Abstract：
:Recent trends in drug discovery include methods to identify dual and triple activating drugs. This approach is being successfully employed in malaria, cancer, asthma, insulin resistance, etc. Molecular field analysis has been employed in correlating pharmacological data and field parameters. In this paper we introduce the concept of additivity of molecular fields to correlate molecular fields of dual activators and their pIC(50) values. PPARalpha and PPARgamma dual activators, which affect hypertriglyceridemia and hyperglycemia, have been chosen to validate the molecular field additivity concept. Three CoMFA models namely alpha-model, gamma-model and dual-model have been developed. The validity of this concept has been ascertained by (a) comparing contour maps, (b) by comparing CoMFA results with FlexX docking results and (c) by analyzing newly designed molecules.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Khanna S,Sobhia ME,Bharatam PVdoi
10.1021/jm049383skeywords:
subject
Has Abstractpub_date
2005-04-21 00:00:00pages
3015-25issue
8eissn
0022-2623issn
1520-4804journal_volume
48pub_type
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