]-1h-1,2,4-triazol-4-yl]benzoic acid Chemical compound CC1=CC(C)=CC(C)=C1CC1=NNC(=S)N1C1=CC=C(C(O)=O)C=C1 PPLVOPZFVJSNHO-UHFFFAOYSA-N 0.000 claims description 6
- QEFJESBYPQLVCP-UHFFFAOYSA-N 4-phenyl-3-[(2-phenylphenyl)methyl]-1h-1,2,4-triazole-5-thione Chemical compound C=1C=CC=CC=1N1C(=S)NN=C1CC1=CC=CC=C1C1=CC=CC=C1 QEFJESBYPQLVCP-UHFFFAOYSA-N 0.000 claims description 6
- AYAYMNNHDDTQDQ-UHFFFAOYSA-N 4-phenyl-3-[[3-(trifluoromethyl)phenyl]methyl]-1h-1,2,4-triazole-5-thione Chemical compound FC(F)(F)C1=CC=CC(CC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 AYAYMNNHDDTQDQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 150000003583 thiosemicarbazides Chemical class 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
- BFCRXVMQMULSPW-UHFFFAOYSA-N 2-(3-benzyl-5-sulfanylidene-1h-1,2,4-triazol-4-yl)benzonitrile Chemical compound C=1C=CC=C(C#N)C=1N1C(=S)NN=C1CC1=CC=CC=C1 BFCRXVMQMULSPW-UHFFFAOYSA-N 0.000 claims description 5
- MAZCWWLDDYYJJE-UHFFFAOYSA-N 3-[(2-chlorophenyl)-hydroxymethyl]-4-cyclooctyl-1h-1,2,4-triazole-5-thione Chemical compound C=1C=CC=C(Cl)C=1C(O)C1=NNC(=S)N1C1CCCCCCC1 MAZCWWLDDYYJJE-UHFFFAOYSA-N 0.000 claims description 5
- DOKKSJAWUZPXJW-UHFFFAOYSA-N 3-[(3-butoxyphenoxy)methyl]-4-phenyl-1h-1,2,4-triazole-5-thione Chemical compound CCCCOC1=CC=CC(OCC=2N(C(=S)NN=2)C=2C=CC=CC=2)=C1 DOKKSJAWUZPXJW-UHFFFAOYSA-N 0.000 claims description 5
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
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- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
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- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
- C07D409/06—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 carbon chain containing only aliphatic carbon atoms
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- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| SE0301232A SE0301232D0 (sv) | 2003-04-25 | 2003-04-25 | Novel use |
| PCT/SE2004/000618 WO2004096781A1 (en) | 2003-04-25 | 2004-04-22 | Use of derivatives of 2, 4-dihydro-[1,2,4]triazole-3-thione as inhibitors o fteh enzyme myeloperoxidase (mpo) |
Publications (2)
| Publication Number | Publication Date |
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| JP2006524686A true JP2006524686A (ja) | 2006-11-02 |
| JP2006524686A5 JP2006524686A5 (enExample) | 2007-06-14 |
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| EP (1) | EP1620410A1 (enExample) |
| JP (1) | JP2006524686A (enExample) |
| KR (1) | KR20060006064A (enExample) |
| CN (1) | CN1780822A (enExample) |
| AU (1) | AU2004234320A1 (enExample) |
| BR (1) | BRPI0409498A (enExample) |
| CA (1) | CA2523020A1 (enExample) |
| MX (1) | MXPA05011207A (enExample) |
