2. Academic Validation
  3. 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

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

  • J Med Chem. 2008 Sep 25;51(18):5522-32. doi: 10.1021/jm800295d.
Adrian J Folkes 1,  Khatereh Ahmadi,  Wendy K Alderton,  Sonia Alix,  Stewart J Baker,  Gary Box,  Irina S Chuckowree,  Paul A Clarke,  Paul Depledge,  Suzanne A Eccles,  Lori S Friedman,  Angela Hayes,  Timothy C Hancox,  Arumugam Kugendradas,  Letitia Lensun,  Pauline Moore,  Alan G Olivero,  Jodie Pang,  Sonal Patel,  Giles H Pergl-Wilson,  Florence I Raynaud,  Anthony Robson,  Nahid Saghir,  Laurent Salphati,  Sukhjit Sohal,  Mark H Ultsch,  Melanie Valenti,  Heidi J A Wallweber,  Nan Chi Wan,  Christian Wiesmann,  Paul Workman,  Alexander Zhyvoloup,  Marketa J Zvelebil,  Stephen J Shuttleworth
Affiliations

Affiliation

  • 1 Piramed Pharma, 957 Buckingham Avenue, Slough, Berks SL1 4NL, United Kingdom. [email protected]
PMID: 18754654 DOI: 10.1021/jm800295d
Abstract

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.

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