ZA200502664B - Chirale oxazole-arylpropionic acid derivatives andtheir use as PPAR agonists. - Google Patents

Info

Publication number

ZA200502664B

ZA200502664B ZA200502664A ZA200502664A ZA200502664B ZA 200502664 B ZA200502664 B ZA 200502664B ZA 200502664 A ZA200502664 A ZA 200502664A ZA 200502664 A ZA200502664 A ZA 200502664A ZA 200502664 B ZA200502664 B ZA 200502664B

Authority

ZA

South Africa

Prior art keywords

phenyl

methyl

ethoxy

propionic acid

oxazol

Prior art date

2002-10-07

Links

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• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 title claims description 18
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 title claims description 18
• 239000000556 agonist Substances 0.000 title claims description 12
• 239000002253 acid Substances 0.000 title description 48
• 238000000034 method Methods 0.000 claims description 212
• 150000001875 compounds Chemical class 0.000 claims description 175
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 140
• 238000011282 treatment Methods 0.000 claims description 50
• 239000001257 hydrogen Substances 0.000 claims description 48
• 229910052739 hydrogen Inorganic materials 0.000 claims description 48
• -1 4-isopropoxy-phenyl Chemical group 0.000 claims description 46
• 150000002148 esters Chemical class 0.000 claims description 45
• 239000000203 mixture Substances 0.000 claims description 44
• 150000003839 salts Chemical class 0.000 claims description 41
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 25
• 235000019260 propionic acid Nutrition 0.000 claims description 25
• 201000010099 disease Diseases 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 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 description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 15
• 150000002367 halogens Chemical class 0.000 claims description 15
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• 239000000126 substance Substances 0.000 claims description 15
• 206010012601 diabetes mellitus Diseases 0.000 claims description 13
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• 238000002360 preparation method Methods 0.000 claims description 11
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• 230000006806 disease prevention Effects 0.000 claims description 9
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
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• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
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• 239000011737 fluorine Chemical group 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
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• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 5
• 230000002062 proliferating effect Effects 0.000 claims description 5
• 125000001424 substituent group Chemical group 0.000 claims description 5
• ZKPUTZIBAWOQDX-VWLOTQADSA-N (2s)-3-[2,6-dimethyl-4-[[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]methoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=C(C)C(C[C@H](OCC)C(O)=O)=C(C)C=C1OCC1=C(C)OC(C=2C=CC(=CC=2)C(C)C)=N1 ZKPUTZIBAWOQDX-VWLOTQADSA-N 0.000 claims description 4
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
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• 101150014691 PPARA gene Proteins 0.000 claims description 4
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• 239000013543 active substance Substances 0.000 claims description 4
• 125000004104 aryloxy group Chemical group 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• VRKSVSMXWDYEDJ-NRFANRHFSA-N (2s)-2-ethoxy-3-[2-methyl-4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]propanoic acid Chemical compound C1=C(C)C(C[C@H](OCC)C(O)=O)=CC=C1OCC1=C(C)OC(C=2C=CC=CC=2)=N1 VRKSVSMXWDYEDJ-NRFANRHFSA-N 0.000 claims description 3
• APZWKRKCKQRLAW-VWLOTQADSA-N (2s)-3-[4-[[2-(4-tert-butylphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-ethoxyphenyl]-2-ethoxypropanoic acid Chemical compound C1=C(OCC)C(C[C@H](OCC)C(O)=O)=CC=C1OCC1=C(C)OC(C=2C=CC(=CC=2)C(C)(C)C)=N1 APZWKRKCKQRLAW-VWLOTQADSA-N 0.000 claims description 3
• 241001465754 Metazoa Species 0.000 claims description 3
• 230000001419 dependent effect Effects 0.000 claims description 3
• LRPJSHRTQQCJNQ-DEOSSOPVSA-N (2s)-2-ethoxy-3-[2-methoxy-4-[[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(OC)C(C[C@H](OCC)C(O)=O)=CC=C1OCC1=C(C)OC(C=2C=CC(=CC=2)C(C)C)=N1 LRPJSHRTQQCJNQ-DEOSSOPVSA-N 0.000 claims description 2
• RDFAZCQKJPQUQU-SANMLTNESA-N (2s)-3-[4-[[2-(4-tert-butylphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-propan-2-yloxyphenyl]-2-ethoxypropanoic acid Chemical compound C1=C(OC(C)C)C(C[C@H](OCC)C(O)=O)=CC=C1OCC1=C(C)OC(C=2C=CC(=CC=2)C(C)(C)C)=N1 RDFAZCQKJPQUQU-SANMLTNESA-N 0.000 claims description 2
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
• 239000002671 adjuvant Substances 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• DTWMPESKZJOAMA-NRFANRHFSA-N (2s)-2-ethoxy-3-[4-[[2-(3-methoxyphenyl)-1,3-oxazol-4-yl]methoxy]-2-methylphenyl]propanoic acid Chemical compound C1=C(C)C(C[C@H](OCC)C(O)=O)=CC=C1OCC1=COC(C=2C=C(OC)C=CC=2)=N1 DTWMPESKZJOAMA-NRFANRHFSA-N 0.000 claims 1
• 125000004861 4-isopropyl phenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
• 239000002361 compost Substances 0.000 claims 1
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• 238000002560 therapeutic procedure Methods 0.000 claims 1
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