Pharmacophore applications

Bureau, R., Daveu, C., Lancelot, J.C. and Rault, S. (2002a) Molecular design based on 3D-pharmacophore. Application to 5-HT subtypes receptors./. Chem. Inf. Comput. Sci., 42, 429—436. 

Hoffmann RD, Li H, Langer T. Feature-based pharmacophores application to some biological systems. In Giiner OF, ed. Pharmacophore Perception, Development, and Use in Drug Design. La Jolla IUL Biotechnology Series, 2000 301-318. 

Application of the CCM to small sets (n < 6) of enzyme inhibitors revealed correlations between the inhibitory activity and the chirality measure of the inhibitors, calculated by Eq. (26) for the entire structure or for the substructure that interacts with the enzyme (pharmacophore) [41], This was done for arylammonium inhibitors of trypsin, Di-dopamine receptor inhibitors, and organophosphate inhibitors of trypsin, acetylcholine esterase, and butyrylcholine esterase. Because the CCM values are equal for opposite enantiomers, the method had to be applied separately to the two families of enantiomers (R- and S-enantiomers). 

Sheridan R P, R Ndakantan, J S Dixon and R Venkataraghavan 1986. The Ensemble Approach to Distanc Geometry Application to the Nicotinic Pharmacophore. Journal of Medicinal Chemistry 29 899-906. 

The align/pharmacophore experiment orients the molecules to obtain maximum similarity in chemical features. This application can then generate a pharmacophore model consistent with all the molecules. 

RP Sheridan, R Nilakatan, JS Dixson, R Venkataraghavan. The ensemble approach to distance geometry Application to the nicotinic pharmacophore. J Med Chem 29 899-906, 1986. 

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. 

YC Martin, MG Bures, EA Danaher, I DeLazzer, I Lico, PA Pavlik. A fast new approach to pharmacophore mapping and its application to dopaminergic and benzodiazepine agonists. I Comput Aided Mol Des 7 83-102, 1993. 

This method represents the most common and traditional application of computational tools to rational drug design. From a list of molecules of known activity, one can establish a 3D-pharmacophore hypothesis that is then transformed into a 3D-search query. This query is then used to search a 3D database for structures that fit the hypothesis within a certain tolerance. If the yield of active molecules is significant, then the query can be used to predict activities on novel compounds. In our situation, the enantiophore is built from the superposition of a list of sample molecules, which are all well separated on a given CSR Hence, the common features of this series of molecules can become a good enantiophore hypothesis for the enantiores-olution on this CSR... 

Mason JS, Morize 1, Menard PR, Cheney DL, Hulme C, Labaudiniere RF. New 4-point pharmacophore method for molecular similarity and diversity applications Overview of the method and applications, including a novel approach to the design of combinatorial libraries containing privileged substructures. I Med Chem 1999 42 3251-64. 

Lee, M.L. Schneider, G. (2001) Scaffold Architecture and Pharmacophoric Properties of Natural Products and Trade Drugs Application in the Design of Natural Product-Based Combinatorial Libraries. Journal of Combinatorial Chemistry, 3, 284-289. 

McGregor, M. J., Muskal, S. M. Pharmacophore fingerprinting. 2. Application to primary library design. 

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