2. Academic Validation
  3. Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors

Identification of 2-oxatriazines as highly potent pan-PI3K/mTOR dual inhibitors

  • Bioorg Med Chem Lett. 2011 Aug 15;21(16):4773-8. doi: 10.1016/j.bmcl.2011.06.063.
Christoph M Dehnhardt 1,  Aranapakam M Venkatesan,  Zecheng Chen,  Efren Delos-Santos,  Semiramis Ayral-Kaloustian,  Natasja Brooijmans,  Ker Yu,  Irwin Hollander,  Larry Feldberg,  Judy Lucas,  Robert Mallon
Affiliations

Affiliation

  • 1 Medicinal Chemistry, Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, USA. christoph.dehnhardt@pfizer.com
PMID: 21763134 DOI: 10.1016/j.bmcl.2011.06.063
Abstract

We recently described several highly potent, triazine (1) and triazolopyrimidine (2) scaffold-based, dual PI3K/mTOR-inhibitors (e.g., 1, PKI-587) that were efficacious in both in vitro and in vivo models. In order to further optimize these compounds we devised a novel series, the 2-oxatriazines, which also exhibited excellent potency and good metabolic stability. Some 2-oxatriazines showed promising in vivo biomarker suppression and induced Apoptosis in the MDA-MB-361 breast Cancer xenograft model.

Figures