5-Substituted pyridylisoxazoles as effective inhibitors of platelet aggregation

Abstract

A series of 5 substituted 3 pyridylisoxazoles were synthesized using [3+2] cycloaddition of nitrile oxides to alkynes with variation of substituents at position 5 of the isoxazole ring without additional synthetic stages and with retention of 2 pyridyl , 3 pyridyl, and 4 pyridyl substitu ents at position 3 of the isoxazole ring. Substituted pyridylisoxazoles are the potential anti aggregatory agents showing in vitro activity in the concentration range from 1•10 -6 mol L -1 to 1•10 -4 mol L -1 toward the human platelet rich blood plasma with arachidonic acid being used as the inductor of aggregation. These compounds do not act as cyclooxygenase or thromboxane synthase inhibitors, nor as thrombin inhibitors.

Calcium-mediated one-pot preparation of isoxazoles with deuterium incorporation

“…The corresponding chloroaldoximes were synthesized by the procedure reported previously. 17 A reaction tube was loaded with chloroaldoxime (0.3 mmol) and calcium carbide (2 mmol). Then, 1.5 ml of CCl 4 (or toluene) was added, the resulting mixture was stirred until a suspension formed, and deionized water (4 mmol) was added.…”

Acetylene in Organic Synthesis: Recent Progress and New Uses

“…Besides, these reactions afford many useful heterocyclic compounds. In particular, [3 + 2]-cycloaddition reactions of acetylene with active dipoles are increasingly used in synthesis of five-membered heterocycles [ 41 , 42 , 43 , 44 , 122 , 123 , 124 , 125 , 126 , 127 , 128 ].…”

Effective Synthesis of 3,4‐Diaryl‐isoxazole‐5‐carboxamides and their Antiproliferative Properties

“…4,5‐Diarylisoxazole scaffold can be found in a wide variety of non steroidal anti‐inflammatory drugs (NSAIDs),, inhibitors of platelet aggregation, tubulin polymerization inhibitors,, estrogen receptor modulators, antiviral, anti‐diabetic, anti‐convulsant, and other agents . Polyoxygenated 4,5‐diarylisoxazoles with 3‐carboxamide groups (Figure , A) were reported to inhibit heat shock protein Hsp90, a chaperone that assists folding of various proteins including those implicated in malignancy.…”