JP4295458B2 - Ppar−ガンマ活性調節用化合物 - Google Patents
Ppar−ガンマ活性調節用化合物 Download PDFInfo
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- JP4295458B2 JP4295458B2 JP2001506989A JP2001506989A JP4295458B2 JP 4295458 B2 JP4295458 B2 JP 4295458B2 JP 2001506989 A JP2001506989 A JP 2001506989A JP 2001506989 A JP2001506989 A JP 2001506989A JP 4295458 B2 JP4295458 B2 JP 4295458B2
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- Prior art keywords
- alkyl
- mmol
- halogen
- chloro
- compound
- 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 - Lifetime
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- 150000001875 compounds Chemical class 0.000 title claims description 256
- 102000000536 PPAR gamma Human genes 0.000 title claims 3
- 108010016731 PPAR gamma Proteins 0.000 title claims 3
- 230000000694 effects Effects 0.000 title description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 151
- 150000002367 halogens Chemical class 0.000 claims description 150
- -1 —CF 3 Chemical group 0.000 claims description 135
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 104
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 84
- 125000001424 substituent group Chemical group 0.000 claims description 78
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- 125000000217 alkyl group Chemical group 0.000 claims description 63
- 125000003545 alkoxy group Chemical group 0.000 claims description 60
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 28
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052757 nitrogen Chemical group 0.000 claims description 18
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 17
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 11
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- 208000008589 Obesity Diseases 0.000 claims description 6
- 235000020824 obesity Nutrition 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 208000030159 metabolic disease Diseases 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 241000699670 Mus sp. Species 0.000 claims description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 208000016097 disease of metabolism Diseases 0.000 claims 3
- 206010003210 Arteriosclerosis Diseases 0.000 claims 1
- 241000282472 Canis lupus familiaris Species 0.000 claims 1
- 241000282693 Cercopithecidae Species 0.000 claims 1
- 241000283086 Equidae Species 0.000 claims 1
- 241000282326 Felis catus Species 0.000 claims 1
- 241000282412 Homo Species 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 241000700159 Rattus Species 0.000 claims 1
- 208000011775 arteriosclerosis disease Diseases 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000002503 metabolic effect Effects 0.000 claims 1
- 238000007911 parenteral administration Methods 0.000 claims 1
- 238000011200 topical administration Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 284
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 246
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 205
- 239000007787 solid Substances 0.000 description 191
- 238000000034 method Methods 0.000 description 172
- 239000000243 solution Substances 0.000 description 135
- 239000000203 mixture Substances 0.000 description 99
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 98
- 235000019439 ethyl acetate Nutrition 0.000 description 92
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 89
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 80
- 230000015572 biosynthetic process Effects 0.000 description 76
- 238000003786 synthesis reaction Methods 0.000 description 76
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 67
- 239000011541 reaction mixture Substances 0.000 description 65
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 63
- 125000004404 heteroalkyl group Chemical group 0.000 description 62
- 125000003118 aryl group Chemical group 0.000 description 58
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 54
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- 239000012044 organic layer Substances 0.000 description 53
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- 239000012267 brine Substances 0.000 description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 40
- 239000000047 product Substances 0.000 description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- CSCPPACGZOOCGX-UHFFFAOYSA-N acetone Substances CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 37
- 238000001914 filtration Methods 0.000 description 34
- 239000003921 oil Substances 0.000 description 34
- 235000019198 oils Nutrition 0.000 description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 33
- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- 238000003818 flash chromatography Methods 0.000 description 30
- 239000011734 sodium Substances 0.000 description 27
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 25
- 238000001816 cooling Methods 0.000 description 24
- 239000012043 crude product Substances 0.000 description 24
- 239000000543 intermediate Substances 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 239000000706 filtrate Substances 0.000 description 22
- 230000003197 catalytic effect Effects 0.000 description 21
- 238000004440 column chromatography Methods 0.000 description 21
- 238000010992 reflux Methods 0.000 description 21
- FDTPBIKNYWQLAE-UHFFFAOYSA-N 2,4-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C(Cl)=C1 FDTPBIKNYWQLAE-UHFFFAOYSA-N 0.000 description 20
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 238000000746 purification Methods 0.000 description 20
- 239000000377 silicon dioxide Substances 0.000 description 19
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
- 239000002904 solvent Substances 0.000 description 18
- 239000013078 crystal Substances 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- HHLCSFGOTLUREE-UHFFFAOYSA-N 1,2,3-trichloro-5-nitrobenzene Chemical compound [O-][N+](=O)C1=CC(Cl)=C(Cl)C(Cl)=C1 HHLCSFGOTLUREE-UHFFFAOYSA-N 0.000 description 15
- 239000012141 concentrate Substances 0.000 description 15
- 239000010410 layer Substances 0.000 description 15
- 239000000843 powder Substances 0.000 description 15
- VJZJJIJZNTWGLA-UHFFFAOYSA-N 3,5-dichloro-4-naphthalen-2-ylsulfanylaniline Chemical compound ClC1=CC(N)=CC(Cl)=C1SC1=CC=C(C=CC=C2)C2=C1 VJZJJIJZNTWGLA-UHFFFAOYSA-N 0.000 description 14
- 125000001624 naphthyl group Chemical group 0.000 description 14
- 125000004076 pyridyl group Chemical group 0.000 description 14
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 239000000460 chlorine Substances 0.000 description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
- DPHCXXYPSYMICK-UHFFFAOYSA-N 2-chloro-1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(Cl)=C1 DPHCXXYPSYMICK-UHFFFAOYSA-N 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- 125000005842 heteroatom Chemical group 0.000 description 11