| NO (1) | NO20055565L (enExample) |
| SE (1) | SE0301232D0 (enExample) |
| WO (1) | WO2004096781A1 (enExample) |
| ZA (1) | ZA200508623B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008517907A (ja) * | 2004-10-25 | 2008-05-29 | アストラゼネカ・アクチエボラーグ | 新規な使用 |
| JP2012506386A (ja) * | 2008-10-21 | 2012-03-15 | メタボレックス, インコーポレイテッド | アリールgpr120受容体アゴニストおよびその使用 |
| JP2014533261A (ja) * | 2011-11-11 | 2014-12-11 | ファイザー・インク | 2−チオピリミジノン |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR039385A1 (es) * | 2002-04-19 | 2005-02-16 | Astrazeneca Ab | Derivados de tioxantina como inhibidores de la mieloperoxidasa |
| SE0302756D0 (sv) * | 2003-10-17 | 2003-10-17 | Astrazeneca Ab | Novel Compounds |
| KR20140006070A (ko) | 2004-11-18 | 2014-01-15 | 신타 파마슈티칼스 코프. | Hsp90 활성을 조절하는 트리아졸 화합물 |
| MY140748A (en) | 2004-12-06 | 2010-01-15 | Astrazeneca Ab | Novel pyrrolo [3,2-d] pyrimidin-4-one derivatives and their use in therapy |
| TW200804383A (en) | 2006-06-05 | 2008-01-16 | Astrazeneca Ab | New compounds |
| PE20110341A1 (es) | 2006-08-15 | 2011-06-21 | Novartis Ag | COMPUESTOS HETEROCICLICOS QUE MODULAN LA ACTIVIDAD DE LA ESTEROIL-CoA-DESATURASA |
| EP1921073A1 (en) | 2006-11-10 | 2008-05-14 | Laboratorios del Dr. Esteve S.A. | 1,2,4-Triazole derivatives as sigma receptor inhibitors |
| US20090053176A1 (en) * | 2007-08-23 | 2009-02-26 | Astrazeneca Ab | New Combination 937 |
| KR20100135711A (ko) | 2007-12-20 | 2010-12-27 | 엔비보 파마슈티칼즈, 인코퍼레이티드 | 사중치환된 벤젠 |
| CN101723909B (zh) * | 2008-10-29 | 2011-12-28 | 天津药物研究院 | 三唑酮类化合物、其制备方法和用途 |
| WO2011133581A1 (en) | 2010-04-19 | 2011-10-27 | General Atomics | Methods and compositions for assaying enzymatic activity of myeloperoxidase in blood samples |
| EP2560640A1 (en) | 2010-04-19 | 2013-02-27 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of a hsp90 inhibitory compounds and a egfr inhibitor |
| WO2013067162A1 (en) | 2011-11-02 | 2013-05-10 | Synta Pharmaceuticals Corp. | Cancer therapy using a combination of hsp90 inhibitors with topoisomerase i inhibitors |
| JP2014534228A (ja) | 2011-11-02 | 2014-12-18 | シンタ ファーマシューティカルズ コーポレーション | 白金含有剤とhsp90阻害剤の組合せ療法 |
| CA2854188A1 (en) | 2011-11-14 | 2013-05-23 | Synta Pharmaceuticals Corp. | Combination therapy of hsp90 inhibitors with braf inhibitors |
| FR2988000A1 (fr) * | 2012-03-16 | 2013-09-20 | Thomas Wandji | Composition pharmaceutique active dans la therapie des affections virales humaines et animales |
| CN111372579B (zh) * | 2017-10-30 | 2023-08-22 | 神经孔疗法股份有限公司 | 取代的苯基磺酰基苯基三唑硫酮和其用途 |
| KR20200083843A (ko) | 2018-12-31 | 2020-07-09 | 공주대학교 산학협력단 | 4-(2-플루오로페닐)-3-(3-메톡시벤질)-1h-1,2,4-트리아졸-5(4h)-온 및 이의 퇴행성 뇌질환 및 대사성 질환 치료제로서의 용도 |
| CN110313401A (zh) * | 2019-07-12 | 2019-10-11 | 华南农业大学 | 一种促进企剑白墨墨兰组织培养过程中芽分化的方法 |
