JP5536757B2 - Ａｍｐにより活性化されたプロテインキナーゼ（ａｍｐｋ）アクチベーターとしてのチエノピリドン誘導体 - Google Patents
Ａｍｐにより活性化されたプロテインキナーゼ（ａｍｐｋ）アクチベーターとしてのチエノピリドン誘導体 Download PDFInfo
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- JP5536757B2 JP5536757B2 JP2011507805A JP2011507805A JP5536757B2 JP 5536757 B2 JP5536757 B2 JP 5536757B2 JP 2011507805 A JP2011507805 A JP 2011507805A JP 2011507805 A JP2011507805 A JP 2011507805A JP 5536757 B2 JP5536757 B2 JP 5536757B2
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- JP
- Japan
- Prior art keywords
- pyridin
- hydroxy
- dihydro
- thieno
- phenyl
- 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.)
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- 102100036009 5'-AMP-activated protein kinase catalytic subunit alpha-2 Human genes 0.000 title claims description 62
- 101000783681 Homo sapiens 5'-AMP-activated protein kinase catalytic subunit alpha-2 Proteins 0.000 title claims description 62
- 239000012190 activator Substances 0.000 title claims description 12
- 102000001253 Protein Kinase Human genes 0.000 title description 3
- 108060006633 protein kinase Proteins 0.000 title description 3
- -1 phenyl- Chemical group 0.000 claims description 113
- 150000001875 compounds Chemical class 0.000 claims description 111
- 150000003839 salts Chemical class 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 56
- 239000002904 solvent Substances 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 24
- 206010012601 diabetes mellitus Diseases 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 239000012453 solvate Substances 0.000 claims description 16
- 239000003814 drug Substances 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
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 201000011510 cancer Diseases 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 9
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- KQFDGZOTTHQOMD-UHFFFAOYSA-N 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=NC=CC=4)C(=O)NC=3SC=2)C=C1 KQFDGZOTTHQOMD-UHFFFAOYSA-N 0.000 claims description 6
- 208000008589 Obesity Diseases 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- HKWQMQBRXWPSSR-UHFFFAOYSA-N 2-chloro-4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2Cl)C=C1 HKWQMQBRXWPSSR-UHFFFAOYSA-N 0.000 claims description 5
- HVTRFLDXUYTKMF-UHFFFAOYSA-N 3-[4-(2-fluorophenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C(=CC=CC=3)F)C=2C(O)=C1C1=CC=CC=C1 HVTRFLDXUYTKMF-UHFFFAOYSA-N 0.000 claims description 5
- ZVZONVVWRDQGNE-UHFFFAOYSA-N 3-[4-(2-fluorophenyl)phenyl]-4-hydroxy-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C(=CC=CC=3)F)C=2C(O)=C1C1=CC=CN=C1 ZVZONVVWRDQGNE-UHFFFAOYSA-N 0.000 claims description 5
- TUNBRRYXMOAFGR-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=CC(F)=CC=3)C=2C(O)=C1C1=CC=CC=C1 TUNBRRYXMOAFGR-UHFFFAOYSA-N 0.000 claims description 5
- XBRXAVIHKNUPSS-UHFFFAOYSA-N 4-[4-(4-hydroxy-6-oxo-5-phenyl-7h-thieno[2,3-b]pyridin-3-yl)phenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 XBRXAVIHKNUPSS-UHFFFAOYSA-N 0.000 claims description 5
- HRBOTPOUTZIVDY-UHFFFAOYSA-N 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 HRBOTPOUTZIVDY-UHFFFAOYSA-N 0.000 claims description 5
- ZCZUMSNNMVMMAS-UHFFFAOYSA-N 4-hydroxy-3-[4-(2-hydroxyphenyl)phenyl]-5-pyridin-4-yl-7H-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CN=CC=4)C(=O)NC=3SC=2)C=C1 ZCZUMSNNMVMMAS-UHFFFAOYSA-N 0.000 claims description 5