- 150000002828 nitro derivatives Chemical class 0.000 description 11
- 229940124530 sulfonamide Drugs 0.000 description 11
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 150000003456 sulfonamides Chemical class 0.000 description 10
- SOXFHMGBUBJGBA-UHFFFAOYSA-N 1-(2,3-dichloro-5-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC(Cl)=C1Cl SOXFHMGBUBJGBA-UHFFFAOYSA-N 0.000 description 9
- NRPIYJFJAXEQGE-UHFFFAOYSA-N 3-chloro-4-naphthalen-2-ylsulfanylaniline Chemical compound ClC1=CC(N)=CC=C1SC1=CC=C(C=CC=C2)C2=C1 NRPIYJFJAXEQGE-UHFFFAOYSA-N 0.000 description 9
- DJRUWESABPZMRB-UHFFFAOYSA-N 5-(trifluoromethyl)-3h-1,3-benzothiazole-2-thione Chemical compound FC(F)(F)C1=CC=C2SC(=S)NC2=C1 DJRUWESABPZMRB-UHFFFAOYSA-N 0.000 description 9
- 150000001448 anilines Chemical class 0.000 description 9
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 9
- 239000007858 starting material Substances 0.000 description 9
- NLPZRWDNWKLLCI-UHFFFAOYSA-N 2-sulfanylidene-3h-1,3-benzothiazole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2SC(=S)NC2=C1 NLPZRWDNWKLLCI-UHFFFAOYSA-N 0.000 description 8
- XRIDVJQTZRUCDJ-UHFFFAOYSA-N 2-sulfanylidene-3h-1,3-benzothiazole-6-carbonitrile Chemical compound C1=C(C#N)C=C2SC(S)=NC2=C1 XRIDVJQTZRUCDJ-UHFFFAOYSA-N 0.000 description 8
- IIPWXGDGKTVTQN-UHFFFAOYSA-N 3,5-dichloro-4-[(6-chloro-1,3-benzothiazol-2-yl)oxy]aniline Chemical compound ClC1=CC(N)=CC(Cl)=C1OC1=NC2=CC=C(Cl)C=C2S1 IIPWXGDGKTVTQN-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 8
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 8
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 8
- ZHQQQRTYWQXNSU-UHFFFAOYSA-N 2,3-dichloro-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC(Cl)=C1Cl ZHQQQRTYWQXNSU-UHFFFAOYSA-N 0.000 description 7
- MDGLCBYUTKFWIH-UHFFFAOYSA-N 2,4-dichloro-n-[3,5-dichloro-4-[(5-cyano-1,3-benzothiazol-2-yl)sulfanyl]phenyl]benzenesulfonamide Chemical compound ClC1=CC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CC(Cl)=C1SC1=NC2=CC(C#N)=CC=C2S1 MDGLCBYUTKFWIH-UHFFFAOYSA-N 0.000 description 7
- NGWFPHVJKBUZOA-UHFFFAOYSA-N 2-chloro-n-[3,5-dichloro-4-[(6-cyano-1,3-benzothiazol-2-yl)sulfanyl]phenyl]-4-(trifluoromethyl)benzenesulfonamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CC(Cl)=C1SC1=NC2=CC=C(C#N)C=C2S1 NGWFPHVJKBUZOA-UHFFFAOYSA-N 0.000 description 7
- ONFDICKGBCAECF-UHFFFAOYSA-N 2-chloro-n-[3-chloro-4-[(6-cyano-1,3-benzothiazol-2-yl)sulfanyl]phenyl]-4-(trifluoromethyl)benzenesulfonamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CC=C1SC1=NC2=CC=C(C#N)C=C2S1 ONFDICKGBCAECF-UHFFFAOYSA-N 0.000 description 7
- MEJGHHKHYNUQKQ-UHFFFAOYSA-N 2-methoxy-4-nitrobenzenethiol Chemical compound COC1=CC([N+]([O-])=O)=CC=C1S MEJGHHKHYNUQKQ-UHFFFAOYSA-N 0.000 description 7
- YDRKHDJUGAULIN-UHFFFAOYSA-N 2-sulfanylidene-3h-1,3-benzothiazole-5-carbonitrile Chemical compound N#CC1=CC=C2SC(S)=NC2=C1 YDRKHDJUGAULIN-UHFFFAOYSA-N 0.000 description 7
- ITRFJJLSAYPVGB-UHFFFAOYSA-N 3-(2,6-dichloro-4-nitrophenoxy)-6-methylquinoline Chemical compound C=1C2=CC(C)=CC=C2N=CC=1OC1=C(Cl)C=C([N+]([O-])=O)C=C1Cl ITRFJJLSAYPVGB-UHFFFAOYSA-N 0.000 description 7
- DWQWGLBICRJMCM-UHFFFAOYSA-N 5-chloro-2-(2-methoxy-4-nitrophenyl)sulfanyl-1,3-benzothiazole Chemical compound COC1=CC([N+]([O-])=O)=CC=C1SC1=NC2=CC(Cl)=CC=C2S1 DWQWGLBICRJMCM-UHFFFAOYSA-N 0.000 description 7
