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    • 2. 发明申请
    • DERIVES DE 6-(6-SUBSTITUE-TRIAZOLOPYRIDAZINE-SULFANYL) 5-FLUORO-BENZOTHIAZOLES ET 5-FLUORO-BENZIMIDAZOLES : PREPARATION, APPLICATION COMME MEDICAMENTS ET UTILISATION COMME INHIBITEURS DE MET
    • 6-(6-取代的三唑基亚氨基 - 苏氨酸)5-氟 - 苯并咪唑的衍生物及其制备方法及其作为药物的用途及其作为抑制剂的用途
    • WO2010089509A1
    • 2010-08-12
    • PCT/FR2010/050180
    • 2010-02-04
    • SANOFI-AVENTISNEMECEK, ConceptionUGOLINI, Antonio
    • NEMECEK, ConceptionUGOLINI, Antonio
    • C07D277/82C07D487/04A61K31/5025A61P35/00
    • C07D277/82C07D487/04
    • L'invention concerne les nouveaux produits de formule (I): dans laquelle (II) représente une liaison simple ou double; F représente un atome de fluor, Ra représente H, HaI, alcoxy, O-cycloalkyle, -O- hétérocycloalkyle; -NH-cycloalkyle, -NH-hétérocycloalkyle, hétéroaryle,phényle, NHCOaIk, NHCOcycloalk ou NR1 R2; X représente S, SO ou SO2, A représente NH ou S; W représente H, alkyle ou COR avec R représente cycloalkyle; alkyle éventuellement substitué par NR3R4, alcoxy, hydroxy, phényle, hétéroaryle, ou hétérocycloalkyle; alcoxy éventuellement substitué par NR3R4, càd un radical O-(CH2)n-NR3R4, un radical O-phényle ou O-(CH2)n-phényle, avec phényle éventuellement substitué et n= 1 à 4; ou le radical NR1 R2; R1 représente H ou al k et R2 représente H, cycloalkyle ou alkyle; R3 et R4 représentent H, alk, cycloalkyle, hétéroaryle ou phényle; R1, R2 et/ou R3,R4 forment avec N un cycle renfermant éventuellement O, S, N et/ou NH; tous hétérocycloalkyle, hétéroaryle et phényle et cycliques étant éventuellement substitués; ces produits étant sous toutes les formes isomères et les sels, à titre de médicaments notamment comme inhibiteurs de MET.
    • 本发明涉及式(I)的新产物,其中:(II)是单键或双键; F是氟原子,R a是H,H I,烷氧基,O-环烷基,-O-杂环烷基; -NH-环烷基,-NH-杂环烷基,杂芳基,苯基,NHCO 2,NHCO环或NR 1 R 2; X是S,SO或SO 2,A是NH或S; W是H,烷基或COR,其中R是环烷基; 任选被NR 3 R 4,烷氧基,羟基,苯基,杂芳基或杂环烷基取代的烷基; 任选被NR 3 R 4取代的烷氧基,即O-(CH 2)n -NR 3 R 4基团,O-苯基或O-(CH 2)n - 苯基,任选被取代且n = 1-4的苯基; 或NR1R2基团; R1是H或烷基,R2是H,环烷基或烷基; R3和R4是H,烷基,环烷基,杂芳基或苯基; R1,R2和/或R3,R4与任选含有O,S,N和/或NH的N一起形成一个循环; 杂环烷基,杂芳基和苯基,并且全部被任选取代; 其中所述产物可以是任何异构体或盐形式,并且可以用作药物,特别是作为MET抑制剂。
    • 5. 发明申请
    • INDOLIZINES AS KINASE PROTEIN INHIBITORS
    • 作为激酶蛋白抑制剂
    • WO03024967A3
    • 2003-09-04
    • PCT/EP0211131
    • 2002-09-17
    • AVENTIS PHARMA SARATCLIFFE ANDREW JAMESWALSH RODGER JOHN AITCHISONMAJID TAHIR NADEEMTHURAIRATNAM SUKANTHINIAMENDOLA SHELLYALDOUS DAVID JOHNSOUNESS JOHN EDWARDNEMECEK CONCEPTIONWENTZLER SYLVIEVENOT CORINNE
    • RATCLIFFE ANDREW JAMESWALSH RODGER JOHN AITCHISONMAJID TAHIR NADEEMTHURAIRATNAM SUKANTHINIAMENDOLA SHELLYALDOUS DAVID JOHNSOUNESS JOHN EDWARDNEMECEK CONCEPTIONWENTZLER SYLVIEVENOT CORINNE
    • A61K31/495A61K31/498A61K31/4985A61K31/5377A61K31/551A61K45/00A61P35/00A61P43/00C07D487/04C07D471/04
    • A61K31/495C07D487/04
    • The present invention concerns compounds of general formula (I): in which: R1 represents hydrogen, R4, -C(=Y)-NHR4, -SO2NHR4, -C(=Z1)-R4, -SO2-R4 or -C(=Z1)-OR4; R2 represents hydrogen, cyano, halogen or -C°C-R5;R3 represents hydrogen, acyl, alkoxycarbonyl, alkyl, aroyl, aryl, aryloxycarbonyl, carboxy, cycloalkenyl, cycloalkyl, heteroaroyl, heteroaryl, heterocycloalkyl or -C(=O)-NY1Y2; R4 represents optionally substituted alkyl, cycloalkyl, cycloalkenyl ,heterocycloalkyl, aryl or heteroaryl R5 represents hydrogen or alkyl;R6 represents alkyl, acyl, alkoxycarbonyl, alkylsulfonyl, aryl, arylsulfonyl, aroyl, cycloalkyl, cycloalkenyl, heteroaryl, heteroarylsulfonyl, heteroaroyl and heterocycloalkyl;R7 represents optionally substituted alkyl, cycloalkyl or cycloalkylalkyl, R8 represents hydrogen, alkyl, alkenyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl;R9 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; R10 represents hydrogen or lower alkyl;R11 represents alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl or heterocycloalkylalkyl; or alkyl optionally substituted by -NY1Y2;R12 represents aryl or heteroaryl; or alkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl or heterocycloalkylalkyl each optionally substituted Y represents O, S or NCN;Y1 and Y2 (Y3 and Y4) are independently in particular hydrogen, alkyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl or heterocycloalkyl; or the group -NY1Y2 may form 5-7 membered ring or the group -NY3Y4 (-NY5Y6) may form a cyclic amine;Z (Z1)represents O or S; Z2 represents O or S(O)p;n is zero or an integer 1 or 2; m is 1 or 2;p is 1 or 2;and their corresponding N-oxides, their prodrugs; their pharmaceutically acceptable salts and solvates (e.g. hydrates), also together with one or more pharmaceutically acceptable carriers or excipients, such novel indolizines derivatives with inhibitory effects towards kinase proteins and especially for use for preventing or treating diseases that may be modulated by the inhibition of such kinase proteins and particularly solid tumours.
