CA2462514A1 - Dicarboxylic acid derivatives, their preparation and therapeutical use - Google Patents
Dicarboxylic acid derivatives, their preparation and therapeutical use Download PDFInfo
- Publication number
- CA2462514A1 CA2462514A1 CA002462514A CA2462514A CA2462514A1 CA 2462514 A1 CA2462514 A1 CA 2462514A1 CA 002462514 A CA002462514 A CA 002462514A CA 2462514 A CA2462514 A CA 2462514A CA 2462514 A1 CA2462514 A1 CA 2462514A1
- Authority
- CA
- Canada
- Prior art keywords
- pent
- methyl
- phenyl
- ethoxy
- ynyl
- 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.)
- Abandoned
Links
- 238000002360 preparation method Methods 0.000 title claims description 19
- 150000001990 dicarboxylic acid derivatives Chemical class 0.000 title abstract description 4
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 319
- 239000000203 mixture Substances 0.000 claims abstract description 76
- 238000000034 method Methods 0.000 claims abstract description 64
- 238000011282 treatment Methods 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 claims abstract description 24
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 claims abstract description 24
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 151
- 150000002367 halogens Chemical class 0.000 claims description 151
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- -1 C3-6-cycloalkoxy Chemical group 0.000 claims description 68
- 125000001424 substituent group Chemical group 0.000 claims description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 44
- 125000003118 aryl group Chemical group 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 30
- 125000000732 arylene group Chemical group 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
- 229910052727 yttrium Inorganic materials 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 13
- 125000005549 heteroarylene group Chemical group 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
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 13
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 12
- 239000005977 Ethylene Substances 0.000 claims description 12
- 230000003287 optical effect Effects 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- VVGPJSVVDAOBHS-UHFFFAOYSA-N ethyl 3-[4-[5-[4-[5-[4-(2,3-diethoxy-3-oxopropyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoate Chemical compound C1=CC(CC(OCC)C(=O)OCC)=CC=C1OCC=CC#CC1=CC=C(C#CC=CCOC=2C=CC(CC(OCC)C(=O)OCC)=CC=2)C=C1 VVGPJSVVDAOBHS-UHFFFAOYSA-N 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 9
- 206010022489 Insulin Resistance Diseases 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 9
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 8
- 208000008589 Obesity Diseases 0.000 claims description 8
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 8
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 235000020824 obesity Nutrition 0.000 claims description 8
