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    Compounds and methods for the inhibition of compounds cruzi
    1.
    发明申请
    Compounds and methods for the inhibition of compounds cruzi 审中-公开

    公开(公告)号：US20060167269A1

    公开(公告)日：2006-07-27

    申请号：US10483096

    申请日：2002-07-11

    申请人： Andrew Hamilton ,  Wesley Van Voorhis ,  Kohei Yokoyama ,  Fredericks Bucker ,  Junko Ohkanda ,  Michael Gelb ,  Jeffrey Lockman

    发明人： Andrew Hamilton ,  Wesley Van Voorhis ,  Kohei Yokoyama ,  Fredericks Bucker ,  Junko Ohkanda ,  Michael Gelb ,  Jeffrey Lockman

    IPC分类号： C07D233/61 ,  A61K31/4172

    CPC分类号： C07D233/64 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12

    摘要： The present invention relates to compounds according to the formula (I): Where RA is a C1-C10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group according to the formula (II): RB is a C1-C10 substituted or unsubstituted linear, branch-chained or cyclic alkyl or alkenyl group or a phenyl group of the formula (III): R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are each independently selected from H, C1-C10 (preferably a C1-C4) alkyl or alkenyl group, CF3, F, Cl, Br, I, CN, NO2, NH2, NHR, NRR, COR (acyl group), OR (hydroxyl or ether group), CO2R (carboxylic acid or ester group), or COSR (thioester group) where R is H or a C1-C10 (preferably a C1-C4) alkyl or alkenyl group, an unsubstituted or substituted aryl (preferably, phenyl) or heterocycle group, or a (IV) group, where R3 is H, a C1-C10 (preferably a C1-C4) alkyl, alkenyl, ether or a thioether group; and R11 and R12 are independently selected from H or a C1-C3 alkyl or alkenyl group, or a pharmaceutically acceptable salt thereof and methods for treating infections caused by protozoal, fungal and/or bacterial agents such as Trypanosoma cruzi, Mycobacterium spp., Leishmania spp., Cryptococcus spp., Aspergillus spp., Histoplasma spp., Candida spp., especially Candida albicans, Pneumocystis carinii, Trichophyton spp., Microsporum spp., Malassezia spp., Rhizopus spp., Pseudallescheria spp., Blastomyces dermatitidis and Coccidiodes spp., among others.

    Compound and Methods For the Treatment of Cancer and Malaria
    2.
    发明申请
    Compound and Methods For the Treatment of Cancer and Malaria 审中-公开
    化合物和治疗癌症和疟疾的方法

    公开(公告)号：US20080312287A1

    公开(公告)日：2008-12-18

    申请号：US11886105

    申请日：2006-03-17

    申请人： Andrew Hamilton ,  Frederick Buckner ,  Matthew Glenn ,  Wesley Van Voorhis ,  Said Sebti

    发明人： Andrew Hamilton ,  Frederick Buckner ,  Matthew Glenn ,  Wesley Van Voorhis ,  Said Sebti

    IPC分类号： A61K31/4439 ,  C07D403/02 ,  A61K31/4178 ,  A61P35/00 ,  A61P33/06 ,  C07D401/02

    CPC分类号： C07D233/24 ,  C07D233/42 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D409/12 ,  C07D413/14

    摘要： Formula (I): Where R1 is an optionally substituted C3-C12 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)yR′ group (preferably forming an optionally substituted C2-C5 acyl group), or a S(O)xR′ group, where y is 0 or 1 and x is 0, 1 or 2 and R′ is H or an optionally substituted C1-C12 alkyl group, or R′ is an optionally substituted C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group; R5, R6, R7, R8, R9 and R10 are each independently selected from H, an optionally substituted C1-C12 hydrocarbyl group, including a C5-C12 cycloalkyl group, an optionally substituted heterocyclic group, an optionally substituted aromatic group or an optionally substituted heteroaromatic group, or R5 and R6, R7 and R8 or R9 and R10 together form a keto (C═O) group; RN is H, an optionally substituted C1-C12 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; Ra is H, a C1-C12 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.

    摘要翻译： 式（I）：其中R1是任选取代的C 3 -C 12烃基（优选环状烷基），任选取代的杂环基，任选取代的芳基或任选取代的杂芳基; R是C（O）y 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是0或1，x是0,1或2，R' 是H或任选取代的C 1 -C 12烷基，或R'是任选取代的C 5 -C 12环烷基，任选取代的杂环基，任选取代的芳基或任选取代的杂芳基; R5，R6，R7，R8，R9和R10各自独立地选自H，任选取代的C 1 -C 12烃基，包括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 杂芳基或R5和R6，R7和R8或R9和R10一起形成酮（CO）基团; RN为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; Ra是H，C1-C12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。