1.
J Am Chem Soc
; 123(9): 2107-8, 2001 Mar 07.
Article
in English
| MEDLINE
| ID: mdl-11456854
Subject(s)
Alkyl and Aryl Transferases/antagonists & inhibitors , Alkyl and Aryl Transferases/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Farnesyltranstransferase , Magnetic Resonance Spectroscopy , Molecular Conformation , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 11(4): 537-40, 2001 Feb 26.
Article
in English
| MEDLINE
| ID: mdl-11229765
ABSTRACT
The evaluation of SAR associated with the insertion of carbonyl groups at various positions of N-arylpiperazinone farnesyltransferase inhibitors is described herein. 1-Aryl-2,3-diketopiperazine derivatives exhibited the best balance of potency and pharmacokinetic profile relative to the parent 1-aryl-2-piperazinones.
Subject(s)
Alkyl and Aryl Transferases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Piperazines/pharmacology , Animals , Dogs , Enzyme Inhibitors/pharmacokinetics , Farnesyltranstransferase , Structure-Activity Relationship
3.
Org Lett
; 2(22): 3473-6, 2000 Nov 02.
Article
in English
| MEDLINE
| ID: mdl-11082012
ABSTRACT
[reaction: see text] Synthesis of the 8-amino-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine ring system was accomplished by intramolecular cyclization of an iminium ion, derived from condensation of an amine and a substituted gamma-(1-imidazolyl)butyraldehyde. The reaction was used to produce conformationally restricted farnesyltransferase inhibitor analogues which exhibit improved in vivo metabolic stability.
Subject(s)
Alkyl and Aryl Transferases/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Imidazoles/chemical synthesis , Pyridines/chemical synthesis , Administration, Oral , Animals , Dogs , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacokinetics , Enzyme Inhibitors/pharmacology , Farnesyltranstransferase , Imidazoles/chemistry , Imidazoles/pharmacokinetics , Imidazoles/pharmacology , Indicators and Reagents , Models, Molecular , Molecular Conformation , Pyridines/chemistry , Pyridines/pharmacokinetics , Pyridines/pharmacology , Structure-Activity Relationship
4.
J Med Chem
; 42(19): 3779-84, 1999 Sep 23.
Article
in English
| MEDLINE
| ID: mdl-10508426
