Synthesis and antithrombotic activity of 1-benzyl-N′-benzylidenepiperidine-3-carbohydrazide derivatives. Issue 3 (April 2020)

• Record Type: Journal Article
• Authors: Tosan, Fatemeh; Hashemi, Mohammad M.; Kobarfard, Farzad; Monajjemi, Majid; Ayatollahi, Seyed A.
• Is Part Of: Blood coagulation and fibrinolysis. Volume 31:Issue 3(2020)
• Publication Date: 2020-04
• Subjects: 1-(benzyl)-N′-(benzylidene) piperidine-3-carbohydrazide -- anticoagulation activity -- antiplatelet -- aryl hydrazone -- nipecotic acid -- piperidine -- platelet aggregation; Blood -- Coagulation -- Periodicals; Fibrinolysis -- Periodicals; Hemostasis -- Periodicals; Thrombosis -- Periodicals; Blood Coagulation -- Periodicals; Fibrinolysis -- Periodicals; Hemostasis -- Periodicals; Thrombosis -- Periodicals; 612.115
• DOI: 10.1097/MBC.0000000000000877
• Languages: English
• ISSNs: 0957-5235

Abstract

Abstract : N/A: Platelet aggregation inhibition and interfering with clot formation are essential tools for antithrombotic therapy and there is a need for discovering new antithrombotic agents. In this study, we synthesized a series of benzylidenepiperidine-3-carbohydrazide derivatives (1f–11f), bearing various selected substituents on both the piperidine ring nitrogen and the hydrazide nitrogen. The synthesized compounds were characterized by FTIR, 1 HNMR spectroscopic techniques, CHN/O elemental analysis and electrospray ionization mass spectra. All new 1-benzyl- N ′-benzylidenepiperidine-3-carbohydrazides were evaluated for their antiplatelet aggregation activities (against platelet aggregation induced by AA, ADP and collagen separately) and anticoagulant activities [protrombin time (PT) and partial thromboplastin time (PTT)]. Antiplatelet aggregation activity of the new derivatives was measured using human plasma on an APACT 4004 aggregometer. All the compounds were mainly effective on ADP pathway of platelet aggregation compared with collagen and AA pathways. The most potent compound on platelet aggregation induced by ADP is compound 2f with 87% aggregation inhibition activity at 0.5 mmol/l concentration. The synthesized compounds were further investigated for their anticoagulant action via the two PT and PTT models. They all showed higher PT and PTT values compared with the blank control sample. The most potent compounds are 5f, 6f, 7f and 1f. All compounds were obtained in good yield and further evaluated for their antiplatelet and anticoagulant activity.