CoMFA and CoMSIA 3D QSAR analysis on N1-arylsulfonylindole compounds as 5-HT6 antagonists.
Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were conducted on a series of N(1)-arylsulfonylindole compounds as 5-HT(6) antagonists. Evaluation of 20 compounds served to establish the models. The lowest energy conformer of compound 1 obtained from random search was used as template for alignment. The best predictions were obtained with CoMFA standard model (q2 = 0.643, r2 = 0.939 ) and with CoMSIA combined steric, electrostatic, hydrophobic, and hydrogen bond acceptor fields (q2 = 0.584, r2 = 0.902 ). Both the models were validated by an external test set of eight compounds giving satisfactory predictive r2 values of 0.604 and 0.654, respectively. The information obtained from CoMFA and CoMSIA 3D contour maps can be used for further design of specific 5-HT(6) antagonists.
Doddareddy
Munikumar Reddy
MR
Biochemicals Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, South Korea.
Cho
Yong Seo
YS
Koh
Hun Yeong
HY
Pae
Ae Nim
AN
D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000737:chemistry* / Q000494:pharmacology*
D007211:Indoles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C097216:serotonin 6 receptor