JP4330883B2 - 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 - Google Patents
糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 Download PDFInfo
- Publication number
- JP4330883B2 JP4330883B2 JP2002589001A JP2002589001A JP4330883B2 JP 4330883 B2 JP4330883 B2 JP 4330883B2 JP 2002589001 A JP2002589001 A JP 2002589001A JP 2002589001 A JP2002589001 A JP 2002589001A JP 4330883 B2 JP4330883 B2 JP 4330883B2
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- methyl
- ethoxy
- oxazol
- propionic acid
- 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.)
- Expired - Fee Related
Links
- 238000011282 treatment Methods 0.000 title claims description 45
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 title claims description 18
- 108010016731 PPAR gamma Proteins 0.000 title claims description 17
- 206010012601 diabetes mellitus Diseases 0.000 title claims description 9
- 150000001732 carboxylic acid derivatives Chemical group 0.000 title description 6
- 150000007978 oxazole derivatives Chemical class 0.000 title description 2
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 title 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 title 1
- 239000012190 activator Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 238
- -1 carboxy, aminocarbonyl Chemical group 0.000 claims description 195
- 238000000034 method Methods 0.000 claims description 128
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 229910052739 hydrogen Inorganic materials 0.000 claims description 39
- 239000001257 hydrogen Substances 0.000 claims description 35
- 150000002148 esters Chemical class 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 30
- 125000003545 alkoxy group Chemical group 0.000 claims description 29
- 239000002253 acid Substances 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 150000001721 carbon Chemical group 0.000 claims description 25
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 102000023984 PPAR alpha Human genes 0.000 claims description 17
- 102000000536 PPAR gamma Human genes 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 15
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 150000002431 hydrogen Chemical class 0.000 claims description 9
- 201000001320 Atherosclerosis Diseases 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 150000002632 lipids Chemical class 0.000 claims description 8
- 206010020772 Hypertension Diseases 0.000 claims description 7
- 239000000556 agonist Substances 0.000 claims description 7
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 6
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 6
- DAYKLWSKQJBGCS-NRFANRHFSA-N aleglitazar Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-NRFANRHFSA-N 0.000 claims description 5
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 5
- 230000006806 disease prevention Effects 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- XEFJJUDMFIMCGL-VWLOTQADSA-N (2s)-2-methoxy-3-[4-[3-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]propoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OC)C(O)=O)=CC=C1OCCCC(=C(O1)C)N=C1C1=CC=C(C(F)(F)F)C=C1 XEFJJUDMFIMCGL-VWLOTQADSA-N 0.000 claims description 4
- WAEQTAKZLFYNLE-QHCPKHFHSA-N (2s)-3-[4-[2-[2-(3,5-dimethoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-methoxypropanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC(OC)=CC(OC)=C1 WAEQTAKZLFYNLE-QHCPKHFHSA-N 0.000 claims description 4
- DAYKLWSKQJBGCS-UHFFFAOYSA-N 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(CC(OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DAYKLWSKQJBGCS-UHFFFAOYSA-N 0.000 claims description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical group C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000001301 oxygen Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 239000011593 sulfur Substances 0.000 claims description 4
- NJKDMEJQXHMOJP-UHFFFAOYSA-N 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]-2-propoxypropanoic acid Chemical compound C1=2C=CSC=2C(CC(OCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 NJKDMEJQXHMOJP-UHFFFAOYSA-N 0.000 claims description 3
- 125000005907 alkyl ester group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 229940080774 Peroxisome proliferator-activated receptor gamma agonist Drugs 0.000 claims description 2
- 239000002671 adjuvant Substances 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 238000010511 deprotection reaction Methods 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 196
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 179
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- 239000007787 solid Substances 0.000 description 132
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 113
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 111
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 88
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 239000002904 solvent Substances 0.000 description 73
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 69
- 239000000243 solution Substances 0.000 description 69
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 66
- 239000013078 crystal Substances 0.000 description 65
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 57
- 239000000203 mixture Substances 0.000 description 56
- 239000011541 reaction mixture Substances 0.000 description 55
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- 238000002844 melting Methods 0.000 description 53
- 230000008018 melting Effects 0.000 description 53
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 52
- 238000006243 chemical reaction Methods 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- 239000000460 chlorine Substances 0.000 description 39
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 39
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 38
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 37
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 239000003921 oil Substances 0.000 description 37
- 235000019198 oils Nutrition 0.000 description 37
- 229910000027 potassium carbonate Inorganic materials 0.000 description 35
- 238000003818 flash chromatography Methods 0.000 description 33
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000012267 brine Substances 0.000 description 32
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 32
- 229910004298 SiO 2 Inorganic materials 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
- 235000011152 sodium sulphate Nutrition 0.000 description 29
- 239000000725 suspension Substances 0.000 description 29
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 29
- 238000003756 stirring Methods 0.000 description 28
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 27
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 26
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 235000019439 ethyl acetate Nutrition 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 24
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 24
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 22
- 238000010992 reflux Methods 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 21
- 239000012044 organic layer Substances 0.000 description 21
- BCAWRAILVSDAAU-UHFFFAOYSA-N 1-methoxy-3-nitronaphthalene Chemical compound C1=CC=C2C(OC)=CC([N+]([O-])=O)=CC2=C1 BCAWRAILVSDAAU-UHFFFAOYSA-N 0.000 description 20
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 235000019341 magnesium sulphate Nutrition 0.000 description 20
- MMJCDOWKUCLEQX-UHFFFAOYSA-M (1,2-diethoxy-2-oxoethyl)-triphenylphosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C(=O)OCC)OCC)C1=CC=CC=C1 MMJCDOWKUCLEQX-UHFFFAOYSA-M 0.000 description 18
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 18
- 239000012230 colorless oil Substances 0.000 description 18
- WTWBUQJHJGUZCY-UHFFFAOYSA-N cuminaldehyde Chemical compound CC(C)C1=CC=C(C=O)C=C1 WTWBUQJHJGUZCY-UHFFFAOYSA-N 0.000 description 18
- 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 description 18
- 239000012074 organic phase Substances 0.000 description 17
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 16
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- DYSJMQABFPKAQM-UHFFFAOYSA-N 1-benzothiophene-2-carboxylic acid Chemical compound C1=CC=C2SC(C(=O)O)=CC2=C1 DYSJMQABFPKAQM-UHFFFAOYSA-N 0.000 description 15
- 150000001299 aldehydes Chemical class 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 description 15
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
- 239000000284 extract Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- 239000007819 coupling partner Substances 0.000 description 14
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 14
- 238000007127 saponification reaction Methods 0.000 description 14
- LORPDGZOLAPNHP-UHFFFAOYSA-N 4-hydroxynaphthalene-1-carbaldehyde Chemical compound C1=CC=C2C(O)=CC=C(C=O)C2=C1 LORPDGZOLAPNHP-UHFFFAOYSA-N 0.000 description 13
- 238000005575 aldol reaction Methods 0.000 description 13
- 239000008346 aqueous phase Substances 0.000 description 13
- FSEUPUDHEBLWJY-HWKANZROSA-N diacetylmonoxime Chemical compound CC(=O)C(\C)=N\O FSEUPUDHEBLWJY-HWKANZROSA-N 0.000 description 13
- 239000006260 foam Substances 0.000 description 13
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 13
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 13
- SVONRAPFKPVNKG-UHFFFAOYSA-N 2-ethoxyethyl acetate Chemical compound CCOCCOC(C)=O SVONRAPFKPVNKG-UHFFFAOYSA-N 0.000 description 12
- MNOJRWOWILAHAV-UHFFFAOYSA-N 3-bromophenol Chemical compound OC1=CC=CC(Br)=C1 MNOJRWOWILAHAV-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000012300 argon atmosphere Substances 0.000 description 12
- 239000003054 catalyst Substances 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- SYIDEIWVKFMPNA-UHFFFAOYSA-N ethyl 2-ethoxy-3-(4-hydroxy-2-methylphenyl)propanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C=C1C SYIDEIWVKFMPNA-UHFFFAOYSA-N 0.000 description 12
- 239000011734 sodium Substances 0.000 description 12
- GHTATVPRMJRIPA-UHFFFAOYSA-N 5-bromo-1-benzofuran-7-ol Chemical compound OC1=CC(Br)=CC2=C1OC=C2 GHTATVPRMJRIPA-UHFFFAOYSA-N 0.000 description 11
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- 239000000706 filtrate Substances 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 239000007788 liquid Substances 0.000 description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- VFZRZRDOXPRTSC-UHFFFAOYSA-N 3,5-Dimethoxybenzaldehyde Chemical compound COC1=CC(OC)=CC(C=O)=C1 VFZRZRDOXPRTSC-UHFFFAOYSA-N 0.000 description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 238000006751 Mitsunobu reaction Methods 0.000 description 10
- 239000012876 carrier material Substances 0.000 description 10
- 238000004296 chiral HPLC Methods 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- GRTGGSXWHGKRSB-UHFFFAOYSA-N dichloromethyl methyl ether Chemical compound COC(Cl)Cl GRTGGSXWHGKRSB-UHFFFAOYSA-N 0.000 description 10
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 9
- XLLIQLLCWZCATF-UHFFFAOYSA-N 2-methoxyethyl acetate Chemical compound COCCOC(C)=O XLLIQLLCWZCATF-UHFFFAOYSA-N 0.000 description 9
- FKDDAMHBDUWVKO-UHFFFAOYSA-N 3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=C(C)C=C(C=O)C=C1C FKDDAMHBDUWVKO-UHFFFAOYSA-N 0.000 description 9
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 9
- 102000004877 Insulin Human genes 0.000 description 9
- 108090001061 Insulin Proteins 0.000 description 9
- 238000005481 NMR spectroscopy Methods 0.000 description 9
- 235000011054 acetic acid Nutrition 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 239000012442 inert solvent Substances 0.000 description 9
- 229940125396 insulin Drugs 0.000 description 9
- 239000011777 magnesium Substances 0.000 description 9
- 229910052749 magnesium Inorganic materials 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 229910000104 sodium hydride Inorganic materials 0.000 description 9
- SIRKPSSXHXSLMR-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethyl methanesulfonate Chemical compound CS(=O)(=O)OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 SIRKPSSXHXSLMR-UHFFFAOYSA-N 0.000 description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 238000010168 coupling process Methods 0.000 description 8
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 8
- 238000006170 formylation reaction Methods 0.000 description 8
