[Three dimensional quantitative structure activity relationship of P450(17) alpha inhibitors of 17-substituted steroids].
OBJECTIVE
To develop a three dimensional quantitative structure activity relationship (3D-QSAR) model and gain further insights into the requirements for potential P450(17) alpha inhibitors.


RESULTS
A predictive 3D pharmacophore model was established based on comparative molecular field analysis (CoMFA). The correlation between the activities and structures was significant with cross-validated value (R2cv), non-cross-validated value (R2) and standard error of estimate (SEE) of 0.538, 0.799 and 0.257, respectively. According to this model, the predicted inhibition activities of three compounds synthesized in our laboratory were compatible to actual activities.


CONCLUSIONS
This model would contribute to the understanding of the interaction between the inhibitors and P450(17) alpha and rational design of novel lead molecules.
Miao
J
J
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China.
Ling
Y Z
YZ
Zhu
N
N
Lei
X P
XP
D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013256:Steroids / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013256:Steroids; D013254:Steroid 17-alpha-Hydroxylase