Three-dimensional pharmacophore search

An alternative approach utilized a pharmacophore model based on the bound conformation of sLe. Three-dimensional pharmacophore searches by Kondo et al. [127] and Brandley et al. [131] led to the antagonists 52 (rlCf5 0.15) and 53 (rlCso 0.5) (Figure 16.22) [127]. 

DP Mamott, IG Dougall, P Meghani, Y-J Liu, DR Flower. Lead generation using pharmacophore mapping and three-dimensional database searching Application to muscarinic M3 receptor antagonists. J Med Chem 42 3210-3216, 1999. 

Gund P. Three-dimensional pharmacophoric pattern searching. Prog Mol Subcell Biol 1977 5 117-43. 

Gund P. Three-dimensional pharmacophore pattern searching. In Hahn FE, editor, Progress in molecular and subcellular biology. Berlin Springer-Verlag, 1977. p.117-43. 

Kurogi, Y. and Guner, O.F. Pharmacophore modeling and three-dimensional database searching for dmg design using catalyst. Curr. 

Greenidge, P.A., Carlsson, B., Biadh, L.G., and Gillner, M. Pharmacophores incorporating numerous excluded volumes defined by x-ray crystallographic structure in three-dimensional database searching application to the thyroid hormone receptor./. Med. Chem. 1998, 41, 2503-2512. 

Another issue that should be addressed briefly is the relationship between size and resolution of a conformational model particularly in terms of coverage of the low-energy regions of the accessible conformational space. The coverage should at any rate be consistent with the precision of the application which uses the conformational model. During three-dimensional pharmacophore generation for database search purposes, the restriction is given by the tolerance of the pharmacophore query. It has been shown in principle that a limited number of... 

The database search process starts with a rapid screening process within which molecules possessing properties required from potential hits are sorted out from those that can be excluded a priori. The screen involves substructure match followed by screens matching three-dimensional pharmacophore features, molecular shapes or exclusion volumes and text constraints (ID properties) if present in the query (through Oracle). All this greatly reduces the number of potential hit compounds in the database. The next step of the search pro-... 

Gund conceived the first prototypic program designed to search for molecules that match three-dimensional pharmacophoric patterns (201,202). This program, MOLPAT, performed atom-by-atom searches to verify comparable interatomic distances between... 

Nicklaus, M.C., Neamati, N., Hong, H., Mazumder, A., Sunder, S., Chen, J. et al. (1997) HlV-1 integrase pharmacophore discovery of inhibitors through three-dimensional database searching. 

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