Pyrazolo Derivatives As Potent Adenosine Receptor Antagonists: an Overview on the Structure-activity Relationships

Overview

Journal Int J Med Chem

Specialty Chemistry

Date 2015 May 9

PMID 25954519

Citations 1

Authors

Siew Lee Cheong

Gopalakrishnan Venkatesan

Priyankar Paira

Ramasamy Jothibasu

Alexander Laurence Mandel

Stephanie Federico

Giampiero Spalluto

Giorgia Pastorin

Affiliations

Soon will be listed here.

Abstract

In the past few decades, medicinal chemistry research towards potent and selective antagonists of human adenosine receptors (namely, A1, A2A, A2B, and A3) has been evolving rapidly. These antagonists are deemed therapeutically beneficial in several pathological conditions including neurological and renal disorders, cancer, inflammation, and glaucoma. Up to this point, many classes of compounds have been successfully synthesized and identified as potent human adenosine receptor antagonists. In this paper, an overview of the structure-activity relationship (SAR) profiles of promising nonxanthine pyrazolo derivatives is reported and discussed. We have emphasized the SAR for some representative structures such as pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]pyrimidines; pyrazolo-[3,4-c] or -[4,3-c]quinolines; pyrazolo-[4,3-d]pyrimidinones; pyrazolo-[3,4-d]pyrimidines and pyrazolo-[1,5-a]pyridines. This overview not only clarifies the structural requirements deemed essential for affinity towards individual adenosine receptor subtypes, but it also sheds light on the rational design and optimization of existing structural templates to allow us to conceive new, more potent adenosine receptor antagonists.

Citing Articles

Discovery of a High Affinity Adenosine A/A Receptor Antagonist with a Novel 7-Amino-pyrazolo[3,4-]pyridazine Scaffold.

Suchankova A, Stampelou M, Koutsouki K, Pousias A, Dhingra L, Barkan K ACS Med Chem Lett. 2022; 13(6):923-934.

PMID: 35707146 PMC: 9190043. DOI: 10.1021/acsmedchemlett.2c00052.

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