29936-60-5Relevant academic research and scientific papers
Antinociceptive and antiinflammatory activities and QSAR studies on 2-substituted-4,5-diphenyl-1H-imidazoles
Puratchikody,Doble, Mukesh
, p. 1083 - 1090 (2007)
This paper describes the pharmacological evaluation pertaining to antinociceptive (hot plate and tail flick) and antiinflammatory (based on Carrageenan-induced paw oedema) activities, and QSAR studies on 2-substituted-4,5-diphenyl-1H-imidazoles. Compounds with phenyl substitution with -F, -Cl, -NH2, -N(CH3)2, -OH and -OCH3 at the p-position showed higher activity than the other substitutions in all the three studies. QSARs developed for the 60 and 120 s hot plate data indicate that the models for both the cases not only fit the data very well (R2 > 0.9, Radj2 > 0.86), but also have very good predictive capability (q2 > 0.81). The descriptors used in the model relate to surface area, volume, dipole moment and ADME properties of the molecule. Good QSARs for the 60 and 120 s tail flick data are developed. The models fit the data well (R2 > 0.8, Radj2 > 0.74), and in addition have good predictive capability (q2 > 0.66). Surface area, specifically polar surface area, HOMO and molecular connectivity index appear in the models. Very good QSAR model is developed for the antiinflammatory data (R2 = 0.86, Radj2 = 0.822 and q2 = 0.64) with aqueous solubility, number of hydrogen bond donor groups, surface area and principal moment of inertia as the molecular descriptors.
Influence of Bio-Isosteric Replacement on the Formation of Templating Methanol and Acetonitrile Solvates in Lophines
Kitchen, Thomas,Melvin, Connor,Mohd Najib, Mohd Nadzri,Batsanov, Andrei S.,Edkins, Katharina
, p. 4531 - 4538 (2016/08/11)
Bio-isosteric replacement is a frequently used tool in medicinal chemistry. While the pharmacological activity is not influenced by the exchange of substituents, the solid-state characteristics and formation of different crystal forms may well be altered dramatically, jeopardizing the processability and safety of the drug compound. In this study we investigate a series of triphenylimidazole (TPI) derivatives as model compounds with the bio-isosteric exchange of only one halogen position (F, Cl, Br, I). Crystallization from two industrially used solvents (methanol and acetonitrile) reveals solvate formation of all TPIs, for which the basic hydrogen bonded motif does not change. The three-dimensional packing depends on the size of the substituent and changes from fluoro- to chloro- and bromo-substitution but remains the same for the larger iodo-substituent. From acetonitrile, only F-TPI and Cl-TPI form an isomorphic channel solvate, which in both cases desolvates reversibly to an isomorphic crystal form. Due to the halogen atom lining of the channels, bromine and iodine are too large to generate a stable packing. This study illustrates the importance of understanding the influence of bio-isosteric substitution on the solid state, in order to best utilize this common tool.
