813445-19-1Relevant academic research and scientific papers
Preparation and biological evaluation of conformationally constrained BACE1 inhibitors
Winneroski, Leonard L.,Schiffler, Matthew A.,Erickson, Jon A.,May, Patrick C.,Monk, Scott A.,Timm, David E.,Audia, James E.,Beck, James P.,Boggs, Leonard N.,Borders, Anthony R.,Boyer, Robert D.,Brier, Richard A.,Hudziak, Kevin J.,Klimkowski, Valentine J.,Garcia Losada, Pablo,Mathes, Brian M.,Stout, Stephanie L.,Watson, Brian M.,Mergott, Dustin J.
, p. 3260 - 3268 (2015)
Abstract The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described.
Synthesis of 3-phenylsulfonylmethyl cyclohexylaminobenzamide-derived antagonists of CC chemokine receptor 2 (CCR2)
Yang, Michael G.,Xiao, Zili,Shi, Qing,Cherney, Robert J.,Tebben, Andrew J.,De Lucca, George V.,Santella III, Joseph B.,Mo, Ruowei,Cvijic, Mary Ellen,Zhao, Qihong,Barrish, Joel C.,Carter, Percy H.
, p. 1384 - 1387 (2012/03/26)
We report the synthesis of 3-phenylsulfonylmethyl cyclohexylaminobenzamides (4) as CCR2 inhibitors for the potential treatment of inflammatory diseases. Several of the compounds display nanomolar binding affinity for CCR2. The in vitro structure-activity
N-UREIDOALKYL-AMINO COMPOUNDS AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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, (2008/06/13)
The present application describes modulators of chemokine receptors of formula (I), or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.