- TUIDQYRZDZRHPQ-UHFFFAOYSA-N 5-chloropyridin-3-ol Chemical compound OC1=CN=CC(Cl)=C1 TUIDQYRZDZRHPQ-UHFFFAOYSA-N 0.000 description 7
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- ZPLNWHLILOVMLZ-UHFFFAOYSA-N 2-(2,6-dichloro-4-nitrophenyl)sulfanylnaphthalene Chemical compound ClC1=CC([N+](=O)[O-])=CC(Cl)=C1SC1=CC=C(C=CC=C2)C2=C1 ZPLNWHLILOVMLZ-UHFFFAOYSA-N 0.000 description 6
- OZDPHFHMBGPBNA-UHFFFAOYSA-N 2-(2-chloro-4-nitrophenyl)sulfanyl-1,3-benzothiazole-5-carboxylic acid Chemical compound N=1C2=CC(C(=O)O)=CC=C2SC=1SC1=CC=C([N+]([O-])=O)C=C1Cl OZDPHFHMBGPBNA-UHFFFAOYSA-N 0.000 description 6
- ZKJDQFSQNHWORY-UHFFFAOYSA-N 2-(2-chloro-4-nitrophenyl)sulfanyl-5-(trifluoromethyl)-1,3-benzothiazole Chemical compound ClC1=CC([N+](=O)[O-])=CC=C1SC1=NC2=CC(C(F)(F)F)=CC=C2S1 ZKJDQFSQNHWORY-UHFFFAOYSA-N 0.000 description 6
- YLYCJXDZYCMWPK-UHFFFAOYSA-N 2-(2-chloro-4-nitrophenyl)sulfanylnaphthalene Chemical compound ClC1=CC([N+](=O)[O-])=CC=C1SC1=CC=C(C=CC=C2)C2=C1 YLYCJXDZYCMWPK-UHFFFAOYSA-N 0.000 description 6
- ZGILLTVEEBNDOB-UHFFFAOYSA-N 2-chloro-5-nitrobenzonitrile Chemical compound [O-][N+](=O)C1=CC=C(Cl)C(C#N)=C1 ZGILLTVEEBNDOB-UHFFFAOYSA-N 0.000 description 6
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 6
- RNVHFNUPNYTNMZ-UHFFFAOYSA-N 3-(2,6-dichloro-4-nitrophenoxy)quinoline-6-carboxylic acid Chemical compound C=1C2=CC(C(=O)O)=CC=C2N=CC=1OC1=C(Cl)C=C([N+]([O-])=O)C=C1Cl RNVHFNUPNYTNMZ-UHFFFAOYSA-N 0.000 description 6
- HKGNZXXYXCKJHO-UHFFFAOYSA-N 315228-19-4 Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C=C1F HKGNZXXYXCKJHO-UHFFFAOYSA-N 0.000 description 6
- NKYDKCVZNMNZCM-UHFFFAOYSA-N 5-chloro-3h-1,3-benzothiazole-2-thione Chemical compound ClC1=CC=C2SC(S)=NC2=C1 NKYDKCVZNMNZCM-UHFFFAOYSA-N 0.000 description 6
- ILDUPWKUQLPLKK-UHFFFAOYSA-N 5-methyl-3h-1,3-benzothiazole-2-thione Chemical compound CC1=CC=C2SC(S)=NC2=C1 ILDUPWKUQLPLKK-UHFFFAOYSA-N 0.000 description 6
- BSNXPXPWIJKKDH-UHFFFAOYSA-N 6-methylquinolin-3-ol Chemical compound N1=CC(O)=CC2=CC(C)=CC=C21 BSNXPXPWIJKKDH-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- 239000007868 Raney catalyst Substances 0.000 description 6
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 6
- 229910000564 Raney nickel Inorganic materials 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 125000000753 cycloalkyl group Chemical group 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 239000002198 insoluble material Substances 0.000 description 6
- LKXXVBDWRNDBKS-UHFFFAOYSA-N methyl 2-(2,6-dichloro-4-nitrophenyl)sulfanyl-1,3-benzothiazole-5-carboxylate Chemical compound N=1C2=CC(C(=O)OC)=CC=C2SC=1SC1=C(Cl)C=C([N+]([O-])=O)C=C1Cl LKXXVBDWRNDBKS-UHFFFAOYSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 125000002098 pyridazinyl group Chemical group 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- FWPIDFUJEMBDLS-UHFFFAOYSA-L tin(II) chloride dihydrate Substances O.O.Cl[Sn]Cl FWPIDFUJEMBDLS-UHFFFAOYSA-L 0.000 description 6
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 5
- BHUBIKDIYMVADH-UHFFFAOYSA-N 1-[3-chloro-2-[(5-chloro-1,3-benzothiazol-2-yl)sulfanyl]-5-nitrophenyl]ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC(Cl)=C1SC1=NC2=CC(Cl)=CC=C2S1 BHUBIKDIYMVADH-UHFFFAOYSA-N 0.000 description 5
