2. Academic Validation
  3. PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor

PKI-179: an orally efficacious dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor

  • Bioorg Med Chem Lett. 2010 Oct 1;20(19):5869-73. doi: 10.1016/j.bmcl.2010.07.104.
Aranapakam M Venkatesan 1,  Zecheng Chen,  Osvaldo dos Santos,  Christoph Dehnhardt,  Efren Delos Santos,  Semiramis Ayral-Kaloustian,  Robert Mallon,  Irwin Hollander,  Larry Feldberg,  Judy Lucas,  Ker Yu,  Inder Chaudhary,  Tarek S Mansour
Affiliations

Affiliation

  • 1 Chemical Sciences, PGRD, Pfizer Inc, Legacy Wyeth Research, 401 N. Middletown Rd, Pearl River, NY 10965, USA. [email protected]
PMID: 20797855 DOI: 10.1016/j.bmcl.2010.07.104
Abstract

A series of mono-morpholino 1,3,5-triazine derivatives (8a-8q) bearing a 3-oxa-8-azabicyclo[3.2.1]octane were prepared and evaluated for PI3-kinase/mTOR activity. Replacement of one of the bis-morpholines in lead compound 1 (PKI-587) with 3-oxa-8-azabicyclo[3.2.1]octane and reduction of the molecular weight yielded 8m (PKI-179), an orally efficacious dual PI3-kinase/mTOR Inhibitor. The in vitro activity, in vivo efficacy, and PK properties of 8m are discussed.

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