Selectivity drug design

Key Words Serotonin agonists serotonin antagonists selectivity drug design standard series deconstruction-reconstruction-elaboration serendipity. 

Cruciani G, S dementi and M Baroni 1993. Variable Selection in PLS Analysis. In Kubinyi H (Editor) 31 QSAR in Drug Design. Leiden, ESCOM, pp. 551-564. 

Murray CW, Clark DE, Auton TR, Firth MA, Li J, Sykes RA, Waszkowycz B, Westhead DR, Young SC. PRO SELECT combining structure-based drug design and combinatorial chemistry for rapid lead discovery. J Comput Aided Mol Des 1997 11 193-207. 

However, in the very end both projects failed with respect to drug design The Hb ligands do not permeate the erythrocyte membrane, and the trimethoprim analogs lost the high selectivity for bacterial DHFRs. 

Gschwend DA, Sirawaraporn W, Santi DV, Kuntz ID. Specificity in structure-based drug design identification of a novel, selective inhibitor of Pneumocystis carinii dihydrofolate reductase. Proteins Struct Funct Genet 1997 29 59-67. 

Carlsson, A (1999) The discovery of the SSRIs a milestone in neuropsychopharmacology and rational drug design. In Selective Serotonin Reuptake Inhibitors (SSRIs) Past, Present and Future (Ed. Stanford, SC), RG Landes Co., Austin, TX, pp. 1-7. 

RN Smith, C Hansch, MM Ames. Selection of a reference partitioning system for drug design work. I Pharm Sci 64 599-606, 1975. 

C. L. Shaffer, ACS ProSpectives Conference Series Discovery and Selection of Successful Drug Candidates with special emphasis on Structure-based Drug Design, Cambridge, MA, 2009. 

Our next step was to assess whether the methodology used to calculate hydration free energy differences for simple carbonyl-containing compounds9 was suitable for heteroaromatic bases. Since our drug design strategy entailed analysis of purine riboside hydration, a series of azanaphthalenes was initially selected for analysis in part because of their structural similarity to purines and in part because of the extensive... 

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