Synthesis of novel diarylpyrazole derivatives and investigation biological activity

SUMMARYNSAI drugs commonly used as a therapeutic agent for treatment of pain and inflammation. In a patient who needs effective anti-inflammatory treatment and has a high risk of both gastrointestinal bleeding and cardiovascular thrombosis, the use of selective COX-2 inhibitors with antiplatelet agents is recommended. Therefore in comparison to treatment of inflammation using COX-2 inhibitors and thromboxane synthase enzyme inhibitors separately, the development of an inhibitor of both enzymes at the same time as dual COX-2/TxS inhibitors has been identified appropriate approach.For this purpose we decided to synthesize new compounds possessing both anti-inflammatory and antiplatelet activities. The committed to diarylpyrazol structure, twenty seven new compounds were synthesized. COX-1, COX-2 and antiplatelet activities were demonstrated. They were fully elucidated using spectral techniques and elemental analysis.The obtained twenty seven compounds reported herein were evaluated for their ability to inhibition of platelet aggregation and COX enzyme. (2E)-3-{1-[4-(methylsulfonyl)phenyl]-3-pyridin-3-yl-1H-pyrazol-4-yl}-N-(pyridin-3-yl-methyl)acrylamide (5n), (2E)-3-{1-[4-(methylsulfonyl)phenyl]-3-pyridin-3-yl-1H-pyrazol-4-yl}-N-(2-pyridin-2-yl-ethyl)acrylamide (5p), (2E)-3-{1-[4-(methylsulfonyl)phenyl]-3-pyridin-3-yl-1H-pyrazol-4-yl}-N-(2-pyridin-4-yl-ethyl)acrylamide (5s), (2E)-3-(1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-N-(pyridin-2-yl-methyl)acrylamide (10d) and (2E)-3-(1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-N-(2-pyridin-2-yl-ethyl)acrylamide (10g) demonstrated COX-2 inhibition as well as inhibition of AA-induced platelet aggregation. Their COX-2 inhibition values are 58%, 66%, 66%, 43%, and 49%, respectively and inhibition of platelet aggregation values are 89%, 90%, 100%, 100%, 100%, respectively. Additionally, it is found that (2E)-3-(1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-N-(2-pyridin-3-yl-ethyl)acrylamide (10h) and (2E)-3-(1-phenyl-3-pyridin-4-yl-1H-pyrazol-4-yl)-N-(2-pyridin-4-yl-ethyl)acrylamide (10i) derivatives have shown inhibition on AA-induced platelet aggregation, 93% and 71%, respectively, with no inhibition on COX enzyme. To obtain more efficient compounds for platelet aggregation this thesis will form basis for our further research.