A manual method for applying the Hansch approach to drug design.
A procedure is described in which an initial small group of compounds is selected, tested, and ordered according to potency. The potency order in the group is then compared to the tabulated potency order calculated for various parameter dependencies relating to hydrophobic, electronic, and steric effects. From this activity pattern analysis the probable operative parameters can be deduced and a new substituent selection made for the synthesis of potentially more potent analogues. Application of the method is illustrated with a series of examples. It differs from a previously described decision tree, single compound stepwise approach in that it involves the batchwise analysis of small groups of compounds, usually the preferred procedure for logistical reasons if the compounds are relatively easy to synthesize.
D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors; D000662:Amphetamines / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis; D001549:Benzamides / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003521:Cyclopropanes / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D005342:Fibrinolysis / Q000187:drug effects; D006147:Guanine / Q000031:analogs & derivatives / Q000494:pharmacology; D006148:Guanine Deaminase / Q000037:antagonists & inhibitors; D007004:Hypoglycemic Agents / Q000138:chemical synthesis; D007189:Indans / Q000494:pharmacology; D008930:Mitochondria, Liver / Q000187:drug effects; D010323:Passive Cutaneous Anaphylaxis / Q000187:drug effects; D010625:Phenylethanolamine N-Methyltransferase / Q000037:antagonists & inhibitors; D010671:Phenylurea Compounds / Q000494:pharmacology; D010753:Phosphoranes / Q000138:chemical synthesis / Q000494:pharmacology; D010788:Photosynthesis / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
D000662:Amphetamines; D000893:Anti-Inflammatory Agents; D001549:Benzamides; D001555:Benzene Derivatives; D002257:Carbonic Anhydrase Inhibitors; D003521:Cyclopropanes; D007004:Hypoglycemic Agents; D007189:Indans; D010671:Phenylurea Compounds; D010753:Phosphoranes; D011422:Propionates; D011688:Purinones; D013449:Sulfonamides; D006147:Guanine; D000429:Alcohol Oxidoreductases; D014969:Xanthine Oxidase; D010625:Phenylethanolamine N-Methyltransferase; D006148:Guanine Deaminase