Synthesis and Evaluation of Anti-Inflammatory, Analgesic, Ulcerogenicity, and Nitric Oxide Releasing studies of Novel Pyrimidine Analogs as non-Ulcerogenic Derivatives

Nileema S. Modhave¹*, Trupti S Chitre², Vidya P Pawar²,
¹Pad. Dr. D. Y. Patil Institute of Pharmacy, Sec.29, Nigadi Pradhikarn, Akurdi, Pune-411044
²A.I.S.S.M.S. College of pharmacy, Near RTO, Kennedy Road, Pune-411001, Maharashtra, India

A B S T R A C T
Most non-steroidal anti-inflammatory drugs (NSAIDs) suffer from the deadlier gastrointestinal (GI) toxicities. In the present research work, the main objective was to develop new chemical entities as potential anti-inflammatory agents with no GI toxicities. Seven derivatives based on interesting Pyrimidine heterocyclic scaffold viz. 2-[2-(6-methyl-2-oxo/thio-4-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonyl) hydrazinyl]-2-oxoethyl nitrate were synthesized.  These compounds were tested in vivo for their anti-inflammatory, analgesic, and ulcerogenicproperties, and subjected to histopathological studies. Two compound IV₆) and (IV₇) was the most potent in this series. The compounds that showed significantly reduced GI ulcerogenicity also showed promising results in histopathologicalstudies, and they were found to cause no mucosal injury. All the synthesized compounds were found to exhibit significant nitric oxide releasing activity in an in vitro method. In conclusion, the designed hybrid molecules were found to be significantly promising.
Keywords: Anti-inflammatory, Analgesic, NSAIDs.