Structure-activity relationship studies in medicinal chemistry and drug design
Sanjay K. Srivastava · OhioLink ETD Center (Ohio Library and Information Network) · 1992
[Structure activity relationship studies is a very important part of drug design in medicinal chemistry. A number of problems related to drug design were studied using the Computer Automated Structure Evaluation (CASE), Multiple-CASE (MULTICASE) methodologies and molecular modeling techniques. These involved the study of antisecretory and cytoprotective (antiulcer) compounds, where chemical functionalities relevant to antiulcer action were identified. In another congeneric database, dopamine-{dollar}{bsol}beta{dollar}-hydroxylase inhibitors, a geometric relationship between the two hypothesized binding sites were established in addition to determining the structural backbone of the inhibitor required for efficient binding. A successful attempt was also made at designing new multidrug resistant reversal drugs in another project, where the designed compounds were actually experimentally tested for verification of their predicted activity. The study led to the identification of four new active compounds. A problem relating to the study of dose-response was also addressed and a method was established for scaling activity data using a modified logit curve equation. In another project, the mispairing of guanine as a result of its C-8 substitution was studied. A new hypothesis was proposed which shows that C-8 substitution of guanine leads to an oxidized structure which could favorably pair both with cytosine and thymine with equal ease giving rise to possible mutation.]