Molecular surface comparison. 2. Similarity of electrostatic vector fields in drug design.
In the first article of this series a real-time graphics method was described for molecular similarity of scalar properties. This has now been extended for the comparison of molecular vector properties, most notably electrostatic field. A comparison of the various techniques of calculating fields is presented that includes a new method based on natural orbital fitted point charges. In the two examples described, namely, a series of benzodiazepine agonists and a set of serotonin 5-HT3 antagonists, the program has been shown to produce useful pharmacophoric overlaps that can be used in the design of novel therapeutic agents.
Blaney
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FE
SmithKline Beecham Pharmaceuticals, Harlow, Essex, England.
Edge
C
C
Phippen
R W
RW
D014151:Anti-Anxiety Agents / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry; D001552:Benzazepines / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D002243:Carbolines / Q000737:chemistry; D003975:Diazepam / Q000737:chemistry; D015195:Drug Design; D004560:Electricity; D058785:GABA-A Receptor Agonists; D017829:Granisetron / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D007536:Isomerism; D008968:Molecular Conformation; D017294:Ondansetron / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry; D011724:Pyridazines / Q000737:chemistry; D011955:Receptors, Drug / Q000737:chemistry* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry*; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014229:Triazolam / Q000737:chemistry; D000077526:Tropisetron
D014151:Anti-Anxiety Agents; D001549:Benzamides; D001552:Benzazepines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002243:Carbolines; D003975:Diazepam; D058785:GABA-A Receptor Agonists; D017829:Granisetron; D007211:Indoles; D017294:Ondansetron; D004364:Pharmaceutical Preparations; D011720:Pyrazoles; D011724:Pyridazines; D011955:Receptors, Drug; D011985:Receptors, Serotonin; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D014229:Triazolam; D000077526:Tropisetron; C075685:BRL 46470; C021604:CL 218872; C096767:BRL 24682; C039570:9-chloro-7-(2-chlorophenyl)-5H-pyrimido(5,4-d)(2)benzazepine; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one; C038933:ZK 91296