- ISXUOTBGTHNDDA-UHFFFAOYSA-N 4-hydroxy-3-[4-(4-hydroxyphenyl)phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound C1=CC(O)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 ISXUOTBGTHNDDA-UHFFFAOYSA-N 0.000 claims description 5
- DTPQCCSCLMZLMM-UHFFFAOYSA-N 4-hydroxy-3-[4-(4-methylphenyl)phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound C1=CC(C)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 DTPQCCSCLMZLMM-UHFFFAOYSA-N 0.000 claims description 5
- WGOZPEQUBLQTLC-UHFFFAOYSA-N 4-hydroxy-3-[4-(4-methylphenyl)phenyl]-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound C1=CC(C)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=NC=CC=4)C(=O)NC=3SC=2)C=C1 WGOZPEQUBLQTLC-UHFFFAOYSA-N 0.000 claims description 5
- GOSMRIZUTRINQV-UHFFFAOYSA-N 4-hydroxy-3-[4-[3-(hydroxymethyl)phenyl]phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OCC1=CC=CC(C=2C=CC(=CC=2)C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)=C1 GOSMRIZUTRINQV-UHFFFAOYSA-N 0.000 claims description 5
- FSVYOZALIBZRKZ-UHFFFAOYSA-N 4-hydroxy-3-[4-[4-(hydroxymethyl)phenyl]phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound C1=CC(CO)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 FSVYOZALIBZRKZ-UHFFFAOYSA-N 0.000 claims description 5
- YHTGTTPAZVKQBC-UHFFFAOYSA-N 4-hydroxy-5-phenyl-3-(4-phenylphenyl)-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=CC=CC=3)C=2C(O)=C1C1=CC=CC=C1 YHTGTTPAZVKQBC-UHFFFAOYSA-N 0.000 claims description 5
- HZYVPJJDGTUBNS-UHFFFAOYSA-N 4-hydroxy-5-phenyl-3-(4-pyridin-3-ylphenyl)-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=NC=CC=3)C=2C(O)=C1C1=CC=CC=C1 HZYVPJJDGTUBNS-UHFFFAOYSA-N 0.000 claims description 5
- YCARLBRXUQWPTN-UHFFFAOYSA-N 4-hydroxy-5-phenyl-3-(4-pyridin-4-ylphenyl)-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=CN=CC=3)C=2C(O)=C1C1=CC=CC=C1 YCARLBRXUQWPTN-UHFFFAOYSA-N 0.000 claims description 5
- DJYMHZDZGLVPAE-UHFFFAOYSA-N 4-hydroxy-5-phenyl-3-(6-phenylpyridin-3-yl)-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=NC(=CC=3)C=3C=CC=CC=3)C=2C(O)=C1C1=CC=CC=C1 DJYMHZDZGLVPAE-UHFFFAOYSA-N 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 4
- VYXPVECHTHYTBA-UHFFFAOYSA-N 4-hydroxy-3-(2-hydroxy-4-pyridin-4-ylphenyl)-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC(C=2C=CN=CC=2)=CC=C1C(C=1C=2O)=CSC=1NC(=O)C=2C1=CC=CC=C1 VYXPVECHTHYTBA-UHFFFAOYSA-N 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 3
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims description 3
- HPTTXYJXYLWZMP-UHFFFAOYSA-N 2-chloro-4-hydroxy-3-[4-(2-methoxyphenyl)phenyl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound COC1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2Cl)C=C1 HPTTXYJXYLWZMP-UHFFFAOYSA-N 0.000 claims description 3
- JCRPTFPMOYQHRY-UHFFFAOYSA-N 4-hydroxy-3-[4-[3-(hydroxymethyl)phenyl]phenyl]-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OCC1=CC=CC(C=2C=CC(=CC=2)C=2C=3C(O)=C(C=4C=NC=CC=4)C(=O)NC=3SC=2)=C1 JCRPTFPMOYQHRY-UHFFFAOYSA-N 0.000 claims description 3
- MGJOTBAPEZWQAT-UHFFFAOYSA-N 4-hydroxy-3-[6-(2-methoxyphenyl)pyridin-3-yl]-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound COC1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=N1 MGJOTBAPEZWQAT-UHFFFAOYSA-N 0.000 claims description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 claims description 3
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- HTLCUUIJMHNWKW-UHFFFAOYSA-N 2-[4-(4-hydroxy-6-oxo-5-phenyl-7h-thieno[2,3-b]pyridin-3-yl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 HTLCUUIJMHNWKW-UHFFFAOYSA-N 0.000 claims description 2
- RUETUANXMSSUKN-UHFFFAOYSA-N 3-[3-(1,3-benzodioxol-5-yl)phenyl]-4-hydroxy-5-phenyl-7H-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=C(C=CC=3)C=3C=C4OCOC4=CC=3)C=2C(O)=C1C1=CC=CC=C1 RUETUANXMSSUKN-UHFFFAOYSA-N 0.000 claims description 2
- XRKVCIPNBVUNOM-UHFFFAOYSA-N 3-[4-(2,4-dihydroxyphenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC(O)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 XRKVCIPNBVUNOM-UHFFFAOYSA-N 0.000 claims description 2
- PSKVUXBFAOLMEV-UHFFFAOYSA-N 3-[4-(2,4-dimethoxyphenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound COC1=CC(OC)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 PSKVUXBFAOLMEV-UHFFFAOYSA-N 0.000 claims description 2
- DKTCYOOIYQCHPU-UHFFFAOYSA-N 3-[4-(3,5-dimethoxyphenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound COC1=CC(OC)=CC(C=2C=CC(=CC=2)C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)=C1 DKTCYOOIYQCHPU-UHFFFAOYSA-N 0.000 claims description 2
- MNNIVGYMKHHKLK-UHFFFAOYSA-N 3-[4-(3-fluorophenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=C(F)C=CC=3)C=2C(O)=C1C1=CC=CC=C1 MNNIVGYMKHHKLK-UHFFFAOYSA-N 0.000 claims description 2
- DPMPJJRQUVLLNX-UHFFFAOYSA-N 3-[4-(3-fluorophenyl)phenyl]-4-hydroxy-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=C(F)C=CC=3)C=2C(O)=C1C1=CC=CN=C1 DPMPJJRQUVLLNX-UHFFFAOYSA-N 0.000 claims description 2
- DYXZTQMFFQSTDS-UHFFFAOYSA-N 3-[4-(4-fluoro-2-hydroxyphenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound OC1=CC(F)=CC=C1C1=CC=C(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)C=C1 DYXZTQMFFQSTDS-UHFFFAOYSA-N 0.000 claims description 2
- APOWVDDKGUFNPB-UHFFFAOYSA-N 3-[4-(4-fluoro-2-methoxyphenyl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound COC1=CC(F)=CC=C1C1=CC=C(C=2C=3C(O)=C(C(=O)NC=3SC=2)C=2C=CC=CC=2)C=C1 APOWVDDKGUFNPB-UHFFFAOYSA-N 0.000 claims description 2
- YLVCSWFJCLXOGO-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)-3-methoxyphenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound COC1=CC(C=2C=3C(O)=C(C(=O)NC=3SC=2)C=2C=CC=CC=2)=CC=C1C1=CC=C(F)C=C1 YLVCSWFJCLXOGO-UHFFFAOYSA-N 0.000 claims description 2
- BBQKBMPOBKLSQN-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)phenyl]-4-hydroxy-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=CC(F)=CC=3)C=2C(O)=C1C1=CC=CN=C1 BBQKBMPOBKLSQN-UHFFFAOYSA-N 0.000 claims description 2
- CLIWKRAIDQNDQU-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)phenyl]-4-hydroxy-5-pyridin-4-yl-7H-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=CC(F)=CC=3)C=2C(O)=C1C1=CC=NC=C1 CLIWKRAIDQNDQU-UHFFFAOYSA-N 0.000 claims description 2
- FDLAYOULWSBJHH-UHFFFAOYSA-N 3-[4-(4-hydroxy-6-oxo-5-phenyl-7h-thieno[2,3-b]pyridin-3-yl)phenyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C=2C=CC(=CC=2)C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)=C1 FDLAYOULWSBJHH-UHFFFAOYSA-N 0.000 claims description 2
- ZEDRAAJXGARDIS-UHFFFAOYSA-N 3-[4-(4-hydroxy-6-oxo-5-phenyl-7h-thieno[2,3-b]pyridin-3-yl)phenyl]benzonitrile Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C=3C=C(C=CC=3)C#N)C=2C(O)=C1C1=CC=CC=C1 ZEDRAAJXGARDIS-UHFFFAOYSA-N 0.000 claims description 2
- HTSCUWYKAYZEFP-UHFFFAOYSA-N 3-[4-(furan-3-yl)phenyl]-4-hydroxy-5-phenyl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C3=COC=C3)C=2C(O)=C1C1=CC=CC=C1 HTSCUWYKAYZEFP-UHFFFAOYSA-N 0.000 claims description 2
