Session Information
Date: Tuesday, June 6, 2017
Session Title: Therapy in Movement Disorders
Session Time: 1:45pm-3:15pm
Location: Exhibit Hall C
Objective: In the present study, we intended to develop novel 1,2,4 triazole as potent A(2A)AR antagonists against parkinson’s disease.
Background: Parkinson’s disease (PD) is a general, age-associated, progressive, neurodegenerative, neurological disease and its effective treatment is seriously jeopardized with loss of drug action, motor problem and failure to circumvent disease progression. Thus, novel approaches to therapy are urgently required. In this regard, agents targeting adenosine A(2A) receptors (A(2A)ARs) provides a viable option. The expected introduction of ST1535 and ST4206, a 1,2,4 triazole based antagonist in clinical trial provide a rational for the development of new A(2A)AR antagonists.
Methods: The skeleton of 1,2,4 triazole was developed using cyclo-condensation reaction with primary amines. These molecules were subsequently evaluated for in vitro anti‑Parkinson’s activity by free radical scavenging assay. The crystal structure of adenosine A2A receptor was undertaken with the aim to selectively antagonize its effect.
Results: The synthesized molecules were found in accordance with Drug Likeliness recommendations for new chemical entity (NCE) exhibiting good bioavailability. Anti‑Parkinson’s screening suggested, compound 6b, 6d and 6a having electron withdrawing group as potent inhibitors with 80%, 92% and 96 % free radical scavenging activity, respectively. In selective inhibition study of compounds with the adenosine A2A receptor, it has been suggested that, above molecules selectively and efficiently create interaction with Ala59, Ile66, Phe168, Ile80, Tyr271 and Ile274 of A2A receptor protein domain with Ki (Inhibition constant) raging from 427.37nM to 4.89µM disclosing 6a as a most potent analogue.
Conclusions: The results of study enumerated 6a as a potent A(2A)ARs antagonist providing benefit against Parkinson’s disease via excellent free radical scavenging activity with excellent bioavailability.
To cite this abstract in AMA style:
A. Verma, V. Kumar, U. Singh. Design and discovery of 1,2,4 triazole derivatives as adenosine A2A receptor antagonist against parkinson’s disease [abstract]. Mov Disord. 2017; 32 (suppl 2). https://www.mdsabstracts.org/abstract/design-and-discovery-of-124-triazole-derivatives-as-adenosine-a2a-receptor-antagonist-against-parkinsons-disease/. Accessed May 16, 2025.« Back to 2017 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/design-and-discovery-of-124-triazole-derivatives-as-adenosine-a2a-receptor-antagonist-against-parkinsons-disease/