321853-38-7Relevant articles and documents
Synthesis and structure - Activity relationships of chiral allosteric modifiers of hemoglobin
Grella,Danso-Danquah,Safo,Joshi,Kister,Marden,Hoffman,Abraham
, p. 4726 - 4737 (2000)
A series of allosteric effectors of hemoglobin, 2-(aryloxy)-2-alkanoic acids, was prepared to investigate the effect of the stereocenter on allosteric activity. The chiral analogues were based on the lead compound, RSR13 (3b), with different alkyl/alkanoic and cycloalkyl/cycloalkanoic groups positioned at the acidic chiral center. Of the 23 racemic molecules synthesized, 5 were selected for resolution based on structure - activity relationships. One chiral analogue, (-)-(1R,2R)-1-[4-[[(3,5-dimethylanilino)carbonyl]methyl]phenoxy]-2-methylcycl opentanecarboxylic acid (11), exhibited greater in vitro activity in hemoglobin solutions than its antipode, racemate, and RSR13. Compound (-)-(1R,2R)-11 was equipotent with RSR13 in whole blood, is a candidate for in vivo animal studies, and if efficacious and safe has a potential for use in humans. In general, it was found that chirality affects allosteric effector activity with measurable differences observed between enantiomers and the racemates.
