ES2715377T3 - Derivados de pirrol bicíclicos útiles como agonistas de GPR120 - Google Patents
Derivados de pirrol bicíclicos útiles como agonistas de GPR120 Download PDFInfo
- Publication number
- ES2715377T3 ES2715377T3 ES14717256T ES14717256T ES2715377T3 ES 2715377 T3 ES2715377 T3 ES 2715377T3 ES 14717256 T ES14717256 T ES 14717256T ES 14717256 T ES14717256 T ES 14717256T ES 2715377 T3 ES2715377 T3 ES 2715377T3
- Authority
- ES
- Spain
- Prior art keywords
- trifluoromethyl
- pyrrol
- methoxy
- propanoic acid
- difluorophenyl
- 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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- -1 Bicyclic pyrrole derivatives Chemical class 0.000 title claims abstract description 124
- 101000890672 Homo sapiens Free fatty acid receptor 4 Proteins 0.000 title claims description 49
- 102100040134 Free fatty acid receptor 4 Human genes 0.000 title claims description 44
- 239000000556 agonist Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 340
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 70
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims abstract description 9
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims abstract description 8
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims abstract description 7
- 238000000034 method Methods 0.000 claims description 171
- 239000000203 mixture Substances 0.000 claims description 72
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 69
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 61
- 235000019260 propionic acid Nutrition 0.000 claims description 61
- 239000008103 glucose Substances 0.000 claims description 54
- 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 53
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
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- 235000020824 obesity Nutrition 0.000 claims description 42
- 208000035475 disorder Diseases 0.000 claims description 40
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 35
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 19
- 206010022489 Insulin Resistance Diseases 0.000 claims description 15
- 239000003937 drug carrier Substances 0.000 claims description 14
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 13
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 12
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 11
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 10
- 206010014486 Elevated triglycerides Diseases 0.000 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 208000001132 Osteoporosis Diseases 0.000 claims description 9
- 201000010390 abdominal obesity-metabolic syndrome 1 Diseases 0.000 claims description 9
- 230000004054 inflammatory process Effects 0.000 claims description 9
- 208000011661 metabolic syndrome X Diseases 0.000 claims description 9
- NIFBQQGEBZISQK-UHFFFAOYSA-N 3-[4-[[1-(2,4-difluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-3,5-difluorophenyl]propanoic acid Chemical compound FC1=CC(CCC(=O)O)=CC(F)=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(F)C=C1F NIFBQQGEBZISQK-UHFFFAOYSA-N 0.000 claims description 8
- 230000001771 impaired effect Effects 0.000 claims description 8
- QIWPBBKPALGRJN-UHFFFAOYSA-N 3-[4-[[1-(4-chloro-2-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-dimethylphenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=C(C)C(OCC=2N(C=CC=2C(F)(F)F)C=2C(=CC(Cl)=CC=2)F)=C1 QIWPBBKPALGRJN-UHFFFAOYSA-N 0.000 claims description 7
- HPVQBGVHNITFBF-UHFFFAOYSA-N 3-[3,5-difluoro-4-[[1-(2-fluoro-4-methylphenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]phenyl]propanoic acid Chemical compound FC1=CC(C)=CC=C1N1C(COC=2C(=CC(CCC(O)=O)=CC=2F)F)=C(C(F)(F)F)C=C1 HPVQBGVHNITFBF-UHFFFAOYSA-N 0.000 claims description 5
- OFBNLLCFNSAYID-UHFFFAOYSA-N 3-[4-[[1-(2-fluoro-4-methylphenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-dimethylphenyl]propanoic acid Chemical compound FC1=CC(C)=CC=C1N1C(COC=2C(=C(C)C(CCC(O)=O)=CC=2)C)=C(C(F)(F)F)C=C1 OFBNLLCFNSAYID-UHFFFAOYSA-N 0.000 claims description 5
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- BPAWJLHOPBKQCC-UHFFFAOYSA-N 3-[3,5-difluoro-4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]phenyl]propanoic acid Chemical compound FC1=CC(CCC(=O)O)=CC(F)=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(F)C=C1 BPAWJLHOPBKQCC-UHFFFAOYSA-N 0.000 claims description 4
