84673-46-1Relevant academic research and scientific papers
Synthesis and Pharmacological Characterization of Novel trans-Cyclopropylmethyl-Linked Bivalent Ligands That Exhibit Selectivity and Allosteric Pharmacology at the Dopamine D3 Receptor (D3R)
Kumar, Vivek,Moritz, Amy E.,Keck, Thomas M.,Bonifazi, Alessandro,Ellenberger, Michael P.,Sibley, Christopher D.,Free, R. Benjamin,Shi, Lei,Lane, J. Robert,Sibley, David R.,Newman, Amy Hauck
, p. 1478 - 1494 (2017/03/08)
The development of bitopic ligands directed toward D2-like receptors has proven to be of particular interest to improve the selectivity and/or affinity of these ligands and as an approach to modulate and bias their efficacies. The structural similarities between dopamine D3 receptor (D3R)-selective molecules that display bitopic or allosteric pharmacology and those that are simply competitive antagonists are subtle and intriguing. Herein we synthesized a series of molecules in which the primary and secondary pharmacophores were derived from the D3R-selective antagonists SB269,652 (1) and SB277011A (2) whose structural similarity and pharmacological disparity provided the perfect templates for SAR investigation. Incorporating a trans-cyclopropylmethyl linker between pharmacophores and manipulating linker length resulted in the identification of two bivalent noncompetitive D3R-selective antagonists, 18a and 25a, which further delineates SAR associated with allosterism at D3R and provides leads toward novel drug development.
Synthesis of &γ-Aminobutyric Acid Analogue of Restricted Conformation. Part 1. The 2-Aminocycloalkylacetic Acids
Kennewell, Peter D.,Matharu, Saroop S.,Taylor, John B.,Westwood, Robert,Sammes, Peter G.
, p. 2553 - 2562 (2007/10/02)
The syntheses of cis- and trans-2-aminocyclopropyl, -cyclobutyl, -cyclopentyl, and cyclohexylacetic acids as γ-aminobutyric acid analogues of restricted conformation are described.Mass spectral evidence fully supports the stereochemical assignements of configurational isomers.