- 125000000524 functional group Chemical group 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- VLYCNXQUNYCCNW-UHFFFAOYSA-M (1-methoxy-2-oxo-2-phenylmethoxyethyl)-triphenylphosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C(OC)C(=O)OCC1=CC=CC=C1 VLYCNXQUNYCCNW-UHFFFAOYSA-M 0.000 description 7
- UZCXCVNBSPOTNE-LBPRGKRZSA-N (4s)-4-benzyl-3-(2-ethoxyacetyl)-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)COCC)[C@H]1CC1=CC=CC=C1 UZCXCVNBSPOTNE-LBPRGKRZSA-N 0.000 description 7
- JXQGDDMZTWHASG-UHFFFAOYSA-N 4-hydroxy-1-benzothiophene-7-carbaldehyde Chemical compound OC1=CC=C(C=O)C2=C1C=CS2 JXQGDDMZTWHASG-UHFFFAOYSA-N 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000012298 atmosphere Substances 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 230000008020 evaporation Effects 0.000 description 7
- 239000000543 intermediate Substances 0.000 description 7
- SJGHJZQBVMTNEY-UHFFFAOYSA-N methyl 2-ethoxy-3-(4-hydroxy-1-benzofuran-7-yl)propanoate Chemical compound CCOC(C(=O)OC)CC1=CC=C(O)C2=C1OC=C2 SJGHJZQBVMTNEY-UHFFFAOYSA-N 0.000 description 7
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 7
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 7
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 7
- YUQUPSUDOOOQRB-NSHDSACASA-N (4s)-4-benzyl-3-(2-methoxyacetyl)-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)COC)[C@H]1CC1=CC=CC=C1 YUQUPSUDOOOQRB-NSHDSACASA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 6
- BEOBZEOPTQQELP-UHFFFAOYSA-N 4-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=C(C=O)C=C1 BEOBZEOPTQQELP-UHFFFAOYSA-N 0.000 description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 6
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- JLEKJZUYWFJPMB-UHFFFAOYSA-N ethyl 2-methoxyacetate Chemical compound CCOC(=O)COC JLEKJZUYWFJPMB-UHFFFAOYSA-N 0.000 description 6
- 125000004494 ethyl ester group Chemical group 0.000 description 6
- 230000022244 formylation Effects 0.000 description 6
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 6
- JJVNINGBHGBWJH-UHFFFAOYSA-N ortho-vanillin Chemical compound COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 description 6
- 229910052763 palladium Inorganic materials 0.000 description 6
- 238000002953 preparative HPLC Methods 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 6
- GCMUDSUJOMUXKE-UHFFFAOYSA-N 1-benzothiophen-7-ol Chemical compound OC1=CC=CC2=C1SC=C2 GCMUDSUJOMUXKE-UHFFFAOYSA-N 0.000 description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 5
- OXXANRBXZLQMNL-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-4-(chloromethyl)-5-methyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC(=CC=2)C(C)(C)C)=N1 OXXANRBXZLQMNL-UHFFFAOYSA-N 0.000 description 5
- NDBNMDJZTBKWJG-UHFFFAOYSA-N 2-[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethanol Chemical compound OCCC1=C(C)OC(C=2C=CC(Cl)=CC=2)=N1 NDBNMDJZTBKWJG-UHFFFAOYSA-N 0.000 description 5
- NBEFMISJJNGCIZ-UHFFFAOYSA-N 3,5-dimethylbenzaldehyde Chemical compound CC1=CC(C)=CC(C=O)=C1 NBEFMISJJNGCIZ-UHFFFAOYSA-N 0.000 description 5
- GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 5
- MKVKUPXFFIQNFD-UHFFFAOYSA-N 3-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 MKVKUPXFFIQNFD-UHFFFAOYSA-N 0.000 description 5
- BPCAWAAYLBWMBX-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-(4-propan-2-yloxyphenyl)-1,3-oxazole Chemical compound C1=CC(OC(C)C)=CC=C1C1=NC(CCl)=C(C)O1 BPCAWAAYLBWMBX-UHFFFAOYSA-N 0.000 description 5
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 5
- MULZWPFQTUDZPD-UHFFFAOYSA-N 5-methyl-2-phenyl-1,3-oxazole Chemical compound O1C(C)=CN=C1C1=CC=CC=C1 MULZWPFQTUDZPD-UHFFFAOYSA-N 0.000 description 5
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 5
- 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 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 5
- 238000009833 condensation Methods 0.000 description 5
- 230000005494 condensation Effects 0.000 description 5
- 229940043279 diisopropylamine Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- ZCQHNKSDNBIROD-UHFFFAOYSA-N ethyl 2-ethoxy-3-(4-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yl)propanoate Chemical compound C1CCCC2=C1C(O)=CC=C2CC(OCC)C(=O)OCC ZCQHNKSDNBIROD-UHFFFAOYSA-N 0.000 description 5
- 239000008103 glucose Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- KFFMOQYWYSAVTB-UHFFFAOYSA-N methyl 2-ethoxy-3-(4-hydroxy-1-benzothiophen-7-yl)propanoate Chemical compound CCOC(C(=O)OC)CC1=CC=C(O)C2=C1SC=C2 KFFMOQYWYSAVTB-UHFFFAOYSA-N 0.000 description 5
- USDXIKOXOFEJJG-UHFFFAOYSA-N methyl 2-ethoxy-3-(7-hydroxy-1-benzothiophen-4-yl)propanoate Chemical compound CCOC(C(=O)OC)CC1=CC=C(O)C2=C1C=CS2 USDXIKOXOFEJJG-UHFFFAOYSA-N 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical group CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- RSFWWSHVDCHJKI-QFIPXVFZSA-N (2s)-2-ethoxy-3-[3-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound COC1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 RSFWWSHVDCHJKI-QFIPXVFZSA-N 0.000 description 4
- ZDZSGCSKJUPAFA-QFIPXVFZSA-N (2s)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound CC1=CC(C[C@H](OCC)C(O)=O)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZDZSGCSKJUPAFA-QFIPXVFZSA-N 0.000 description 4
- KFOIIJNEPVIAGS-ZDUSSCGKSA-N (4s)-4-benzyl-3-(2-propoxyacetyl)-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)COCCC)[C@H]1CC1=CC=CC=C1 KFOIIJNEPVIAGS-ZDUSSCGKSA-N 0.000 description 4
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 4
- CFBCZETZIPZOGW-UHFFFAOYSA-N 1-benzofuran-4-ol Chemical compound OC1=CC=CC2=C1C=CO2 CFBCZETZIPZOGW-UHFFFAOYSA-N 0.000 description 4
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 4
- RJMWEZDCGAXBLF-UHFFFAOYSA-N 2-[2-(2-ethoxy-4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethanol Chemical compound CCOC1=CC(F)=CC=C1C1=NC(CCO)=C(C)O1 RJMWEZDCGAXBLF-UHFFFAOYSA-N 0.000 description 4
- CAMXLIDWAPOXML-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-ethylphenyl)-5-methyl-1,3-oxazole Chemical compound C1=CC(CC)=CC=C1C1=NC(CCl)=C(C)O1 CAMXLIDWAPOXML-UHFFFAOYSA-N 0.000 description 4
- NTEKLXSIBOMJQM-UHFFFAOYSA-N 4-[2-[4-(bromomethyl)-2,6-dimethylphenoxy]ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=C(C)C=C(CBr)C=C1C NTEKLXSIBOMJQM-UHFFFAOYSA-N 0.000 description 4
- NWJFOUPLSSRYLJ-UHFFFAOYSA-N 4-[2-[[7-(bromomethyl)-1-benzothiophen-4-yl]oxy]ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound N=1C(CCOC=2C=3C=CSC=3C(CBr)=CC=2)=C(C)OC=1C1=CC=CC=C1 NWJFOUPLSSRYLJ-UHFFFAOYSA-N 0.000 description 4
- UHZLERYEWPUBHM-UHFFFAOYSA-N 4-butoxybutyl acetate Chemical compound CCCCOCCCCOC(C)=O UHZLERYEWPUBHM-UHFFFAOYSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- 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 description 4
- ISDBWOPVZKNQDW-UHFFFAOYSA-N 4-phenylbenzaldehyde Chemical compound C1=CC(C=O)=CC=C1C1=CC=CC=C1 ISDBWOPVZKNQDW-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 238000003776 cleavage reaction Methods 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000007903 gelatin capsule Substances 0.000 description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 108020001756 ligand binding domains Proteins 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- MANFPIBZNWRLOW-UHFFFAOYSA-N methyl 3-(4-hydroxynaphthalen-1-yl)-2-methoxypropanoate Chemical compound C1=CC=C2C(CC(OC)C(=O)OC)=CC=C(O)C2=C1 MANFPIBZNWRLOW-UHFFFAOYSA-N 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
- 150000002989 phenols Chemical class 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 150000003077 polyols Chemical class 0.000 description 4
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 4
- 230000007017 scission Effects 0.000 description 4
- 239000000377 silicon dioxide Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- JOWUSAGCZMIOJF-QFIPXVFZSA-N (2s)-2-ethoxy-3-[2-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound C1=C(OC)C(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JOWUSAGCZMIOJF-QFIPXVFZSA-N 0.000 description 3
- UCSKUJJLQHGTGX-QFIPXVFZSA-N (2s)-2-ethoxy-3-[3-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 UCSKUJJLQHGTGX-QFIPXVFZSA-N 0.000 description 3
- OJOFMLDBXPDXLQ-VIFPVBQESA-N (4s)-4-benzyl-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N[C@H]1CC1=CC=CC=C1 OJOFMLDBXPDXLQ-VIFPVBQESA-N 0.000 description 3
- NEDVFUDLYJBFEM-AWEZNQCLSA-N (4s)-4-benzyl-3-(2-but-3-enoxyacetyl)-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)COCCC=C)[C@H]1CC1=CC=CC=C1 NEDVFUDLYJBFEM-AWEZNQCLSA-N 0.000 description 3
- YUNPXAJJLKAZBF-JCMHNJIXSA-N (z)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxyprop-2-enoic acid Chemical compound CC1=CC(\C=C(/OCC)C(O)=O)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 YUNPXAJJLKAZBF-JCMHNJIXSA-N 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- BQYBIZJTLUWSLE-UHFFFAOYSA-N 2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethanol Chemical compound OCCC1=C(C)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 BQYBIZJTLUWSLE-UHFFFAOYSA-N 0.000 description 3
- DPVIFLGTFFTKQK-UHFFFAOYSA-N 2-but-3-enoxyacetic acid Chemical compound OC(=O)COCCC=C DPVIFLGTFFTKQK-UHFFFAOYSA-N 0.000 description 3
- VNRVGMGCSUNMGF-UHFFFAOYSA-N 2-ethoxy-3-[2-methyl-4-[3-(5-methyl-2-phenyl-1,3-oxazol-4-yl)propoxy]phenyl]propanoic acid Chemical compound C1=C(C)C(CC(OCC)C(O)=O)=CC=C1OCCCC1=C(C)OC(C=2C=CC=CC=2)=N1 VNRVGMGCSUNMGF-UHFFFAOYSA-N 0.000 description 3
- UWKLVLBGJRXBSH-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-3-propylphenyl]propanoic acid Chemical compound CCCC1=CC(CC(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 UWKLVLBGJRXBSH-UHFFFAOYSA-N 0.000 description 3
- NVGFMQAAGRNKHI-UHFFFAOYSA-N 2-ethoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1h-inden-4-yl]propanoic acid Chemical compound C1=2CCCC=2C(CC(OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 NVGFMQAAGRNKHI-UHFFFAOYSA-N 0.000 description 3
- QMAQLCVJIYANPZ-UHFFFAOYSA-N 2-propoxyethyl acetate Chemical compound CCCOCCOC(C)=O QMAQLCVJIYANPZ-UHFFFAOYSA-N 0.000 description 3
- ASOFZHSTJHGQDT-UHFFFAOYSA-N 3,5-difluorobenzaldehyde Chemical compound FC1=CC(F)=CC(C=O)=C1 ASOFZHSTJHGQDT-UHFFFAOYSA-N 0.000 description 3
- VCTKYTBWZTZPHF-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC=CC=2)=N1 VCTKYTBWZTZPHF-UHFFFAOYSA-N 0.000 description 3
- ZLQYYSXCBGMNKF-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-5,6,7,8-tetrahydronaphthalene-1-carbaldehyde Chemical compound N=1C(CCOC=2C=3CCCCC=3C(C=O)=CC=2)=C(C)OC=1C1=CC=CC=C1 ZLQYYSXCBGMNKF-UHFFFAOYSA-N 0.000 description 3
- YHDXWGMBOSHLNH-UHFFFAOYSA-N 4-[2-[4-(bromomethyl)naphthalen-1-yl]oxyethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound N=1C(CCOC=2C3=CC=CC=C3C(CBr)=CC=2)=C(C)OC=1C1=CC=CC=C1 YHDXWGMBOSHLNH-UHFFFAOYSA-N 0.000 description 3
- UKNKHGKCPNYFCL-UHFFFAOYSA-N 7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophene-4-carbaldehyde Chemical compound N=1C(CCOC=2C=3SC=CC=3C(C=O)=CC=2)=C(C)OC=1C1=CC=CC=C1 UKNKHGKCPNYFCL-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 0 Cc1c(*)c(N*=*(*=C)C(O*)=O)c(*)c(*)c1OC*=* Chemical compound Cc1c(*)c(N*=*(*=C)C(O*)=O)c(*)c(*)c1OC*=* 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 3
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 3
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 3
- 230000027455 binding Effects 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 230000005595 deprotonation Effects 0.000 description 3
- 238000010537 deprotonation reaction Methods 0.000 description 3
- 230000008034 disappearance Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012039 electrophile Substances 0.000 description 3
- QUGJYNGNUBHTNS-UHFFFAOYSA-N ethyl 2-(benzhydrylideneamino)acetate Chemical compound C=1C=CC=CC=1C(=NCC(=O)OCC)C1=CC=CC=C1 QUGJYNGNUBHTNS-UHFFFAOYSA-N 0.000 description 3
- ZBPGUNCFZKOHJD-UHFFFAOYSA-N ethyl 2-ethoxy-3-(4-hydroxy-3-methoxyphenyl)propanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C(OC)=C1 ZBPGUNCFZKOHJD-UHFFFAOYSA-N 0.000 description 3
- QRJKKAHZAFRLQA-UHFFFAOYSA-N ethyl 2-ethoxy-3-(4-hydroxynaphthalen-1-yl)propanoate Chemical compound C1=CC=C2C(CC(OCC)C(=O)OCC)=CC=C(O)C2=C1 QRJKKAHZAFRLQA-UHFFFAOYSA-N 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 108020001507 fusion proteins Proteins 0.000 description 3
- 102000037865 fusion proteins Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 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 3
- 238000010791 quenching Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 238000001890 transfection Methods 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- MATIMUHSLXVNGU-UHFFFAOYSA-M (1,2-dimethoxy-2-oxoethyl)-triphenylphosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C(=O)OC)OC)C1=CC=CC=C1 MATIMUHSLXVNGU-UHFFFAOYSA-M 0.000 description 2
- 125000002688 (2,2,2-trifluoroethoxy)acetyl group Chemical group FC(COCC(=O)*)(F)F 0.000 description 2
- PRZXVPAIHJGJKL-JOCHJYFZSA-N (2r)-2-ethoxy-3-[2-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound C1=C(C)C(C[C@@H](OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 PRZXVPAIHJGJKL-JOCHJYFZSA-N 0.000 description 2
- ISNFDEWNTANWIW-DEOSSOPVSA-N (2s)-2-but-3-enoxy-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=C(C)C=C(C[C@H](OCCC=C)C(O)=O)C=C1C ISNFDEWNTANWIW-DEOSSOPVSA-N 0.000 description 2
- FBXYIRYPHCXXFI-MHZLTWQESA-N (2s)-2-but-3-enoxy-3-[4-[2-[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(CCOC=2C=3C=CSC=3C(C[C@H](OCCC=C)C(O)=O)=CC=2)=C(C)O1 FBXYIRYPHCXXFI-MHZLTWQESA-N 0.000 description 2
- PRZXVPAIHJGJKL-QFIPXVFZSA-N (2s)-2-ethoxy-3-[2-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound C1=C(C)C(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 PRZXVPAIHJGJKL-QFIPXVFZSA-N 0.000 description 2
- FPFPBJJEDIYYGK-QFIPXVFZSA-N (2s)-2-ethoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 FPFPBJJEDIYYGK-QFIPXVFZSA-N 0.000 description 2
- ONHGGZJYRMVQKP-VWLOTQADSA-N (2s)-2-ethoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 ONHGGZJYRMVQKP-VWLOTQADSA-N 0.000 description 2
- NXMDZTVQMITUKX-NDEPHWFRSA-N (2s)-2-ethoxy-3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1 NXMDZTVQMITUKX-NDEPHWFRSA-N 0.000 description 2
- KCWIZUQRJKWLAR-HKBQPEDESA-N (2s)-2-ethoxy-3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1 KCWIZUQRJKWLAR-HKBQPEDESA-N 0.000 description 2
- NZVGUNNFYQRWCJ-VWLOTQADSA-N (2s)-2-ethoxy-3-[4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(C(F)(F)F)C=C1 NZVGUNNFYQRWCJ-VWLOTQADSA-N 0.000 description 2
- HPYPAVJBAFUABQ-DEOSSOPVSA-N (2s)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 HPYPAVJBAFUABQ-DEOSSOPVSA-N 0.000 description 2
- TZBXCHPIDLANIH-PMERELPUSA-N (2s)-2-methoxy-3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1 TZBXCHPIDLANIH-PMERELPUSA-N 0.000 description 2
- RZOXULQOOIZTDM-DEOSSOPVSA-N (2s)-2-methoxy-3-[4-[2-[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(C(C)C)C=C1 RZOXULQOOIZTDM-DEOSSOPVSA-N 0.000 description 2
- WTAWYJWDXKPZHM-DEOSSOPVSA-N (2s)-2-methoxy-3-[4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(C(F)(F)F)C=C1 WTAWYJWDXKPZHM-DEOSSOPVSA-N 0.000 description 2
- QMYSZCHFOGMIFT-QHCPKHFHSA-N (2s)-2-methoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1h-inden-4-yl]propanoic acid Chemical compound C1=2CCCC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 QMYSZCHFOGMIFT-QHCPKHFHSA-N 0.000 description 2
- CPEKGAYUQODHAQ-QHCPKHFHSA-N (2s)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-propoxypropanoic acid Chemical compound CC1=CC(C[C@H](OCCC)C(O)=O)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 CPEKGAYUQODHAQ-QHCPKHFHSA-N 0.000 description 2
- YCZZSZLFUGCZMT-QHCPKHFHSA-N (2s)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]-2-propan-2-yloxypropanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OC(C)C)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 YCZZSZLFUGCZMT-QHCPKHFHSA-N 0.000 description 2
- BEWOTDRBFGEFJO-VWLOTQADSA-N (2s)-3-[4-[2-[2-(3,5-dimethoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-propan-2-yloxypropanoic acid Chemical compound COC1=CC(OC)=CC(C=2OC(C)=C(CCOC=3C=4C=CSC=4C(C[C@H](OC(C)C)C(O)=O)=CC=3)N=2)=C1 BEWOTDRBFGEFJO-VWLOTQADSA-N 0.000 description 2
- CSLKMCGKJYRBFB-QHCPKHFHSA-N (2s)-3-[4-[2-[2-(3,5-dimethylphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-methoxypropanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC(C)=CC(C)=C1 CSLKMCGKJYRBFB-QHCPKHFHSA-N 0.000 description 2
- VKCAWPUDKQTBAP-SANMLTNESA-N (2s)-3-[4-[2-[2-(3,5-dimethylphenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]-2-methoxypropanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC(C)=CC(C)=C1 VKCAWPUDKQTBAP-SANMLTNESA-N 0.000 description 2
- QAGRHPRAMRZFQG-LJAQVGFWSA-N (2s)-3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-propoxypropanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1 QAGRHPRAMRZFQG-LJAQVGFWSA-N 0.000 description 2
- MMTVCYJDBFLUQP-PMERELPUSA-N (2s)-3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]-2-(2,2,2-trifluoroethoxy)propanoic acid Chemical compound N=1C(CCOC=2C3=CC=CC=C3C(C[C@H](OCC(F)(F)F)C(O)=O)=CC=2)=C(C)OC=1C(C=C1)=CC=C1C1=CC=CC=C1 MMTVCYJDBFLUQP-PMERELPUSA-N 0.000 description 2
- LOCIDZKFPDRDOE-YTTGMZPUSA-N (2s)-3-[4-[2-[5-methyl-2-(4-phenylphenyl)-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]-2-propoxypropanoic acid Chemical compound C12=CC=CC=C2C(C[C@H](OCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C(C=C1)=CC=C1C1=CC=CC=C1 LOCIDZKFPDRDOE-YTTGMZPUSA-N 0.000 description 2
- WFXYMHGEGKSOTB-DEOSSOPVSA-N (2s)-3-[4-[2-[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-(2,2,2-trifluoroethoxy)propanoic acid Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(CCOC=2C=3C=CSC=3C(C[C@H](OCC(F)(F)F)C(O)=O)=CC=2)=C(C)O1 WFXYMHGEGKSOTB-DEOSSOPVSA-N 0.000 description 2
- WLCITMKILUZREK-ZDUSSCGKSA-N (4s)-4-benzyl-3-(2-propan-2-yloxyacetyl)-1,3-oxazolidin-2-one Chemical compound C1OC(=O)N(C(=O)COC(C)C)[C@H]1CC1=CC=CC=C1 WLCITMKILUZREK-ZDUSSCGKSA-N 0.000 description 2
- JNVFAWVRLBKKLP-DHIFEGFHSA-N (4s)-4-benzyl-3-[(2s)-2-ethoxy-3-[2-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OCC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C(=C1)OC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 JNVFAWVRLBKKLP-DHIFEGFHSA-N 0.000 description 2
- QFPUUEGCNKAWRJ-DHIFEGFHSA-N (4s)-4-benzyl-3-[(2s)-2-ethoxy-3-[3-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OCC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=C1OC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 QFPUUEGCNKAWRJ-DHIFEGFHSA-N 0.000 description 2
- ICRKXDUCFUDWTA-IZEXYCQBSA-N (4s)-4-benzyl-3-[(2s)-2-ethoxy-3-[3-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OCC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=C1C)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 ICRKXDUCFUDWTA-IZEXYCQBSA-N 0.000 description 2
- ZAFQMJGCSVAOOB-YZNIXAGQSA-N (4s)-4-benzyl-3-[(2s)-2-methoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-4-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=1C=CSC=11)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 ZAFQMJGCSVAOOB-YZNIXAGQSA-N 0.000 description 2
- XZPVSEOSONPYSP-SMCANUKXSA-N (4s)-4-benzyl-3-[(2s)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxypropanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OCC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=C1C)=CC(C)=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 XZPVSEOSONPYSP-SMCANUKXSA-N 0.000 description 2
- OBOURQKCUXGDRV-UFLGCHLJSA-N (4s)-4-benzyl-3-[(2s,3r)-2-but-3-enoxy-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-3-hydroxypropanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@@H]1N(C(OC1)=O)C(=O)[C@@H](OCCC=C)[C@H](O)C1=CC(C)=C(C(=C1)C)OCCC=1N=C(OC=1C)C=1C=CC=CC=1)C1=CC=CC=C1 OBOURQKCUXGDRV-UFLGCHLJSA-N 0.000 description 2
- RDIRAXBAFHGXKX-RVQNBHMFSA-N (4s)-4-benzyl-3-[(2s,3r)-2-ethoxy-3-hydroxy-3-[2-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C1=C(OC)C([C@@H](O)[C@H](OCC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 RDIRAXBAFHGXKX-RVQNBHMFSA-N 0.000 description 2
- AGKYSLUMYJQCHT-XGNZJKERSA-N (4s)-4-benzyl-3-[(2s,3r)-2-ethoxy-3-hydroxy-3-[3-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound COC1=CC([C@@H](O)[C@H](OCC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 AGKYSLUMYJQCHT-XGNZJKERSA-N 0.000 description 2
- JTFVFWSXAGDEPC-GOVYPMRZSA-N (4s)-4-benzyl-3-[(2s,3r)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxy-3-hydroxypropanoyl]-1,3-oxazolidin-2-one Chemical compound CC1=CC([C@@H](O)[C@H](OCC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC(C)=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 JTFVFWSXAGDEPC-GOVYPMRZSA-N 0.000 description 2
- DZJDQBHPKHPGTL-FXZLDBAYSA-N (4s)-4-benzyl-3-[(2s,3r)-3-hydroxy-2-methoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1h-inden-4-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C1=2CCCC=2C([C@@H](O)[C@H](OC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DZJDQBHPKHPGTL-FXZLDBAYSA-N 0.000 description 2
- QBTOORLTFCPLAW-HAHDFKILSA-N (z)-3-[2,3-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxyprop-2-enoic acid Chemical compound CC1=C(C)C(\C=C(/OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 QBTOORLTFCPLAW-HAHDFKILSA-N 0.000 description 2
- OCYUOPZKSSJBGB-HAHDFKILSA-N (z)-3-[2,6-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxyprop-2-enoic acid Chemical compound C1=C(C)C(\C=C(/OCC)C(O)=O)=C(C)C=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 OCYUOPZKSSJBGB-HAHDFKILSA-N 0.000 description 2
- KYVBNYUBXIEUFW-UHFFFAOYSA-N 1,1,3,3-tetramethylguanidine Chemical compound CN(C)C(=N)N(C)C KYVBNYUBXIEUFW-UHFFFAOYSA-N 0.000 description 2
- BGJSXRVXTHVRSN-UHFFFAOYSA-N 1,3,5-trioxane Chemical compound C1OCOCO1 BGJSXRVXTHVRSN-UHFFFAOYSA-N 0.000 description 2
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 2
- DLIOGFQTFUVFFB-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]butane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=C(C(F)(F)F)C=C1 DLIOGFQTFUVFFB-UHFFFAOYSA-N 0.000 description 2
- BMRZGYNNZTVECK-UHFFFAOYSA-N 1-benzothiophen-4-ol Chemical compound OC1=CC=CC2=C1C=CS2 BMRZGYNNZTVECK-UHFFFAOYSA-N 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- CVBUKMMMRLOKQR-UHFFFAOYSA-N 1-phenylbutane-1,3-dione Chemical compound CC(=O)CC(=O)C1=CC=CC=C1 CVBUKMMMRLOKQR-UHFFFAOYSA-N 0.000 description 2
- PHELOKYCCWVWFE-UHFFFAOYSA-N 2,2-dimethoxyacetic acid Chemical compound COC(OC)C(O)=O PHELOKYCCWVWFE-UHFFFAOYSA-N 0.000 description 2
- DPHNJPUOMLRELT-UHFFFAOYSA-N 2,3-dihydro-1h-inden-4-ol Chemical compound OC1=CC=CC2=C1CCC2 DPHNJPUOMLRELT-UHFFFAOYSA-N 0.000 description 2
- QWBBPBRQALCEIZ-UHFFFAOYSA-N 2,3-dimethylphenol Chemical compound CC1=CC=CC(O)=C1C QWBBPBRQALCEIZ-UHFFFAOYSA-N 0.000 description 2
- IUNJCFABHJZSKB-UHFFFAOYSA-N 2,4-dihydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C(O)=C1 IUNJCFABHJZSKB-UHFFFAOYSA-N 0.000 description 2
- OEFXUNBFONWAIE-UHFFFAOYSA-N 2,6-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC(C)=C(C=O)C(C)=C1 OEFXUNBFONWAIE-UHFFFAOYSA-N 0.000 description 2
- SGMMCAQDRSMDCY-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C(=C1)C)=C(C)C=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 SGMMCAQDRSMDCY-UHFFFAOYSA-N 0.000 description 2
- QLZRIYCSFPZPPF-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[3-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C(=C1)C)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 QLZRIYCSFPZPPF-UHFFFAOYSA-N 0.000 description 2
- REVYIMBUWLAAAT-UHFFFAOYSA-N 2-(2-benzoylanilino)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoic acid Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C1=CC=CC=C11)=CC=C1CC(C(O)=O)NC1=CC=CC=C1C(=O)C1=CC=CC=C1 REVYIMBUWLAAAT-UHFFFAOYSA-N 0.000 description 2
- JYWHQBLLIBQGCU-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethanol Chemical compound OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JYWHQBLLIBQGCU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
- FJXJTQXLGPLGJM-UHFFFAOYSA-N 2-anthracen-1-yl-1,1,1-trifluoropropan-2-ol Chemical compound C1=CC=C2C=C3C(C(O)(C)C(F)(F)F)=CC=CC3=CC2=C1 FJXJTQXLGPLGJM-UHFFFAOYSA-N 0.000 description 2
- YTVQIZRDLKWECQ-UHFFFAOYSA-N 2-benzoylcyclohexan-1-one Chemical compound C=1C=CC=CC=1C(=O)C1CCCCC1=O YTVQIZRDLKWECQ-UHFFFAOYSA-N 0.000 description 2
- UFOOHABDIYQMKS-UHFFFAOYSA-N 2-butoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(CC(OCCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 UFOOHABDIYQMKS-UHFFFAOYSA-N 0.000 description 2
- PRZXVPAIHJGJKL-UHFFFAOYSA-N 2-ethoxy-3-[2-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound C1=C(C)C(CC(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 PRZXVPAIHJGJKL-UHFFFAOYSA-N 0.000 description 2
