title: 4-methyl-1,2,4-triazol-3-yl heterocycle as an alternative to the 1-methylimidazol-5-yl moiety in the farnesyltransferase inhibitor ZARNESTRA.
abstract: Replacement of the 1-methylimidazol-5-yl moiety in the farnesyltransferase inhibitor ZARNESTRA series by a 4-methyl-1,2,4-triazol-3-yl group gave us compounds with similar structure-activity relationship profiles showing that this triazole is potentially a good surrogate to imidazole for farnesyltransferase inhibition.
authors.affiliation: Medicinal Chemistry Department Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), Campus de Maigremont BP615, 27106, Val de Reuil, France. pangibau@prdfr.jnj.com
authors.forename: Patrick
authors.initials: P
authors.lastname: Angibaud
authors.forename: Ashis K
authors.initials: AK
authors.lastname: Saha
authors.forename: Xavier
authors.initials: X
authors.lastname: Bourdrez
authors.forename: David W
authors.initials: DW
authors.lastname: End
authors.forename: Eddy
authors.initials: E
authors.lastname: Freyne
authors.forename: Patricia
authors.initials: P
authors.lastname: Lezouret
authors.forename: Geert
authors.initials: G
authors.lastname: Mannens
authors.forename: Laurence
authors.initials: L
authors.lastname: Mevellec
authors.forename: Christophe
authors.initials: C
authors.lastname: Meyer
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pilatte
authors.forename: Virginie
authors.initials: V
authors.lastname: Poncelet
authors.forename: Bruno
authors.initials: B
authors.lastname: Roux
authors.forename: Gerda
authors.initials: G
authors.lastname: Smets
authors.forename: Jacky
authors.initials: J
authors.lastname: Van Dun
authors.forename: Marc
authors.initials: M
authors.lastname: Venet
authors.forename: Walter
authors.initials: W
authors.lastname: Wouters
mesh_terms: D000284:Administration, Oral; D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051231:Farnesyltranstransferase; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D008968:Molecular Conformation; D015363:Quinolones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D015363:Quinolones; D014230:Triazoles; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; C402769:tipifarnib