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- LMBCWHWDEHGPPP-UHFFFAOYSA-N ethyl 2-[3-[5-[4-[5-[3-(2-ethoxy-2-oxoethyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=CC(OCC=CC#CC=2C=CC(=CC=2)C#CC=CCOC=2C=C(CC(=O)OCC)C=CC=2)=C1 LMBCWHWDEHGPPP-UHFFFAOYSA-N 0.000 claims description 6
- GIQLZHBNNGSTAI-UHFFFAOYSA-N methyl 2-[4-[5-[4-[5-[4-(2-methoxy-2-oxoethoxy)-3-methylphenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]-2-methylphenoxy]acetate Chemical compound C1=C(C)C(OCC(=O)OC)=CC=C1OCC=CC#CC1=CC=C(C#CC=CCOC=2C=C(C)C(OCC(=O)OC)=CC=2)C=C1 GIQLZHBNNGSTAI-UHFFFAOYSA-N 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- WBNNGLSTECFJOB-UHFFFAOYSA-N 3-[4-[3-[4-[4-[4-[4-(2-carboxy-2-ethoxyethyl)phenoxy]but-2-en-2-yl]phenyl]phenyl]but-2-enoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=C(C)C1=CC=C(C=2C=CC(=CC=2)C(C)=CCOC=2C=CC(CC(OCC)C(O)=O)=CC=2)C=C1 WBNNGLSTECFJOB-UHFFFAOYSA-N 0.000 claims description 5
- LMKKIEZOWSKCSP-UHFFFAOYSA-N 3-[4-[5-[3-[5-[4-(2-carboxy-2-ethoxyethyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=CC#CC1=CC=CC(C#CC=CCOC=2C=CC(CC(OCC)C(O)=O)=CC=2)=C1 LMKKIEZOWSKCSP-UHFFFAOYSA-N 0.000 claims description 5
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 5
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 125000004419 alkynylene group Chemical group 0.000 claims description 5
- JUSNPTWMMHEGAV-UHFFFAOYSA-N ethyl 3-[4-[5-[3-[5-[4-(2,3-diethoxy-3-oxopropyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoate Chemical compound C1=CC(CC(OCC)C(=O)OCC)=CC=C1OCC=CC#CC1=CC=CC(C#CC=CCOC=2C=CC(CC(OCC)C(=O)OCC)=CC=2)=C1 JUSNPTWMMHEGAV-UHFFFAOYSA-N 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- LNEUYBRZSMGUTG-UHFFFAOYSA-N methyl 2-(2-benzoylanilino)-3-[4-[5-[4-[5-[4-[2-(2-benzoylanilino)-3-methoxy-3-oxopropyl]phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]propanoate Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)OC)CC(C=C1)=CC=C1OCC=CC#CC(C=C1)=CC=C1C#CC=CCOC(C=C1)=CC=C1CC(C(=O)OC)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 LNEUYBRZSMGUTG-UHFFFAOYSA-N 0.000 claims description 5
- NHHPYFYSDKUBBA-UHFFFAOYSA-N methyl 2-[4-[3-[3-[3-[4-(2-methoxy-2-oxoethyl)phenoxy]prop-1-ynyl]phenyl]prop-2-ynoxy]phenyl]acetate Chemical compound C1=CC(CC(=O)OC)=CC=C1OCC#CC1=CC=CC(C#CCOC=2C=CC(CC(=O)OC)=CC=2)=C1 NHHPYFYSDKUBBA-UHFFFAOYSA-N 0.000 claims description 5
- 201000009104 prediabetes syndrome Diseases 0.000 claims description 5
- PPRHTQAPLDSYQI-UHFFFAOYSA-N 3-[4-[5-[4-[5-[4-(2-carboxy-2-ethoxyethyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=CC#CC1=CC=C(C#CC=CCOC=2C=CC(CC(OCC)C(O)=O)=CC=2)C=C1 PPRHTQAPLDSYQI-UHFFFAOYSA-N 0.000 claims description 4
- UTPUMVWOJOGZEJ-UHFFFAOYSA-N 3-[4-[5-[7-[5-[4-(2-carboxy-2-ethoxyethyl)phenoxy]-3-methylpent-3-en-1-ynyl]-9-oxofluoren-2-yl]-3-methylpent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=C(C)C#CC1=CC=C(C=2C(=CC(=CC=2)C#CC(C)=CCOC=2C=CC(CC(OCC)C(O)=O)=CC=2)C2=O)C2=C1 UTPUMVWOJOGZEJ-UHFFFAOYSA-N 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 125000004450 alkenylene group Chemical group 0.000 claims description 4
- XIZNCWWEFYUEAA-UHFFFAOYSA-N ethyl 2-[3-chloro-4-[5-[3-[5-[2-chloro-4-(2-ethoxy-2-oxoethyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]acetate Chemical compound ClC1=CC(CC(=O)OCC)=CC=C1OCC=CC#CC1=CC=CC(C#CC=CCOC=2C(=CC(CC(=O)OCC)=CC=2)Cl)=C1 XIZNCWWEFYUEAA-UHFFFAOYSA-N 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- BHOWJSLAKFIFLM-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[5-[4-[5-[4-[2-(2-benzoylanilino)-2-carboxyethyl]phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]propanoic acid Chemical compound C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)O)CC(C=C1)=CC=C1OCC=CC#CC(C=C1)=CC=C1C#CC=CCOC(C=C1)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 BHOWJSLAKFIFLM-UHFFFAOYSA-N 0.000 claims description 3
- FZZCXQUCZGBGHX-UHFFFAOYSA-N 2-[3-[5-[4-[5-[3-(2-ethoxy-2-oxoethyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]acetic acid Chemical compound CCOC(=O)CC1=CC=CC(OCC=CC#CC=2C=CC(=CC=2)C#CC=CCOC=2C=C(CC(O)=O)C=CC=2)=C1 FZZCXQUCZGBGHX-UHFFFAOYSA-N 0.000 claims description 3
- RUUYBSUGPKIZTP-UHFFFAOYSA-N 2-[4-[5-[3-[5-[4-(carboxymethyl)-2-chlorophenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]-3-chlorophenyl]acetic acid Chemical compound ClC1=CC(CC(=O)O)=CC=C1OCC=CC#CC1=CC=CC(C#CC=CCOC=2C(=CC(CC(O)=O)=CC=2)Cl)=C1 RUUYBSUGPKIZTP-UHFFFAOYSA-N 0.000 claims description 3
- JZAWFMKYEBDTTA-UHFFFAOYSA-N 2-[4-[5-[4-[5-[4-(2-methoxy-2-oxoethoxy)-3-methylphenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]-2-methylphenoxy]acetic acid Chemical compound C1=C(C)C(OCC(=O)OC)=CC=C1OCC=CC#CC1=CC=C(C#CC=CCOC=2C=C(C)C(OCC(O)=O)=CC=2)C=C1 JZAWFMKYEBDTTA-UHFFFAOYSA-N 0.000 claims description 3
- DONNNMTWKHKHJE-UHFFFAOYSA-N 3-[4-[5-[4-[5-[4-(2,3-diethoxy-3-oxopropyl)phenoxy]-3-methylpent-3-en-1-ynyl]phenyl]-3-methylpent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=C(C)C#CC1=CC=C(C#CC(C)=CCOC=2C=CC(CC(OCC)C(=O)OCC)=CC=2)C=C1 DONNNMTWKHKHJE-UHFFFAOYSA-N 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- JCRANWNIHQRJDR-UHFFFAOYSA-N ethyl 3-[3-bromo-4-[5-[4-[5-[2-bromo-4-(2,3-diethoxy-3-oxopropyl)phenoxy]pent-3-en-1-ynyl]phenyl]pent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoate Chemical compound BrC1=CC(CC(OCC)C(=O)OCC)=CC=C1OCC=CC#CC1=CC=C(C#CC=CCOC=2C(=CC(CC(OCC)C(=O)OCC)=CC=2)Br)C=C1 JCRANWNIHQRJDR-UHFFFAOYSA-N 0.000 claims description 3
- XPMMPSAWBQQBTK-UHFFFAOYSA-N ethyl 3-[4-[5-[4-[4-[5-[4-(2,3-diethoxy-3-oxopropyl)phenoxy]-3-methylpent-3-en-1-ynyl]phenyl]phenyl]-3-methylpent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoate Chemical compound C1=CC(CC(OCC)C(=O)OCC)=CC=C1OCC=C(C)C#CC1=CC=C(C=2C=CC(=CC=2)C#CC(C)=CCOC=2C=CC(CC(OCC)C(=O)OCC)=CC=2)C=C1 XPMMPSAWBQQBTK-UHFFFAOYSA-N 0.000 claims description 3
- MJUXCMADIDYWNI-UHFFFAOYSA-N 2-[4-[3-[3-[3-[4-(2-methoxy-2-oxoethyl)phenoxy]prop-1-ynyl]phenyl]prop-2-ynoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)OC)=CC=C1OCC#CC1=CC=CC(C#CCOC=2C=CC(CC(O)=O)=CC=2)=C1 MJUXCMADIDYWNI-UHFFFAOYSA-N 0.000 claims description 2
- HKZFMPNKPKSHEJ-UHFFFAOYSA-N 2-[4-[3-[4-[4-[4-[4-(carboxymethoxy)-3-methylphenyl]sulfanylbut-2-en-2-yl]phenyl]phenyl]but-2-enylsulfanyl]-2-methylphenyl]acetic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C(C)=CCSC=2C=C(C)C(OCC(O)=O)=CC=2)C=CC=1C(C)=CCSC1=CC=C(CC(O)=O)C(C)=C1 HKZFMPNKPKSHEJ-UHFFFAOYSA-N 0.000 claims description 2
- XGIZHRCWEIVWOO-UHFFFAOYSA-N 2-[4-[3-[4-[4-[4-[4-(carboxymethyl)-2-chlorophenoxy]but-2-en-2-yl]phenyl]phenyl]but-2-enoxy]-3-chlorophenyl]acetic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C(C)=CCOC=2C(=CC(CC(O)=O)=CC=2)Cl)C=CC=1C(C)=CCOC1=CC=C(CC(O)=O)C=C1Cl XGIZHRCWEIVWOO-UHFFFAOYSA-N 0.000 claims description 2
- JLDGRPBLIDIBPF-UHFFFAOYSA-N 2-[4-[5-[3-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]phenyl]-3-methylpent-2-en-4-ynyl]sulfanyl-2-methylphenyl]acetic acid Chemical compound C=1C=CC(C#CC(C)=CCSC=2C=C(C)C(OCC(O)=O)=CC=2)=CC=1C#CC(C)=CCSC1=CC=C(CC(O)=O)C(C)=C1 JLDGRPBLIDIBPF-UHFFFAOYSA-N 0.000 claims description 2
- TUEVAUYICVNLHE-UHFFFAOYSA-N 2-[4-[5-[3-[5-[4-(carboxymethyl)-2-chlorophenoxy]-3-methylpent-3-en-1-ynyl]phenyl]-3-methylpent-2-en-4-ynoxy]-3-chlorophenyl]acetic acid Chemical compound C=1C=CC(C#CC(C)=CCOC=2C(=CC(CC(O)=O)=CC=2)Cl)=CC=1C#CC(C)=CCOC1=CC=C(CC(O)=O)C=C1Cl TUEVAUYICVNLHE-UHFFFAOYSA-N 0.000 claims description 2
- KOZLTKXZTIBFPO-UHFFFAOYSA-N 2-[4-[5-[4-[4-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]phenyl]phenyl]-3-methylpent-2-en-4-ynyl]sulfanyl-2-methylphenyl]acetic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C#CC(C)=CCSC=2C=C(C)C(OCC(O)=O)=CC=2)C=CC=1C#CC(C)=CCSC1=CC=C(CC(O)=O)C(C)=C1 KOZLTKXZTIBFPO-UHFFFAOYSA-N 0.000 claims description 2
- OWTIKXUBXJGGOL-UHFFFAOYSA-N 2-[4-[5-[4-[4-[5-[4-(carboxymethyl)-2-chlorophenoxy]-3-methylpent-3-en-1-ynyl]phenyl]phenyl]-3-methylpent-2-en-4-ynoxy]-3-chlorophenyl]acetic acid Chemical compound C=1C=C(C=2C=CC(=CC=2)C#CC(C)=CCOC=2C(=CC(CC(O)=O)=CC=2)Cl)C=CC=1C#CC(C)=CCOC1=CC=C(CC(O)=O)C=C1Cl OWTIKXUBXJGGOL-UHFFFAOYSA-N 0.000 claims description 2
- CWBJXYVTWCDXHE-UHFFFAOYSA-N 2-[4-[5-[4-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]phenyl]-3-methylpent-2-en-4-ynyl]sulfanyl-2-methylphenyl]acetic acid Chemical compound C=1C=C(C#CC(C)=CCSC=2C=C(C)C(OCC(O)=O)=CC=2)C=CC=1C#CC(C)=CCSC1=CC=C(CC(O)=O)C(C)=C1 CWBJXYVTWCDXHE-UHFFFAOYSA-N 0.000 claims description 2
- XZYXNIDTGVZNCN-UHFFFAOYSA-N 2-[4-[5-[4-[5-[4-(carboxymethyl)-2-chlorophenoxy]-3-methylpent-3-en-1-ynyl]phenyl]-3-methylpent-2-en-4-ynoxy]-3-chlorophenyl]acetic acid Chemical compound C=1C=C(C#CC(C)=CCOC=2C(=CC(CC(O)=O)=CC=2)Cl)C=CC=1C#CC(C)=CCOC1=CC=C(CC(O)=O)C=C1Cl XZYXNIDTGVZNCN-UHFFFAOYSA-N 0.000 claims description 2
- XWAVVQXAJZJKJM-UHFFFAOYSA-N 2-[4-[5-[7-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]-9-oxofluoren-2-yl]-3-methylpent-2-en-4-ynyl]sulfanyl-2-methylphenoxy]acetic acid Chemical compound C=1C=C(C2=CC=C(C=C2C2=O)C#CC(C)=CCSC=3C=C(C)C(OCC(O)=O)=CC=3)C2=CC=1C#CC(C)=CCSC1=CC=C(OCC(O)=O)C(C)=C1 XWAVVQXAJZJKJM-UHFFFAOYSA-N 0.000 claims description 2
