[Three dimensional quantitative structure-activity relationship of farnesyl protein transferase inhibitors].
OBJECTIVE
To build a three dimensional structure model that correlates the biological activities and the structures of a series of farnesyl protein transferase (FPT) inhibitors exemplified by the compound of 2, 3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(2-biphenylylcarbonyl)-1H-1, 4-benzodiazepine.


RESULTS
Thirty-two FPT inhibitors with two types of scaffold were analyzed. Active conformations of which were studied using system search, a 3D-QSAR model were constructed using the method of comparative molecular field analysis (CoMFA). The resulting of cross-validated RCV2 = 0.602, non-cross-validated R2 = 0.958, SE = 0.270 and F = 124.5 indicate that the 3D-model possesses an ability to predict activities of new inhibitors.


CONCLUSIONS
The information of CoMFA model offers an approach to designing new FPT inhibitors.
Wan
S B
SB
Institute of Materia Medica, Chinese Academy of Medical Scineces, Peking Union Medical College, Beijing 100050, China.
Yi
X
X
Guo
Z R
ZR
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship
C481912:2,3,4,5-tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(2-biphenylylcarbonyl)-1H-1,4-benzodiazepine; D004791:Enzyme Inhibitors; D007093:Imidazoles; D001569:Benzodiazepines; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase