Discovery of a highly potent, orally active mitosis/angiogenesis inhibitor r1530 for the treatment of solid tumors

  • ACS Med Chem Lett. 2013 Jan 15;4(2):259-63. doi: 10.1021/ml300351e.
Jin-Jun Liu  1 ,  Brian Higgins  1 ,  Grace Ju  1 ,  Kenneth Kolinsky  1 ,  Kin-Chun Luk  1 ,  Kathryn Packman  1 ,  Giacomo Pizzolato  1 ,  Yi Ren  1 ,  Kshitij Thakkar  1 ,  Christian Tovar  1 ,  Zhuming Zhang  1 ,  Peter M Wovkulich  1
Affiliations
  • 1. Discovery Chemistry, Discovery Oncology, and Chemical Synthesis, Hoffmann-La Roche Inc. , 340 Kingsland Street, Nutley, New Jersey 07110, United States.
PMID: 24900658 DOI: 10.1021/ml300351e
Abstract

A new series of 7,8-disubstituted pyrazolobenzodiazepines based on the lead compound 1 have been synthesized and evaluated for their effects on Mitosis and angiogenesis. Described herein is the design, synthesis, SAR, and antitumor activity of these compounds leading to the identification of R1530, which was selected for clinical evaluation.

Keywords
FGFr and PDGFr-β; VGFr-2; antitumor effect; mitosis/angiogenesis inhibitor; pyrazolobenzodiazepines.
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