2. Academic Validation
  3. Bridgehead modification of trihalocycloheptabenzopyridine leads to a potent farnesyl protein transferase inhibitor with improved oral metabolic stability

Bridgehead modification of trihalocycloheptabenzopyridine leads to a potent farnesyl protein transferase inhibitor with improved oral metabolic stability

  • Bioorg Med Chem Lett. 2004 Dec 6;14(23):5899-902. doi: 10.1016/j.bmcl.2004.09.020.
F George Njoroge 1,  Bancha Vibulbhan,  Xiongwei Shi,  Corey Strickland,  Paul Kirschmeier,  Robert Bishop,  Amin Nomeir,  Viyyoor Girijavallabhan
Affiliations

Affiliation

  • 1 Schering-Plough Research Institute, 2015 Galloping Hill Road, K-15-3-3545, Kenilworth, NJ 07033, USA. [email protected]
PMID: 15501065 DOI: 10.1016/j.bmcl.2004.09.020
Abstract

Modification of the ethano bridge of the core structure of the antitumor agent, SARASAR (SCH66336) with concomitant introduction of a sulfonamide moiety off the distal piperidine afforded inhibitor 9-(S-), a compound with greatly improved PK profile. Other compounds with enhanced FPTase inhibitory activity were obtained as exemplified by amide 10-(S-) and urea 11-(S-): these compounds demonstrated activity in picomolar range.

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