公开(公告)号：US06610684B2

公开(公告)日：2003-08-26

申请号：US09739534

申请日：2000-12-14

申请人： Daniel W. Zaharevitz ,  Rick P. Gussio ,  Ravi K. Jalluri ,  Edward A. Sausville ,  Conrad Kunick ,  Laurent Meijer

发明人： Daniel W. Zaharevitz ,  Rick P. Gussio ,  Ravi K. Jalluri ,  Edward A. Sausville ,  Conrad Kunick ,  Laurent Meijer

IPC分类号： C07D48704

CPC分类号： C07D487/04 ,  C07D495/14

摘要： A new class of cyclin dependent kinase inhibitors that also have antiproliferative activity in human tumor cell line assays are described. Most of these compounds satisfy the formula wherein A is oxygen or sulfur coupled to the right by a single or double bond; R2 is selected from the group consisting of hydrogen, aryl, lower aliphatic substituents, particularly alkyl and lower alkyl ester; R4-R7 are independently selected from the group consisting of alkoxy, amino, acyl, aliphatic substituents, particularly alkyl, alkenyl and alkinyl substituents, aliphatic alcohols, particularly alkyl alcohols, aliphatic nitriles, particularly alkyl nitriles, cyano, nitro, carboxyl, halogen, hydrogen, hydroxyl, imino, and &agr;, &bgr;, unsaturated ketones; R8-R11 are independently selected from the group consisting of aliphatic substituents, particularly alkyl, alkenyl and alkinyl substituents, particularly lower aliphatic substituents, alipahatic alcohols, particularly alkyl alcohols, alkoxy, acyl, cyano, nitro, epoxy, haloalkyl groups, halogen, hydrogen and hydroxyl; R12 is selected from the group consisting of aliphatic groups, particularly lower alkyl groups, aliphatic alcohols, particularly alkyl alcohols, carboxylic acids and hydrogen. Compositions comprising effective amounts of such compounds also are described. These compounds and compositions can be used in a method for inhibiting the proliferation of living cells in a subject comprising administering an effective amount of the compound(s), or composition(s) comprising the compound(s), to a subject to inhibit the proliferation of living cells, such as neoplastic cells.

摘要翻译： 描述了一类在人肿瘤细胞系测定中也具有抗增殖活性的细胞周期蛋白依赖性激酶抑制剂。 这些化合物中的大多数满足甲醛，A是通过单键或双键向右连接的氧或硫; R2选自氢，芳基，低级脂族取代基，特别是烷基和低级烷基酯; R 4 -R 7独立地选自烷氧基，氨基，酰基，脂族取代基，特别是烷基，烯基和炔基取代基，脂族醇，特别是烷基醇，脂族腈，特别是烷基腈，氰基，硝基，羧基，卤素， 氢，羟基，亚氨基和α，β，不饱和酮; R8-R11独立地选自脂族取代基，特别是烷基，烯基和炔基取代基，特别是低级脂族取代基，脂肪族醇，特别是烷基醇，烷氧基，酰基，氰基，硝基，环氧基，卤代烷基，卤素，氢 和羟基; R 12选自脂族基团，特别是低级烷基，脂族醇，特别是烷基醇，羧酸和氢。 还描述了包含有效量的这种化合物的组合物。 这些化合物和组合物可用于抑制受试者中活细胞增殖的方法，包括向受试者施用有效量的化合物或包含该化合物的组合物以抑制受试者的抑制 活细胞增殖，如肿瘤细胞。