Topic
Substituent
About: Substituent is a research topic. Over the lifetime, 42877 publications have been published within this topic receiving 516716 citations. The topic is also known as: side chain & side group.
Papers published on a yearly basis
Papers
More filters
•
TL;DR: Molecular modeling studies with inhibitors and caffeine showed that it is possible to explain the potency of the quinolones to inhibit CYP1A2 on a molecular level, and an equation to estimate the potency was developed by quantitative structure-activity relationship analysis.
Abstract: The inhibitory effect of 44 quinolone antibacterials and derivatives (common structure, 4-oxoquinoline-3-carboxylic acid) on cytochrome P450 isoform CYP1A2 activity was tested using human liver microsomes and caffeine 3-demethylation as a specific test system for this enzyme. By direct comparison of molecules differing structurally in only one position, the following structure-activity relationships were found. 39-Oxo derivatives had a reduced or similar activity and M1 metabolites (cleavage of piperazinyl substituent) had a greater inhibitory activity, compared with the parent molecule. Alkylation of the 7-piperazinyl substituent resulted in a reduced inhibitory potency. Naphthyridines with an unsubstituted piperazinyl group at position 7 displayed a greater inhibitory potency than did corresponding quinoline derivatives. Derivatives with a fluorine substitution at position 8 had only a minor effect. Molecular modeling studies with inhibitors and caffeine showed that it is possible to explain the potency of the quinolones to inhibit CYP1A2 on a molecular level. The keto group, the carboxylate group, and the core nitrogen at position 1 are likely to be the most important groups for binding to the active site of CYP1A2, because the molecular electrostatic potential of all inhibitors is very similar to that of caffeine in these regions. The presence of a piperazinyl substituent, however, seems to be no prerequisite for inhibitory potency. Finally, an equation to estimate the potency to inhibit CYP1A2 was developed by quantitative structure-activity relationship analysis.
89 citations
••
TL;DR: The study shows that NMR merely probes the presence/absence of the methyl group in thymine/uracil, without any relation to the strength of the hydrogen bonds involved, and one cannot infer the Watson-Crick hydrogen-bond strength from the NMR shielding constant of adenine C2.
Abstract: Recently, Vakonakis and LiWang (J. Am. Chem. Soc. 2004, 126, 5688) reported experimental evidence for stronger hydrogen bonds in RNA A:U than in DNA A:T base pairs, which was based on differences in NMR shielding for adenine C2. We have analyzed the proposed correlation between NMR shielding and hydrogen-bond strength using density functional theory. Although we agree with the conclusion that A:U is more strongly bound, we find no correlation between the hydrogen-bond strength and the NMR shielding of C2. Our study shows that NMR merely probes the presence/absence of the methyl group in thymine/uracil, without any relation to the strength of the hydrogen bonds involved. In other words, one cannot infer the Watson−Crick hydrogen-bond strength from the NMR shielding constant of adenine C2.
89 citations
•
30 Aug 2000TL;DR: A class of substituted and/or ring-fused pyrazolo[3,4-b]pyridine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent on the pyrazole nitrogen atom adjacent the pyridine nucleus, are selective ligands for GABAA receptors, in particular having high affinity for the β2 and β3 subunit thereof, and are accordingly of benefit in the treatment and prevention of adverse neurological disorders, including anxiety and convulsions as mentioned in this paper.
Abstract: A class of substituted and/or ring-fused pyrazolo[3,4-b]pyridine derivatives, possessing an optionally substituted cycloalkyl, phenyl or heteroaryl substituent on the pyrazole nitrogen atom adjacent the pyridine nucleus, and an optionally substituted cycloalkyl-alkoxy, aryl-alkoxy or heteroaryl-alkoxy substituent on the carbon atom adjacent the pyridine ring nitrogen atom, are selective ligands for GABAA receptors, in particular having high affinity for the β2 and/or β3 subunit thereof, and are accordingly of benefit in the treatment and/or prevention of adverse neurological disorders, including anxiety and convulsions.
89 citations
••
TL;DR: The stereochemistry of reduced flavin and its potential relevance in flavin-dependent biological dehydrogenations is discussed and the inversion barrier was found to be ∼10 kcal/mol in acetone solutions and to be independent of the size of the N(5) substituent.
Abstract: The pyramidal inversion of the N(5)-centre of several reduced flavins was measured by NMR. The inversion barrier was found to be ∼10 kcal/mol in acetone solutions and to be independent of the size of the N(5) substituent. An increase of the inversion barrier of ∼5 kcal/mol was observed in the case where the N(5) substituent could only be in axial position, and an increase of ∼3.5 kcal/mol was observed for an acyl-like N(5) substituent. In aqueous solution the inversion barrier increases by ∼3 kcal/mol. The stereochemistry of reduced flavin and its potential relevance in flavin-dependent biological dehydrogenations is discussed.
89 citations
••
TL;DR: In this article, the liquid-liquid phase equilibria of the following imidazolium ionic liquids (ILs), {1-ethyl-3-ethylimidazolate, or 1-butyl-3 -ethylimide-drug-drugs (THMD), bis{(trifluoromethyl)sylfonyl}imide [EEIM][Tf2N], or [BEIM][TAIM], + water or + 1-octanol], have been measured.
Abstract: The liquid–liquid phase equilibria (LLE) of the following imidazolium ionic liquids (ILs), {1-ethyl-3-ethylimidazolium, or 1-butyl-3-ethylimidazolium, or 1-hexyl-3-ethylimidazolium bis{(trifluoromethyl)sylfonyl}imide [EEIM][Tf2N], or [BEIM][Tf2N], or [HEIM][Tf2N], + water or + 1-octanol}, and {1-butyl-3-ethylimidazolium hexafluorophosphate [BEIM][PF6] + water or + 1-octanol}, have been measured. The effect of anion type ([Tf2N]- compared to [PF6]-) and the effect of structural components of an ionic liquid including alkyl chain length on the cation and the ethyl substituent instead of methyl at the cation on the physical-chemical properties of the IL and on the phase behavior were studied. An upper critical solution temperature (UCST) was observed in every system. An increase in the alkyl chain length increases the mutual solubility with 1-octanol and partly with water. Ionic liquids with the ethyl substituent on the cation [HEIM][Tf2N] show higher solubility in 1-octanol in comparison with the methyl sub...
89 citations