QSAR Analysis of 5-Substituted 2-Benzoylaminobenzoic Acids as PPAR Modulator

Abstract: A quantitative structure activity relationship (QSAR) study on a series of analogs of 5-aryl thiazolidine-2, 4-diones with activity on PPAR-α and PPAR-γ was made using combination of various thermodynamic, electronic and spatial descriptors. Several statistical regression expressions were obtained using multiple linear regression analysis. The best QSAR model was further validated by leave one out cross validation method. The studied revealed that for dual PPAR-α/γ activity dipole-dipole energy and PMI-Z play significant role and contributed positively for PPAR-γ and PPAR-α activity respectively. Thus, QSAR brings important structural insight to aid the design of dual PPAR-α/γ receptor agonist

2D-QSAR Analysis of Oxadiazole Substituted α-Isopropoxy phenylpropionic Acids as PPAR-α & PPAR-λ Agonists

A quantitative structure activity relationship study on a series of oxadiazole substituted α-isopropoxy phenylpropionic acids with activity on PPAR-α and PPAR-λ was made using combination of various physiochemical descriptors. Several statistical regression expressions were obtained using stepwise multiple linear regression analysis. The best quantitative structure activity relationship model was further validated by leave one out cross validation method. Steric parameter (molar refractivity) was found to have significant correlationship with PPAR-λ agonist activity and hydrophobic (Hansch substituent constant), electronic parameter (field effect) were found to have significant correlationship with PPAR-α agonist activity. The increment in the number of carbon atom (indicative variable) between the oxadiazole tail and central phenoxy moiety increases the PPAR-λ agonist activity whereas decreases the PPAR-α agonist activit

QSAR modeling of thalidomide analogs as antiangiogenic and prostate cancer inhibitor using AM1 calculations

238-246Quantitative structure activity relationship studies have been made on thalidomide analogues acting as dual inhibitors of angiogenesis and prostrate cancer using a combination of various electronic, thermodynamic and spatial descriptors. The QSAR studies show that the presence of fluorine atom is essential for both activities. LUMO and partition coefficient play a significant role in antiangiogenic activity while repulsive energy and molar refractivity contribute to anticancer activity. The correlation of inhibitory activity with charge density at 6th, 8th and 16th position of template implies electronic interaction of the molecule with receptor site

QSAR analysis of 5-aryl thiazolidine-2,4-diones as PPAR-<img src='/image/spc_char/alpha.gif' border=0> and PPAR-<img src='/image/spc_char/gamma2.gif' border=0> agonists

1242-1249A quantitative structure activity relationship (QSAR) study on a series of analogs of 5-arylthiazolidine-2, 4-diones with activity on PPAR- and PPAR- has been made using combination of various thermodynamic, electronic and spatial descriptors. Several statistical regression expressions are obtained using multiple linear regression analysis. The best QSAR model is further validated by leave one out cross validation method. The studies reveal that for dual PPAR-/ activity modification at R2 position in molecule is more favourable and also lower value of resultant dipole moment play a key role in activity. Thus, QSAR brings important structural insight to aid the design of dual PPAR-/ receptor agonist

QSAR analysis of analogs of bis[2-(acylamino) phenyl] disulfides, 2-(acylamino)benzenethiols and S-[2-(acylamino) phenyl] alkanethioates as antihyperlipidemic agents <b></b>

1481-1486A series of antihyperlipidemic analogs of bis[2-(acylamino)phenyl]disulfides, 2-(acylamino) benzenethiols and S-[2-(acylamino)phenyl] alkanethioates has been subjected to quantitative structure activity relationship analysis. They show that the cholesteryl ester transfer protein inhibitors as determined in the human are having significant correlation with steric (Principle moment of inertia of X-component) and thermodynamic (logP and bend energy) properties of the molecule. Molecular modelling and QSAR analysis suggest that substitution at R1 with bulkier group is more favourable for cholesteryl ester transfer protein (CETP) inhibitory activity while keeping R2 unsubstituted or substituted with smaller groups results in more potent CETP inhibitors

<span style="mso-bidi-language:HI">QSAR studies of 2,3-diarylpyrazolo[1<b><i><span style="mso-bidi-font-family:Arial;mso-bidi-language:HI">,</span></i></b><span style="mso-bidi-font-family:Arial;mso-bidi-language:HI">5-<i>b</i>]<b><i>-</i></b><span style="mso-bidi-language:HI">pyridazine analogs as cyclooxygenase-2 inhibitors </span></span></span>

2763-2769Cyclooxygenase-2 inhibitors arc of current interest, because these alleviate inflammation, fever, pain, rheumatic and osteoarthritis without side effects, produced by classical NSAlDs. QSAR analysis helps in exploring molecular insight, which are responsible for drug-receptor interactions. QSAR studies have been performed on a series of some 2,3-diaryl-pyrazolo[1,5-b)pyridazine analogs as COX-2 inhibitors using substituent constant in lead structure for 2D and physicochemical properties of molecules for 3D-QSAR analysis respectively. The correlations have been established using regression analysis techniques. 2D-QSAR analysis study has revealed that the substitution of hydrophobic group in the 2,3-diaryl-pyrazolo[1<span style="mso-bidi-font-family:Arial; mso-bidi-language:HI">,<span style="mso-bidi-font-family:Arial; mso-bidi-language:HI">5-b)pyridazines at R2 position is favourable while substitution of bulkier group at R2 position is unfavourable for COX-2 inhibitory activity. In 3D-model, Morl4u and Mor29v are 3D-MoRSE code have been calculated by summing atom weights which have been viewed by a different angular scattering function contributed positively to COX-2 inhibitory activity. G (O..O) is a conformational dependent descriptor based on the geometry of the molecule contributed negatively to COX-2 inhibitory activity. </span

Development of pharmacophoric model of condensed pyridine and pyrimidine analogs as hydroxymethyl glutaryl coenzyme A reductase inhibitors

32-36Quantitative structure-activity relationship (QSAR) has been established on a series of thirty-eight compounds of four different sets of condensed pyridine and pyrimidine analogs, for their hydroxymethyl glutaryl coenzyme (HMG-CoA) reductase inhibitor activity, in order to understand the essential structural requirement for binding with receptor, in terms of common biophoric and secondary sites employing APEX-3D software. Among several 3D pharmacophoric models with different sizes and arrangements, one model was selected based on r² = 0.8, chance<0.001, match equivalent to 0.38 and all the 38 compounds were considered. The results suggest that hydrophobicity, hydrogen acceptor and optimum steric refractivity play a dominant role in the inhibition of HMG-CoA reductase. The information obtained from the present study can be used to design and predict more potent molecules as HMG-CoA reductase inhibitors, prior to their synthesis