title: Synthesis and evaluation of dual antiplatelet activity of bispidine derivatives of N-substituted pyroglutamic acids.
abstract: N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular, the compound 4j offered significant protection against collagen epinephrine induced pulmonary thromboembolism as well as ferric chloride induced arterial thrombosis, without affecting bleeding tendency in mice. Therefore, the present study suggests that the compound 4j displays a remarkable antithrombotic efficacy much better than aspirin and clopidogrel.
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Misra
authors.affiliation: Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: K S
authors.initials: KS
authors.lastname: Anil Kumar
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Jain
authors.affiliation: National Institute of Pharmaceutical Education and Research, Raebareli 229 010, India.
authors.forename: Kirti
authors.initials: K
authors.lastname: Bajaj
authors.affiliation: National Institute of Pharmaceutical Education and Research, Raebareli 229 010, India.
authors.forename: Shyamali
authors.initials: S
authors.lastname: Shandilya
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: Smriti
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Shukla
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Barthwal
authors.affiliation: Pharmacology Division, CSIR-Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India.
authors.forename: Madhu
authors.initials: M
authors.lastname: Dikshit
authors.affiliation: Medicinal and Process Chemistry Division, CSIR- Central Drug Research Institute, Sec-10, Janakipuram, Lucknow 226 031, India. Electronic address: dk_dikshit@cdri.res.in.
authors.forename: Dinesh K
authors.initials: DK
authors.lastname: Dikshit
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D051379:Mice; D010973:Platelet Adhesiveness / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D011761:Pyrrolidonecarboxylic Acid / Q000009:adverse effects / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D013927:Thrombosis / Q000097:blood / Q000473:pathology / Q000517:prevention & control*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D010975:Platelet Aggregation Inhibitors; C495809:bispidine; D011761:Pyrrolidonecarboxylic Acid
keywords: Anti-platelet; Bispidine; Collagen; Pyroglutamic acid; U46619