2D QSAR studies on thyroid hormone receptor ligands.

2D QSAR studies were carried out for a series of 55 ligands for the Thyroid receptors, TRalpha and TRbeta. Significant cross-validated correlation coefficients (q(2)=0.781 (TRalpha) and 0.693 (TRbeta)) were obtained. The models' predictive abilities were proved more valuable than the classical 2D-QSAR, and were further investigated by means of an external test set of 13 compounds. The predicted values are in good agreement with experimental values, suggesting that the models could be useful in the design of novel, more potent TR ligands. