CA2478520A1 - Thiazole and oxazole derivatives which modulate ppar activity - Google Patents

Info

Publication number

CA2478520A1

CA2478520A1 CA002478520A CA2478520A CA2478520A1 CA 2478520 A1 CA2478520 A1 CA 2478520A1 CA 002478520 A CA002478520 A CA 002478520A CA 2478520 A CA2478520 A CA 2478520A CA 2478520 A1 CA2478520 A1 CA 2478520A1

Authority

CA

Canada

Prior art keywords

methyl

phenyl

compound

thiazol

trifluoromethyl

Prior art date

2002-03-07

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
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• 230000000694 effects Effects 0.000 title abstract description 13
• 101150014691 PPARA gene Proteins 0.000 title description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 title description 2
• 150000007978 oxazole derivatives Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 516
• 238000000034 method Methods 0.000 claims abstract description 32
• 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 17
• 150000003839 salts Chemical class 0.000 claims abstract description 16
• 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 13
• 241000124008 Mammalia Species 0.000 claims abstract description 12
• 239000001257 hydrogen Substances 0.000 claims description 135
• 229910052739 hydrogen Inorganic materials 0.000 claims description 135
• -1 ethoxy, isopropoxy, n-propoxy, t-butoxy, n-butoxy Chemical group 0.000 claims description 103
• 150000002431 hydrogen Chemical class 0.000 claims description 77
• 125000000217 alkyl group Chemical group 0.000 claims description 67
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 44
• 229910052760 oxygen Inorganic materials 0.000 claims description 34
• 125000000304 alkynyl group Chemical group 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
• 125000003545 alkoxy group Chemical group 0.000 claims description 23
• 229910052736 halogen Inorganic materials 0.000 claims description 22
• 150000002367 halogens Chemical class 0.000 claims description 22
• 125000003342 alkenyl group Chemical group 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 15
• 229910052717 sulfur Inorganic materials 0.000 claims description 15
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000005842 heteroatom Chemical group 0.000 claims description 12
• 125000002993 cycloalkylene group Chemical group 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 9
• 125000001188 haloalkyl group Chemical group 0.000 claims description 8
• 125000001072 heteroaryl group Chemical group 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 201000001320 Atherosclerosis Diseases 0.000 claims description 7
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
• 125000003107 substituted aryl group Chemical group 0.000 claims description 7
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 6
• BTHTYPIDOTXIMQ-UHFFFAOYSA-N 2-[2,6-dimethyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC(C)=C(OCC(O)=O)C(C)=C1 BTHTYPIDOTXIMQ-UHFFFAOYSA-N 0.000 claims description 5
• SXAOVCZJVBKWNV-UHFFFAOYSA-N 2-[2-methoxy-5-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(OC)=CC(SCC2=C(N=C(S2)C=2C=CC(=CC=2)C(F)(F)F)C)=C1C SXAOVCZJVBKWNV-UHFFFAOYSA-N 0.000 claims description 5
• UEOKXESYLLOOPO-UHFFFAOYSA-N 2-[3,5-dimethyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=C(C)C=C(OCC(O)=O)C=C1C UEOKXESYLLOOPO-UHFFFAOYSA-N 0.000 claims description 5
• AACIXTSGMFRFAX-UHFFFAOYSA-N 2-[3-methoxy-5-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound COC1=CC(OCC(O)=O)=CC(C)=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 AACIXTSGMFRFAX-UHFFFAOYSA-N 0.000 claims description 5
• FYWUOWGVPTVJNV-UHFFFAOYSA-N 2-[5-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-2-propan-2-ylphenoxy]acetic acid Chemical compound C1=C(OCC(O)=O)C(C(C)C)=CC(SCC2=C(N=C(S2)C=2C=CC(=CC=2)C(F)(F)F)C)=C1C FYWUOWGVPTVJNV-UHFFFAOYSA-N 0.000 claims description 5
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• OYDWHPGDTLGSKX-UHFFFAOYSA-N 1-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclopentane-1-carboxylic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1(C(O)=O)CCCC1 OYDWHPGDTLGSKX-UHFFFAOYSA-N 0.000 claims description 4
• DDIWEYHLKGCWLH-UHFFFAOYSA-N 1-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1(C(O)=O)CC1 DDIWEYHLKGCWLH-UHFFFAOYSA-N 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• HQUHMUAHNKEKBE-UHFFFAOYSA-N 2-[2,5-dimethyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC(C)=C(OCC(O)=O)C=C1C HQUHMUAHNKEKBE-UHFFFAOYSA-N 0.000 claims description 3
• JIJNRQAPLDIKEJ-UHFFFAOYSA-N 2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-5-propan-2-ylphenoxy]acetic acid Chemical compound CC(C)C1=CC(OCC(O)=O)=C(C)C=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 JIJNRQAPLDIKEJ-UHFFFAOYSA-N 0.000 claims description 3
• SMLLFAYWFOGLIE-UHFFFAOYSA-N 2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]-2-phenylacetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1C)=CC=C1OC(C(O)=O)C1=CC=CC=C1 SMLLFAYWFOGLIE-UHFFFAOYSA-N 0.000 claims description 3
• VNEQJQIWZLEZKJ-UHFFFAOYSA-N 2-[3-methoxy-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]-2-methylpropanoic acid Chemical compound COC1=CC(C(C)(C)C(O)=O)=CC=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 VNEQJQIWZLEZKJ-UHFFFAOYSA-N 0.000 claims description 3
• URHSUAIFIXFSFV-UHFFFAOYSA-N 2-[4-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclohexyl]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1CCC(CC(O)=O)CC1 URHSUAIFIXFSFV-UHFFFAOYSA-N 0.000 claims description 3
• LKSOUOBHAZNKFE-UHFFFAOYSA-N 2-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-2,6-di(propan-2-yl)phenoxy]acetic acid Chemical compound CC(C)C1=C(OCC(O)=O)C(C(C)C)=CC(SCC2=C(N=C(S2)C=2C=CC(=CC=2)C(F)(F)F)C)=C1 LKSOUOBHAZNKFE-UHFFFAOYSA-N 0.000 claims description 3
• DVWURGKSJLDMLH-UHFFFAOYSA-N 2-[5-(methoxymethyl)-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound COCC1=CC(OCC(O)=O)=C(C)C=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 DVWURGKSJLDMLH-UHFFFAOYSA-N 0.000 claims description 3
• SPIHNOZNJYIWEG-UHFFFAOYSA-N 2-[5-acetamido-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC(=O)NC1=CC(OCC(O)=O)=C(C)C=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 SPIHNOZNJYIWEG-UHFFFAOYSA-N 0.000 claims description 3
• JYBJPICHZOJTAF-UHFFFAOYSA-N 2-[5-chloro-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC(C)=C(OCC(O)=O)C=C1Cl JYBJPICHZOJTAF-UHFFFAOYSA-N 0.000 claims description 3
• XOOSHDNHFWJPFP-UHFFFAOYSA-N 2-[5-ethyl-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CCC1=CC(OCC(O)=O)=C(C)C=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 XOOSHDNHFWJPFP-UHFFFAOYSA-N 0.000 claims description 3
• QCDNMSBIAQWUKE-UHFFFAOYSA-N 2-[5-methoxy-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]phenyl]sulfanylacetic acid Chemical compound COC1=CC(SCC(O)=O)=C(C)C=C1OCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 QCDNMSBIAQWUKE-UHFFFAOYSA-N 0.000 claims description 3
• VQOUEAIDXMETIV-UHFFFAOYSA-N 2-[5-methoxy-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound COC1=CC(OCC(O)=O)=C(C)C=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 VQOUEAIDXMETIV-UHFFFAOYSA-N 0.000 claims description 3
• VGUHAIFLYNPBDW-UHFFFAOYSA-N 2-methyl-2-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC=C(C(C)(C)C(O)=O)C=C1 VGUHAIFLYNPBDW-UHFFFAOYSA-N 0.000 claims description 3
• BEMFECXVAHZOJO-UHFFFAOYSA-N 3-[2,4-dimethoxy-5-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(OC)=CC(OC)=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 BEMFECXVAHZOJO-UHFFFAOYSA-N 0.000 claims description 3
• HWVUOUOJVCMKGU-UHFFFAOYSA-N 3-[2,5-dimethoxy-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]propanoic acid Chemical compound C1=C(CCC(O)=O)C(OC)=CC(SCC2=C(N=C(S2)C=2C=CC(=CC=2)C(F)(F)F)C)=C1OC HWVUOUOJVCMKGU-UHFFFAOYSA-N 0.000 claims description 3
• NZRXUODRBKKPPF-UHFFFAOYSA-N 3-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]propanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC=C(OCCC(O)=O)C=C1 NZRXUODRBKKPPF-UHFFFAOYSA-N 0.000 claims description 3
• RICOCBHLOVJGHX-UHFFFAOYSA-N 3-methyl-3-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]butanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC=C(C(C)(C)CC(O)=O)C=C1 RICOCBHLOVJGHX-UHFFFAOYSA-N 0.000 claims description 3
• AUFCIMVSEPPGHN-UHFFFAOYSA-N 4-methyl-4-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]pentanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC=C(C(C)(C)CCC(O)=O)C=C1 AUFCIMVSEPPGHN-UHFFFAOYSA-N 0.000 claims description 3
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• NABVXOJDCAFYIK-UHFFFAOYSA-N 2,2-difluoro-2-[5-methoxy-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]phenyl]sulfanylacetic acid Chemical compound COC1=CC(SC(F)(F)C(O)=O)=C(C)C=C1OCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 NABVXOJDCAFYIK-UHFFFAOYSA-N 0.000 claims description 2
• JFOBZYWLCOLFPS-UHFFFAOYSA-N 2-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1CC1C(O)=O JFOBZYWLCOLFPS-UHFFFAOYSA-N 0.000 claims description 2
• BTCJJHQONSMXEO-UHFFFAOYSA-N 2-[5-fluoro-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC(C)=C(OCC(O)=O)C=C1F BTCJJHQONSMXEO-UHFFFAOYSA-N 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 2
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
• 238000004519 manufacturing process Methods 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 58
• 239000003814 drug Substances 0.000 abstract description 6
• 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 abstract description 4
• 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 abstract description 4
• 229940124597 therapeutic agent Drugs 0.000 abstract description 2
• 238000002360 preparation method Methods 0.000 description 162
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 115
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 107
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 76
• 235000019439 ethyl acetate Nutrition 0.000 description 55
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
• 239000000047 product Substances 0.000 description 44
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 43
• 239000000243 solution Substances 0.000 description 43
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
• 230000015572 biosynthetic process Effects 0.000 description 36
• 238000003786 synthesis reaction Methods 0.000 description 35
• 239000007787 solid Substances 0.000 description 29
• 239000011541 reaction mixture Substances 0.000 description 27
• 239000003921 oil Substances 0.000 description 23
• 235000019198 oils Nutrition 0.000 description 23
• 238000000746 purification Methods 0.000 description 23
• 239000012267 brine Substances 0.000 description 20
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
• 239000002904 solvent Substances 0.000 description 20
• JQVJAQPUFIIRJP-UHFFFAOYSA-N 5-(chloromethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole Chemical compound S1C(CCl)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 JQVJAQPUFIIRJP-UHFFFAOYSA-N 0.000 description 19
• 239000002253 acid Substances 0.000 description 19
• 238000003818 flash chromatography Methods 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
• 229960000583 acetic acid Drugs 0.000 description 18
• 239000010410 layer Substances 0.000 description 18
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
• 229910000024 caesium carbonate Inorganic materials 0.000 description 15
• 239000012043 crude product Substances 0.000 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 description 14
• 239000010409 thin film Substances 0.000 description 14
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 13
• 238000010828 elution Methods 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 125000004432 carbon atom Chemical group C* 0.000 description 12
• JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 12
• 238000010992 reflux Methods 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
• 238000006243 chemical reaction Methods 0.000 description 10
• 150000002148 esters Chemical class 0.000 description 10
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
• 239000012071 phase Substances 0.000 description 10
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 9
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
• 101150041968 CDC13 gene Proteins 0.000 description 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
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• WXEBMNUBHOTIPB-UHFFFAOYSA-N methyl 2-[2-methoxy-5-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetate Chemical compound C1=C(OC)C(OCC(=O)OC)=CC(C)=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 WXEBMNUBHOTIPB-UHFFFAOYSA-N 0.000 description 2
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