    • 本发明涉及通式(I)的化合物:其中:R1表示氢,R4,-C(= Y)-NHR4,-SO2NHR4,-C(= Z1)-R4,-SO2-R4或-C = Z1)-OR 4; R 2表示氢,氰基,卤素或-C≡C-R 5; R 3表示氢,酰基,烷氧基羰基,烷基,芳酰基,芳基,芳氧基羰基,羧基,环烯基,环烷基,杂芳酰基,杂芳基,杂环烷基或-C(= O) - NY1Y2; R 4表示任选取代的烷基,环烷基,环烯基,杂环烷基,芳基或杂芳基R 5表示氢或烷基; R 6表示烷基,酰基,烷氧基羰基,烷基磺酰基,芳基,芳基磺酰基,芳酰基,环烷基,环烯基,杂芳基,杂芳基磺酰基,杂芳酰基和杂环烷基; R 8代表烷基,芳基,芳基烷基,环烷基,环烷基烷基,杂芳基,杂芳基烷基,杂环烷基或杂环烷基烷基; R 9代表任选取代的烷基,环烷基或环烷基烷基,R 8代表氢,烷基,烯基,芳基, R 10表示氢或低级烷基; R 11表示烷基,芳基,芳基烷基,环烷基,环烷基烷基,杂芳基,杂芳基烷基,杂环烷基或杂环烷基烷基; 或任选被-NY 1 Y 2取代的烷基; R 12表示芳基或杂芳基; 或任选被取代的Y代表O,S或NCN的烷基,环烷基,环烷基烷基,杂环烷基或杂环烷基烷基; Y 1和Y 2(Y 3和Y 4)独立地是氢,烷基,芳基,环烷基,环烯基,杂芳基或杂环烷基; 或-NY1Y2基可以形成5-7元环,或者-NY3Y4(-NY5Y6)可以形成环状胺; Z(Z1)表示O或S; Z2表示O或S(O)p; n为零或整数1或2; m为1或2; p为1或2;及其相应的N-氧化物,其前药; 其药学上可接受的盐和溶剂合物(例如水合物),还与一种或多种药学上可接受的载体或赋形剂一起,具有对激酶蛋白具有抑制作用的新型中氮茚衍生物,特别是用于预防或治疗可能受抑制作用 这种激酶蛋白,特别是实体瘤。
    • 6. 发明申请
    • NOVEL USE FOR PYRROLE DERIVATIVES
    • 用于光子衍生物的新用途
    • WO1997000073A1
    • 1997-01-03
    • PCT/FR1996000887
    • 1996-06-12
    • RHONE-POULENC RORER S.A.BACQUE, EricBASHIARDES, GeorgesDEREU, NorbertNEMECEK, Conception
    • RHONE-POULENC RORER S.A.
    • A61K31/44
    • C07D471/04A61K31/4439C07D487/04C07D513/04
    • A novel therapeutical use of pyrrole derivatives of general formula (I), wherein Het is a ring fused with pyrrole to form a pyrrolothiazole, tetrahydro-5,6,7,8-indolizine, dihydro-pyrrolothiazine or dihydropyrrolizine ring, R1 is a carboxamide, cyano, carboxy, alkyloxycarbonyl, acyl or imidazolylcarbonyl radical, R2 is a hydrogen or halogen atom or an alkyl, alkenyl, trihalomethyl or cyano radical, R3 is a hydrogen or halogen atom or a hydroxy or alkyl radical, and Het' is a pyridyl, pyridyl N-oxide or thiazolyl radical, the alkyl or acyl radicals being straight or branched and having 1-4 carbon atoms, and the alkenyl radicals being straight or branched and having 2-4 carbon atoms, and salts thereof, if any, for preparing a drug for treating conditions in which TNF is involved.
    • 通式(I)的吡咯衍生物的新型治疗用途,其中Het是与吡咯稠合形成吡咯噻唑,四氢-5,6,7,8-中氮茚,二氢吡咯并噻嗪或二氢吡咯烷环的环,R 1是甲酰胺 ,氰基,羧基,烷氧基羰基,酰基或咪唑基羰基,R2是氢或卤素原子或烷基,烯基,三卤甲基或氰基,R3是氢或卤素原子或羟基或烷基,Het'是吡啶基 ,N-氧化吡啶基或噻唑基,所述烷基或酰基为直链或支链并具有1-4个碳原子,所述链烯基为直链或支链并具有2-4个碳原子,及其盐(如果有的话), 制备用于治疗涉及TNF的病症的药物。