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    • 5. 发明申请
    • ACETAMIDINE DERIVATIVES AND THEIR USE AS INHIBITORS FOR THE NITRIC OXIDE SYNTHASE
    • 乙酰胺衍生物及其作为氮氧化物合成酶的抑制剂
    • WO1996019440A1
    • 1996-06-27
    • PCT/GB1995002978
    • 1995-12-20
    • THE WELLCOME FOUNDATION LIMITEDOPLINGER, Jeffrey, AlanGARVEY, Edward, PatrickFURFINE, Eric, StevenSHEARER, Barry, GeorgeCOLLINS, Jon, Loren
    • THE WELLCOME FOUNDATION LIMITED
    • C07C257/14
    • C07D249/08A61K31/155A61K31/416C07C257/14C07C257/18C07C311/46C07C323/41C07C323/60C07C335/36C07C2602/08C07D213/74C07D217/04C07D217/22C07D231/12C07D231/56C07D233/56C07D277/40C07D333/20
    • A class of acetamidine derivatives of general formula (I), methods for the manufacture thereof in therapy, particularly as inhibitors of nitric oxide synthase, is disclosed or a salt thereof, wherein R is hydrogen, a C1-6 hydrocarbyl group optionally substituted by halo, halo, nitro, cyano or a group XR wherein X is oxygen, C(O)m wherein m is 1 or 2, S(O)n wherein n is 0, 1 or 2, or a group NR wherein R is hydrogen or C1-6 alkyl; and R is hydrogen, C1-6 alkyl, or a group NR R wherein R and R are independently hydrogen or C1-6 alkyl, provided that R is not NR R when X is oxygen or S(O)n; R and R are independently selected from hydrogen or halo; R is a C1-14 hydrocarbyl group which may optionally contain one or two heteroatoms, the group R being optionally substituted by one or more groups independently selected from halo; N3; nitro; CF3; ZR wherein Z is oxygen, C(O)m', wherein m' is 1 or 2, S(O)n', wherein n' is 0, 1 or 2, or a group NR wherein R is hydrogen or C1-6 alkyl and R is hydrogen, C1-6 alkyl or a group NR R wherein R and R are independently hydrogen or C1-6 alkyl; or R is substituted by a group (a), wherein R has a definition the same as for R ; with the proviso that when R is a C1-6 alkyl group and R is a C1-14 hydrocarbyl substituted by two groups ZR wherein one group ZR is CO2H, the other group ZR is not NH2.
    • 公开了一类通式(I)的乙脒衍生物,其在治疗中的制备方法,特别是作为一氧化氮合酶抑制剂的方法,或其盐,其中R 1为氢,任选地为C 1-6烃基 被卤素,卤素,硝基,氰基或XR 3基团取代,其中X是氧,C(O)m,其中m是1或2,S(O)n,其中n是0,1或2, NR 4其中R 4是氢或C 1-6烷基; 并且R 3是氢,C 1-6烷基或NR 5 R 6基团,其中R 5和R 6独立地是氢或C 1-6烷基,条件是R 3是 当X为氧或S(O)n时,不为NR 5 R 6; R 1a和R 1b独立地选自氢或卤素; R 2是可任选地含有一个或两个杂原子的C 1-14烃基,R 2任选被一个或多个独立地选自卤素的基团取代; N3; 硝基; CF3; ZR 7其中Z是氧,C(O)m',其中m'是1或2,S(O)n',其中n'是0,1或2,或NR 8的基团其中R 8是氢或C 1-6烷基,R 7是氢,C 1-6烷基或NR 9 R 10基团,其中R 9和R 10独立地是氢或C 1-6 烷基; 或R 2由基团(a)取代,其中R 11具有与R 1相同的定义; 条件是当R 1为C 1-6烷基且R 2为被两个ZR 7基团取代的C 1-14烃基时,其中一个基团ZR 7为CO 2 H,另一组ZR < 7>不是NH2。
