Design, synthesis, and testing of potential antisickling agents. 4. Structure-activity relationships of benzyloxy and phenoxy acids.
In this paper we further establish the activity of two classes of small molecules, benzyloxy and phenoxy acids, as potent inhibitors of hemoglobin S (HbS) gelation. Structural modifications with a large number of each class confirm our earlier work that the highest activity is observed with compounds that contain dihalogenated aromatic rings with attached polar side chains. We have also found a halogenated aromatic malonic acid derivative to be quite active. Compounds reported in this paper are compared with other antigelling agents studied in our laboratory. Comments are made concerning the antigelling activity and binding sites of four derivatives and their effect on the allosteric mechanism of hemoglobin (Hb) function.
D000085:Acetates / Q000138:chemical synthesis* / Q000627:therapeutic use; D000818:Animals; D000986:Antisickling Agents / Q000138:chemical synthesis*; D001593:Benzyl Compounds / Q000138:chemical synthesis* / Q000627:therapeutic use; D001665:Binding Sites; D006016:Glycolates / Q000138:chemical synthesis*; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D010100:Oxygen; D010642:Phenoxyacetates / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000085:Acetates; D000986:Antisickling Agents; D001593:Benzyl Compounds; D006016:Glycolates; D010642:Phenoxyacetates; D010100:Oxygen