| WO2021226161A1 (en) * | 2020-05-06 | 2021-11-11 | Biohaven Therapeutics Ltd. | Process for the preparation of verdiperstat |
| PL444904A1 (pl) * | 2023-05-15 | 2024-11-18 | Uniwersytet Medyczny Im. Piastów Śląskich We Wrocławiu | Nowe pochodne 4,6-dimetylo-2-sulfanylopirydyny sprzężone z pierścieniem 1,2,4-triazolu, sposób syntezy pochodnych oraz zastosowanie pochodnych |
| US11926602B1 (en) * | 2023-08-23 | 2024-03-12 | King Faisal University | 4-amino-5-(4-fluoro-3-phenoxyphenyl)-4H-1,2,4-triazole-3-thiol derivatives as antifungal agents |
Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02270865A (ja) * | 1988-11-29 | 1990-11-05 | Warner Lambert Co | 3,5‐ジ‐t‐ブチル‐4‐ヒドロキシフエニル‐1,3,4‐チアジアゾール及びオキサジアゾール並びに3,5‐ジ‐t‐ブチル‐4‐ヒドロキシフエニル‐1,2,4‐チアジアゾール,オキサジアゾール及びトリアゾール |
| JPH04225917A (ja) * | 1990-04-19 | 1992-08-14 | Merrell Dow Pharmaceut Inc | 記憶増強剤として有用な5−アリ−ル−4−アルキル−3h−1,2,4−トリアゾール−3−チオン類 |
| US5489598A (en) * | 1994-06-08 | 1996-02-06 | Warner-Lambert Company | Cytoprotection utilizing aryltriazol-3-thiones |
| US5498720A (en) * | 1993-08-26 | 1996-03-12 | Lee; An-Rong | Certain triazole compounds and their pharmaceutical uses |
| JPH10147568A (ja) * | 1996-11-19 | 1998-06-02 | Mitsui Chem Inc | ナフタレン誘導体およびそれを有効成分として含有する医薬品 |
| JPH10175970A (ja) * | 1996-12-19 | 1998-06-30 | Mitsui Chem Inc | ベンゾチオフェン誘導体およびそれを有効成分として含有する医薬品 |
| WO2002066447A1 (en) * | 2001-02-21 | 2002-08-29 | Ono Pharmaceutical Co., Ltd. | 4h-1,2,4-triazole-3(2h)-thione deratives as sphingomyelinase inhibitors |
| US20020168761A1 (en) * | 2000-01-24 | 2002-11-14 | Gour Barbara J. | Peptidomimetic modulators of cell adhesion |
| JP2005538060A (ja) * | 2002-06-12 | 2005-12-15 | ケモセントリックス, インコーポレイテッド | 抗炎症性組成物および使用の方法 |
| JP2006522744A (ja) * | 2003-04-11 | 2006-10-05 | ノボ ノルディスク アクティーゼルスカブ | グルココルチコイド受容体アゴニスト療法に伴う副作用を最小化するための、11β−ヒドロキシステロイドデヒドロゲナーゼ1型阻害剤およびグルココルチコイド受容体アゴニストを使用する併用療法 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2362101A (en) * | 2000-05-12 | 2001-11-14 | Astrazeneca Ab | Treatment of chronic obstructive pulmonary disease |
-
2003
- 2003-04-25 SE SE0301232A patent/SE0301232D0/xx unknown
-
2004
- 2004-04-22 AU AU2004234320A patent/AU2004234320A1/en not_active Abandoned
- 2004-04-22 MX MXPA05011207A patent/MXPA05011207A/es unknown
- 2004-04-22 CN CNA2004800111102A patent/CN1780822A/zh active Pending
- 2004-04-22 CA CA002523020A patent/CA2523020A1/en not_active Abandoned
- 2004-04-22 JP JP2006508031A patent/JP2006524686A/ja active Pending
- 2004-04-22 KR KR1020057020226A patent/KR20060006064A/ko not_active Withdrawn
- 2004-04-22 EP EP04729000A patent/EP1620410A1/en not_active Withdrawn
- 2004-04-22 BR BRPI0409498-0A patent/BRPI0409498A/pt not_active IP Right Cessation
