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    • 8. 发明申请
    • COMPOUNDS AND METHODS FOR THE TREATMENT OF MALARIA AND CANCER
    • 治疗疟疾和癌症的化合物和方法
    • WO2006102159A2
    • 2006-09-28
    • PCT/US2006/009861
    • 2006-03-17
    • YALE UNIVERSITYUNIVERSITY OF SOUTH FLORIDAUNIVERSITY OF WASHINGTONSEBTI, SaidHAMILTON, AndrewBUCKNER, FrederickGLENN, MatthewVOORHIS, Wesley, Van
    • HAMILTON, AndrewBUCKNER, FrederickGLENN, MatthewVOORHIS, Wesley, Van
    • A61K31/59
    • C07D233/24C07D233/42C07D401/12C07D401/14C07D405/14C07D409/12C07D413/14
    • Formula (I): Where R 1 is an optionally substituted C 3 -C 12 hydrocarbyl group (preferably a cyclic alkyl group), an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R is a C(O) y R' group (preferably forming an optionally substituted C 2 -C 5 acyl group), or a S(O) x R' group, where y is 0 or 1 and x is 0, 1 or 2 and R' is H or an optionally substituted C 1 -C 12 alkyl group, or R' is an optionally substituted C 5 -C 12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R 5 , R 6 , R 7 , R 8 , R 9 and R 10 are each independently selected from H, an optionally substituted C 1 -C 12 hydrocarbyl group, including a C 5 -C 12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group, or R 5 and R 6 , R 7 and R 8 or R 9 and R 10 together form a keto (C=O) group; R N is H, an optionally substituted C 1 -C 12 hydrocarbyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group, or an optionally substituted heteroaromatic group; A is Formula (II): a Formula (III): group, or a Formula (IV) or Formula (V) group, where Z is N, O or S; R a is H, a C 1 -C 12 optionally substituted hydrocarbyl group or an optionally substituted aromatic group; n is from 0 to 3; and pharmaceutically acceptable salts thereof. Compounds according to the invention are useful in one or more aspects to inhibit farnesyl transferase, or to treat malaria, neoplasia, a hyperproliferative disease state or arthritis, including rheumaroid arthritis or osteoarthritis.
    • 式(I):其中R 1是任选取代的C 3 -C 12烃基(优选环状烷基),任选地 取代的杂环基,任选取代的芳基或任选取代的杂芳基; R是C(O)n R'基团(优选形成任选取代的C 2 -C 5酰基)或S (O)x R'基团,其中y为0或1,x为0,1或2,R'为H或任选取代的C 1 -C 3烷基, 或者R'是任选取代的C 5 -C 12环烷基,任选取代的杂环基,任选取代的芳族基团 或任选取代的杂芳基; R 5,R 6,R 7,R 8,R 9和R 9,和 R 10各自独立地选自H,任选取代的C 1 -C 12烃基,包括C 5 - 任选取代的杂环基,任选取代的芳族基团或任选取代的杂芳族基团,或R 5和R 6, R< 7>和< 8>或R 9>和< 10>一起形成酮(C = O)组; R N是H,任选取代的C 1 -C 12烃基,任选取代的杂环基,任选取代的芳族基团,或 任选取代的杂芳族基团; A是式(II):式(III):基团,或式(IV)或式(V)基团,其中Z是N,O或S; R a是H,C 1 -C 12 - 任选取代的烃基或任选取代的芳族基团; n为0〜3; 及其药学上可接受的盐。 根据本发明的化合物在一个或多个方面可用于抑制法呢基转移酶或治疗疟疾,瘤形成,过度增生性疾病状态或关节炎,包括风湿性关节炎或骨关节炎。