- WJXLMLSINJTNQL-UHFFFAOYSA-N 2-ethoxy-3-[3-fluoro-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound FC1=CC(CC(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 WJXLMLSINJTNQL-UHFFFAOYSA-N 0.000 description 2
- UCSKUJJLQHGTGX-UHFFFAOYSA-N 2-ethoxy-3-[3-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoic acid Chemical compound CC1=CC(CC(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 UCSKUJJLQHGTGX-UHFFFAOYSA-N 0.000 description 2
- FGFOIHAETBQZCQ-UHFFFAOYSA-N 2-ethoxy-3-[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]-1-benzofuran-7-yl]propanoic acid Chemical compound C1=2C=COC=2C(CC(OCC)C(O)=O)=CC=C1OCC(=C(O1)C)N=C1C1=CC=CC=C1 FGFOIHAETBQZCQ-UHFFFAOYSA-N 0.000 description 2
- IHSPYTNGAPOLLC-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1-benzofuran-7-yl]propanoic acid Chemical compound C1=2CCOC=2C(CC(OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 IHSPYTNGAPOLLC-UHFFFAOYSA-N 0.000 description 2
- ONHGGZJYRMVQKP-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(CC(OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 ONHGGZJYRMVQKP-UHFFFAOYSA-N 0.000 description 2
- VPJCAJLVMQCQIC-UHFFFAOYSA-N 2-ethoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-4-yl]propanoic acid Chemical compound C1=2SC=CC=2C(CC(OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 VPJCAJLVMQCQIC-UHFFFAOYSA-N 0.000 description 2
- AFNWRNDORVJZIM-UHFFFAOYSA-N 2-ethoxy-4-fluorobenzaldehyde Chemical compound CCOC1=CC(F)=CC=C1C=O AFNWRNDORVJZIM-UHFFFAOYSA-N 0.000 description 2
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- DISQJIGBPABART-UHFFFAOYSA-N 2-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C(C)=C1 DISQJIGBPABART-UHFFFAOYSA-N 0.000 description 2
- OGVPJBJWJCZBTH-UHFFFAOYSA-N 2-methyl-4-phenylmethoxybenzaldehyde Chemical compound C1=C(C=O)C(C)=CC(OCC=2C=CC=CC=2)=C1 OGVPJBJWJCZBTH-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- CASRSOJWLARCRX-UHFFFAOYSA-N 3,5-dichlorobenzaldehyde Chemical compound ClC1=CC(Cl)=CC(C=O)=C1 CASRSOJWLARCRX-UHFFFAOYSA-N 0.000 description 2
- TUAMRELNJMMDMT-UHFFFAOYSA-N 3,5-xylenol Chemical compound CC1=CC(C)=CC(O)=C1 TUAMRELNJMMDMT-UHFFFAOYSA-N 0.000 description 2
- UAQFYLPPITUEEL-UHFFFAOYSA-N 3-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]propan-1-ol Chemical compound C1=CC(OC)=CC=C1C1=NC(CCCO)=C(C)O1 UAQFYLPPITUEEL-UHFFFAOYSA-N 0.000 description 2
- ZDZSGCSKJUPAFA-UHFFFAOYSA-N 3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxypropanoic acid Chemical compound CC1=CC(CC(OCC)C(O)=O)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZDZSGCSKJUPAFA-UHFFFAOYSA-N 0.000 description 2
- KQXDPYDFFKAXBV-UHFFFAOYSA-N 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]-2-(2-methylpropoxy)propanoic acid Chemical compound C1=2C=CSC=2C(CC(OCC(C)C)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 KQXDPYDFFKAXBV-UHFFFAOYSA-N 0.000 description 2
- DVIBSRAWYQNSOH-UHFFFAOYSA-N 3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]-2-propoxypropanoic acid Chemical compound C12=CC=CC=C2C(CC(OCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 DVIBSRAWYQNSOH-UHFFFAOYSA-N 0.000 description 2
- DATMRYCOCUCNMI-UHFFFAOYSA-N 3-[4-[2-[2-(3,5-dichlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-methoxypropanoic acid Chemical compound C1=2C=CSC=2C(CC(OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC(Cl)=CC(Cl)=C1 DATMRYCOCUCNMI-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- QSAZQMOSZQCHHU-UHFFFAOYSA-N 3-bromonaphthalen-1-ol Chemical compound C1=CC=C2C(O)=CC(Br)=CC2=C1 QSAZQMOSZQCHHU-UHFFFAOYSA-N 0.000 description 2
- DCUMQZBCQUTJLD-UHFFFAOYSA-N 3-fluoro-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C=C1F DCUMQZBCQUTJLD-UHFFFAOYSA-N 0.000 description 2
- WQMFMUXUSKUPGA-UHFFFAOYSA-N 3-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C=C1C WQMFMUXUSKUPGA-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- OAJKLGVKPDGGRF-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazole Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(CCl)=C(C)O1 OAJKLGVKPDGGRF-UHFFFAOYSA-N 0.000 description 2
- UWKSFZMISAANMN-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 UWKSFZMISAANMN-UHFFFAOYSA-N 0.000 description 2
- ARNRJVCAJCQWGM-UHFFFAOYSA-N 4-[2-(1-benzothiophen-7-yloxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound N=1C(CCOC=2C=3SC=CC=3C=CC=2)=C(C)OC=1C1=CC=CC=C1 ARNRJVCAJCQWGM-UHFFFAOYSA-N 0.000 description 2
- WPTJTIFMBBNBPY-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzofuran-7-carbaldehyde Chemical compound N=1C(CCOC=2C=3C=COC=3C(C=O)=CC=2)=C(C)OC=1C1=CC=CC=C1 WPTJTIFMBBNBPY-UHFFFAOYSA-N 0.000 description 2
- WAOPPOQPYOBXNE-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophene-7-carbaldehyde Chemical compound N=1C(CCOC=2C=3C=CSC=3C(C=O)=CC=2)=C(C)OC=1C1=CC=CC=C1 WAOPPOQPYOBXNE-UHFFFAOYSA-N 0.000 description 2
- CUKCSPFRQLTLQR-UHFFFAOYSA-N 4-[2-[2-(3,5-dichlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophene-7-carbaldehyde Chemical compound N=1C(CCOC=2C=3C=CSC=3C(C=O)=CC=2)=C(C)OC=1C1=CC(Cl)=CC(Cl)=C1 CUKCSPFRQLTLQR-UHFFFAOYSA-N 0.000 description 2
- ZBPGJTSCLNQVKW-UHFFFAOYSA-N 4-[3-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]propoxy]naphthalene-1-carbaldehyde Chemical compound C1=CC(OC)=CC=C1C1=NC(CCCOC=2C3=CC=CC=C3C(C=O)=CC=2)=C(C)O1 ZBPGJTSCLNQVKW-UHFFFAOYSA-N 0.000 description 2
- WBIZZNFQJPOKDK-UHFFFAOYSA-N 4-hydroxy-2-methoxybenzaldehyde Chemical compound COC1=CC(O)=CC=C1C=O WBIZZNFQJPOKDK-UHFFFAOYSA-N 0.000 description 2
- JDWWIEFMFPWBST-UHFFFAOYSA-N 4-hydroxy-2-methylbenzaldehyde Chemical compound CC1=CC(O)=CC=C1C=O JDWWIEFMFPWBST-UHFFFAOYSA-N 0.000 description 2
- UYGBSRJODQHNLQ-UHFFFAOYSA-N 4-hydroxy-3,5-dimethylbenzaldehyde Chemical compound CC1=CC(C=O)=CC(C)=C1O UYGBSRJODQHNLQ-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- KIDJISUVJMVGAN-UHFFFAOYSA-N 4-methyl-2-phenyl-1,3-oxazole Chemical compound CC1=COC(C=2C=CC=CC=2)=N1 KIDJISUVJMVGAN-UHFFFAOYSA-N 0.000 description 2
- GVJZBESEMAEOKW-UHFFFAOYSA-N 4-phenylmethoxy-1-benzofuran Chemical compound C=1C=CC=2OC=CC=2C=1OCC1=CC=CC=C1 GVJZBESEMAEOKW-UHFFFAOYSA-N 0.000 description 2
- VPNLOALQDLCYLJ-UHFFFAOYSA-N 4-phenylmethoxy-1-benzofuran-7-carbaldehyde Chemical compound C1=2C=COC=2C(C=O)=CC=C1OCC1=CC=CC=C1 VPNLOALQDLCYLJ-UHFFFAOYSA-N 0.000 description 2
- ASKNPZYETHGEPD-UHFFFAOYSA-N 4-phenylmethoxy-5,6,7,8-tetrahydronaphthalene-1-carbaldehyde Chemical compound C1=2CCCCC=2C(C=O)=CC=C1OCC1=CC=CC=C1 ASKNPZYETHGEPD-UHFFFAOYSA-N 0.000 description 2
- NNJNHCMIHWEFLW-UHFFFAOYSA-N 5-methyl-2-phenyl-4-[2-(5,6,7,8-tetrahydronaphthalen-1-yloxy)ethyl]-1,3-oxazole Chemical compound N=1C(CCOC=2C=3CCCCC=3C=CC=2)=C(C)OC=1C1=CC=CC=C1 NNJNHCMIHWEFLW-UHFFFAOYSA-N 0.000 description 2
- SUDLCNYXNJYAAN-UHFFFAOYSA-N 7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1h-indene-4-carbaldehyde Chemical compound N=1C(CCOC=2C=3CCCC=3C(C=O)=CC=2)=C(C)OC=1C1=CC=CC=C1 SUDLCNYXNJYAAN-UHFFFAOYSA-N 0.000 description 2
- BEOWNAJAPVJDQN-UHFFFAOYSA-N 7-phenylmethoxy-1-benzothiophene-4-carbaldehyde Chemical compound C1=2SC=CC=2C(C=O)=CC=C1OCC1=CC=CC=C1 BEOWNAJAPVJDQN-UHFFFAOYSA-N 0.000 description 2
- AMKGKYQBASDDJB-UHFFFAOYSA-N 9$l^{2}-borabicyclo[3.3.1]nonane Chemical compound C1CCC2CCCC1[B]2 AMKGKYQBASDDJB-UHFFFAOYSA-N 0.000 description 2
- FEJUGLKDZJDVFY-UHFFFAOYSA-N 9-borabicyclo[3.3.1]nonane Substances C1CCC2CCCC1B2 FEJUGLKDZJDVFY-UHFFFAOYSA-N 0.000 description 2
- 240000008025 Alternanthera ficoidea Species 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- ADKRMHYKGNTPHE-UHFFFAOYSA-N C(C)OC(CCC1=CC=C(C2=C1SC=C2)OCCC=2N=C(OC2C)C2=CC=CC=C2)=O Chemical compound C(C)OC(CCC1=CC=C(C2=C1SC=C2)OCCC=2N=C(OC2C)C2=CC=CC=C2)=O ADKRMHYKGNTPHE-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 102000005720 Glutathione transferase Human genes 0.000 description 2
- 108010070675 Glutathione transferase Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- OSXAUIHEBSPJLW-UHFFFAOYSA-N [2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]methanol Chemical compound OCC1=C(C)OC(C=2C=CC(Cl)=CC=2)=N1 OSXAUIHEBSPJLW-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical class 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 229940073608 benzyl chloride Drugs 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 2
- FAVAVMFXAKZTMV-UHFFFAOYSA-N dibutylboranyl trifluoromethanesulfonate Chemical compound CCCCB(CCCC)OS(=O)(=O)C(F)(F)F FAVAVMFXAKZTMV-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N dimethylaminoacetic acid Natural products CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000007345 electrophilic aromatic substitution reaction Methods 0.000 description 2
- ZDMKXUAKGJIVKL-UQQQWYQISA-N ethyl (z)-3-[2,6-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxyprop-2-enoate Chemical compound C1=C(C)C(/C=C(\OCC)C(=O)OCC)=C(C)C=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 ZDMKXUAKGJIVKL-UQQQWYQISA-N 0.000 description 2
- OJDHEKYTZPAOKF-UHFFFAOYSA-N ethyl 2-(2-benzoylanilino)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoate Chemical class C=1C=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(C(=O)OCC)CC(C1=CC=CC=C11)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 OJDHEKYTZPAOKF-UHFFFAOYSA-N 0.000 description 2
- AZBAAIJMRJPLPJ-UHFFFAOYSA-N ethyl 2-(benzhydrylideneamino)-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)=NC(C(=O)OCC)CC(C1=CC=CC=C11)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 AZBAAIJMRJPLPJ-UHFFFAOYSA-N 0.000 description 2
- BUXDQDLLTJLOMF-UHFFFAOYSA-N ethyl 2-amino-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoate Chemical compound C12=CC=CC=C2C(CC(N)C(=O)OCC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 BUXDQDLLTJLOMF-UHFFFAOYSA-N 0.000 description 2
- QILYFXLRBLGXGA-UHFFFAOYSA-N ethyl 2-ethoxy-3-(4-hydroxy-2,3-dihydro-1-benzofuran-7-yl)propanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C2=C1OCC2 QILYFXLRBLGXGA-UHFFFAOYSA-N 0.000 description 2
- UMCXXWCZXZOMQK-UHFFFAOYSA-N ethyl 2-ethoxy-3-[2-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C1=C(C)C(CC(OCC)C(=O)OCC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 UMCXXWCZXZOMQK-UHFFFAOYSA-N 0.000 description 2
- CKSRFHWWBKRUKA-UHFFFAOYSA-N ethyl 2-ethoxyacetate Chemical compound CCOCC(=O)OCC CKSRFHWWBKRUKA-UHFFFAOYSA-N 0.000 description 2
- ZDLTYAPTJOUZPD-UHFFFAOYSA-N ethyl 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoate Chemical compound C1=2C=CSC=2C(CC(C(=O)OCC)OC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 ZDLTYAPTJOUZPD-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 239000013613 expression plasmid Substances 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 238000006197 hydroboration reaction Methods 0.000 description 2
- 150000002466 imines Chemical class 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical compound COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 2
- XDFHARSFMWVRAR-UHFFFAOYSA-N methyl 2-ethoxy-3-(4-phenylmethoxy-1-benzofuran-7-yl)propanoate Chemical compound C1=2C=COC=2C(CC(OCC)C(=O)OC)=CC=C1OCC1=CC=CC=C1 XDFHARSFMWVRAR-UHFFFAOYSA-N 0.000 description 2
- HDCRYKSWIARJEJ-UHFFFAOYSA-N methyl 3-[2,6-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxypropanoate Chemical compound C1=C(C)C(CC(OCC)C(=O)OC)=C(C)C=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 HDCRYKSWIARJEJ-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000010606 normalization Methods 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000013600 plasmid vector Substances 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical group CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 238000002821 scintillation proximity assay Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 2
- 239000011877 solvent mixture Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- VCGRFBXVSFAGGA-UHFFFAOYSA-N (1,1-dioxo-1,4-thiazinan-4-yl)-[6-[[3-(4-fluorophenyl)-5-methyl-1,2-oxazol-4-yl]methoxy]pyridin-3-yl]methanone Chemical compound CC=1ON=C(C=2C=CC(F)=CC=2)C=1COC(N=C1)=CC=C1C(=O)N1CCS(=O)(=O)CC1 VCGRFBXVSFAGGA-UHFFFAOYSA-N 0.000 description 1
- FCRDIJHLAPKHSP-UHFFFAOYSA-M (1,2-dimethoxy-2-oxoethyl)-triphenylphosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C(C(=O)OC)OC)C1=CC=CC=C1 FCRDIJHLAPKHSP-UHFFFAOYSA-M 0.000 description 1
- HOEGDWCFMUAHKZ-UHFFFAOYSA-M (1-ethoxy-2-oxo-2-phenylmethoxyethyl)-triphenylphosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C(OCC)C(=O)OCC1=CC=CC=C1 HOEGDWCFMUAHKZ-UHFFFAOYSA-M 0.000 description 1
- PRDUTBIGRDZMPE-QFIPXVFZSA-N (2s)-2-ethoxy-3-[4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(C(F)(F)F)C=C1 PRDUTBIGRDZMPE-QFIPXVFZSA-N 0.000 description 1
- BLSUWVUDRWYROL-NRFANRHFSA-N (2s)-2-methoxy-3-[4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(C(F)(F)F)C=C1 BLSUWVUDRWYROL-NRFANRHFSA-N 0.000 description 1
- CLQWOCHQHSSRFZ-NRFANRHFSA-N (2s)-2-methoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-4-yl]propanoic acid Chemical compound C1=2SC=CC=2C(C[C@H](OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 CLQWOCHQHSSRFZ-NRFANRHFSA-N 0.000 description 1
- MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
- MVTLKLQYFVUIQQ-FMVGUACGSA-N (4S)-4-benzyl-3-[(2S)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-3-hydroxy-2-propoxypropanoyl]-1,3-oxazolidin-2-one Chemical compound CCCO[C@@H](C(C1=CC(=C(C(=C1)C)OCCC2=C(OC(=N2)C3=CC=CC=C3)C)C)O)C(=O)N4[C@H](COC4=O)CC5=CC=CC=C5 MVTLKLQYFVUIQQ-FMVGUACGSA-N 0.000 description 1
- NMLXQUPBFVGTKS-YZNIXAGQSA-N (4s)-4-benzyl-3-[(2s)-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=1SC=CC=11)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 NMLXQUPBFVGTKS-YZNIXAGQSA-N 0.000 description 1
- ZJSNAJOWMDGQKP-UVMMSNCQSA-N (4s)-4-benzyl-3-[(2s)-2-methoxy-3-[4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]naphthalen-1-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C1=CC=CC=C11)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(C(F)(F)F)C=C1 ZJSNAJOWMDGQKP-UVMMSNCQSA-N 0.000 description 1
- NAWWVUPHFOSHIP-UCGGBYDDSA-N (4s)-4-benzyl-3-[(2s)-2-methoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1h-inden-4-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=1CCCC=11)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 NAWWVUPHFOSHIP-UCGGBYDDSA-N 0.000 description 1
- PXRAHRZYFRZHTJ-CDZUIXILSA-N (4s)-4-benzyl-3-[(2s)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-propoxypropanoyl]-1,3-oxazolidin-2-one Chemical compound C([C@H](OCCC)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)C(C=C1C)=CC(C)=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 PXRAHRZYFRZHTJ-CDZUIXILSA-N 0.000 description 1
- LGVGJRRASCALHL-XTHXZNCLSA-N (4s)-4-benzyl-3-[(2s,3r)-2-ethoxy-3-hydroxy-3-[3-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoyl]-1,3-oxazolidin-2-one Chemical compound CC1=CC([C@@H](O)[C@H](OCC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 LGVGJRRASCALHL-XTHXZNCLSA-N 0.000 description 1
- MVTLKLQYFVUIQQ-VLDRXUDMSA-N (4s)-4-benzyl-3-[(2s,3r)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-3-hydroxy-2-propoxypropanoyl]-1,3-oxazolidin-2-one Chemical compound CC1=CC([C@@H](O)[C@H](OCCC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC(C)=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 MVTLKLQYFVUIQQ-VLDRXUDMSA-N 0.000 description 1
- RJMAOQHXCDDACN-NSQMQTOTSA-N (4s)-4-benzyl-3-[(2s,3r)-3-hydroxy-2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C1=2C=CSC=2C([C@@H](O)[C@H](OC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 RJMAOQHXCDDACN-NSQMQTOTSA-N 0.000 description 1
- ZDHYLZABGTZBCA-NSQMQTOTSA-N (4s)-4-benzyl-3-[(2s,3r)-3-hydroxy-2-methoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-4-yl]propanoyl]-1,3-oxazolidin-2-one Chemical compound C1=2SC=CC=2C([C@@H](O)[C@H](OC)C(=O)N2C(OC[C@@H]2CC=2C=CC=CC=2)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 ZDHYLZABGTZBCA-NSQMQTOTSA-N 0.000 description 1
- ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
- MOWXJLUYGFNTAL-DEOSSOPVSA-N (s)-[2-chloro-4-fluoro-5-(7-morpholin-4-ylquinazolin-4-yl)phenyl]-(6-methoxypyridazin-3-yl)methanol Chemical compound N1=NC(OC)=CC=C1[C@@H](O)C1=CC(C=2C3=CC=C(C=C3N=CN=2)N2CCOCC2)=C(F)C=C1Cl MOWXJLUYGFNTAL-DEOSSOPVSA-N 0.000 description 1
- CRSBERNSMYQZNG-UHFFFAOYSA-N 1 -dodecene Natural products CCCCCCCCCCC=C CRSBERNSMYQZNG-UHFFFAOYSA-N 0.000 description 1
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 1
- APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 1
- VWVZFHRDLPHBEG-UHFFFAOYSA-N 1-(chloromethyl)-4-methylsulfanylbenzene Chemical group CSC1=CC=C(CCl)C=C1 VWVZFHRDLPHBEG-UHFFFAOYSA-N 0.000 description 1
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 1
- ABDDQTDRAHXHOC-QMMMGPOBSA-N 1-[(7s)-5,7-dihydro-4h-thieno[2,3-c]pyran-7-yl]-n-methylmethanamine Chemical compound CNC[C@@H]1OCCC2=C1SC=C2 ABDDQTDRAHXHOC-QMMMGPOBSA-N 0.000 description 1
- HHAISVSEJFEWBZ-UHFFFAOYSA-N 1-[4-(trifluoromethyl)phenyl]ethanone Chemical compound CC(=O)C1=CC=C(C(F)(F)F)C=C1 HHAISVSEJFEWBZ-UHFFFAOYSA-N 0.000 description 1
- WXVRAHOQLYAQCR-UHFFFAOYSA-N 1-benzofuran-7-ol Chemical compound OC1=CC=CC2=C1OC=C2 WXVRAHOQLYAQCR-UHFFFAOYSA-N 0.000 description 1
- WSSVAOKEXMFMIO-UHFFFAOYSA-N 1-benzothiophene-7-carbaldehyde Chemical compound O=CC1=CC=CC2=C1SC=C2 WSSVAOKEXMFMIO-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- FRQUHSBKTAMSDF-UHFFFAOYSA-N 1-methyl-3-phenylmethoxybenzene Chemical compound CC1=CC=CC(OCC=2C=CC=CC=2)=C1 FRQUHSBKTAMSDF-UHFFFAOYSA-N 0.000 description 1
- SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- XYHKNCXZYYTLRG-UHFFFAOYSA-N 1h-imidazole-2-carbaldehyde Chemical compound O=CC1=NC=CN1 XYHKNCXZYYTLRG-UHFFFAOYSA-N 0.000 description 1
- GXNIBKDLIAXMSO-UHFFFAOYSA-N 2,3-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C(C)=C1C GXNIBKDLIAXMSO-UHFFFAOYSA-N 0.000 description 1
- GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 1
- QFKHDWGVSHELTI-UHFFFAOYSA-N 2-(3,5-dimethoxyphenyl)-5-methyl-1,3-oxazole Chemical compound COC1=CC(OC)=CC(C=2OC(C)=CN=2)=C1 QFKHDWGVSHELTI-UHFFFAOYSA-N 0.000 description 1
- KPAQCVQLDBKLMI-UHFFFAOYSA-N 2-(4-ethylphenyl)-4,5-dimethyl-3-oxido-1,3-oxazol-3-ium Chemical compound C1=CC(CC)=CC=C1C1=[N+]([O-])C(C)=C(C)O1 KPAQCVQLDBKLMI-UHFFFAOYSA-N 0.000 description 1
- JNVJRVZMMBUJRU-UHFFFAOYSA-N 2-(4-tert-butylphenyl)-4,5-dimethyl-3-oxido-1,3-oxazol-3-ium Chemical compound CC1=C(C)OC(C=2C=CC(=CC=2)C(C)(C)C)=[N+]1[O-] JNVJRVZMMBUJRU-UHFFFAOYSA-N 0.000 description 1
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
- GZDBPNUSRJIBPV-UHFFFAOYSA-N 2-[(4-methoxybenzoyl)amino]pent-4-enoic acid Chemical compound COC1=CC=C(C(=O)NC(CC=C)C(O)=O)C=C1 GZDBPNUSRJIBPV-UHFFFAOYSA-N 0.000 description 1
- UGXWZSYRAMYNQM-UHFFFAOYSA-N 2-[(4-methoxyphenyl)methoxy]-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound C1=CC(OC)=CC=C1COC1=CC(OCCC2=C(OC(=N2)C=2C=CC=CC=2)C)=CC=C1C=O UGXWZSYRAMYNQM-UHFFFAOYSA-N 0.000 description 1
- XEOFBNBBWJTDHH-UHFFFAOYSA-N 2-[2-(4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethanol Chemical compound OCCC1=C(C)OC(C=2C=CC(F)=CC=2)=N1 XEOFBNBBWJTDHH-UHFFFAOYSA-N 0.000 description 1
- BFRYADIHODFLMO-UHFFFAOYSA-N 2-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]ethanol Chemical compound C1=CC(OC)=CC=C1C1=NC(CCO)=C(C)O1 BFRYADIHODFLMO-UHFFFAOYSA-N 0.000 description 1
- IOAVXXNHSPGPEQ-UHFFFAOYSA-N 2-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophene-7-carbaldehyde Chemical compound CC1=C(N=C(O1)C1=CC=CC=C1)CCOC1=CC2=C(S1)C(=CC=C2)C=O IOAVXXNHSPGPEQ-UHFFFAOYSA-N 0.000 description 1
- YNLZFUVCWREMDV-UHFFFAOYSA-N 2-[5-methyl-2-(4-propan-2-yloxyphenyl)-1,3-oxazol-4-yl]ethanol Chemical group C1=CC(OC(C)C)=CC=C1C1=NC(CCO)=C(C)O1 YNLZFUVCWREMDV-UHFFFAOYSA-N 0.000 description 1
- RLUBOGSLLVLKSI-UHFFFAOYSA-N 2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]acetic acid Chemical compound OC(=O)CC1=C(C)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 RLUBOGSLLVLKSI-UHFFFAOYSA-N 0.000 description 1
- GYTYDWMMZVDZDI-UHFFFAOYSA-N 2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]acetonitrile Chemical compound N#CCC1=C(C)OC(C=2C=CC(=CC=2)C(F)(F)F)=N1 GYTYDWMMZVDZDI-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- RDGGXMVNPQUEHN-UHFFFAOYSA-N 2-butoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(CC(OCCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 RDGGXMVNPQUEHN-UHFFFAOYSA-N 0.000 description 1
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 1
- VIRWKAJWTKAIMA-UHFFFAOYSA-N 2-chloroethyl acetate Chemical compound CC(=O)OCCCl VIRWKAJWTKAIMA-UHFFFAOYSA-N 0.000 description 1
- TWYDDIUJXKZHMY-UHFFFAOYSA-N 2-ethoxy-3-[2-methyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]prop-2-enoic acid Chemical compound C1=C(C)C(C=C(OCC)C(O)=O)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 TWYDDIUJXKZHMY-UHFFFAOYSA-N 0.000 description 1
- FPFPBJJEDIYYGK-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(CC(OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 FPFPBJJEDIYYGK-UHFFFAOYSA-N 0.000 description 1
- VYUZENSTYNLNMY-UHFFFAOYSA-N 2-ethoxy-3-[4-[2-[2-(2-ethoxy-4-fluorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(CC(OCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(F)C=C1OCC VYUZENSTYNLNMY-UHFFFAOYSA-N 0.000 description 1
- WPDWUPQOYHNKGO-UHFFFAOYSA-N 2-hexoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoic acid Chemical compound C1=2C=CSC=2C(CC(OCCCCCC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 WPDWUPQOYHNKGO-UHFFFAOYSA-N 0.000 description 1
- VLOVDVHGLAKZNA-UHFFFAOYSA-N 2-hydroxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C(O)=C1 VLOVDVHGLAKZNA-UHFFFAOYSA-N 0.000 description 1
- HPYPAVJBAFUABQ-UHFFFAOYSA-N 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoic acid Chemical compound C12=CC=CC=C2C(CC(OC)C(O)=O)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 HPYPAVJBAFUABQ-UHFFFAOYSA-N 0.000 description 1
- IEPUYXOIRBTXDI-UHFFFAOYSA-N 2-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound C1=C(C=O)C(OC)=CC(OCCC2=C(OC(=N2)C=2C=CC=CC=2)C)=C1 IEPUYXOIRBTXDI-UHFFFAOYSA-N 0.000 description 1
- BEAJOJQJFRHQTF-UHFFFAOYSA-N 2-methyl-4-[[5-methyl-2-(4-propan-2-ylphenyl)-1,3-oxazol-4-yl]methoxy]benzaldehyde Chemical compound C1=CC(C(C)C)=CC=C1C1=NC(COC=2C=C(C)C(C=O)=CC=2)=C(C)O1 BEAJOJQJFRHQTF-UHFFFAOYSA-N 0.000 description 1
- 239000001431 2-methylbenzaldehyde Substances 0.000 description 1
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
- RQCBPOPQTLHDFC-UHFFFAOYSA-N 2-phenyl-1,3-oxazole Chemical compound C1=COC(C=2C=CC=CC=2)=N1 RQCBPOPQTLHDFC-UHFFFAOYSA-N 0.000 description 1
- OAIRTVZAAFZBMR-UHFFFAOYSA-N 2-propan-2-yloxyacetic acid Chemical compound CC(C)OCC(O)=O OAIRTVZAAFZBMR-UHFFFAOYSA-N 0.000 description 1
- HCDJVEYJSSTYSW-UHFFFAOYSA-N 2-propan-2-yloxyethyl acetate Chemical compound CC(C)OCCOC(C)=O HCDJVEYJSSTYSW-UHFFFAOYSA-N 0.000 description 1
- SGUYGLMQEOSQTH-UHFFFAOYSA-N 2-propoxyacetic acid Chemical compound CCCOCC(O)=O SGUYGLMQEOSQTH-UHFFFAOYSA-N 0.000 description 1
- HCDMJFOHIXMBOV-UHFFFAOYSA-N 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-4,7-dihydropyrrolo[4,5]pyrido[1,2-d]pyrimidin-2-one Chemical compound C=1C2=C3N(CC)C(=O)N(C=4C(=C(OC)C=C(OC)C=4F)F)CC3=CN=C2NC=1CN1CCOCC1 HCDMJFOHIXMBOV-UHFFFAOYSA-N 0.000 description 1
- BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- ZSPTYLOMNJNZNG-UHFFFAOYSA-N 3-Buten-1-ol Chemical compound OCCC=C ZSPTYLOMNJNZNG-UHFFFAOYSA-N 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M 3-Methylbutanoic acid Natural products CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- WNEODWDFDXWOLU-QHCPKHFHSA-N 3-[3-(hydroxymethyl)-4-[1-methyl-5-[[5-[(2s)-2-methyl-4-(oxetan-3-yl)piperazin-1-yl]pyridin-2-yl]amino]-6-oxopyridin-3-yl]pyridin-2-yl]-7,7-dimethyl-1,2,6,8-tetrahydrocyclopenta[3,4]pyrrolo[3,5-b]pyrazin-4-one Chemical compound C([C@@H](N(CC1)C=2C=NC(NC=3C(N(C)C=C(C=3)C=3C(=C(N4C(C5=CC=6CC(C)(C)CC=6N5CC4)=O)N=CC=3)CO)=O)=CC=2)C)N1C1COC1 WNEODWDFDXWOLU-QHCPKHFHSA-N 0.000 description 1
- COCHMAAUXSQMED-UHFFFAOYSA-N 3-acetyl-1,3-oxazolidin-2-one Chemical compound CC(=O)N1CCOC1=O COCHMAAUXSQMED-UHFFFAOYSA-N 0.000 description 1
- PRRZDZJYSJLDBS-UHFFFAOYSA-N 3-bromo-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CBr PRRZDZJYSJLDBS-UHFFFAOYSA-N 0.000 description 1
- VOIZNVUXCQLQHS-UHFFFAOYSA-N 3-bromobenzoic acid Chemical compound OC(=O)C1=CC=CC(Br)=C1 VOIZNVUXCQLQHS-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 description 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
- QSBHJTCAPWOIIE-UHFFFAOYSA-N 3-fluoro-4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1F QSBHJTCAPWOIIE-UHFFFAOYSA-N 0.000 description 1
- JSHLOPGSDZTEGQ-UHFFFAOYSA-N 3-methoxy-4-phenylmethoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC=C1OCC1=CC=CC=C1 JSHLOPGSDZTEGQ-UHFFFAOYSA-N 0.000 description 1
- ZHKFCGUCHAGTKP-UHFFFAOYSA-N 3-oxido-1,3-oxazol-3-ium Chemical compound [O-][N+]=1C=COC=1 ZHKFCGUCHAGTKP-UHFFFAOYSA-N 0.000 description 1
- ZZAJWNVELRILMW-UHFFFAOYSA-N 4,5-dimethyl-3-oxido-2-(4-propan-2-yloxyphenyl)-1,3-oxazol-3-ium Chemical compound C1=CC(OC(C)C)=CC=C1C1=[N+]([O-])C(C)=C(C)O1 ZZAJWNVELRILMW-UHFFFAOYSA-N 0.000 description 1
- GDBJQVBITXTAMN-UHFFFAOYSA-N 4,5-dimethyl-3-oxido-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-3-ium Chemical compound CC1=C(C)OC(C=2C=CC(=CC=2)C(F)(F)F)=[N+]1[O-] GDBJQVBITXTAMN-UHFFFAOYSA-N 0.000 description 1
- WOYTZASJYGTKTB-UHFFFAOYSA-N 4-(chloromethyl)-2-(2-chlorophenyl)-5-methyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C(=CC=CC=2)Cl)=N1 WOYTZASJYGTKTB-UHFFFAOYSA-N 0.000 description 1
- IAKHDTQJFDTTSR-UHFFFAOYSA-N 4-(chloromethyl)-2-(3-chlorophenyl)-5-methyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=C(Cl)C=CC=2)=N1 IAKHDTQJFDTTSR-UHFFFAOYSA-N 0.000 description 1
- ANSKJZIDWXDAJW-UHFFFAOYSA-N 4-(chloromethyl)-2-phenyl-1,3-oxazole Chemical compound ClCC1=COC(C=2C=CC=CC=2)=N1 ANSKJZIDWXDAJW-UHFFFAOYSA-N 0.000 description 1
- JENJJHITVICDPG-UHFFFAOYSA-N 4-[2-(1-benzofuran-4-yloxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound N=1C(CCOC=2C=3C=COC=3C=CC=2)=C(C)OC=1C1=CC=CC=C1 JENJJHITVICDPG-UHFFFAOYSA-N 0.000 description 1
- YNBUQZFTPYBGAL-UHFFFAOYSA-N 4-[2-(1-benzofuran-7-yloxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound N=1C(CCOC=2C=3OC=CC=3C=CC=2)=C(C)OC=1C1=CC=CC=C1 YNBUQZFTPYBGAL-UHFFFAOYSA-N 0.000 description 1
- FYTMNIUOPNRWSJ-UHFFFAOYSA-N 4-[2-(2,3-dihydro-1h-inden-4-yloxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound N=1C(CCOC=2C=3CCCC=3C=CC=2)=C(C)OC=1C1=CC=CC=C1 FYTMNIUOPNRWSJ-UHFFFAOYSA-N 0.000 description 1
- SVUPWUVRSNNTGK-UHFFFAOYSA-N 4-[2-(2,3-dimethylphenoxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=CC(C)=C1C SVUPWUVRSNNTGK-UHFFFAOYSA-N 0.000 description 1
- PYBOYEALZOESAB-UHFFFAOYSA-N 4-[2-(2,6-dimethylphenoxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=C(C)C=CC=C1C PYBOYEALZOESAB-UHFFFAOYSA-N 0.000 description 1
- JWCXYBIIZAXJGJ-UHFFFAOYSA-N 4-[2-(3,5-dimethylphenoxy)ethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC(C)=CC(C)=C1 JWCXYBIIZAXJGJ-UHFFFAOYSA-N 0.000 description 1
- SWOZKIRLVQUDTI-UHFFFAOYSA-N 4-[2-[4-(bromomethyl)naphthalen-2-yl]oxyethyl]-5-methyl-2-phenyl-1,3-oxazole Chemical compound BrCC1=CC(=CC2=CC=CC=C12)OCCC=1N=C(OC1C)C1=CC=CC=C1 SWOZKIRLVQUDTI-UHFFFAOYSA-N 0.000 description 1
- LFLCDDBQWMIJGZ-UHFFFAOYSA-N 4-[2-[5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl]ethoxy]naphthalene-1-carbaldehyde Chemical compound N=1C(CCOC=2C3=CC=CC=C3C(C=O)=CC=2)=C(C)OC=1C1=CC=C(C(F)(F)F)C=C1 LFLCDDBQWMIJGZ-UHFFFAOYSA-N 0.000 description 1
- KVCQTKNUUQOELD-UHFFFAOYSA-N 4-amino-n-[1-(3-chloro-2-fluoroanilino)-6-methylisoquinolin-5-yl]thieno[3,2-d]pyrimidine-7-carboxamide Chemical compound N=1C=CC2=C(NC(=O)C=3C4=NC=NC(N)=C4SC=3)C(C)=CC=C2C=1NC1=CC=CC(Cl)=C1F KVCQTKNUUQOELD-UHFFFAOYSA-N 0.000 description 1
- ARIREUPIXAKDAY-UHFFFAOYSA-N 4-butylbenzaldehyde Chemical compound CCCCC1=CC=C(C=O)C=C1 ARIREUPIXAKDAY-UHFFFAOYSA-N 0.000 description 1
- JVVRCYWZTJLJSG-UHFFFAOYSA-N 4-dimethylaminophenol Chemical compound CN(C)C1=CC=C(O)C=C1 JVVRCYWZTJLJSG-UHFFFAOYSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-dimethylaminopyridine Substances CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 1
- SBUOVJUWZCSGMJ-UHFFFAOYSA-N 4-ethyl-5-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-oxazole Chemical compound O1C(C)=C(CC)N=C1C1=CC=C(C(F)(F)F)C=C1 SBUOVJUWZCSGMJ-UHFFFAOYSA-N 0.000 description 1
- NRFKZFFVTGGEQF-UHFFFAOYSA-N 4-fluoro-3-methylbenzaldehyde Chemical compound CC1=CC(C=O)=CC=C1F NRFKZFFVTGGEQF-UHFFFAOYSA-N 0.000 description 1
- RRCVJJPQXAYIHF-UHFFFAOYSA-N 4-methoxy-n-(2-oxohex-5-en-3-yl)benzamide Chemical compound COC1=CC=C(C(=O)NC(CC=C)C(C)=O)C=C1 RRCVJJPQXAYIHF-UHFFFAOYSA-N 0.000 description 1
- WEJUBKBMBACIPT-UHFFFAOYSA-N 4-phenylmethoxy-1-benzothiophene-7-carbaldehyde Chemical compound C1=2C=CSC=2C(C=O)=CC=C1OCC1=CC=CC=C1 WEJUBKBMBACIPT-UHFFFAOYSA-N 0.000 description 1
- VXVHJLATONZLDT-UHFFFAOYSA-N 4-phenylmethoxynaphthalene-1-carbaldehyde Chemical compound C12=CC=CC=C2C(C=O)=CC=C1OCC1=CC=CC=C1 VXVHJLATONZLDT-UHFFFAOYSA-N 0.000 description 1
- WDANSDASCKBVKH-UHFFFAOYSA-N 4-propan-2-yloxybenzaldehyde Chemical compound CC(C)OC1=CC=C(C=O)C=C1 WDANSDASCKBVKH-UHFFFAOYSA-N 0.000 description 1
- OTXINXDGSUFPNU-UHFFFAOYSA-N 4-tert-butylbenzaldehyde Chemical compound CC(C)(C)C1=CC=C(C=O)C=C1 OTXINXDGSUFPNU-UHFFFAOYSA-N 0.000 description 1
- SCWNNOCLLOHZIG-UHFFFAOYSA-N 5,6,7,8-tetrahydro-1-naphthol Chemical compound C1CCCC2=C1C=CC=C2O SCWNNOCLLOHZIG-UHFFFAOYSA-N 0.000 description 1
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 1
- JRQXNAQWKXCZLC-UHFFFAOYSA-N 5-methyl-2-thiophen-2-yl-1,3-oxazole Chemical compound O1C(C)=CN=C1C1=CC=CS1 JRQXNAQWKXCZLC-UHFFFAOYSA-N 0.000 description 1
- LXWHDSZMLWRALI-UHFFFAOYSA-N 5-methyl-4-[2-(3-methylphenoxy)ethyl]-2-phenyl-1,3-oxazole Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=CC(C)=C1 LXWHDSZMLWRALI-UHFFFAOYSA-N 0.000 description 1
- IPVZMSJBHIXBNT-UHFFFAOYSA-N 5-phenylmethoxy-1,2,3,4-tetrahydronaphthalene Chemical compound C=1C=CC=2CCCCC=2C=1OCC1=CC=CC=C1 IPVZMSJBHIXBNT-UHFFFAOYSA-N 0.000 description 1
- KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 1
- IEWLBVWMUAPXNP-UHFFFAOYSA-N 7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzofuran-4-carbaldehyde Chemical compound N=1C(CCOC=2C=3OC=CC=3C(C=O)=CC=2)=C(C)OC=1C1=CC=CC=C1 IEWLBVWMUAPXNP-UHFFFAOYSA-N 0.000 description 1
- CYJRNFFLTBEQSQ-UHFFFAOYSA-N 8-(3-methyl-1-benzothiophen-5-yl)-N-(4-methylsulfonylpyridin-3-yl)quinoxalin-6-amine Chemical compound CS(=O)(=O)C1=C(C=NC=C1)NC=1C=C2N=CC=NC2=C(C=1)C=1C=CC2=C(C(=CS2)C)C=1 CYJRNFFLTBEQSQ-UHFFFAOYSA-N 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- 238000006220 Baeyer-Villiger oxidation reaction Methods 0.000 description 1
- AHEUBQVOBOAIKG-UHFFFAOYSA-N CC1=C(N=C(O1)C2=CC=C(C=C2)C(F)(F)F)CCOC3=CC=C(C4=CC=CC=C43)NC(=O)O Chemical compound CC1=C(N=C(O1)C2=CC=C(C=C2)C(F)(F)F)CCOC3=CC=C(C4=CC=CC=C43)NC(=O)O AHEUBQVOBOAIKG-UHFFFAOYSA-N 0.000 description 1
- BNXNNBCSJKHXGU-UHFFFAOYSA-N CC1=CC(=CC=C1)OCCC2=NC=CO2 Chemical compound CC1=CC(=CC=C1)OCCC2=NC=CO2 BNXNNBCSJKHXGU-UHFFFAOYSA-N 0.000 description 1
- BQJHVBJETFFBON-UHFFFAOYSA-M COC(C(=O)OC)OC.[Cl-].C(C1=CC=CC=C1)OC(=O)C(OC)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 Chemical compound COC(C(=O)OC)OC.[Cl-].C(C1=CC=CC=C1)OC(=O)C(OC)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1 BQJHVBJETFFBON-UHFFFAOYSA-M 0.000 description 1
- PFEMYSJMQBIRAK-UHFFFAOYSA-N COC1=CC=C(C=C1)C=1OC(=C(N1)CCCOC1=CC=CC2=CC=CC=C12)C Chemical compound COC1=CC=C(C=C1)C=1OC(=C(N1)CCCOC1=CC=CC2=CC=CC=C12)C PFEMYSJMQBIRAK-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 230000004568 DNA-binding Effects 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical group CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 206010048554 Endothelial dysfunction Diseases 0.000 description 1
- 241000672609 Escherichia coli BL21 Species 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 240000001414 Eucalyptus viminalis Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 108010001515 Galectin 4 Proteins 0.000 description 1
- 102100039556 Galectin-4 Human genes 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000741788 Homo sapiens Peroxisome proliferator-activated receptor alpha Proteins 0.000 description 1
- 101100273566 Humulus lupulus CCL10 gene Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 238000008214 LDL Cholesterol Methods 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 101000741806 Mus musculus Peroxisome proliferator-activated receptor gamma Proteins 0.000 description 1
- AYCPARAPKDAOEN-LJQANCHMSA-N N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methyl-4-thieno[3,2-d]pyrimidinyl)amino]-1,4-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide Chemical compound C1([C@H](NC(=O)N2C(C=3NN=C(NC=4C=5SC=CC=5N=C(C)N=4)C=3C2)(C)C)CN(C)C)=CC=CC=C1 AYCPARAPKDAOEN-LJQANCHMSA-N 0.000 description 1
- 230000006181 N-acylation Effects 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000007399 Nuclear hormone receptor Human genes 0.000 description 1
- 108020005497 Nuclear hormone receptor Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- GTRLPTDRWWVQIM-UHFFFAOYSA-N OC1=CC=CC=2C=COC21.C2=C(C=CC=C2O)C Chemical compound OC1=CC=CC=2C=COC21.C2=C(C=CC=C2O)C GTRLPTDRWWVQIM-UHFFFAOYSA-N 0.000 description 1
- IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 1
- 108010015181 PPAR delta Proteins 0.000 description 1
- 108010044210 PPAR-beta Proteins 0.000 description 1
- 108091008768 PPARγ1 Proteins 0.000 description 1
- 108091008767 PPARγ2 Proteins 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 238000000297 Sandmeyer reaction Methods 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930182558 Sterol Chemical class 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- LINDOXZENKYESA-UHFFFAOYSA-N TMG Natural products CNC(N)=NC LINDOXZENKYESA-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- LXRZVMYMQHNYJB-UNXOBOICSA-N [(1R,2S,4R)-4-[[5-[4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methylthiophene-2-carbonyl]pyrimidin-4-yl]amino]-2-hydroxycyclopentyl]methyl sulfamate Chemical compound CC1=C(C=C(S1)C(=O)C1=C(N[C@H]2C[C@H](O)[C@@H](COS(N)(=O)=O)C2)N=CN=C1)[C@@H]1NCCC2=C1C=C(Cl)C=C2 LXRZVMYMQHNYJB-UNXOBOICSA-N 0.000 description 1
- IMUHNRWTDUVXOU-UHFFFAOYSA-N [2-[2-bis(3,5-dimethylphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(3,5-dimethylphenyl)phosphane Chemical compound COC=1C=CC=C(P(C=2C=C(C)C=C(C)C=2)C=2C=C(C)C=C(C)C=2)C=1C=1C(OC)=CC=CC=1P(C=1C=C(C)C=C(C)C=1)C1=CC(C)=CC(C)=C1 IMUHNRWTDUVXOU-UHFFFAOYSA-N 0.000 description 1
- DSWICQDUYHOEPQ-UHFFFAOYSA-N [Mg]C=C Chemical class [Mg]C=C DSWICQDUYHOEPQ-UHFFFAOYSA-N 0.000 description 1
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M acrylate group Chemical group C(C=C)(=O)[O-] NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229940062328 actos Drugs 0.000 description 1
- 125000002252 acyl group Chemical class 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 238000006136 alcoholysis reaction Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 230000001708 anti-dyslipidemic effect Effects 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 238000005899 aromatization reaction Methods 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 229940062310 avandia Drugs 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- XKMXKELBOACIRS-UHFFFAOYSA-N benzyl 2,2-dimethoxyacetate Chemical compound COC(OC)C(=O)OCC1=CC=CC=C1 XKMXKELBOACIRS-UHFFFAOYSA-N 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N beta-methyl-butyric acid Natural products CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000006015 bromomethoxy group Chemical group 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- JYYOBHFYCIDXHH-UHFFFAOYSA-N carbonic acid;hydrate Chemical compound O.OC(O)=O JYYOBHFYCIDXHH-UHFFFAOYSA-N 0.000 description 1
- QNEFNFIKZWUAEQ-UHFFFAOYSA-N carbonic acid;potassium Chemical compound [K].OC(O)=O QNEFNFIKZWUAEQ-UHFFFAOYSA-N 0.000 description 1
- 230000007211 cardiovascular event Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 239000001913 cellulose Chemical class 0.000 description 1
- 229920002678 cellulose Chemical class 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- 238000005661 deetherification reaction Methods 0.000 description 1
- 238000003795 desorption Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- YSSSPARMOAYJTE-UHFFFAOYSA-N dibenzo-18-crown-6 Chemical compound O1CCOCCOC2=CC=CC=C2OCCOCCOC2=CC=CC=C21 YSSSPARMOAYJTE-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- HBEDSQVIWPRPAY-UHFFFAOYSA-N dihydro-benzofuran Natural products C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 1
- 229940069096 dodecene Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 230000008694 endothelial dysfunction Effects 0.000 description 1
- 238000005837 enolization reaction Methods 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- ZKSJQKFNOKHQMS-ZHZULCJRSA-N ethyl (z)-2-ethoxy-3-(4-phenylmethoxy-1-benzofuran-7-yl)prop-2-enoate Chemical compound C1=2C=COC=2C(/C=C(\OCC)C(=O)OCC)=CC=C1OCC1=CC=CC=C1 ZKSJQKFNOKHQMS-ZHZULCJRSA-N 0.000 description 1
- OEDZSQXSTXQCFE-UQQQWYQISA-N ethyl (z)-3-[2,3-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxyprop-2-enoate Chemical compound CC1=C(C)C(/C=C(\OCC)C(=O)OCC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 OEDZSQXSTXQCFE-UQQQWYQISA-N 0.000 description 1
- XMTQNPFULYPTID-ULJHMMPZSA-N ethyl (z)-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-2-ethoxyprop-2-enoate Chemical compound CC1=CC(/C=C(\OCC)C(=O)OCC)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 XMTQNPFULYPTID-ULJHMMPZSA-N 0.000 description 1
- HCEAVHCXNQDCKC-UHFFFAOYSA-N ethyl 2-(2-methylpropoxy)acetate Chemical compound CCOC(=O)COCC(C)C HCEAVHCXNQDCKC-UHFFFAOYSA-N 0.000 description 1
- ZFELUNTWQDERLR-UHFFFAOYSA-N ethyl 2-[(4-methoxybenzoyl)amino]acetate Chemical compound CCOC(=O)CNC(=O)C1=CC=C(OC)C=C1 ZFELUNTWQDERLR-UHFFFAOYSA-N 0.000 description 1
- XQGBTMWJVXKFPD-UHFFFAOYSA-N ethyl 2-[(4-methoxybenzoyl)amino]pent-4-enoate Chemical compound CCOC(=O)C(CC=C)NC(=O)C1=CC=C(OC)C=C1 XQGBTMWJVXKFPD-UHFFFAOYSA-N 0.000 description 1
- WBRFOQWYFICASQ-UHFFFAOYSA-N ethyl 2-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl]propanoate Chemical compound C(C)OC(C(C)C1=CC=C(C2=C1SC=C2)OCCC=1N=C(OC=1C)C1=CC=CC=C1)=O WBRFOQWYFICASQ-UHFFFAOYSA-N 0.000 description 1
- IRPDSGCFLMKJMN-UHFFFAOYSA-N ethyl 2-but-3-enoxy-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-3-hydroxypropanoate Chemical compound CC1=CC(C(O)C(OCCC=C)C(=O)OCC)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRPDSGCFLMKJMN-UHFFFAOYSA-N 0.000 description 1
- RYDRXAWKBOXCTO-UHFFFAOYSA-N ethyl 2-but-3-enoxy-3-[3,5-dimethyl-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]-3-methylsulfonyloxypropanoate Chemical compound CC1=CC(C(OS(C)(=O)=O)C(OCCC=C)C(=O)OCC)=CC(C)=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 RYDRXAWKBOXCTO-UHFFFAOYSA-N 0.000 description 1
- GUYSRRJLAXTUJS-UHFFFAOYSA-N ethyl 2-but-3-enoxyacetate Chemical compound CCOC(=O)COCCC=C GUYSRRJLAXTUJS-UHFFFAOYSA-N 0.000 description 1
- SVBSJWKYFYUHTF-UHFFFAOYSA-N ethyl 2-butoxyacetate Chemical compound CCCCOCC(=O)OCC SVBSJWKYFYUHTF-UHFFFAOYSA-N 0.000 description 1
- QUBCZUWEIGSGTC-UHFFFAOYSA-N ethyl 2-ethoxy-3-(4-hydroxy-3-methylphenyl)propanoate Chemical compound CCOC(=O)C(OCC)CC1=CC=C(O)C(C)=C1 QUBCZUWEIGSGTC-UHFFFAOYSA-N 0.000 description 1
- NEZZVJPJHSBBTP-UHFFFAOYSA-N ethyl 2-ethoxy-3-[3-methyl-4-[(2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]propanoate Chemical compound CC1=CC(CC(OCC)C(=O)OCC)=CC=C1OCC1=COC(C=2C=CC=CC=2)=N1 NEZZVJPJHSBBTP-UHFFFAOYSA-N 0.000 description 1
- PSKBVXDOVJKKDJ-UHFFFAOYSA-N ethyl 2-ethoxy-3-[4-[[2-(2-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-methylphenyl]propanoate Chemical compound C1=C(C)C(CC(OCC)C(=O)OCC)=CC=C1OCC1=C(C)OC(C=2C(=CC=CC=2)OC)=N1 PSKBVXDOVJKKDJ-UHFFFAOYSA-N 0.000 description 1
- MWJSNGPPMNJHLM-UHFFFAOYSA-N ethyl 2-ethoxy-3-[4-[[2-(4-ethylphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2-methylphenyl]propanoate Chemical compound C1=C(C)C(CC(OCC)C(=O)OCC)=CC=C1OCC1=C(C)OC(C=2C=CC(CC)=CC=2)=N1 MWJSNGPPMNJHLM-UHFFFAOYSA-N 0.000 description 1
- KGTLKPTVUHNZPU-UHFFFAOYSA-N ethyl 2-ethoxy-3-[7-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-2,3-dihydro-1h-inden-4-yl]propanoate Chemical compound C1=2CCCC=2C(CC(OCC)C(=O)OCC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 KGTLKPTVUHNZPU-UHFFFAOYSA-N 0.000 description 1
- MDLKBDQEABGPBL-UHFFFAOYSA-N ethyl 2-hexoxyacetate Chemical compound CCCCCCOCC(=O)OCC MDLKBDQEABGPBL-UHFFFAOYSA-N 0.000 description 1
- OQXCOYIDAMKYLV-UHFFFAOYSA-N ethyl 2-methoxy-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]naphthalen-1-yl]propanoate Chemical compound C12=CC=CC=C2C(CC(C(=O)OCC)OC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=CC=C1 OQXCOYIDAMKYLV-UHFFFAOYSA-N 0.000 description 1
- JECQALZMHMNOLO-UHFFFAOYSA-N ethyl 2-propan-2-yloxyacetate Chemical compound CCOC(=O)COC(C)C JECQALZMHMNOLO-UHFFFAOYSA-N 0.000 description 1
- ZXONMBCEAFIRDT-UHFFFAOYSA-N ethyl 2-propoxyacetate Chemical compound CCCOCC(=O)OCC ZXONMBCEAFIRDT-UHFFFAOYSA-N 0.000 description 1
- RRMWCENXYWGJJP-UHFFFAOYSA-N ethyl 3-[4-[2-[2-(3,5-dichlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-2-methoxypropanoate Chemical compound C1=2C=CSC=2C(CC(C(=O)OCC)OC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC(Cl)=CC(Cl)=C1 RRMWCENXYWGJJP-UHFFFAOYSA-N 0.000 description 1
- KLUURLGCYUODHK-UHFFFAOYSA-N ethyl 3-[4-[2-[2-(3,5-dichlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-7-yl]-3-hydroxy-2-methoxypropanoate Chemical compound C1=2C=CSC=2C(C(O)C(OC)C(=O)OCC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC(Cl)=CC(Cl)=C1 KLUURLGCYUODHK-UHFFFAOYSA-N 0.000 description 1
- RBNXDUOHRCYKPS-UHFFFAOYSA-N ethyl 3-[4-[[2-(4-tert-butylphenyl)-5-methyl-1,3-oxazol-4-yl]methoxy]-2,3-dihydro-1-benzofuran-7-yl]-2-ethoxypropanoate Chemical compound C1=2CCOC=2C(CC(OCC)C(=O)OCC)=CC=C1OCC(=C(O1)C)N=C1C1=CC=C(C(C)(C)C)C=C1 RBNXDUOHRCYKPS-UHFFFAOYSA-N 0.000 description 1
- XRVUKWWXWXQSOE-UHFFFAOYSA-N ethyl 3-hydroxy-2-methoxy-3-[4-[3-[2-(4-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]propoxy]naphthalen-1-yl]propanoate Chemical compound C12=CC=CC=C2C(C(O)C(OC)C(=O)OCC)=CC=C1OCCCC(=C(O1)C)N=C1C1=CC=C(OC)C=C1 XRVUKWWXWXQSOE-UHFFFAOYSA-N 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000014101 glucose homeostasis Effects 0.000 description 1
- 159000000011 group IA salts Chemical class 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- 102000054223 human PPARA Human genes 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000003914 insulin secretion Effects 0.000 description 1
- 229960004903 invert sugar Drugs 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000004322 lipid homeostasis Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- VWRPCNHJAAWVOL-UHFFFAOYSA-M lithium 2-ethoxy-3-[3-methoxy-4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound [Li+].CCOC(Cc1ccc(OCCc2nc(oc2C)-c2ccccc2)c(OC)c1)C([O-])=O VWRPCNHJAAWVOL-UHFFFAOYSA-M 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 235000004213 low-fat Nutrition 0.000 description 1
- 238000004020 luminiscence type Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000000691 measurement method Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- OFXSXYCSPVKZPF-UHFFFAOYSA-N methoxyperoxymethane Chemical group COOOC OFXSXYCSPVKZPF-UHFFFAOYSA-N 0.000 description 1
- AKQBNHXVDBKXFJ-KTKRTIGZSA-N methyl 2-[[(Z)-4-oxo-4-phenylbut-2-en-2-yl]amino]propanoate Chemical compound COC(C(C)N\C(=C/C(C1=CC=CC=C1)=O)\C)=O AKQBNHXVDBKXFJ-KTKRTIGZSA-N 0.000 description 1
- SBJWLSPXCKUTGI-UHFFFAOYSA-N methyl 2-ethoxy-3-[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]-1-benzofuran-7-yl]propanoate Chemical compound C1=2C=COC=2C(CC(OCC)C(=O)OC)=CC=C1OCC(=C(O1)C)N=C1C1=CC=CC=C1 SBJWLSPXCKUTGI-UHFFFAOYSA-N 0.000 description 1
- VCLKCOZZCBSASL-UHFFFAOYSA-N methyl 2-ethoxy-3-[7-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]-1-benzothiophen-4-yl]propanoate Chemical compound C1=2SC=CC=2C(CC(OCC)C(=O)OC)=CC=C1OCC(=C(O1)C)N=C1C1=CC=CC=C1 VCLKCOZZCBSASL-UHFFFAOYSA-N 0.000 description 1
- YVWPDYFVVMNWDT-UHFFFAOYSA-N methyl 2-ethoxypropanoate Chemical compound CCOC(C)C(=O)OC YVWPDYFVVMNWDT-UHFFFAOYSA-N 0.000 description 1
- ZCHKUYKKXSMUQM-UHFFFAOYSA-N methyl 3-[7-[2-[2-(4-chlorophenyl)-5-methyl-1,3-oxazol-4-yl]ethoxy]-1-benzothiophen-4-yl]-2-ethoxypropanoate Chemical compound C1=2SC=CC=2C(CC(OCC)C(=O)OC)=CC=C1OCCC(=C(O1)C)N=C1C1=CC=C(Cl)C=C1 ZCHKUYKKXSMUQM-UHFFFAOYSA-N 0.000 description 1
- 229940032007 methylethyl ketone Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical class [SiH3]* 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- KQPMFNHZHBLVRR-UHFFFAOYSA-N oxalic acid;hydrochloride Chemical compound Cl.OC(=O)C(O)=O KQPMFNHZHBLVRR-UHFFFAOYSA-N 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- XMGMFRIEKMMMSU-UHFFFAOYSA-N phenylmethylbenzene Chemical group C=1C=CC=CC=1[C]C1=CC=CC=C1 XMGMFRIEKMMMSU-UHFFFAOYSA-N 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- ICZHJFWIOPYQCA-UHFFFAOYSA-N pirkle's alcohol Chemical compound C1=CC=C2C(C(O)C(F)(F)F)=C(C=CC=C3)C3=CC2=C1 ICZHJFWIOPYQCA-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 229920001223 polyethylene glycol Chemical class 0.000 description 1
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000005588 protonation Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000003653 radioligand binding assay Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000003757 reverse transcription PCR Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 235000019719 rose oil Nutrition 0.000 description 1
- 239000010666 rose oil Substances 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 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
- XIIOFHFUYBLOLW-UHFFFAOYSA-N selpercatinib Chemical compound OC(COC=1C=C(C=2N(C=1)N=CC=2C#N)C=1C=NC(=CC=1)N1CC2N(C(C1)C2)CC=1C=NC(=CC=1)OC)(C)C XIIOFHFUYBLOLW-UHFFFAOYSA-N 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 231100000847 severe hepatotoxicity Toxicity 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- FDRCDNZGSXJAFP-UHFFFAOYSA-M sodium chloroacetate Chemical compound [Na+].[O-]C(=O)CCl FDRCDNZGSXJAFP-UHFFFAOYSA-M 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- UAXOELSVPTZZQG-UHFFFAOYSA-N tiglic acid Natural products CC(C)=C(C)C(O)=O UAXOELSVPTZZQG-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- DKZBBWMURDFHNE-UHFFFAOYSA-N trans-coniferylaldehyde Natural products COC1=CC(C=CC=O)=CC=C1O DKZBBWMURDFHNE-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- AVCVDUDESCZFHJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound [Cl-].C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 AVCVDUDESCZFHJ-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229940005605 valeric acid Drugs 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61P3/06—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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- 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
- 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
-
- 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
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (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)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01111745 | 2001-05-15 | ||
| PCT/EP2002/004962 WO2002092084A1 (en) | 2001-05-15 | 2002-05-06 | Carboxylic acid substituted oxazole derivatives for use as ppar-alpha and -gamma activators in the treatment of diabetes |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009028181A Division JP2009138011A (ja) | 2001-05-15 | 2009-02-10 | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2004529174A JP2004529174A (ja) | 2004-09-24 |
| JP2004529174A5 JP2004529174A5 (OSRAM) | 2005-08-25 |
| JP4330883B2 true JP4330883B2 (ja) | 2009-09-16 |
Family
ID=8177436
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002589001A Expired - Fee Related JP4330883B2 (ja) | 2001-05-15 | 2002-05-06 | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 |
| JP2009028181A Pending JP2009138011A (ja) | 2001-05-15 | 2009-02-10 | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009028181A Pending JP2009138011A (ja) | 2001-05-15 | 2009-02-10 | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 |
Country Status (38)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009138011A (ja) * | 2001-05-15 | 2009-06-25 | F Hoffmann La Roche Ag | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| KR100545507B1 (ko) * | 2000-05-26 | 2006-01-24 | 니뽄 신야쿠 가부시키가이샤 | 복소환 유도체 |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| US7718802B2 (en) | 2001-08-10 | 2010-05-18 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| US7655658B2 (en) * | 2001-08-10 | 2010-02-02 | Palatin Technologies, Inc. | Thieno [2,3-D]pyrimidine-2,4-dione melanocortin-specific compounds |
| JP2005504043A (ja) * | 2001-08-10 | 2005-02-10 | パラチン テクノロジーズ インク． | 生物学的に活性な金属ペプチド類のペプチド模倣体類 |
| US7456184B2 (en) * | 2003-05-01 | 2008-11-25 | Palatin Technologies Inc. | Melanocortin receptor-specific compounds |
| US7732451B2 (en) * | 2001-08-10 | 2010-06-08 | Palatin Technologies, Inc. | Naphthalene-containing melanocortin receptor-specific small molecule |