- YWZXPBPGLOHPKN-UHFFFAOYSA-N 3-[4-(furan-3-yl)phenyl]-4-hydroxy-5-pyridin-3-yl-7h-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C3=COC=C3)C=2C(O)=C1C1=CC=CN=C1 YWZXPBPGLOHPKN-UHFFFAOYSA-N 0.000 claims description 2
- ZBVDTJFDNXUALS-UHFFFAOYSA-N 3-[4-(furan-3-yl)phenyl]-4-hydroxy-5-pyridin-4-yl-7H-thieno[2,3-b]pyridin-6-one Chemical compound O=C1NC=2SC=C(C=3C=CC(=CC=3)C3=COC=C3)C=2C(O)=C1C1=CC=NC=C1 ZBVDTJFDNXUALS-UHFFFAOYSA-N 0.000 claims description 2
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- HXNBUOOSTZVERZ-UHFFFAOYSA-N 4-[4-(4-hydroxy-6-oxo-5-phenyl-7h-thieno[2,3-b]pyridin-3-yl)-2-methoxyphenyl]benzoic acid Chemical compound COC1=CC(C=2C=3C(O)=C(C=4C=CC=CC=4)C(=O)NC=3SC=2)=CC=C1C1=CC=C(C(O)=O)C=C1 HXNBUOOSTZVERZ-UHFFFAOYSA-N 0.000 claims description 2
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
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- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
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- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
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- 230000011664 signaling Effects 0.000 description 1
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- 229910002027 silica gel Inorganic materials 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
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- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- GLQWRXYOTXRDNH-UHFFFAOYSA-N thiophen-2-amine Chemical compound NC1=CC=CS1 GLQWRXYOTXRDNH-UHFFFAOYSA-N 0.000 description 1
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- 230000032258 transport Effects 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
- C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
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- Emergency Medicine (AREA)
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- Communicable Diseases (AREA)
- Oncology (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Epidemiology (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| EP08290423.6 | 2008-05-05 | ||
| EP08290423 | 2008-05-05 | ||
| PCT/EP2009/002606 WO2009135580A1 (en) | 2008-05-05 | 2009-04-08 | Thienopyridone derivatives as amp-activated protein kinase (ampk) activators |
Publications (3)
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| JP2011519876A JP2011519876A (ja) | 2011-07-14 |
| JP2011519876A5 JP2011519876A5 (enExample) | 2012-06-07 |
| JP5536757B2 true JP5536757B2 (ja) | 2014-07-02 |
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| WO2011107494A1 (de) | 2010-03-03 | 2011-09-09 | Sanofi | Neue aromatische glykosidderivate, diese verbindungen enthaltende arzneimittel und deren verwendung |
| EP2552435A1 (en) | 2010-04-02 | 2013-02-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and compositions comprising ampk activator (metformin/troglitazone) for the treatment of myotonic dystrophy type 1 (dm1) |
| US8530413B2 (en) | 2010-06-21 | 2013-09-10 | Sanofi | Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments |
| TW201221505A (en) | 2010-07-05 | 2012-06-01 | Sanofi Sa | Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament |
| TW201215387A (en) | 2010-07-05 | 2012-04-16 | Sanofi Aventis | Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament |
| TW201215388A (en) | 2010-07-05 | 2012-04-16 | Sanofi Sa | (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments |
| RU2013114184A (ru) * | 2010-09-01 | 2014-10-10 | Байер Интеллектуэль Проперти Гмбх | Гербицидно-активные кетосультамы и дикетопиридины |
| CN103517896B (zh) * | 2011-03-07 | 2016-09-21 | 葛兰素史密斯克莱有限责任公司 | 喹啉酮衍生物 |
| WO2013037390A1 (en) | 2011-09-12 | 2013-03-21 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| WO2013045413A1 (en) | 2011-09-27 | 2013-04-04 | Sanofi | 6-(4-hydroxy-phenyl)-3-alkyl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| US8889730B2 (en) | 2012-04-10 | 2014-11-18 | Pfizer Inc. | Indole and indazole compounds that activate AMPK |
| EP2679591A1 (en) | 2012-06-29 | 2014-01-01 | Poxel | Thienopyridone derivatives useful as activators of AMPK |
| CA2905242C (en) | 2013-03-15 | 2016-11-29 | Pfizer Inc. | Indole compounds that activate ampk |
| EP3089748A4 (en) | 2014-01-02 | 2017-09-27 | Massachusetts Eye & Ear Infirmary | Treating ocular neovascularization |
| WO2015114663A1 (en) | 2014-01-30 | 2015-08-06 | Council Of Scientific & Industrial Research | Novel thieno [2,3-d]pyrimidin-4(3h)-one compounds with antimycobacterial properties |
| WO2016205534A1 (en) * | 2015-06-16 | 2016-12-22 | Lazo John S | Inhibitors of ptp4a3 for the treatment of cancer |
| SG10202105964RA (en) * | 2015-06-25 | 2021-07-29 | Univ Health Network | Hpk1 inhibitors and methods of using same |
| CN108463218A (zh) | 2015-09-30 | 2018-08-28 | 药物分子研究所 | 减弱寄生虫毒性的方法 |
| US11584755B2 (en) | 2017-09-26 | 2023-02-21 | Ideaya Biosciences, Inc. | Dihydrothieno[3,2-b]pyridine compounds |
| WO2019106087A1 (en) * | 2017-11-29 | 2019-06-06 | Syddansk Universitet | Ampk inhibitors |
| BR112022023359A2 (pt) | 2020-05-19 | 2023-04-18 | Kallyope Inc | Ativadores de ampk |
| JP2023531726A (ja) | 2020-06-26 | 2023-07-25 | キャリーオペ，インク． | Ａｍｐｋアクチベーター |
| WO2022072397A1 (en) | 2020-09-30 | 2022-04-07 | Bioverativ Therapeutics Inc. | Ampk activators and methods of use thereof |
| WO2022106892A1 (en) | 2020-11-17 | 2022-05-27 | Instituto De Medicina Molecular | Anti-malarial compounds |
| WO2023092094A2 (en) | 2021-11-19 | 2023-05-25 | The Broad Institute, Inc. | Bifunctional chimeric molecules for labeling of kinases with target binding moieties and methods of use thereof |
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| GB8627698D0 (en) * | 1986-11-20 | 1986-12-17 | Boots Co Plc | Therapeutic agents |
| DE4444815A1 (de) * | 1994-12-15 | 1996-06-20 | Merck Patent Gmbh | Thienopyridone |
| AR040123A1 (es) * | 2002-05-31 | 2005-03-16 | Upjohn Co | Compuestos tiofeno, antihelminticos e insecticidas |
| US7119205B2 (en) * | 2003-05-16 | 2006-10-10 | Abbott Laboratories | Thienopyridones as AMPK activators for the treatment of diabetes and obesity |
| WO2006093518A2 (en) * | 2004-06-25 | 2006-09-08 | Apath, Llc | Thienyl compounds for treating virus-related conditions |
| US7563813B2 (en) * | 2005-05-13 | 2009-07-21 | Wyeth | Iminothiazolidinone derivatives as SFRP-1 antagonists |
| EP1754483A1 (en) | 2005-08-18 | 2007-02-21 | Merck Sante | Use of thienopyridone derivatives as AMPK activators and pharmaceutical compositions containing them |
| US20090149495A1 (en) * | 2005-12-20 | 2009-06-11 | Katalin Nogradi | Compounds |
| AU2009235784B2 (en) * | 2008-04-11 | 2013-09-19 | Merck Patent Gmbh | Thienopyridone derivatives as AMP-activated protein kinase (AMPK) activators |
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