A 3D-QSAR model for CYP2D6 inhibition in the aryloxypropanolamine series.
A comparative molecular similarity index analysis (CoMSiA) has been performed for cytochrome P450 2D6 inhibition on a series of aryloxypropanolamines to determine the factors contributing to this activity. The model is in agreement with a CYP2D6 homology model constructed on the basis of the mammalian CYP2C5 crystal structure. The energy minimized conformations were generated using the systematic search methodology in Sybyl 6.7. The model not only elucidated the relationship between structure and biological activity but, more importantly, provided useful strategies to modulate CYP2D6 affinity in the aryloxypropanolamine series.
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 4000, Princeton, NJ 08543-4000, USA.
Roy J
RJ
Vaz
Akbar
A
Nayeem
Kenneth
K
Santone
Gamini
G
Chandrasena
Ashvinikumar V
AV
Gavai
D000818:Animals; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D011412:Propanolamines / Q000737:chemistry* / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D013379:Substrate Specificity
D065690:Cytochrome P-450 CYP2D6 Inhibitors; D011412:Propanolamines