Bridgehead modification of trihalocycloheptabenzopyridine leads to a potent farnesyl protein transferase inhibitor with improved oral metabolic stability.
Article Details
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Njoroge FG, Vibulbhan B, Shi X, Strickland C, Kirschmeier P, Bishop R, Nomeir A, Girijavallabhan V
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.
- PubMed ID
- 15501065 [ View in PubMed]
- 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.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Lonafarnib Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha IC 50 (nM) 2 N/A N/A Details Lonafarnib Protein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha IC 50 (nM) 500000 N/A N/A Details