Forecasting the antimalarial activities of arylamidinoureas from their measured physicochemical properties.
1 The octanol : water partition coefficient (PC), protein binding coefficients to albumin (Ba) and haemoglobin (Bh), proton magnetic resonance (PMR) chemical shifts and pKa of 8 arylamidinoureas have been measured. 2 There were statistically significant correlations for 7 of the 8 compounds between the predicted lipophilicity parameter eta and log PC, Ba and Bh, and also between Hammett's electronic parameter sigma and the PMR and pKa observations. 3 3-Chloro,4-nitrophenylamidinourea showed a larger deviation from these correlations than any other compound. Geometric calculations based on the covalent radii and bond angles of the molecule suggested that the neighbouring chloro and nitro substituents were interacting sterically. 4 Molecular orbital calculations and the observed ultra-violet spectrum provided further evidence for such an interaction, and suggested that the nitro group is twisted out of the plane of the benzene ring in this molecule. 5 Such steric interactions can introduce an additional source of error when attempts are made to correlate the biological and predicted physicochemical properties of compounds. 6 Generalized parameters such as eta and sigma cannot be used with confidence to predict the properties of compounds in which such steric interactions occur.
D000578:Amidines; D000962:Antimalarials / Q000378:metabolism; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D006454:Hemoglobins / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011485:Protein Binding; D011789:Quantum Theory; D012044:Regression Analysis; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives*
D000578:Amidines; D000962:Antimalarials; D006454:Hemoglobins; D012710:Serum Albumin, Bovine; D014508:Urea