2-(1H-吲唑-4-基)-6-(4-甲磺酰基-哌嗪-1-基甲基)-4-吗啉-4-基-噻吩并[3,2-d]嘧啶（GDC-0941）被鉴定为一种用于治疗癌症的强效、选择性、口服生物可利用的I类PI3激酶抑制剂。
The identification of 2-(1H-indazol-4-yl)-6-(4-methanesulfonyl-piperazin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine (GDC-0941) as a potent, selective, orally bioavailable inhibitor of class I PI3 kinase for the treatment of cancer .
作者信息
Folkes Adrian J, Ahmadi Khatereh, Alderton Wendy K, Alix Sonia, Baker Stewart J, Box Gary, Chuckowree Irina S, Clarke Paul A, Depledge Paul, Eccles Suzanne A, Friedman Lori S, Hayes Angela, Hancox Timothy C, Kugendradas Arumugam, Lensun Letitia, Moore Pauline, Olivero Alan G, Pang Jodie, Patel Sonal, Pergl-Wilson Giles H, Raynaud Florence I, Robson Anthony, Saghir Nahid, Salphati Laurent, Sohal Sukhjit, Ultsch Mark H, Valenti Melanie, Wallweber Heidi J A, Wan Nan Chi, Wiesmann Christian, Workman Paul, Zhyvoloup Alexander, Zvelebil Marketa J, Shuttleworth Stephen J
机构信息
Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom.
出版信息
J Med Chem. 2008 Sep 25;51(18):5522-32. doi: 10.1021/jm800295d.
Phosphatidylinositol-3-kinase (PI3K) is an important target in cancer due to the deregulation of the PI3K/ Akt signaling pathway in a wide variety of tumors. A series of thieno[3,2-d]pyrimidine derivatives were prepared and evaluated as inhibitors of PI3 kinase p110alpha. The synthesis, biological activity, and further profiling of these compounds are described. This work resulted in the discovery of 17, GDC-0941, which is a potent, selective, orally bioavailable inhibitor of PI3K and is currently being evaluated in human clinical trials for the treatment of cancer.
磷脂酰肌醇-3-激酶（PI3K）是癌症中的一个重要靶点，因为PI3K/Akt信号通路在多种肿瘤中存在失调。制备了一系列噻吩并[3,2-d]嘧啶衍生物，并将其作为PI3激酶p110α的抑制剂进行评估。描述了这些化合物的合成、生物活性及进一步的分析。这项工作发现了17（GDC-0941），它是一种强效、选择性、口服生物可利用的PI3K抑制剂，目前正在进行治疗癌症的人体临床试验评估。
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