    • 8. 发明申请
    • ENZYME INHIBITORS
    • 酶抑制剂
    • WO1995034534A1
    • 1995-12-21
    • PCT/GB1995001378
    • 1995-06-14
    • THE WELLCOME FOUNDATION LIMITEDHODSON, Harold, FrancisPALMER, Richard, Michael, JohnSAWYER, David, AlanKNOWLES, Richard, GrahamFRANZMANN, Karl, WitoldDRYSDALE, Martin, JamesSMITH, StevenDAVIES, Patricia, IfeyinwaCLARK, Helen, Alice, RebeccaSHEARER, Barry, George
    • THE WELLCOME FOUNDATION LIMITED
    • C07C317/48
    • C07C323/60C07C317/48Y02P20/55
    • A compound of formula (I), wherein R is a C1-6 straight or branched chain alkyl group, a C2-6alkenyl group, a C2-6alkynyl group, a C3-6cycloalkyl group or a C3-6cycloalkyl C1-6alkyl group, each optionally substituted by one to three groups independently selected from: -CN; -NO2; a group -COR wherein R is hydrogen, C1-6alkyl, -OR wherein R is hydrogen or C1-6alkyl, or NR R , wherein R and R are independently selected from hydrogen or C1-6alkyl; a group -S(O)mR , wherein m is 0, 1 or 2, R is hydrogen, C1-6 alkyl, hydroxy or NR R , wherein R and R are independently hydrogen or C1-6 alkyl; a group PO(OR )2, wherein R is hydrogen or C1-6 alkyl; a group NR R , wherein R and R are independently selected from hydrogen, C1-6 alkyl, -COR , wherein R is hydrogen or C1-6alkyl, or -S(O)m'R , wherein m' is 0, 1 or 2 and R is hydrogen or C1-6alkyl; halo; or a group -OR , wherein R is hydrogen, C1-6 alkyl optionally substituted by one to three halo atoms, C6-10 aryl or -COR wherein R is hydrogen or C1-6 alkyl; p is 2 or 3, q is 1 or 2 and n is 0 or 1 and all salts, esters, amides and physiologically acceptable prodrugs thereof; pharmaceutical uses and formulations therefor; and processes for their preparation are disclosed.
    • 式(I)化合物,其中R 1为C 1-6直链或支链烷基,C 2-6烯基,C 2-6炔基,C 3-6环烷基或C 3-6环烷基C 1-6烷基 各自任选被一至三个独立地选自:-CN的基团取代; NO 2; 基团-COR 2其中R 2是氢,C 1-6烷基,-OR 3,其中R 3是氢或C 1-6烷基或NR 4 R 5,其中R 4 >和R 5独立地选自氢或C 1-6烷基; 基团-S(O)m R 6,其中m为0,1或2,R 6为氢,C 1-6烷基,羟基或NR 7 R 8,其中R 7和 R 8独立地是氢或C 1-6烷基; 基团PO(OR 9)2,其中R 9是氢或C 1-6烷基; NR 10 R 11基团,其中R 10和R 11独立地选自氢,C 1-6烷基,-COR 12,其中R 12是氢或C 1-6烷基, 或-S(O)m'R 13,其中m'为0,1或2,R 13为氢或C 1-6烷基; 光环; 或基团-OR 14,其中R 14是氢,任选被一至三个卤素原子取代的C 1-6烷基,C 6-10芳基或-COR 15,其中R 15是氢或C1- 6烷基; p为2或3,q为1或2,n为0或1,所有的盐,酯,酰胺和其生理上可接受的前药; 药用及其制剂; 并公开了其制备方法。
    • 10. 发明申请
    • TRICYCLIC DERIVATIVES AND THEIR USE AS ANTI-CANCER AGENTS
    • 三肽衍生物及其作为抗癌剂的用途
    • WO1995021171A1
    • 1995-08-10
    • PCT/GB1995000203
    • 1995-02-01
    • THE WELLCOME FOUNDATION LIMITEDUNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITEDMILLER, David, DrysdaleCHUNCHATPRASERT, LaddawanSHANNON, Patrick, Vivian, Richard
