117561-97-4Relevant academic research and scientific papers
SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor
Mohammed, Idrees,Parai, Maloy K.,Jiang, Xinpeng,Sharova, Natalia,Singh, Gatikrushna,Stevenson, Mario,Rana, Tariq M.
supporting information; experimental part, p. 465 - 469 (2012/09/22)
We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring C, ring B, ring A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.
Ortho effect in dissociation of substituted N-phenylbenzenesulfonamides
Nadvornik, Jiri,Ludwig, Miroslav
, p. 1380 - 1392 (2007/10/03)
Twenty-five 2,2′-disubstituted N-phenylbenzenesulfonamides (2-X-C6H4SO2NHC6H4-Y-Z′) were synthesised and their purity checked by elemental analysis. This set of model substrates involved all possible combinations of methoxy, methyl, hydrogen, chloro, and nitro substituents. The dissociation constants of the sulfonamides were determined by potentiometric titration in methanol, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, acetone, and acetonitrile. The dissociation constants pKHA obtained were correlated with various sets of substituent constants describing electronic and steric effects of the substituents, and the statistically treated data were used to discuss the contribution of the substituent effects in the dissociation and the difference between the effects transmitted from the two rings. A linear regression model explaining 99% of the variability of experimental data in all the solvents has been found and discussed. Moreover, the experimental data were also interpreted by the methods using latent variables, the principal component analysis (PCA) and conjugated deviation analysis (CDA), and two latent variables were shown to be statistically significant in the description of dissociation. The first obviously describes common action of electronic and steric effects of substituents; the other probably concerns a combined effect of substituent and solvent on the position of acid-base equilibrium.
