A COMPARATIVE-STUDY OF ANTIPLASMIN ACTIVITY OF SOME PYRIDINE-DERIVATIVES AND RELATED-COMPOUNDS

Antiplasmins have therapeutic significance in arresting the uncontroll ed bleeding associated with several disease states. Understanding of t he structure-function relationship of antiplasmins is important in the development of coagulants as well as anticoagulants. A comparative st ructure-activity analysis of antiplasmin activity of some pyridine, pi peridine, indole and thiocyclohexane derivatives with known antiplasmi ns, viz. p-aminomethyl benzoic acid (PAMBA) and epsilon-amino-caproic acid (EACA), has been carried out. The antiplasmin activity of pyridin e, piperidine, indole and thiocyclohexanes appears to depend on over-a ll lipophilicity and the distance between basic centre and carboxyl fu nction present in these compounds where the optimum separation is foun d to be 6.5 Angstrom. Such spatial disposition of basic and carbonyl c entres in these compounds may be responsible for binding to the sites responsible for antiplasmin activity. The lipophilicity may be respons ible for making the compounds available at the site of action and also for their hydrophobic binding.