Twisted Amides Inferred from QSAR Analysis of Hydrophobicity and Electronic Effects on the Affinity of Fluoroaromatic Inhibitors of Carbonic Anhydrase

• Published in: Journal of organic chemistry Vol. 67; no. 2; pp. 582 - 584
• Main Authors: Madder, Ryan D, Kim, Chu-Young, Chandra, Pooja P, Doyon, Jeffrey B, Baird, Teaster A, Fierke, Carol A, Christianson, David W, Voet, Judith G, Jain, Ahamindra
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 25.01.2002
• Subjects: Amides - chemistry; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Carbonic Anhydrase Inhibitors - chemical synthesis; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - metabolism; Chemical Phenomena; Chemistry, Physical; Combinatorial Chemistry Techniques; Drug Design; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Lyases; Magnetic Resonance Spectroscopy; Molecular Structure; Quantitative Structure-Activity Relationship; Sulfonamide; Enzyme; Ab initio method; Combinatorial chemistry; Enzyme inhibitor; Amides; Dissociation constant; Lyases; Hydrophobicity; Experimental study; Synthetic product; Structure activity relation; Chemical compound library; Carbonate dehydratase; Aromatic compound; Electronic effect; Fluorine Organic compounds; Carbon-oxygen lyases; Intramolecular interaction; Hydro-lyases

QSAR has been used to elucidate the origin of the hydrophobicity and binding affinity of a small library of fluoroaromatic inhibitors of F131V carbonic anhydrase II. Our analysis predicted the presence of a twisted amide conformation for several bound inhibitors, which we confirmed crystallographica...