ABSTRACT
The present study describes the synthesis and quantitative structure activity relationships (QSAR) of novel 3-amino-2-(substituted)aminomethyl-5,6-disubstitutedthieno[2,3-d] pyrimidin-4(3H)-ones for their potent H1-receptor antagonist activity on the guinea pig ileum. With the IC50 values in the range of 10(-5) gms/lit, all the compounds tested were found to possess ten fold higher affinity to the H1-receptor than diphenhydramine and cetirizine, but lower than astemizole and loratidine. The sedative potential of these compounds was found to be lower than cetirizine and astemizole but comparable to loratidine. The QSAR study indicates a parabolic relationship of the biological activity mainly with the steric parameters and partly with the lipophilic parameters.
Subject(s)
Heterocyclic Compounds, 2-Ring/chemistry , Histamine H1 Antagonists/chemistry , Pyrimidinones/chemistry , Animals , Blood Pressure/drug effects , Dogs , Female , Guinea Pigs , Heterocyclic Compounds, 2-Ring/pharmacology , Histamine H1 Antagonists/pharmacology , Ileum/drug effects , Ileum/physiology , Male , Mice , Motor Activity/drug effects , Muscle Contraction , Pyrimidinones/pharmacology , Structure-Activity RelationshipABSTRACT
4-Amino-5-substituted thiazole-2(3H)-thiones and thiazolo(4,5-d)-pyrimidin-7(6H)-one-2(3H)-thiones have been synthesized and screened for antimicrobial and pharmacological activities. Significant analgesic, antiinflammatory, anticonvulsant and antimicrobial properties have been found in some of the compounds synthesized. Analgesic and antiinflammatory activities are reported for the first time in thiazole-2(3H)-thiones.
Subject(s)
Thiones/chemical synthesis , Analgesics/chemical synthesis , Animals , Anti-Inflammatory Agents/chemical synthesis , Anticonvulsants/chemical synthesis , Chemical Phenomena , Chemistry, Physical , Drug Evaluation, Preclinical , Male , Mice , RatsABSTRACT
3-Substituted thieno [2, 3-d] pyrimidin-4(3H)-one-2-mercaptoacetic acids and their ethyl esters were synthesized from 2-mercaptothieno [2, 3-d] pyrimidin-4(3H]-ones, which were obtained by cyclization of thienylthioureas in acidic medium. Analgesic, anti-inflammatory, and anticonvulsant activities were found in some of these compounds. Significant antimicrobial activity was exhibited by thienylthioureas.
