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Pyrido[1,2‐a]pyrimidin‐4‐ones: Ligand‐based Design, Synthesis, and Evaluation as an Anti‐inflammatory Agent
Author(s) -
Jadhav Sunil B.,
Fatema Samreen,
Patil Rajesh B.,
Sangshetti Jaiprakash N.,
Farooqui Mazahar
Publication year - 2017
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.2950
Subject(s) - chemistry , in vivo , anti inflammatory , celecoxib , in vitro , cyclooxygenase , pharmacology , carrageenan , stereochemistry , biochemistry , enzyme , medicine , microbiology and biotechnology , biology
In the present study, a series of novel pyrido[1,2‐a]pyrimidin‐4‐one derivatives ( 1 – 45 ) were synthesized, characterized, and evaluated for their anti‐inflammatory activity. The structures of all newly synthesized compounds were confirmed by 1 H NMR, 13 C NMR, mass spectroscopy, and C, H, and N analyses. Preliminary these newly synthesized compounds were evaluated for their in vitro cyclooxygenase (COX)‐2/COX‐1 inhibitory activity. The celecoxib, a COX‐2 inhibitor, was used as a reference standard drug. In this inhibitory study, compounds 42 , 43 , 44 , and 45 were found to have significant in vitro inhibitory profile as compared with the reference drug. These compounds were then subjected to their in vivo anti‐inflammatory assay by using carrageenan‐induced rat paw edema method in next level of screening. Later, these same compounds were tested for their ulcerogenic property. Based on these activity data, the compound 43 ( in vitro COX‐2 activity—IC 50 = 0.4 μM, SI = 400, in vivo anti‐inflammatory activity—72% inhibition after 3 h, and 0.38%—Ulcer index) was emerged as most promising anti‐inflammatory agent with very low ulcerogenic action.