JP2003535840A - グルコース取り込み強化剤としての置換スチルベン - Google Patents
グルコース取り込み強化剤としての置換スチルベンInfo
- Publication number
- JP2003535840A JP2003535840A JP2002501812A JP2002501812A JP2003535840A JP 2003535840 A JP2003535840 A JP 2003535840A JP 2002501812 A JP2002501812 A JP 2002501812A JP 2002501812 A JP2002501812 A JP 2002501812A JP 2003535840 A JP2003535840 A JP 2003535840A
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- compound
- lower alkyl
- benzoic acid
- vinyl
- 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.)
- Withdrawn
Links
- 230000004190 glucose uptake Effects 0.000 title claims abstract description 24
- 235000021286 stilbenes Nutrition 0.000 title claims description 8
- 239000003623 enhancer Substances 0.000 title claims description 3
- 150000001629 stilbenes Chemical class 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims abstract description 91
- 102000003746 Insulin Receptor Human genes 0.000 claims abstract description 56
- 108010001127 Insulin Receptor Proteins 0.000 claims abstract description 56
- 238000000034 method Methods 0.000 claims abstract description 51
- 108090001061 Insulin Proteins 0.000 claims abstract description 46
- 102000004877 Insulin Human genes 0.000 claims abstract description 45
- 229940125396 insulin Drugs 0.000 claims abstract description 45
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 25
- 201000001421 hyperglycemia Diseases 0.000 claims abstract description 16
- 230000002708 enhancing effect Effects 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 139
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 68
- 150000003839 salts Chemical class 0.000 claims description 61
- 229910052739 hydrogen Inorganic materials 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 57
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 57
- -1 4-carboxyphenyl Chemical group 0.000 claims description 45
- 241000124008 Mammalia Species 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 34
- 239000005711 Benzoic acid Substances 0.000 claims description 32
- 235000010233 benzoic acid Nutrition 0.000 claims description 32
- 230000000694 effects Effects 0.000 claims description 30
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 29
- 229920002554 vinyl polymer Polymers 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 27
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 210000004027 cell Anatomy 0.000 claims description 26
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 24
- 108091000080 Phosphotransferase Proteins 0.000 claims description 23
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 23
- 102000020233 phosphotransferase Human genes 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 20
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 15
- 229940095102 methyl benzoate Drugs 0.000 claims description 15
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 238000003786 synthesis reaction Methods 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- 230000004936 stimulating effect Effects 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 239000003472 antidiabetic agent Substances 0.000 claims description 8
- 230000035578 autophosphorylation Effects 0.000 claims description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims description 8
- 102000005962 receptors Human genes 0.000 claims description 8
- 108020003175 receptors Proteins 0.000 claims description 8
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 7
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000008103 glucose Substances 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 238000012360 testing method Methods 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 230000001086 cytosolic effect Effects 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 230000000638 stimulation Effects 0.000 claims description 4
- 150000003440 styrenes Chemical class 0.000 claims description 4
- LXYUSXFFUYVKOV-UHFFFAOYSA-N 1,3-dioxole-4-carboxamide Chemical compound NC(=O)C1=COCO1 LXYUSXFFUYVKOV-UHFFFAOYSA-N 0.000 claims description 3
- QQCLHYVKBBPYQP-ZHACJKMWSA-N 2-[(3-methoxybenzoyl)amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(\C=C\C=3C=CC=CC=3)=CC=2)C(O)=O)=C1 QQCLHYVKBBPYQP-ZHACJKMWSA-N 0.000 claims description 3
- KGOSOKRFYHQOQB-ZHACJKMWSA-N 2-[2-[(3-methoxybenzoyl)amino]-5-[(e)-2-phenylethenyl]phenyl]acetic acid Chemical compound COC1=CC=CC(C(=O)NC=2C(=CC(\C=C\C=3C=CC=CC=3)=CC=2)CC(O)=O)=C1 KGOSOKRFYHQOQB-ZHACJKMWSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 230000003213 activating effect Effects 0.000 claims description 3
- 229940127003 anti-diabetic drug Drugs 0.000 claims description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- YNCZBYQBDIHBAI-CMDGGOBGSA-N 2-[(3,4-dimethoxybenzoyl)amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)NC(C(=C1)C(O)=O)=CC=C1\C=C\C1=CC=CC=C1 YNCZBYQBDIHBAI-CMDGGOBGSA-N 0.000 claims description 2
- KBDXWBSHBDMCBY-VOTSOKGWSA-N 2-[(3,5-dihydroxybenzoyl)amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound C=1C=C(NC(=O)C=2C=C(O)C=C(O)C=2)C(C(=O)O)=CC=1\C=C\C1=CC=CC=C1 KBDXWBSHBDMCBY-VOTSOKGWSA-N 0.000 claims description 2
- IBEULQHGZRBETB-CMDGGOBGSA-N 2-[(3,5-dimethoxybenzoyl)amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound COC1=CC(OC)=CC(C(=O)NC=2C(=CC(\C=C\C=3C=CC=CC=3)=CC=2)C(O)=O)=C1 IBEULQHGZRBETB-CMDGGOBGSA-N 0.000 claims description 2
- IEKZFARDKLYVOL-VOTSOKGWSA-N 2-[[3,5-bis(carboxymethoxy)benzoyl]amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound OC(=O)COC1=CC(OCC(O)=O)=CC(C(=O)NC=2C(=CC(\C=C\C=3C=CC=CC=3)=CC=2)C(O)=O)=C1 IEKZFARDKLYVOL-VOTSOKGWSA-N 0.000 claims description 2
- FVLYDSSWQPVKLX-VOTSOKGWSA-N 2-[[3,5-bis[(4-carboxyphenyl)methoxy]benzoyl]amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1COC1=CC(OCC=2C=CC(=CC=2)C(O)=O)=CC(C(=O)NC=2C(=CC(\C=C\C=3C=CC=CC=3)=CC=2)C(O)=O)=C1 FVLYDSSWQPVKLX-VOTSOKGWSA-N 0.000 claims description 2
- JXADQYKYYZMSRB-SOFGYWHQSA-N 2-[[4-(n-acetyl-4-carboxyanilino)benzoyl]amino]-5-[(e)-2-(2-fluorophenyl)ethenyl]benzoic acid Chemical compound C=1C=C(C(=O)NC=2C(=CC(\C=C\C=3C(=CC=CC=3)F)=CC=2)C(O)=O)C=CC=1N(C(=O)C)C1=CC=C(C(O)=O)C=C1 JXADQYKYYZMSRB-SOFGYWHQSA-N 0.000 claims description 2
- HTIUSSWIYOIONV-ONEGZZNKSA-N 2-[[4-(n-acetyl-4-carboxyanilino)benzoyl]amino]-5-[(e)-2-(4-methoxyphenyl)ethenyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1\C=C\C(C=C1C(O)=O)=CC=C1NC(=O)C1=CC=C(N(C(C)=O)C=2C=CC(=CC=2)C(O)=O)C=C1 HTIUSSWIYOIONV-ONEGZZNKSA-N 0.000 claims description 2
- ISMBURIUYLLRGO-SNAWJCMRSA-N 2-[[4-(n-acetyl-4-methoxycarbonylanilino)benzoyl]amino]-5-[(e)-2-(4-methoxyphenyl)ethenyl]benzoic acid Chemical compound C1=CC(C(=O)OC)=CC=C1N(C(C)=O)C1=CC=C(C(=O)NC=2C(=CC(\C=C\C=3C=CC(OC)=CC=3)=CC=2)C(O)=O)C=C1 ISMBURIUYLLRGO-SNAWJCMRSA-N 0.000 claims description 2
- ZRCMAFOLFIDENN-CMDGGOBGSA-N 2-[benzoyl(methyl)amino]-5-[(e)-2-(4-methoxyphenyl)ethenyl]benzoic acid Chemical compound C1=CC(OC)=CC=C1\C=C\C(C=C1C(O)=O)=CC=C1N(C)C(=O)C1=CC=CC=C1 ZRCMAFOLFIDENN-CMDGGOBGSA-N 0.000 claims description 2
- JTUFBQJZYIMYKF-CMDGGOBGSA-N 2-[n-acetyl-4-(n-acetyl-4-carboxyanilino)anilino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound C=1C=C(C(O)=O)C=CC=1N(C(=O)C)C(C=C1)=CC=C1N(C(C)=O)C(C(=C1)C(O)=O)=CC=C1\C=C\C1=CC=CC=C1 JTUFBQJZYIMYKF-CMDGGOBGSA-N 0.000 claims description 2
- SRROIEBKSKABIC-SNAWJCMRSA-N 4-[(e)-2-[4-[[4-(n-acetyl-4-methoxycarbonylanilino)benzoyl]amino]-3-methoxycarbonylphenyl]ethenyl]benzenesulfonic acid Chemical compound C1=CC(C(=O)OC)=CC=C1N(C(C)=O)C1=CC=C(C(=O)NC=2C(=CC(\C=C\C=3C=CC(=CC=3)S(O)(=O)=O)=CC=2)C(=O)OC)C=C1 SRROIEBKSKABIC-SNAWJCMRSA-N 0.000 claims description 2
- MPAPMBAFBIGDFG-MDZDMXLPSA-N 5-[(e)-2-phenylethenyl]-2-[(3,4,5-trimethoxybenzoyl)amino]benzoic acid Chemical compound COC1=C(OC)C(OC)=CC(C(=O)NC=2C(=CC(\C=C\C=3C=CC=CC=3)=CC=2)C(O)=O)=C1 MPAPMBAFBIGDFG-MDZDMXLPSA-N 0.000 claims description 2
- ZJCWTYYSCATAKU-BQYQJAHWSA-N 5-[[4-(n-acetyl-4-carboxyanilino)benzoyl]amino]-2-[(e)-2-phenylethenyl]benzoic acid Chemical compound C=1C=C(C(=O)NC=2C=C(C(\C=C\C=3C=CC=CC=3)=CC=2)C(O)=O)C=CC=1N(C(=O)C)C1=CC=C(C(O)=O)C=C1 ZJCWTYYSCATAKU-BQYQJAHWSA-N 0.000 claims description 2
- IFESUTSGCHLUCK-VAWYXSNFSA-N 5-benzamido-2-[(e)-2-phenylethenyl]benzoic acid Chemical compound C=1C=C(\C=C\C=2C=CC=CC=2)C(C(=O)O)=CC=1NC(=O)C1=CC=CC=C1 IFESUTSGCHLUCK-VAWYXSNFSA-N 0.000 claims description 2
- PJANXHGTPQOBST-VAWYXSNFSA-N Stilbene Natural products C=1C=CC=CC=1/C=C/C1=CC=CC=C1 PJANXHGTPQOBST-VAWYXSNFSA-N 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- PJANXHGTPQOBST-UHFFFAOYSA-N stilbene Chemical compound C=1C=CC=CC=1C=CC1=CC=CC=C1 PJANXHGTPQOBST-UHFFFAOYSA-N 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 238000011287 therapeutic dose Methods 0.000 claims 2
- CAEJBAWAJVWGQY-NSCUHMNNSA-N 2-[[4-(n-acetyl-4-carboxyanilino)benzoyl]amino]-5-[(e)-2-(4-fluorophenyl)ethenyl]benzoic acid Chemical compound C=1C=C(C(=O)NC=2C(=CC(\C=C\C=3C=CC(F)=CC=3)=CC=2)C(O)=O)C=CC=1N(C(=O)C)C1=CC=C(C(O)=O)C=C1 CAEJBAWAJVWGQY-NSCUHMNNSA-N 0.000 claims 1
- SFPJHSRKXINCLF-OUKQBFOZSA-N 2-[benzoyl(methyl)amino]-5-[(e)-2-phenylethenyl]benzoic acid Chemical compound C=1C=C(\C=C\C=2C=CC=CC=2)C=C(C(O)=O)C=1N(C)C(=O)C1=CC=CC=C1 SFPJHSRKXINCLF-OUKQBFOZSA-N 0.000 claims 1
- XQGIPOSMTIHPEV-ONEGZZNKSA-N 5-[(e)-2-[4-[n-acetyl-4-(n-acetyl-4-carboxyanilino)anilino]phenyl]ethenyl]-2-hydroxybenzoic acid Chemical compound C=1C=C(N(C(C)=O)C=2C=CC(=CC=2)C(O)=O)C=CC=1N(C(=O)C)C(C=C1)=CC=C1\C=C\C1=CC=C(O)C(C(O)=O)=C1 XQGIPOSMTIHPEV-ONEGZZNKSA-N 0.000 claims 1
- NDUPKKOZUXENKU-UHFFFAOYSA-N benzamido benzoate Chemical compound C=1C=CC=CC=1C(=O)NOC(=O)C1=CC=CC=C1 NDUPKKOZUXENKU-UHFFFAOYSA-N 0.000 claims 1
- 238000004166 bioassay Methods 0.000 claims 1
- 229940039227 diagnostic agent Drugs 0.000 claims 1
- 239000000032 diagnostic agent Substances 0.000 claims 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- 230000001419 dependent effect Effects 0.000 abstract description 2
- 230000035945 sensitivity Effects 0.000 abstract description 2
- 235000002639 sodium chloride Nutrition 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 125000005843 halogen group Chemical group 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 238000002360 preparation method Methods 0.000 description 24
- 239000000126 substance Substances 0.000 description 24
- 239000000243 solution Substances 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 18
- BIEFDNUEROKZRA-UHFFFAOYSA-N 2-(2-phenylethenyl)aniline Chemical compound NC1=CC=CC=C1C=CC1=CC=CC=C1 BIEFDNUEROKZRA-UHFFFAOYSA-N 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 150000001263 acyl chlorides Chemical class 0.000 description 6
- 150000001768 cations Chemical class 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 230000006377 glucose transport Effects 0.000 description 5
- JDYGZQFBKJXDHD-UHFFFAOYSA-N methyl 4-[(4-phenylmethoxycarbonylphenyl)carbamoyl]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C(=O)NC1=CC=C(C(=O)OCC=2C=CC=CC=2)C=C1 JDYGZQFBKJXDHD-UHFFFAOYSA-N 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
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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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/88—Carboxylic acid amides having nitrogen atoms of carboxamide groups bound to an acyclic carbon atom and to a carbon atom of a six-membered aromatic ring wherein at least one ortho-hydrogen atom has been replaced
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/56—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/64—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/70—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/84—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups and doubly-bound oxygen atoms bound to the same carbon skeleton with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/45—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton
- C07C309/51—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing nitrogen atoms, not being part of nitro or nitroso groups, bound to the carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/57—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing carboxyl groups bound to the carbon skeleton
- C07C309/61—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing carboxyl groups bound to the carbon skeleton the carbon skeleton being further substituted by nitrogen atoms, not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Public Health (AREA)
- Endocrinology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US20859100P | 2000-06-02 | 2000-06-02 | |
| US60/208,591 | 2000-06-02 | ||
| PCT/US2001/017673 WO2001094295A1 (en) | 2000-06-02 | 2001-06-01 | Substituted stilbenes as glucose uptake enhancers |
Publications (2)
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| JP2003535840A true JP2003535840A (ja) | 2003-12-02 |
| JP2003535840A5 JP2003535840A5 (enExample) | 2008-07-10 |
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| JP2002501812A Withdrawn JP2003535840A (ja) | 2000-06-02 | 2001-06-01 | グルコース取り込み強化剤としての置換スチルベン |
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| SE0102384D0 (sv) * | 2001-07-03 | 2001-07-03 | Pharmacia Ab | New compounds |
| CN101649004B (zh) * | 2009-09-18 | 2012-08-22 | 中国海洋大学 | 具有抗ii型糖尿病活性的海洋寡糖化合物及制备方法 |
| US11681100B2 (en) | 2016-09-30 | 2023-06-20 | 3Sae Technologies, Inc. | Multi-axis positioner |
| WO2018064462A1 (en) | 2016-09-30 | 2018-04-05 | 3Sae Technologies, Inc | Multi-axis relative positioning stage |
| EP3878837A1 (en) * | 2020-03-11 | 2021-09-15 | OM Pharma SA | 2,5- or 2,6-disubstituted hydroquinone derivatives with at least one carboxy, sulfo or amido group useful as medicaments |
| CN114805102A (zh) * | 2022-05-27 | 2022-07-29 | 上海陶术生物科技有限公司 | 双酰胺衍生物中间体及双酰胺衍生物的制备方法 |
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| US5681832A (en) * | 1995-02-17 | 1997-10-28 | The United States Of America As Represented By The Department Of Health And Human Services | Aroylaniline compounds, pharmaceutical compositions, and methods of using same to inhibit viral activity |
| JPH09268169A (ja) | 1996-04-01 | 1997-10-14 | Otsuka Chem Co Ltd | サリチル酸アニリド誘導体、それを有効成分として含む植物病害防除剤 |
| US5830918A (en) * | 1997-01-15 | 1998-11-03 | Terrapin Technologies, Inc. | Nonpeptide insulin receptor agonists |
| FR2759368B1 (fr) | 1997-02-10 | 2001-06-01 | Galderma Rech Dermatologique | Composes biaromatiques, compositions les contenant et utilisations |
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2001
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- 2001-06-01 DE DE60106606T patent/DE60106606T2/de not_active Expired - Fee Related
- 2001-06-01 JP JP2002501812A patent/JP2003535840A/ja not_active Withdrawn
- 2001-06-01 AU AU2001275081A patent/AU2001275081B2/en not_active Ceased
- 2001-06-01 WO PCT/US2001/017673 patent/WO2001094295A1/en not_active Ceased
- 2001-06-01 TW TW090113322A patent/TW579373B/zh not_active IP Right Cessation
- 2001-06-01 AT AT01941753T patent/ATE280148T1/de not_active IP Right Cessation
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Also Published As
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| AU7508101A (en) | 2001-12-17 |
| DE60106606D1 (de) | 2004-11-25 |
| DK1289936T3 (da) | 2005-01-24 |
| CA2411340A1 (en) | 2001-12-13 |
| US6479548B2 (en) | 2002-11-12 |
| WO2001094295A1 (en) | 2001-12-13 |
| TW579373B (en) | 2004-03-11 |
| ES2231504T3 (es) | 2005-05-16 |
| ATE280148T1 (de) | 2004-11-15 |
| AU2001275081B2 (en) | 2005-07-21 |
| US20020032218A1 (en) | 2002-03-14 |
| AR029259A1 (es) | 2003-06-18 |
| DE60106606T2 (de) | 2006-02-16 |
| EP1289936B1 (en) | 2004-10-20 |
| EP1289936A1 (en) | 2003-03-12 |
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