- IXQUZEYQDBFCFO-UHFFFAOYSA-N 3-[4-[[1-(3,4-difluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-3,5-difluorophenyl]propanoic acid Chemical compound FC1=CC(CCC(=O)O)=CC(F)=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(F)C(F)=C1 IXQUZEYQDBFCFO-UHFFFAOYSA-N 0.000 claims description 4
- FCZRXGKCURAHSR-UHFFFAOYSA-N 3-[4-[[1-(3-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-3-methylphenyl]propanoic acid Chemical compound CC1=CC(CCC(O)=O)=CC=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=CC(F)=C1 FCZRXGKCURAHSR-UHFFFAOYSA-N 0.000 claims description 4
- PYJYVJYXEJDCIW-UHFFFAOYSA-N 3-[4-[[1-(4-chloro-2-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-3,5-difluorophenyl]propanoic acid Chemical compound FC1=CC(CCC(=O)O)=CC(F)=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(Cl)C=C1F PYJYVJYXEJDCIW-UHFFFAOYSA-N 0.000 claims description 4
- HJFLCNKHMKXNTP-UHFFFAOYSA-N 3-[3,5-difluoro-4-[[1-(3-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]phenyl]propanoic acid Chemical compound FC1=CC(CCC(=O)O)=CC(F)=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=CC(F)=C1 HJFLCNKHMKXNTP-UHFFFAOYSA-N 0.000 claims description 3
- AAFZQXYOMFVTFA-UHFFFAOYSA-N 3-[4-[[1-(2,4-difluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-dimethylphenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=C(C)C(OCC=2N(C=CC=2C(F)(F)F)C=2C(=CC(F)=CC=2)F)=C1 AAFZQXYOMFVTFA-UHFFFAOYSA-N 0.000 claims description 3
- OBLMTMKEPFASSR-UHFFFAOYSA-N 3-[4-[[1-(3,4-difluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-dimethylphenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=C(C)C(OCC=2N(C=CC=2C(F)(F)F)C=2C=C(F)C(F)=CC=2)=C1 OBLMTMKEPFASSR-UHFFFAOYSA-N 0.000 claims description 3
- QCBCKBRJRKEENZ-UHFFFAOYSA-N 3-[4-[[1-(3-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-dimethylphenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=C(C)C(OCC=2N(C=CC=2C(F)(F)F)C=2C=C(F)C=CC=2)=C1 QCBCKBRJRKEENZ-UHFFFAOYSA-N 0.000 claims description 3
- XHXYLQIKQKCRQX-UHFFFAOYSA-N 3-[4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2,3-dimethylphenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(C)=C(C)C(OCC=2N(C=CC=2C(F)(F)F)C=2C=CC(F)=CC=2)=C1 XHXYLQIKQKCRQX-UHFFFAOYSA-N 0.000 claims description 3
- QHSOFHIZXRQDBL-UHFFFAOYSA-N 3-[4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-3-methylphenyl]propanoic acid Chemical compound CC1=CC(CCC(O)=O)=CC=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(F)C=C1 QHSOFHIZXRQDBL-UHFFFAOYSA-N 0.000 claims description 3
- SXOOWMXNNFBMBQ-UHFFFAOYSA-N 3-[2-chloro-4-[[1-(3-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(Cl)C(CCC(=O)O)=CC=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=CC(F)=C1 SXOOWMXNNFBMBQ-UHFFFAOYSA-N 0.000 claims description 2
- BBFPPGPHADVODG-UHFFFAOYSA-N 3-[4-[[1-(3-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2-(trifluoromethyl)phenyl]propanoic acid Chemical compound C1=C(C(F)(F)F)C(CCC(=O)O)=CC=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=CC(F)=C1 BBFPPGPHADVODG-UHFFFAOYSA-N 0.000 claims description 2
- GFTPHPGCEBWWJF-UHFFFAOYSA-N 3-[4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]-2-(trifluoromethyl)phenyl]propanoic acid Chemical compound C1=C(C(F)(F)F)C(CCC(=O)O)=CC=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(F)C=C1 GFTPHPGCEBWWJF-UHFFFAOYSA-N 0.000 claims description 2
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- IGJDPIDKZDYLQL-UHFFFAOYSA-N 3-[2-chloro-4-[[1-(4-fluorophenyl)-3-(trifluoromethyl)pyrrol-2-yl]methoxy]phenyl]propanoic acid Chemical compound C1=C(Cl)C(CCC(=O)O)=CC=C1OCC1=C(C(F)(F)F)C=CN1C1=CC=C(F)C=C1 IGJDPIDKZDYLQL-UHFFFAOYSA-N 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 abstract description 6
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
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- 235000021317 phosphate Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
- WSHYKIAQCMIPTB-UHFFFAOYSA-M potassium;2-oxo-3-(3-oxo-1-phenylbutyl)chromen-4-olate Chemical compound [K+].[O-]C=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 WSHYKIAQCMIPTB-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 1
- 229960003081 probenecid Drugs 0.000 description 1
- ZIHBOROHTYWINY-UHFFFAOYSA-N propan-1-ol;2,2,2-trifluoroacetic acid Chemical compound CCCO.OC(=O)C(F)(F)F ZIHBOROHTYWINY-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000003762 quantitative reverse transcription PCR Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 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
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 229940083608 sodium hydroxide Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- AJSTXXYNEIHPMD-UHFFFAOYSA-N triethyl borate Chemical compound CCOB(OCC)OCC AJSTXXYNEIHPMD-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229960002703 undecylenic acid Drugs 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- DTOSIQBPPRVQHS-UHFFFAOYSA-N α-Linolenic acid Chemical compound CCC=CCC=CCC=CCCCCCCCC(O)=O DTOSIQBPPRVQHS-UHFFFAOYSA-N 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/333—Radicals substituted by oxygen or sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (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)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2014/021762 WO2015134038A1 (en) | 2014-03-07 | 2014-03-07 | Bicyclic pyrrole derivatives useful as agonists of gpr120 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2715377T3 true ES2715377T3 (es) | 2019-06-04 |
Family
ID=50483489
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES14717256T Active ES2715377T3 (es) | 2014-03-07 | 2014-03-07 | Derivados de pirrol bicíclicos útiles como agonistas de GPR120 |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP3114111B1 (https=) |
| JP (1) | JP6360569B2 (https=) |
| CN (1) | CN106061943B (https=) |
| AU (1) | AU2014385275B2 (https=) |
| CA (1) | CA2941442C (https=) |
| ES (1) | ES2715377T3 (https=) |
| MX (1) | MX368076B (https=) |
| WO (1) | WO2015134038A1 (https=) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021517142A (ja) | 2018-03-15 | 2021-07-15 | アクザム ソシエタ ペル アチオニ | 置換ピラゾールｆｆａ４／ｇｐｒ１２０受容体作動薬 |
| CN110407740A (zh) * | 2019-09-04 | 2019-11-05 | 上海毕得医药科技有限公司 | 一种3-溴-2-乙基吡啶的合成方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| AU2003277576A1 (en) * | 2002-11-08 | 2004-06-07 | Takeda Pharmaceutical Company Limited | Receptor function controlling agent |
| CN1735408A (zh) * | 2002-11-08 | 2006-02-15 | 武田药品工业株式会社 | 受体机能调节剂 |
| AU2004309271A1 (en) * | 2003-12-25 | 2005-07-14 | Takeda Pharmaceutical Company Limited | 3-(4-benzyloxyphenyl)propanoic acid derivatives |
| CN1922165A (zh) * | 2003-12-25 | 2007-02-28 | 武田药品工业株式会社 | 3－(4－苄氧基苯基)丙酸衍生物 |
| JP4859665B2 (ja) * | 2004-03-30 | 2012-01-25 | 武田薬品工業株式会社 | アルコキシフェニルプロパン酸誘導体 |
| AU2007292816B2 (en) * | 2006-09-07 | 2011-11-17 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| CA2662305C (en) * | 2006-09-07 | 2012-04-17 | Amgen Inc. | Heterocyclic gpr40 modulators |
| WO2009117421A2 (en) * | 2008-03-17 | 2009-09-24 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| NZ592603A (en) * | 2008-10-21 | 2013-02-22 | Metabolex Inc | Aryl gpr120 receptor agonists and uses thereof |
| WO2011094890A1 (en) * | 2010-02-02 | 2011-08-11 | Argusina Inc. | Phenylalanine derivatives and their use as non-peptide glp-1 receptor modulators |
| CN105008345A (zh) * | 2013-03-14 | 2015-10-28 | 詹森药业有限公司 | 可用作gpr120的激动剂的双环吡咯衍生物 |
-
2014
- 2014-03-07 CN CN201480076950.0A patent/CN106061943B/zh not_active Expired - Fee Related
- 2014-03-07 MX MX2016011629A patent/MX368076B/es active IP Right Grant
- 2014-03-07 EP EP14717256.3A patent/EP3114111B1/en not_active Not-in-force
- 2014-03-07 CA CA2941442A patent/CA2941442C/en active Active
- 2014-03-07 WO PCT/US2014/021762 patent/WO2015134038A1/en not_active Ceased
- 2014-03-07 AU AU2014385275A patent/AU2014385275B2/en not_active Ceased
- 2014-03-07 JP JP2016573457A patent/JP6360569B2/ja not_active Expired - Fee Related
- 2014-03-07 ES ES14717256T patent/ES2715377T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| AU2014385275A1 (en) | 2016-09-01 |
| CN106061943B (zh) | 2019-11-05 |
| JP6360569B2 (ja) | 2018-07-18 |
| AU2014385275B2 (en) | 2019-05-16 |
| WO2015134038A1 (en) | 2015-09-11 |
| CN106061943A (zh) | 2016-10-26 |
| MX2016011629A (es) | 2016-11-29 |
| EP3114111B1 (en) | 2019-01-09 |
| EP3114111A1 (en) | 2017-01-11 |
| JP2017507188A (ja) | 2017-03-16 |
| MX368076B (es) | 2019-09-17 |
| CA2941442A1 (en) | 2015-09-11 |
| CA2941442C (en) | 2022-01-11 |
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