4-methyl-1,2,4-triazol-3-yl heterocycle as an alternative to the 1-methylimidazol-5-yl moiety in the farnesyltransferase inhibitor ZARNESTRA.
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.
Angibaud
Patrick
P
Medicinal Chemistry Department Johnson & Johnson Pharmaceutical Research & Development (J&JPRD), Campus de Maigremont BP615, 27106, Val de Reuil, France. pangibau@prdfr.jnj.com
Saha
Ashis K
AK
Bourdrez
Xavier
X
End
David W
DW
Freyne
Eddy
E
Lezouret
Patricia
P
Mannens
Geert
G
Mevellec
Laurence
L
Meyer
Christophe
C
Pilatte
Isabelle
I
Poncelet
Virginie
V
Roux
Bruno
B
Smets
Gerda
G
Van Dun
Jacky
J
Venet
Marc
M
Wouters
Walter
W
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
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D015363:Quinolones; D014230:Triazoles; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; C402769:tipifarnib