- 2004-04-22 US US10/554,659 patent/US20070093483A1/en not_active Abandoned
- 2004-04-22 WO PCT/SE2004/000618 patent/WO2004096781A1/en not_active Ceased
-
2005
- 2005-10-24 ZA ZA200508623A patent/ZA200508623B/en unknown
- 2005-11-24 NO NO20055565A patent/NO20055565L/no not_active Application Discontinuation
Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02270865A (ja) * | 1988-11-29 | 1990-11-05 | Warner Lambert Co | 3,5‐ジ‐t‐ブチル‐4‐ヒドロキシフエニル‐1,3,4‐チアジアゾール及びオキサジアゾール並びに3,5‐ジ‐t‐ブチル‐4‐ヒドロキシフエニル‐1,2,4‐チアジアゾール,オキサジアゾール及びトリアゾール |
| JPH04225917A (ja) * | 1990-04-19 | 1992-08-14 | Merrell Dow Pharmaceut Inc | 記憶増強剤として有用な5−アリ−ル−4−アルキル−3h−1,2,4−トリアゾール−3−チオン類 |
| US5498720A (en) * | 1993-08-26 | 1996-03-12 | Lee; An-Rong | Certain triazole compounds and their pharmaceutical uses |
| US5489598A (en) * | 1994-06-08 | 1996-02-06 | Warner-Lambert Company | Cytoprotection utilizing aryltriazol-3-thiones |
| JPH10147568A (ja) * | 1996-11-19 | 1998-06-02 | Mitsui Chem Inc | ナフタレン誘導体およびそれを有効成分として含有する医薬品 |
| JPH10175970A (ja) * | 1996-12-19 | 1998-06-30 | Mitsui Chem Inc | ベンゾチオフェン誘導体およびそれを有効成分として含有する医薬品 |
| US20020168761A1 (en) * | 2000-01-24 | 2002-11-14 | Gour Barbara J. | Peptidomimetic modulators of cell adhesion |
| WO2002066447A1 (en) * | 2001-02-21 | 2002-08-29 | Ono Pharmaceutical Co., Ltd. | 4h-1,2,4-triazole-3(2h)-thione deratives as sphingomyelinase inhibitors |
| JP2005538060A (ja) * | 2002-06-12 | 2005-12-15 | ケモセントリックス, インコーポレイテッド | 抗炎症性組成物および使用の方法 |
| JP2006522744A (ja) * | 2003-04-11 | 2006-10-05 | ノボ ノルディスク アクティーゼルスカブ | グルココルチコイド受容体アゴニスト療法に伴う副作用を最小化するための、11β−ヒドロキシステロイドデヒドロゲナーゼ1型阻害剤およびグルココルチコイド受容体アゴニストを使用する併用療法 |
Non-Patent Citations (1)
| Title |
|---|
| JPN6010051139, PALASKA,E. et al, "Synthesis and anti−inflammatory activity of 1−acylthiosemicarbazides, 1,3,4−oxadiazoles, 1,3,4−thiad", Farmaco, 2002, Vol.57, No.2, p.101−107 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008517907A (ja) * | 2004-10-25 | 2008-05-29 | アストラゼネカ・アクチエボラーグ | 新規な使用 |
| JP2012506386A (ja) * | 2008-10-21 | 2012-03-15 | メタボレックス, インコーポレイテッド | アリールgpr120受容体アゴニストおよびその使用 |
| JP2014533261A (ja) * | 2011-11-11 | 2014-12-11 | ファイザー・インク | 2−チオピリミジノン |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05011207A (es) | 2005-12-14 |
| US20070093483A1 (en) | 2007-04-26 |
| BRPI0409498A (pt) | 2006-05-02 |
| CA2523020A1 (en) | 2004-11-11 |
| AU2004234320A1 (en) | 2004-11-11 |
| CN1780822A (zh) | 2006-05-31 |
| WO2004096781A1 (en) | 2004-11-11 |
| KR20060006064A (ko) | 2006-01-18 |
| NO20055565D0 (no) | 2005-11-24 |
| ZA200508623B (en) | 2007-07-25 |
| SE0301232D0 (sv) | 2003-04-25 |
| NO20055565L (no) | 2006-01-25 |
| EP1620410A1 (en) | 2006-02-01 |
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