    • THE WELLCOME FOUNDATION LIMITEDUNIVERSITY COLLEGE CARDIFF CONSULTANTS LIMITED
    • C07D487/04
    • C07D487/04
    • A compound of formula (I) or a salt or physiologically functional derivative thereof, wherein A is (a), (b), (c), (d), X is O, S, SO, SO2, CH2, CO or NR , wherein R is H, alkyl, aralkyl, aryl, alkenyl, acyl, alkynyl, sulphonyl, substituted sulphonyl, or COOMe; Y is O, S, SO, SO2, CH2, CO or NR ; R is COR , CHO, CH2OH, CH2OR , CONH2, COOR , CONHR , CONR R , CSOR , CSSR , COSR , CSNHR , CSNR R , CNHOR wherein R and R are independently hydrogen, alkoxyalkyl, heterocycloalkyl, heteroaralkyl, or C1-10 optionally substituted hydrocarbyl group which may optionally contain one or two oxygen atoms in the chain; or R and R are a sugar group. R is H, halo, cyano, COOR , alkyl, aryl, alkenyl, alkynyl, alkoxy, (wherein alkyl, aryl, alkenyl, alkynyl and alkoxy can be substituted) or CH2CH2CO2R wherein R is alkyl or aryl; R is H, alkyl, halogen, cyano, amino, COOR , CONHR , COR , CH2OH, CH2OR , CONH2, CONR R , CSOR , CSSR , COSR , CSNHR , CSNR R or CNHOR ; R is H, halogen, cyano, amino, alkyl, COOR , CONHR , COR , CH2OH, CH2OR , CONH2, CONR R , CSOR , CSSR , COSR , CSNHR , CSNR R or CNHOR ; R is H, hydroxy, aryloxy, aralkyloxy, alkyl, substituted alkyl, aralkyl, nitro, amino, halo, cyano COOR or CHO; R is H, aryl, alkyl, aralkyl, nitro, halogen, CHO or COR wherein R is alkyl or aryl; wherein R is not H when R is H and R is not H or Me when A is (c). Processes for their preparation are described, together with their use in medicine, particularly cancer therapy and pharmaceutical formulations comprising the compounds.
    • 式(I)化合物或其盐或生理功能衍生物,其中A为(a),(b),(c),(d),X为O,S,SO,SO 2,CH 2,CO或NR 其中R 7为H,烷基,芳烷基,芳基,烯基,酰基,炔基,磺酰基,取代的磺酰基或COOMe; Y是O,S,SO,SO 2,CH 2,CO或NR 7; R 1是COR 8,CHO,CH 2 OH,CH 2 O 9,CONH 2,COOR 8,CONHR 8,CONR 8 R 9,CSOR 8,CSSR 8, COSR 8,CSNHR 8,CSNR 8 R 9,CNHOR 8,其中R 8和R 9独立地是氢,烷氧基烷基,杂环烷基,杂芳烷基或C 1-10任选取代的烃基 该基团可任选地在链中含有一个或两个氧原子; 或R 8和R 9为糖基团。 R 2是H,卤素,氰基,COOR 8,烷基,芳基,烯基,炔基,烷氧基,(其中烷基,芳基,烯基,炔基和烷氧基可以被取代)或CH 2 CH 2 CO 2 R 12其中R 12 >是烷基或芳基; R 3是H,烷基,卤素,氰基,氨基,COOR 8,CONHR 8,COR 8,CH 2 OH,CH 2 OR 8,CONH 2,CONR 8 R 9, 8,CSSR 8,COSR 8,CSNHR 8,CSNR 8 R 9或CNHOR 8; R 4是H,卤素,氰基,氨基,烷基,COOR 8,CONHR 8,COR 8,CH 2 OH,CH 2 O 8,CONH 2,CONR 8 R 9, 8,CSSR 8,COSR 8,CSNHR 8,CSNR 8 R 9或CNHOR 8; R 5是H,羟基,芳氧基,芳烷氧基,烷基,取代的烷基,芳烷基,硝基,氨基,卤素,氰基COOR 8或CHO; R 6是H,芳基,烷基,芳烷基,硝基,卤素,CHO或COR 13,其中R 13是烷基或芳基; 当A为(c)时,当R 2为H且R 3不为H或Me时,R 8不为H。 描述了其制备方法及其在药物中的用途,特别是癌症治疗和包含该化合物的药物制剂。