- IWTKCDSLCHWCBP-UHFFFAOYSA-N 2-[4-[5-[7-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]-9h-carbazol-2-yl]pent-2-en-4-ynylsulfanyl]-2-methylphenoxy]acetic acid Chemical compound C=1C=C(C2=CC=C(C=C2N2)C#CC=CCSC=3C=C(C)C(OCC(O)=O)=CC=3)C2=CC=1C#CC(C)=CCSC1=CC=C(OCC(O)=O)C(C)=C1 IWTKCDSLCHWCBP-UHFFFAOYSA-N 0.000 claims description 2
- KHVFBHGMDMCCGX-UHFFFAOYSA-N 2-[4-[5-[7-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]-9h-fluoren-2-yl]-3-methylpent-2-en-4-ynyl]sulfanyl-2-methylphenoxy]acetic acid Chemical compound C=1C=C(C2=CC=C(C=C2C2)C#CC(C)=CCSC=3C=C(C)C(OCC(O)=O)=CC=3)C2=CC=1C#CC(C)=CCSC1=CC=C(OCC(O)=O)C(C)=C1 KHVFBHGMDMCCGX-UHFFFAOYSA-N 0.000 claims description 2
- XPCPRYVAXIPMDP-UHFFFAOYSA-N 2-[4-[5-[7-[5-[4-(carboxymethoxy)-3-methylphenyl]sulfanyl-3-methylpent-3-en-1-ynyl]-9h-fluoren-2-yl]pent-2-en-4-ynylsulfanyl]-2-methylphenoxy]acetic acid Chemical compound C=1C=C(C2=CC=C(C=C2C2)C#CC=CCSC=3C=C(C)C(OCC(O)=O)=CC=3)C2=CC=1C#CC(C)=CCSC1=CC=C(OCC(O)=O)C(C)=C1 XPCPRYVAXIPMDP-UHFFFAOYSA-N 0.000 claims description 2
- GTGLNACSGLRJKF-UHFFFAOYSA-N 3-[4-[3-[4-[4-[4-[4-(2-carboxy-2-ethoxyethyl)phenyl]sulfanylbut-2-en-2-yl]phenyl]phenyl]but-2-enoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=C(C)C1=CC=C(C=2C=CC(=CC=2)C(C)=CCSC=2C=CC(CC(OCC)C(O)=O)=CC=2)C=C1 GTGLNACSGLRJKF-UHFFFAOYSA-N 0.000 claims description 2
- CGQFHCSVHQXMGE-UHFFFAOYSA-N 3-[4-[3-[4-[4-[4-[4-(2-carboxy-2-ethoxyethyl)phenyl]sulfanylbut-2-en-2-yl]phenyl]phenyl]but-2-enylsulfanyl]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1SCC=C(C)C1=CC=C(C=2C=CC(=CC=2)C(C)=CCSC=2C=CC(CC(OCC)C(O)=O)=CC=2)C=C1 CGQFHCSVHQXMGE-UHFFFAOYSA-N 0.000 claims description 2
- QMJIUGQLLMFEJB-UHFFFAOYSA-N 3-[4-[3-[4-[4-[4-[4-(carboxymethoxy)-3-methylphenyl]sulfanylbut-2-en-2-yl]phenyl]phenyl]but-2-enoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=C(C)C1=CC=C(C=2C=CC(=CC=2)C(C)=CCSC=2C=C(C)C(OCC(O)=O)=CC=2)C=C1 QMJIUGQLLMFEJB-UHFFFAOYSA-N 0.000 claims description 2
- YMJDOCQKCFJSNK-UHFFFAOYSA-N 3-[4-[3-[4-[4-[4-[4-(carboxymethoxy)-3-methylphenyl]sulfanylbut-2-en-2-yl]phenyl]phenyl]but-2-enylsulfanyl]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1SCC=C(C)C1=CC=C(C=2C=CC(=CC=2)C(C)=CCSC=2C=C(C)C(OCC(O)=O)=CC=2)C=C1 YMJDOCQKCFJSNK-UHFFFAOYSA-N 0.000 claims description 2
- XSISCPYJHDFYSO-UHFFFAOYSA-N 3-[4-[5-[3-[5-[4-(2,3-diethoxy-3-oxopropyl)phenoxy]-3-methylpent-3-en-1-ynyl]phenyl]-3-methylpent-2-en-4-ynoxy]phenyl]-2-ethoxypropanoic acid Chemical compound C1=CC(CC(OCC)C(O)=O)=CC=C1OCC=C(C)C#CC1=CC=CC(C#CC(C)=CCOC=2C=CC(CC(OCC)C(=O)OCC)=CC=2)=C1 XSISCPYJHDFYSO-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
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- A—HUMAN NECESSITIES
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C323/18—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
