Design and synthesis of piperidine farnesyltransferase inhibitors with reduced glucuronidation potential

Autor:	Mitsunobu Hara, Timothy Alan Grese, Rieko Tanaka, Almudena Rubio, Shinji Nara, Shiro Akinaga, Takashi Kuwabara, Yutaka Kanda, Jun Eishima, Nobuyuki Yoda, Nancy K. Harn, Rui Ohashi, Shiro Soga, Douglas Linn Gernert
Rok vydání:	2006
Předmět:	Models Molecular Stereochemistry Farnesyltransferase Clinical Biochemistry Farnesyl pyrophosphate Glucuronidation Nitro compound Protein Prenylation Pharmaceutical Science Crystallography X-Ray Biochemistry Chemical synthesis chemistry.chemical_compound Mice Structure-Activity Relationship Glucuronides Piperidines Drug Discovery Animals Enzyme Inhibitors Molecular Biology chemistry.chemical_classification Farnesyl-diphosphate farnesyltransferase Alkyl and Aryl Transferases biology Molecular Structure Organic Chemistry Rats chemistry Enzyme inhibitor Drug Design biology.protein Microsomes Liver Molecular Medicine Piperidine
Zdroj:	Bioorganicmedicinal chemistry. 15(3)
ISSN:	0968-0896
Popis:	The design and synthesis of a novel piperidine series of farnesyltransferase (FTase) inhibitors with reduced potential for metabolic glucuronidation are described. The various substitution and exchange of the phenyl group at the C-2 position of the previously described 2-(4-hydroxy)phenyl-3-nitropiperidine 1a (FTase IC 50 = 5.4 nM) resulted in metabolically stable compounds with potent FTase inhibition ( 14a IC 50 = 4.3 nM, 20a IC 50 = 3.0 nM, and 50a IC 50 = 16 nM). Molecular modeling studies of these compounds complexed with FTase and farnesyl pyrophosphate are also described.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f2b2a851daa574a25881a4ebed7f9d62 https://pubmed.ncbi.nlm.nih.gov/17127066 Zobrazit plný text záznamu Full Text from ScienceDirect