Synthesis and QSAR of some 3-amino-2-(substituted)aminomethyl-5,6-disubstituted thieno[2,3-d]pyrimidin-4(3H)-ones as novel H1-receptor antagonists.
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.
Shishoo
C J
CJ
Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, India.
Shirsath
V S
VS
Rathod
I S
IS
Brahmbhatt
S B
SB
Pathak
U S
US
Jain
K S
KS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry* / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000737:chemistry* / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009119:Muscle Contraction; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D006574:Heterocyclic Compounds, 2-Ring; D006634:Histamine H1 Antagonists; D011744:Pyrimidinones