- C07C323/20—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton with singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/76—Unsaturated compounds containing keto groups
- C07C59/90—Unsaturated compounds containing keto groups containing singly bound oxygen-containing groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/708—Ethers
- C07C69/712—Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
- C07C69/734—Ethers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (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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DKPA200101524 | 2001-10-17 | ||
DKPA200101524 | 2001-10-17 | ||
PCT/DK2002/000692 WO2003033453A1 (en) | 2001-10-17 | 2002-10-15 | Dicarboxylic acid derivatives, their preparation and therapeutical use |
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CA2462514A1 true CA2462514A1 (en) | 2003-04-24 |
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CA002462514A Abandoned CA2462514A1 (en) | 2001-10-17 | 2002-10-15 | Dicarboxylic acid derivatives, their preparation and therapeutical use |
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US7091245B2 (en) | 2002-09-05 | 2006-08-15 | Novo Novdisk A/S | Compounds, their preparation and use |
US20050080115A1 (en) | 2002-10-28 | 2005-04-14 | Lone Jeppesen | Novel compounds, their preparation and use |
KR20050055790A (ko) * | 2002-10-28 | 2005-06-13 | 노보 노르디스크 에이/에스 | Ppar 매개 질환의 치료에 유용한 신규 화합물 |
US7816385B2 (en) | 2002-12-20 | 2010-10-19 | High Point Pharmaceuticals, Llc | Dimeric dicarboxylic acid derivatives, their preparation and use |
JP2006510687A (ja) * | 2002-12-20 | 2006-03-30 | ノボ ノルディスク アクティーゼルスカブ | 新規化合物、その調製および使用 |
FR2850969B1 (fr) * | 2003-02-12 | 2005-03-25 | Genfit S A | Aminopropanediols acyles et analogues et leurs utilisations therapeutiques |
WO2005097127A2 (en) | 2004-04-02 | 2005-10-20 | Merck & Co., Inc. | Method of treating men with metabolic and anthropometric disorders |
WO2005105726A1 (en) | 2004-05-05 | 2005-11-10 | Novo Nordisk A/S | Novel compounds, their preparation and use |
EP1632245A1 (en) * | 2004-09-02 | 2006-03-08 | Technische Universität Dresden Medizinische Fakultät Carl Gustav Carus | ICA512 couples insulin secretion and gene expression in Beta-cells |
KR101333101B1 (ko) | 2005-06-30 | 2013-11-26 | 하이 포인트 파마슈티칼스, 엘엘씨 | Ppar-델타 활성제로서의 페녹시 아세트산 |
EA201101084A1 (ru) | 2005-12-22 | 2012-04-30 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Феноксиуксусные кислоты в качестве активаторов ppar дельта |
CA2645719A1 (en) * | 2006-03-09 | 2007-09-13 | High Point Pharmaceuticals, Llc | Compounds that modulate ppar activity, their preparation and use |
EA020466B1 (ru) | 2007-06-04 | 2014-11-28 | Синерджи Фармасьютикалз Инк. | Агонисты гуанилатциклазы, пригодные для лечения желудочно-кишечных нарушений, воспаления, рака и других заболеваний |
US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
EP2810951B1 (en) | 2008-06-04 | 2017-03-15 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
