Drug rational

Upton. N. (1994) Mechanisms of action of new antiepileptic drugs Rational design and serendipitous findings. Trentk Pharmacd. Sci.. 15.456-463. 

McNew CD, Michel NC, McCabe PH. Pharmacokinetic interactiai between valproic acid and phenytoin is combination of these drugs rational polypharmacy. Epilepsia (1998) 39... 

T. Clark, Quantum chemoinformatics an oxymoron (Part 2), in Rational Approaches to Drug Design, H.-D. Holtje, W. Sippl (Eds.), Prous Science, Barcelona, 2001, pp. 29-40. 

The lead discovery process is depicted in Figure 10.4-4 and shows how the different methods are interconnected. A lead structure can be discovered by serendipity. In rational drug design all information available about a target serves to direct... 

Patani G A and E J LaVoie 1996. Bioisosterism A Rational Approach in Drug Design. Chemical Reviei 96 3147-3176. 

L. Balbes, Guide to Rational (Computer-aided) Drug De.dgn is online at http // www.ccl.net/cca/documents/drug.design.shtml... 

Rational Drug Design A. Parrill, M. R. Reddy, Eds., Oxford, Oxford (1999). A. P. Johnson, S. M. Green, Encycl. Comput. Chem. 1, 650 (1998). 

Rating programs Rational design Rational drug discovery Rauwolfia serpentina Rauwolscine [131-03-3]... 

GR Marshall, CD Barry, HE Bosshard, RA Dammkoehler, DA Dunn. The conformational parameter m drug design The active analog approach. ACS Symp Ser 112 205-226, 1979. YC Martin. Overview of concepts and methods in computer-assisted rational drug design. Methods Enzymol 203 587-613, 1991. 

Rational drug design is the ultimate goal of medicinal chemistry. By this is understood the design of medicinal agents on the basis of knowledge of the intimate biochemistry of the disease process. 

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... 

Rational design, 148-149, 152 Real-time assays, 83, 88 Receptor(s). See also Drug receptors affinity for, 6, 63 allosteric model of, 143 Clark s work, 3 classical model of, 44-45 concept of, 2-4 conformations, 13-14, 13 Of conservation equation for, 76 constitutive activity of, 49-51 coupling of, 27 definition of, 2 desensitization of, 34 efficacy for, 6... 

Since drug development has turned into a systematic and rational task of optimizing molecules and their interactions with proteins, cells, and organisms, combinatorial chemistry has become a significant part of this endeavor. Combinatorial methods are mainly employed in the initial (preclinical) stages of drug development. 

Common to all three aims is that silico-derived predictions can rationalize experimental efforts either by well-directed very specific molecular biological experiments like site directed mutations or e.g., by reducing the number of compounds to screen experimentally for drug design. 

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