Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure-activity relationship (SAR) study are presented. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available n class="Gene">CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure-activity relationship (SAR) study are presented. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
Authors: Amit S Kalgutkar; Iain Gardner; R Scott Obach; Christopher L Shaffer; Ernesto Callegari; Kirk R Henne; Abdul E Mutlib; Deepak K Dalvie; Jae S Lee; Yasuhiro Nakai; John P O'Donnell; Jason Boer; Shawn P Harriman Journal: Curr Drug Metab Date: 2005-06 Impact factor: 3.731
Authors: Bernard Pirotte; Pascal de Tullio; Quynh-Anh Nguyen; Fabian Somers; Pierre Fraikin; Xavier Florence; Philip Wahl; John Bondo Hansen; Philippe Lebrun Journal: J Med Chem Date: 2010-01-14 Impact factor: 7.446
Authors: H Deng; R Liu; W Ellmeier; S Choe; D Unutmaz; M Burkhart; P Di Marzio; S Marmon; R E Sutton; C M Hill; C B Davis; S C Peiper; T J Schall; D R Littman; N R Landau Journal: Nature Date: 1996-06-20 Impact factor: 49.962