3D-QSAR studies

Rhyn K-B, H C Patel and A J Hopfinger 1995. A 3D-QSAR Study of Anticoccidal Triazlnes Usir Molecular Shape Analysis. Journal of Chemical Information and Computer Science 35 771-778. 

The first NBINS/2 coordinates of the vector V correspond to the hydrophilic surface (MLP < 0), while the remaining coordinates correspond to the hydrophobic surface (MLP > 0). Thus, for each compound, the 3D-LogP offers a fixed number of 200 descriptors allowing its use in 3D-QSAR studies. 

The second important point of this chapter is to evaluate the use of local lipophilicity information in 3D-QSAR studies. For that purpose, we used a set of 49 HIV-1 protease inhibitors that has been widely used in the 3D-QSAR literature. 

MS-WHIM, new 3D theoretical descriptors derived from molecular surface properties a comparative 3D QSAR study in a series of steroids../. Comput. 

Wright AD, de Nys R, Angerhofer CK, Pezzuto JM, Gurrath M (2006) Biological Activities and 3D QSAR Studies of a Series of Delisea pulchra (cf. fimbriata) Derived Natural Products. J Nat Prod 69 1180... 

Stereostructure and electrostatic potential map of 2-(2-piperidi-noethyl)-l,2,3,4,ll,lla-hexahydro-6H-pyrazino[l,2-fc]isoquinoline-l,4-dione was determined by ab initio (RHF/3-21G) and DFT [B3LYP/6-31G (d)] calculations (06T4408). 2-(3-Arylamino-3-oxopropyl)-2,3,4,6,n,nfl-hexahydro-lH-pyrazino[l,2-fc]isoquinolines were included in a set of compounds to carry out the 3D QSAR study (06BMC8249). 

The number of 3D QSAR studies has increased exponentially over the last decade, since a variety of methods are commercially available in user-friendly, gra-... 

La Regina, G., Coluccia, A., Di Pasquali, A., Silvestri, R. Docking and 3D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives./. Med. Chem. 2005, 48, 213-23. 

Hu, X., Stebbins, C. E. Molecular Docking and 3D QSAR Studies of Yersinia Protein Tyrosine Phosphatase YopH Inhibitors. Bioorg. Med. Chem. 2005, 13, 1101-1109. 

Norinder U., Gustavsson A.-L. and Liljefors T. (1997) A 3D-QSAR study of analogs of (Z)-5-decenyl acetate, a pheromone component of the turnip moth, Agrotis segetum. J. Chem. Ecol. 23, 2917-2934. 

D-QSAR. Since compounds are active in three dimensions and their shape and surface properties are major determinants of their activity, the attractiveness of 3D-QSAR methods is intuitively clear. Here conformations of active molecules must be generated and their features captured by use of conformation-dependent descriptors. Despite its conceptual attractiveness, 3D-QSAR faces two major challenges. First, since bioactive conformations are in many cases not known from experiment, they must be predicted. This is often done by systematic conformational analysis and identification of preferred low energy conformations, which presents one of the major uncertainties in 3D-QSAR analysis. In fact, to date there is no computational method available to reliably and routinely predict bioactive molecular conformations. Thus, conformational analysis often only generates a crude approximation of active conformations. In order to at least partly compensate for these difficulties, information from active sites in target proteins is taken into account, if available (receptor-dependent QSAR). Second, once conformations are modeled, they must be correctly aligned in three dimensions, which is another major source of errors in the system set-up for 3D-QSAR studies. 

Stanton DT, Jurs PC (1990) Development and use of charged partial surface area structural descriptors in computer-assisted quantitative structure-property relationship studies. Anal Chem 62 2323—2329. Tetko iy Kovalishyn Vy Livingstone DJ (2001) Volume learning algorithm artificial neural networks for 3D-QSAR studies. J Med Chem 44 2411-2420. 

Nayyar A, Malde A, Coutinho E, Jain R (2006) Synthesis, anti-tuberculosis activity, and 3D-QSAR study of rmg-substituted-2/4-qui-nolinecarbaldehyde derivatives. Bioorg Med Chem 14 7302-7310... 

Manvar AT, Pissurlenkar RR, Virsodia VR et al (2010) Synthesis, in vitro antitubercular activity and 3D-QSAR study of 1,4-dihydropyridines. Mol Divers 14 285-305... 

Aparna V, Jeevan J, Ravi M et al (2006) 3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods. Bioorg Med Chem Lett 16 1014-1020... 

Wiese, T.E., Polin, L.A., Palomino, E., and Brooks, S.C., Induction of the estrogen specific mitogenic response of MCF-7 cells by selected analogues of estradiol-17 beta A 3D QSAR study, J. Med Chem., 40, 3659-3669, 1997. 

In search for potent and systemically available inhibitors of the matrix metalloproteinase MMP-8 (Matter et al. 1999 Matter et al. 2002) following oral administration, a local ADME model was derived to support lead optimization. For an internal series of inhibitors on the tetrahydroisoquinoline scaffold, hydroxamic acids for zinc ion binding in 3-position are essential for MMP affinity in first generation inhibitors. However, those compounds are characterized by insufficient pharmacokinetic properties and low systemic exposure following oral administration. Driven by X-ray and 3D-QSAR studies (CoMFA), alternative Zn2+ binding groups like carboxylates were... 

The adenosine A3 receptor antagonistic activity of these compounds have been further analyzed [104] in 3D-QSAR using molecular shape analysis (MSA) and molecular field analysis (MFA) techniques in Cerius2 (version 4.8) software [50]. hi this, Jurs atomic charge descriptors were used for the MSA study and H+ point charges and CH3 derived steric fields were used for the MFA study. In this 3D-QSAR study, MSA resulted in Eqs. 12 and 13 and MFA led to Eq. 14. 

---