Details

Autor(en) / Beteiligte

• Hoffman, B
• Cho, S J
• Zheng, W
• Wyrick, S
• Nichols, D E
• Mailman, R B
• Tropsha, A

Titel

Quantitative structure-activity relationship modeling of dopamine D(1) antagonists using comparative molecular field analysis, genetic algorithms-partial least-squares, and K nearest neighbor methods

Ist Teil von

• Journal of medicinal chemistry, 1999-08, Vol.42 (17), p.3217-3226

Ort / Verlag

United States

Erscheinungsjahr

1999

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Several quantitative structure-activity relationship (QSAR) methods were applied to 29 chemically diverse D(1) dopamine antagonists. In addition to conventional 3D comparative molecular field analysis (CoMFA), cross-validated R(2) guided region selection (q(2)-GRS) CoMFA (see ref 1) was employed, as were two novel variable selection QSAR methods recently developed in one of our laboratories. These latter methods included genetic algorithm-partial least squares (GA-PLS) and K nearest neighbor (KNN) procedures (see refs 2-4), which utilize 2D topological descriptors of chemical structures. Each QSAR approach resulted in a highly predictive model, with cross-validated R(2) (q(2)) values of 0.57 for CoMFA, 0.54 for q(2)-GRS, 0.73 for GA-PLS, and 0.79 for KNN. The success of all of the QSAR methods indicates the presence of an intrinsic structure-activity relationship in this group of compounds and affords more robust design and prediction of biological activities of novel D(1) ligands.