JP2011528375A (ja) | 2008-07-16 | 2011-11-17 | シナジー ファーマシューティカルズ インコーポレイテッド | 胃腸障害、炎症、癌、およびその他の障害の治療のために有用なグアニル酸シクラーゼのアゴニスト |
CN102264228A (zh) | 2008-10-22 | 2011-11-30 | 默沙东公司 | 用于抗糖尿病药的新的环状苯并咪唑衍生物 |
EP2362731B1 (en) | 2008-10-31 | 2016-04-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
JP2013520502A (ja) | 2010-02-25 | 2013-06-06 | メルク・シャープ・エンド・ドーム・コーポレイション | 有用な抗糖尿病薬である新規な環状ベンズイミダゾール誘導体 |
US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
KR101668514B1 (ko) | 2011-02-25 | 2016-10-21 | 머크 샤프 앤드 돔 코포레이션 | 항당뇨병제로서 유용한 신규 시클릭 아자벤즈이미다졸 유도체 |
WO2013082106A1 (en) | 2011-12-02 | 2013-06-06 | The General Hospital Corporation | Differentiation into brown adipocytes |
US20140045746A1 (en) | 2012-08-02 | 2014-02-13 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
AU2014219020A1 (en) | 2013-02-22 | 2015-07-23 | Merck Sharp & Dohme Corp. | Antidiabetic bicyclic compounds |
US9650375B2 (en) | 2013-03-14 | 2017-05-16 | Merck Sharp & Dohme Corp. | Indole derivatives useful as anti-diabetic agents |
JP6606491B2 (ja) | 2013-06-05 | 2019-11-13 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼcの超高純度アゴニスト、その作成および使用方法 |
WO2015051496A1 (en) | 2013-10-08 | 2015-04-16 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
EP3551176A4 (en) | 2016-12-06 | 2020-06-24 | Merck Sharp & Dohme Corp. | Antidiabetic heterocyclic compounds |
WO2018118670A1 (en) | 2016-12-20 | 2018-06-28 | Merck Sharp & Dohme Corp. | Antidiabetic spirochroman compounds |
CN109200043A (zh) * | 2018-10-23 | 2019-01-15 | 华南农业大学 | 二羧酸(盐)在降低脂肪沉积和预防肥胖方面的应用 |
WO2022020376A1 (en) | 2020-07-22 | 2022-01-27 | Reneo Pharmaceuticals, Inc. | Crystalline ppar-delta agonist |
WO2023147309A1 (en) | 2022-01-25 | 2023-08-03 | Reneo Pharmaceuticals, Inc. | Use of ppar-delta agonists in the treatment of disease |
CN116003245A (zh) * | 2022-12-21 | 2023-04-25 | 苏州永健生物医药有限公司 | 一种2-羟基-3-氧代戊烷二酸的制备方法 |
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FR2331336A1 (fr) * | 1975-11-14 | 1977-06-10 | Rolland Sa A | Acides oxy-4,4' bis(phenoxy-2 alcanocarboxyliques), leurs derives et leur application comme medicament |
US5508296A (en) * | 1991-07-30 | 1996-04-16 | Yamanouchi Pharmaceutical Co., Ltd. | Bisheterocyclic derivative or salt thereof |
HUP0204247A3 (en) * | 2000-01-28 | 2003-10-28 | Novo Nordisk As | Alkynylsubstituted propionic acid derivatives and their use against diabetes and obesity |
AU2831901A (en) * | 2000-01-28 | 2001-08-07 | Novo Nordisk A/S | Propionic acid derivatives and their use in the treatment of diabetes and obesity |
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CN1571766A (zh) | 2005-01-26 |
IL161170A0 (en) | 2004-08-31 |
HUP0401837A2 (hu) | 2004-12-28 |
RU2004114875A (ru) | 2005-09-10 |
WO2003033453A1 (en) | 2003-04-24 |
KR20050036876A (ko) | 2005-04-20 |
EP1438283A1 (en) | 2004-07-21 |
BR0213253A (pt) | 2004-10-26 |
JP2005505616A (ja) | 2005-02-24 |
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