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Updated: Aug 16, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines: A1 adenosine receptor agonist allosteric enhancers having improved potency
Mahendra D Chordia1, Molly Zigler, Lauren J Murphree
1Department of Chemistry, University of Virginia, Charlottesville, VA 22901, USA.
Abstract:
Allosteric enhancers (AEs) of the A(1) adenosine receptor (A(1)AR) have potential as drugs for treating neurological, cardiovascular, and renal diseases. This report describes the synthesis and evaluation of a series of 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines that exhibited AE activity at the A(1)AR. Palladium-mediated condensation of arylboronic acids with 5-bromoindan-1-one generated arylindanones 2a-aj for iodine-catalyzed condensation with thiourea, generating 2-aminothiazolium salts 3a-aj. Binding studies using membranes from cells stably expressing human A(1)ARs, A(2A)ARs, or A(3)ARs evaluated AE activity and receptor subtype selectivity. The EC(50) of the AE activities of compounds 3m-o, 3x, and 3ae were 2.2, 1.5, 0.9, 1.0, and 3.0 muM, respectively, substantially lower than that of the well characterized 2-amino-3-aroylthiophene (PD 81,723), >10 microM. The new compounds also have substantially higher maximal AE activity. These compounds had no AE activity at the A(2A)AR and only minimal activity at the A(3)AR.
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