- MWFKWTVYKGMWEH-UHFFFAOYSA-N 2,3-dichloro-6-nitrobenzoic acid Chemical compound OC(=O)C1=C(Cl)C(Cl)=CC=C1[N+]([O-])=O MWFKWTVYKGMWEH-UHFFFAOYSA-N 0.000 description 5
- QDZGJGWDGLHVNK-UHFFFAOYSA-N 2,6-dichloro-1,3-benzothiazole Chemical compound C1=C(Cl)C=C2SC(Cl)=NC2=C1 QDZGJGWDGLHVNK-UHFFFAOYSA-N 0.000 description 5
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- SFQWZWDEKHDQNG-UHFFFAOYSA-N 2-chloro-n-(3,5-dichloro-4-naphthalen-2-ylsulfanylphenyl)-4-(trifluoromethyl)benzenesulfonamide Chemical compound ClC1=CC(C(F)(F)F)=CC=C1S(=O)(=O)NC(C=C1Cl)=CC(Cl)=C1SC1=CC=C(C=CC=C2)C2=C1 SFQWZWDEKHDQNG-UHFFFAOYSA-N 0.000 description 4
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- VSIPBZFGHOALAI-UHFFFAOYSA-N 5-amino-2-(5-chloropyridin-3-yl)oxybenzonitrile Chemical compound N#CC1=CC(N)=CC=C1OC1=CN=CC(Cl)=C1 VSIPBZFGHOALAI-UHFFFAOYSA-N 0.000 description 4
- PAPCKMYOCPPNCX-UHFFFAOYSA-N 6-chloro-n-(3,5-dichloro-4-naphthalen-2-ylsulfanylphenyl)pyridine-3-sulfonamide Chemical compound C1=NC(Cl)=CC=C1S(=O)(=O)NC(C=C1Cl)=CC(Cl)=C1SC1=CC=C(C=CC=C2)C2=C1 PAPCKMYOCPPNCX-UHFFFAOYSA-N 0.000 description 4
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- QOVYHDHLFPKQQG-NDEPHWFRSA-N N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O Chemical compound N[C@@H](CCC(=O)N1CCC(CC1)NC1=C2C=CC=CC2=NC(NCC2=CN(CCCNCCCNC3CCCCC3)N=N2)=N1)C(O)=O QOVYHDHLFPKQQG-NDEPHWFRSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
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- JJMSGSISSVQAHT-UHFFFAOYSA-N methyl 2-(4-amino-2-chlorophenyl)sulfanyl-1,3-benzothiazole-5-carboxylate Chemical compound N=1C2=CC(C(=O)OC)=CC=C2SC=1SC1=CC=C(N)C=C1Cl JJMSGSISSVQAHT-UHFFFAOYSA-N 0.000 description 4
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- SEDZOYHHAIAQIW-UHFFFAOYSA-N trimethylsilyl azide Chemical compound C[Si](C)(C)N=[N+]=[N-] SEDZOYHHAIAQIW-UHFFFAOYSA-N 0.000 description 1
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Classifications
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| PCT/US2000/018178 WO2001000579A1 (en) | 1999-06-30 | 2000-06-28 | COMPOUNDS FOR THE MODULATION OF PPARη ACTIVITY |
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| US6982251B2 (en) | 2000-12-20 | 2006-01-03 | Schering Corporation | Substituted 2-azetidinones useful as hypocholesterolemic agents |
| US7071181B2 (en) | 2001-01-26 | 2006-07-04 | Schering Corporation | Methods and therapeutic combinations for the treatment of diabetes using sterol absorption inhibitors |
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| Publication number | Publication date |
|---|---|
| NZ530833A (en) | 2005-08-26 |
| JP2003503387A (ja) | 2003-01-28 |
| MX339420B (es) | 2016-05-25 |
| CA2377309C (en) | 2010-11-23 |
| HK1043369B (en) | 2014-06-13 |
| CN1368961A (zh) | 2002-09-11 |
| IL147308A (en) | 2015-06-30 |
| DK1192137T3 (da) | 2013-11-11 |
| CA2377309A1 (en) | 2001-01-04 |
| ZA200200057B (en) | 2003-03-19 |
| WO2001000579A1 (en) | 2001-01-04 |
| MXPA01013199A (es) | 2003-08-20 |
| HK1043369A1 (en) | 2002-09-13 |
| ES2437103T3 (es) | 2014-01-08 |
| EP1192137A1 (en) | 2002-04-03 |
| SG148834A1 (en) | 2009-01-29 |
| NZ516455A (en) | 2004-03-26 |
| EA200200105A1 (ru) | 2002-06-27 |
| CN1171872C (zh) | 2004-10-20 |
| EP1192137B1 (en) | 2013-10-23 |
| IL147308A0 (en) | 2002-08-14 |
| EA004887B1 (ru) | 2004-08-26 |
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