ZA200409693B - Ortho-substituted benzoic acid derivatives for thetreatment of insulin resistance. - Google Patents

Info

Publication number

ZA200409693B

ZA200409693B ZA200409693A ZA200409693A ZA200409693B ZA 200409693 B ZA200409693 B ZA 200409693B ZA 200409693 A ZA200409693 A ZA 200409693A ZA 200409693 A ZA200409693 A ZA 200409693A ZA 200409693 B ZA200409693 B ZA 200409693B

Authority

ZA

South Africa

Prior art keywords

ethyl

oxoethoxy

phenyl

amino

benzoic acid

Prior art date

2002-06-20

Links

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• 208000001072 type 2 diabetes mellitus Diseases 0.000 title claims description 23
• 206010022489 Insulin Resistance Diseases 0.000 title claims description 13
• 150000001558 benzoic acid derivatives Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims description 122
• 239000000203 mixture Substances 0.000 claims description 75
• 150000003839 salts Chemical class 0.000 claims description 68
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 40
• 239000000651 prodrug Substances 0.000 claims description 39
• 229940002612 prodrug Drugs 0.000 claims description 39
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
• 238000000034 method Methods 0.000 claims description 31
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
• 238000011282 treatment Methods 0.000 claims description 27
• 239000003814 drug Substances 0.000 claims description 20
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 19
• 239000005711 Benzoic acid Substances 0.000 claims description 17
• 239000002253 acid Substances 0.000 claims description 17
• 235000010233 benzoic acid Nutrition 0.000 claims description 17
• 239000000126 substance Substances 0.000 claims description 17
• 208000032928 Dyslipidaemia Diseases 0.000 claims description 11
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 11
• 125000006239 protecting group Chemical group 0.000 claims description 10
• 229940124597 therapeutic agent Drugs 0.000 claims description 10
• 201000001320 Atherosclerosis Diseases 0.000 claims description 8
• 208000008589 Obesity Diseases 0.000 claims description 8
• 206010012601 diabetes mellitus Diseases 0.000 claims description 8
• 239000003085 diluting agent Substances 0.000 claims description 8
• 235000020824 obesity Nutrition 0.000 claims description 8
• 238000011161 development Methods 0.000 claims description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 208000035475 disorder Diseases 0.000 claims description 6
• 125000001153 fluoro group Chemical group F* 0.000 claims description 6
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 5
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• 101000952964 Homo sapiens Coatomer subunit gamma-1 Proteins 0.000 claims description 5
• 208000031226 Hyperlipidaemia Diseases 0.000 claims description 5
• 206010020772 Hypertension Diseases 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
• 241000124008 Mammalia Species 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 125000006507 2,4-difluorobenzyl group Chemical group [H]C1=C(F)C([H])=C(F)C(=C1[H])C([H])([H])* 0.000 claims description 3
• PKBOLXLPVJTPMT-UHFFFAOYSA-N 2-[2-[4-[2-[(2-chlorophenyl)methyl-ethylamino]-2-oxoethoxy]phenyl]ethylsulfanyl]benzoic acid Chemical compound C=1C=C(CCSC=2C(=CC=CC=2)C(O)=O)C=CC=1OCC(=O)N(CC)CC1=CC=CC=C1Cl PKBOLXLPVJTPMT-UHFFFAOYSA-N 0.000 claims description 3
• XYDRDIKFEDZLIB-UHFFFAOYSA-N 2-[2-[4-[2-[benzyl(ethyl)amino]-2-oxoethoxy]phenyl]ethoxy]benzoic acid Chemical compound C=1C=C(CCOC=2C(=CC=CC=2)C(O)=O)C=CC=1OCC(=O)N(CC)CC1=CC=CC=C1 XYDRDIKFEDZLIB-UHFFFAOYSA-N 0.000 claims description 3
• MJHCCTXMZXJEMD-UHFFFAOYSA-N 2-[2-[4-[2-[ethyl-[(4-fluorophenyl)methyl]amino]-2-oxoethoxy]phenyl]ethoxy]benzoic acid Chemical compound C=1C=C(CCOC=2C(=CC=CC=2)C(O)=O)C=CC=1OCC(=O)N(CC)CC1=CC=C(F)C=C1 MJHCCTXMZXJEMD-UHFFFAOYSA-N 0.000 claims description 3
• 230000008569 process Effects 0.000 claims description 3
• JETDSOLOBQIIBF-UHFFFAOYSA-N 2-[2-[4-[2-[ethyl-[(2-fluorophenyl)methyl]amino]-2-oxoethoxy]phenyl]ethylsulfanyl]benzoic acid Chemical compound C=1C=C(CCSC=2C(=CC=CC=2)C(O)=O)C=CC=1OCC(=O)N(CC)CC1=CC=CC=C1F JETDSOLOBQIIBF-UHFFFAOYSA-N 0.000 claims description 2
• 125000003352 4-tert-butyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
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• 125000001424 substituent group Chemical group 0.000 claims description 2
• 229910052717 sulfur Inorganic materials 0.000 claims description 2
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
• 125000001318 4-trifluoromethylbenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(F)(F)F 0.000 claims 2
• 230000002265 prevention Effects 0.000 claims 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
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• 239000000047 product Substances 0.000 description 40
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• 239000012074 organic phase Substances 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
• -1 n- pentyl Chemical group 0.000 description 32
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 29
• 239000000872 buffer Substances 0.000 description 22
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
• 239000012071 phase Substances 0.000 description 22
• 235000019341 magnesium sulphate Nutrition 0.000 description 21
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 21
• 239000000243 solution Substances 0.000 description 20
• 239000012267 brine Substances 0.000 description 19
• 238000006243 chemical reaction Methods 0.000 description 19
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• 210000004027 cell Anatomy 0.000 description 17
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• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
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• 241000282414 Homo sapiens Species 0.000 description 14
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 13
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• 235000019257 ammonium acetate Nutrition 0.000 description 13
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