TY - JOUR
T1 - Design, Synthesis, and Testing of Potential Antisickling Agents. 10. (2, 2-Dimethylchroman-6-yl)alkanoic Acids
AU - Fatope, Majekodunmi O.
AU - Abraham, Donald J.
PY - 1987/11/1
Y1 - 1987/11/1
N2 - Five (2,2-dimethylchroman-6-yl)alkanoic acids were synthesized and tested for antigelling activities. It was envisioned that these agents might bind via hydrophobic bonding to nonpolar sites of the “donor-acceptor” regions of hemoglobin S. Several (2,2-dimethylchroman-6-yl)alkanoic acids containing 1–4 carbon atoms on the side-chain residue were designed to interact at the acceptor site, were synthesized, and were found to be moderately potent antigelling agents. The weak activity observed for two of the acids at low concentrations is rationalized in terms of weak binding affinities or multiple binding to active and nonactive sites. The effect of these compounds on shifting the allosteric equilibrium was small or negligible. The low toxicity of one of the (2,2-dimethylchroman-6-yl)alkanoic acids demonstrates the potential use of yet another class of compounds that can be modified in the development of antisickling agents.
AB - Five (2,2-dimethylchroman-6-yl)alkanoic acids were synthesized and tested for antigelling activities. It was envisioned that these agents might bind via hydrophobic bonding to nonpolar sites of the “donor-acceptor” regions of hemoglobin S. Several (2,2-dimethylchroman-6-yl)alkanoic acids containing 1–4 carbon atoms on the side-chain residue were designed to interact at the acceptor site, were synthesized, and were found to be moderately potent antigelling agents. The weak activity observed for two of the acids at low concentrations is rationalized in terms of weak binding affinities or multiple binding to active and nonactive sites. The effect of these compounds on shifting the allosteric equilibrium was small or negligible. The low toxicity of one of the (2,2-dimethylchroman-6-yl)alkanoic acids demonstrates the potential use of yet another class of compounds that can be modified in the development of antisickling agents.
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U2 - 10.1021/jm00394a007
DO - 10.1021/jm00394a007
M3 - Article
C2 - 3669005
AN - SCOPUS:0023568290
SN - 0022-2623
VL - 30
SP - 1973
EP - 1977
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 11
ER -