Comparative 3D QSAR study on β1-, β2-, and β3-adrenoceptor agonists

A quantitative structure–activity relationship study of tryptamine-based derivatives of β1-, β2-, and β3-adrenoceptor agonists was conducted using comparative molecular field analysis (CoMFA). Correlation coefficients (cross-validated r2) of 0.578, 0.595, and 0.558 were obtained for the three subtypes, respectively, in three different CoMFA models. All three CoMFA models have different steric and electrostatic contributions, implying different requirements inside the binding cavity. The CoMFA coefficient contour plots of the three models and comparisons among these plots provide clues regarding the main chemical features responsible for the biological activity variations and also result in predictions which correlate very well with the observed biological activity. Based on the analysis, a summary regeospecific description of the requirements for improving β-adrenoceptor subtype selectivity is given

Electron Delocalization in Aminoguanidine: A Computational Study

The electronic structure, intramolecular interactions, second-order delocalizations, and C−N rotational barriers in aminoguanidine have been studied using ab initio MO and density functional methods. Isomer AG1 with intramolecular hydrogen bonding has been found to be the most stable on the potential energy surface, with nine minima. The influences of the basis set, computational method, and solvent effect on relative stabilities of important isomers of aminoguanidine have been studied. Natural Population Analysis (NPA) indicates that amino substitution in guanidine leads to an increased electron delocalization from the center of the NH2 attachment to the π frame. A strong redistribution of π electron density has been observed in aminoguanidine in relation to guanidine. The protonation energy for aminoguanidine is slightly less than that of guanidine. In protonated aminoguanidine, the π delocalization is more polarized in comparison to that in protonated guanidine. NPA, HOMA, and NICS studies have been carried out to understand electron delocalization in protonated guanidine and aminoguanidine

Isolobal analogy between trivalent boron and divalent silicon

Singlet organosilylenes with a lone pair and an emptyp orbital are isolobal to trivalent borane if a B-H is equated to the lone pair on Si. Using this analogy, a particular isomer of CSi2H2 (2̲4̲) is predicted to be a stable structure. MNDO calculations on 2̲4̲ and many of its possible isomers suggest that 2̲4̲ is at global minimum on the potential energy surface of CSi2H2. Ab initio calculations using a, minimal STO-3G basis set, on some selected structures also support these results

<span style="font-size:12.0pt;line-height:115%; font-family:"Times New Roman";mso-fareast-font-family:"Times New Roman"; mso-ansi-language:EN-IN;mso-fareast-language:EN-IN;mso-bidi-language:HI">Molecular Electrostatic Potential (MESP) studies on the anti-hyperglycemic agents— 2,5-dihydroxyquinones</span>

13-20The mapping of Molecular Electrostatic Potential (MESP) has been carried out on 2,5-dihydroxyquinone derivatives to bring out the common set of electronic characteristic s of molecules that act as effective insulin mimetic agent s. A force- field based systematic conformational search has also been carried out on each system to obtain the least energy conformer The geometry optimization of the lowest energy conformer is carried out using quantum chemical B3LYP/3-21 G method on each system to obtain the wave function. The MESP isosurface plots have been gene rated and the critical point characteristics estimated for these molecules. The coplanarity of the two terminal rings attached to central 2,5-dih ydroxyquinone ring as well as the availability of the nearby oxygen lo ne pair is seen to play important role in defining the anti-diabetic activity of the molecules

Relative Eccentric Distance Sum/Product Indices for QSAR/QSPR: Development, Evaluation, and Application

In the present study, five detour/distance matrix based molecular descriptors (MDs) termed as relative eccentric distance sum/product indices (denoted by ^Rξ₁^SV, ^Rξ₂^SV, ^Rξ₃^SV, ^RPξ₁^SV, and ^RPξ₂^SV), as well as their topochemical versions denoted by (^Rξ₁^cSV, ^Rξ₂^cSV, ^Rξ₃^cSV, ^RPξ₁^cSV, and ^RPξ₂^cSV) have been conceptualized for exclusive use for molecules containing cyclic moieties. The said MDs exhibited exceptionally high discriminating power and high sensitivity toward branching/relative position of substituents in cyclic structures amalgamated with negligible degeneracy. Subsequently, the proposed MDs along with other MDs were successfully utilized for the development of models for the prediction of human glutaminyl cyclase (hQC) inhibitory activity using decision tree (DT), random forest (RF) and moving average analysis (MAA). A data set comprising of 45 analogues of substituted 3-(<i>1H</i>-imidazol-1-yl) propyl thiourea derivatives was used. DT identified proposed relative eccentric distance sum topochemical index-1 as the most important MD. High accuracy of prediction up to 96%, 93%, and 95% was observed in case of models derived from decision tree, random forest, and MAA, respectively. The statistical significance of proposed models was assessed through specificity, sensitivity, overall accuracy, Mathew’s correlation coefficient (MCC), and intercorrelation analysis

In(III) Triflate-Mediated Solvent-Free Synthesis and Activation of Thioglycosides by Ball Milling and Structural Analysis of Long Chain Alkyl Thioglycosides by TEM and Quantum Chemical Methods

Conventional solution-phase synthesis of thioglycosides from glycosyl acetates and thiols in the presence of In­(III) triflate as reported for benzyl thioglucoside failed when applied to the synthesis of phenolic and alkyl thioglycosides. But, it was achieved in high efficiency and diastereospecificity with ease by solvent-free grinding in a ball mill. The acetates in turn were also obtained by the homogenization of free sugars with stoichiometric amounts of acetic anhydride and catalytic In­(OTf)₃ in the mill as neat products. Per-<i>O</i>-benzylated thioglycosides on grinding with an acceptor sugar in the presence of In­(OTf)₃ yield the corresponding <i>O</i>-glycosides efficiently. The latter in the case of a difficult secondary alcohol was nearly exclusive (>98%) in 1,2-<i>cis</i>-selectivity. In contrast, the conventional methods for this purpose require use of a coreagent such as NIS along with the Lewis acid to help generate the electrophilic species that actually is responsible for the activation of the thioglycoside donor in situ. The distinctly different self-assembling features of the peracetylated octadecyl 1-thio-α- and β-d-galactopyranosides observed by TEM could be rationalized by molecular modeling

Synthesis and evaluation of S-4-(3-thienyl)phenyl-α-methylacetic acid

Herein we report an efficient procedure to synthesize S-4-(3-thienyl)phenyl-α-methylacetic acid, an enantiomerically pure intermediate of a recently approved nonsteroidal antiinflammatory cyclooxygenase inhibitor, atliprofen [methyl RS-4-(3-thienyl)phenyl-α-methylacetate]. The interactions of the active S-isomer of the acid were theoretically compared with those of S-ibuprofen through molecular docking studies using COX-1 and COX-2 protein structures. The results were corroborated by in vitro and in vivo studies. An efficient process for the preparation of S-4-(3-thienyl)phenyl-α-methylacetic acid, an enantiomerically pure intermediate of recently approved NSAID atliprofen is reported. The pharmacologically active isomer, S-4-(3-thienyl)phenyl-α-methylacetic acid was compared with S-ibuprofen by docking studies on COX enzyme structures followed by biological evaluations