| JP2005528346A (ja) | 2002-02-25 | 2005-09-22 | イーライ・リリー・アンド・カンパニー | ペルオキシソーム増殖因子活性化受容体調節物質 |
| DK1537091T3 (da) * | 2002-08-30 | 2010-11-08 | Hoffmann La Roche | Hidtil ukendte 2-arylthiazolforbindelser som PPAR alpha- og PPAR gamma-agonister |
| TWI343915B (en) | 2002-10-07 | 2011-06-21 | Hoffmann La Roche | Chirale ppar agonists |
| AU2003302111A1 (en) * | 2002-11-15 | 2004-06-15 | Cadila Healthcare Limited | Substituted aralkyl derivatives |
| DE60323130D1 (de) * | 2002-11-25 | 2008-10-02 | Hoffmann La Roche | Indolderivaten |
| US7268157B2 (en) * | 2002-11-26 | 2007-09-11 | Shenzhen Chipscreen Biosciences, Ltd. | Substituted arylalcanoic acid derivatives as PPAR pan agonists with potent antihyperglycemic and antihyperlipidemic activity |
| FR2849849B1 (fr) * | 2003-01-13 | 2006-08-04 | Merck Sante Sas | Nouveaux acides carboxyliques et derives pour le traitement et la prevention du diabete et des dyslipemies |
| US7727990B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine and keto-piperazine compounds |
| US7968548B2 (en) * | 2003-05-01 | 2011-06-28 | Palatin Technologies, Inc. | Melanocortin receptor-specific piperazine compounds with diamine groups |
| US7727991B2 (en) | 2003-05-01 | 2010-06-01 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific single acyl piperazine compounds |
| US7262303B2 (en) | 2003-09-29 | 2007-08-28 | Hoffman-La Roche Inc. | Process for the production of chiral propionic acid derivatives |
| US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| JP2007509998A (ja) | 2003-11-05 | 2007-04-19 | エフ．ホフマン−ラ ロシュ アーゲー | Ｐｐａｒ活性化剤としてのベンズ環付加された化合物 |
| KR20080042188A (ko) * | 2003-11-05 | 2008-05-14 | 에프. 호프만-라 로슈 아게 | Ｐｐａｒ 작용제로서 페닐 유도체 |
| WO2005056536A1 (en) * | 2003-12-10 | 2005-06-23 | Ranbaxy Laboratories Limited | Antidiabetic agents which exhibit activity against ppar |
| US7709484B1 (en) | 2004-04-19 | 2010-05-04 | Palatin Technologies, Inc. | Substituted melanocortin receptor-specific piperazine compounds |
| CA2564563C (en) | 2004-05-03 | 2011-07-05 | F. Hoffmann-La Roche Ag | Indolyl derivatives as liver-x-receptor modulators |
| CN100344618C (zh) * | 2004-05-24 | 2007-10-24 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的N－芳丙烯酰基取代的酪氨酸衍生物 |
| CN100436430C (zh) * | 2004-05-24 | 2008-11-26 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的烷酰基取代的酪氨酸衍生物 |
| WO2006108491A1 (en) * | 2005-04-11 | 2006-10-19 | Dsm Fine Chemicals Austria Nfg Gmbh & Co Kg | Improved process for preparing oxazole nitriles |
| US20060241073A1 (en) * | 2005-04-20 | 2006-10-26 | Wanders Ronaldus J A | Means and methods for counteracting fatty acid accumulation |
| US7834017B2 (en) | 2006-08-11 | 2010-11-16 | Palatin Technologies, Inc. | Diamine-containing, tetra-substituted piperazine compounds having identical 1- and 4-substituents |
| KR100847780B1 (ko) * | 2006-10-26 | 2008-07-23 | 재단법인서울대학교산학협력재단 | 2-에톡시프로피온산 유도체 또는 이의 약학적으로허용가능한 염, 이의 제조방법 및 이를 유효성분으로함유하는 당뇨병 예방 및 치료제 |
| GB2460784A (en) * | 2007-03-07 | 2009-12-16 | Dong A Pharmtech Co Ltd | Novel phenylpropionic acid derivatives as peroxisome proliferator-activated gamma receptor modulators,method of the same,and pharmaceutical composition |
| PT2100604E (pt) * | 2008-03-10 | 2012-07-24 | Nestec Sa | Ácidos dicarboxílicos de cadeia média e os seus derivados e doenças metabólicas |
| AU2009246626A1 (en) * | 2008-05-15 | 2009-11-19 | Merck Sharp & Dohme Corp. | Oxazolobenzimidazole derivatives |
| KR101285520B1 (ko) | 2008-12-23 | 2013-07-17 | 에프. 호프만-라 로슈 아게 | 만성 질병을 가진 환자의 진단 또는 치료 지원을 위한 구조화된 테스팅 방법 및 그 디바이스 |
| AU2010206249B2 (en) * | 2009-01-23 | 2015-07-09 | F. Hoffmann-La Roche Ag | Pharmaceutical composition comprising aleglitazar |
| CN101805337B (zh) * | 2009-02-13 | 2012-05-23 | 天津药物研究院 | 一类含脯氨酸和异恶唑骨架的化合物、其制备方法和用途 |
| US8450496B2 (en) | 2009-03-24 | 2013-05-28 | Hoffman-La Roche Inc. | Process for the preparation of propionic acid derivatives |
| NZ600273A (en) | 2009-12-07 | 2014-03-28 | Hoffmann La Roche | Process for the preparation of propionic acid derivatives |
| CN102351852B (zh) * | 2011-08-23 | 2014-06-18 | 上海交通大学 | 苯并呋喃类化合物及其制备方法、用途 |
| WO2013181384A1 (en) | 2012-05-31 | 2013-12-05 | Ratiopharm Gmbh | Solid state forms of aleglitazar sodium |
| CN104619689B (zh) * | 2012-09-12 | 2017-08-08 | 霍夫曼-拉罗奇有限公司 | (S)‑2‑甲氧基‑3‑{4‑[2‑(5‑甲基‑2‑苯基‑噁唑‑4‑基)‑乙氧基]‑苯并[b]噻吩‑7‑基}‑丙酸的固体形式及其盐的固体形式 |
| CN109588042A (zh) | 2015-11-18 | 2019-04-05 | 豪夫迈·罗氏有限公司 | 用于治疗糖尿病肾病的阿格列扎 |
| WO2018002215A1 (en) | 2016-06-30 | 2018-01-04 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of cardiomyopathies |
| WO2020156683A1 (en) | 2019-02-01 | 2020-08-06 | F. Hoffmann-La Roche Ag | Aleglitazar for use in the treatment or prevention of major adverse cardiac events |
| WO2020201263A1 (en) | 2019-04-01 | 2020-10-08 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment and prevention of cardiac remodeling |
| JP2024532807A (ja) * | 2021-08-13 | 2024-09-10 | アレバンド ファーマシューティカルズ（ホンコン）リミテッド | 重水素化化合物 |
| JP2025538159A (ja) | 2022-11-08 | 2025-11-26 | ジェンフィット | 肝不全の治療において使用するためのｐｐａｒ－アルファ／ガンマアゴニスト |
| CN118480034B (zh) * | 2023-02-13 | 2025-02-11 | 礼邦医药(香港)有限公司 | 氘代化合物的晶型或盐 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4011326A (en) | 1975-07-29 | 1977-03-08 | Merck & Co., Inc. | 2-Substituted oxazolo[4,5-b]pyridine anti-inflammatory agents |
| US5089514A (en) | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
| RU2032677C1 (ru) * | 1992-05-05 | 1995-04-10 | Бристоль-Мейерз Сквибб Компани | Производные оксазола |
| EP0648212B1 (en) | 1992-07-03 | 2001-10-24 | Smithkline Beecham Plc | Benzoxazole and benzothiazole derivatives as pharmaceutical |
| GB9225386D0 (en) | 1992-12-04 | 1993-01-27 | Smithkline Beecham Plc | Novel compounds |
| DE4317320A1 (de) | 1993-05-25 | 1994-12-01 | Boehringer Mannheim Gmbh | Neue Thiazolidindione und diese enthaltende Arzneimittel |
| GB9326171D0 (en) | 1993-12-22 | 1994-02-23 | Smithkline Beecham Plc | Novel compounds |
| GB9600464D0 (en) | 1996-01-09 | 1996-03-13 | Smithkline Beecham Plc | Novel method |
| GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
| ZA9711051B (en) | 1996-12-10 | 1999-06-09 | Bristol Myers Squibb Co | Benzodioxole benzofuran dihydrobenzofuran and benzodioxane melatonergic agents |
| DE19711616A1 (de) * | 1997-03-20 | 1998-09-24 | Boehringer Mannheim Gmbh | Verbessertes Verfahren zur Herstellung von Thiazolidindionen |
| US6121397A (en) | 1997-07-14 | 2000-09-19 | Xerox Corporation | Polymerization processes using oligomeric compound, monomer and surfactant |
| HN1998000118A (es) | 1997-08-27 | 1999-02-09 | Pfizer Prod Inc | 2 - aminopiridinas que contienen sustituyentes de anillos condensados. |
| ES2200248T3 (es) | 1997-09-19 | 2004-03-01 | Ssp Co., Ltd. | Derivados de acudi fenilpropionico sustituido en alfa y medicamento que los contienen. |
| WO1999008501A2 (en) | 1998-04-23 | 1999-02-25 | Dr. Reddy's Research Foundation | New heterocyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
| GB9817118D0 (en) * | 1998-08-07 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
| GB9914977D0 (en) * | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
| EP1078923B1 (en) | 1999-08-02 | 2006-03-08 | F. Hoffmann-La Roche Ag | Process for the preparation of benzothiophene derivatives |
| EA200300286A1 (ru) * | 2000-08-23 | 2003-08-28 | Эли Лилли Энд Компани | Агонисты активируемых пероксисомальным пролифератором рецепторов |
| PL208074B1 (pl) * | 2001-05-15 | 2011-03-31 | Hoffmann La Roche | Pochodne oksazolu, sposób ich wytwarzania, środek farmaceutyczny i zastosowanie pochodnych oksazolu |
-
2002
- 2002-05-06 PL PL367087A patent/PL208074B1/pl unknown
- 2002-05-06 EP EP02742955A patent/EP1392295B1/en not_active Expired - Lifetime
- 2002-05-06 WO PCT/EP2002/004962 patent/WO2002092084A1/en not_active Ceased
- 2002-05-06 IL IL15858902A patent/IL158589A0/xx unknown
- 2002-05-06 HR HR20030889A patent/HRP20030889B1/xx not_active IP Right Cessation
- 2002-05-06 DK DK02742955T patent/DK1392295T3/da active
- 2002-05-06 ME MEP-2008-775A patent/ME01310B/me unknown
- 2002-05-06 SI SI200230340T patent/SI1392295T1/sl unknown
- 2002-05-06 JP JP2002589001A patent/JP4330883B2/ja not_active Expired - Fee Related
- 2002-05-06 HU HU0400992A patent/HU230224B1/hu not_active IP Right Cessation
- 2002-05-06 ES ES02742955T patent/ES2264482T3/es not_active Expired - Lifetime
- 2002-05-06 SK SK1385-2003A patent/SK287842B6/sk not_active IP Right Cessation
- 2002-05-06 PT PT02742955T patent/PT1392295E/pt unknown
- 2002-05-06 RU RU2003134150/04A patent/RU2278859C2/ru not_active IP Right Cessation
- 2002-05-06 DE DE60211891T patent/DE60211891T2/de not_active Expired - Lifetime
- 2002-05-06 KR KR1020037014816A patent/KR100654516B1/ko not_active Expired - Fee Related
- 2002-05-06 AT AT02742955T patent/ATE327753T1/de active
- 2002-05-06 MX MXPA03010435A patent/MXPA03010435A/es active IP Right Grant
- 2002-05-06 CN CNB028100964A patent/CN100356917C/zh not_active Expired - Fee Related
- 2002-05-06 BR BRPI0209821A patent/BRPI0209821B1/pt not_active IP Right Cessation
- 2002-05-06 AU AU2002342244A patent/AU2002342244B2/en not_active Ceased
- 2002-05-06 NZ NZ529033A patent/NZ529033A/en not_active IP Right Cessation
- 2002-05-06 CA CA002445145A patent/CA2445145C/en not_active Expired - Fee Related
- 2002-05-06 CZ CZ20033037A patent/CZ20033037A3/cs unknown
- 2002-05-09 US US10/142,567 patent/US6642389B2/en not_active Expired - Lifetime
- 2002-05-13 JO JO200242A patent/JO2282B1/en active
- 2002-05-13 MY MYPI20021726A patent/MY136761A/en unknown
- 2002-05-13 AR ARP020101739A patent/AR035892A1/es active IP Right Grant
- 2002-05-14 PA PA20028544901A patent/PA8544901A1/es unknown
- 2002-05-14 GT GT200200085A patent/GT200200085A/es unknown
- 2002-05-14 PE PE2002000399A patent/PE20021152A1/es active IP Right Grant
- 2002-05-14 EG EG2002050495A patent/EG25755A/xx active
-
2003
- 2003-10-23 IL IL158589A patent/IL158589A/en unknown
- 2003-10-31 ZA ZA2003/08538A patent/ZA200308538B/en unknown
- 2003-11-13 EC EC2003004848A patent/ECSP034848A/es unknown
- 2003-11-14 BG BG108362A patent/BG66316B1/bg unknown
- 2003-11-14 MA MA27399A patent/MA27025A1/fr unknown
- 2003-11-14 NO NO20035086A patent/NO333833B1/no not_active IP Right Cessation
-
2006
- 2006-08-22 CY CY20061101162T patent/CY1105160T1/el unknown
-
2009
- 2009-02-10 JP JP2009028181A patent/JP2009138011A/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009138011A (ja) * | 2001-05-15 | 2009-06-25 | F Hoffmann La Roche Ag | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4330883B2 (ja) | 糖尿病の処置においてｐｐａｒ−アルファ及び−ガンマアクチベーターとして使用するためのカルボン酸置換オキサゾール誘導体 | |
| JP4551222B2 (ja) | Ｐｐａｒアゴニストとしての置換４−アルコキシオキサゾール誘導体 | |
| AU2002342244A1 (en) | Carboxylic acid substituted oxazole derivatives for use as PPAR-alpha and -gamma activators in the treatment of diabetes | |
| JP4414886B2 (ja) | キラルなオキサゾール−アリールプロピオン酸誘導体及びｐｐａｒアゴニストとしてのこれらの使用 | |
| HK1083339B (en) | Chirale oxazole-arylpropionic acid derivatives and their use as prar agonists | |
| HK1067534B (en) | Carboxylic acid substituted oxazole derivatives for use as ppar-alpha and -gamma activators in the treatment of diabetes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20071016 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20071018 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080116 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080123 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080215 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080222 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20080313 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20081014 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20090113 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090210 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20090330 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090428 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090522 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20090616 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20090617 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4330883 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120626 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20120626 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130626 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |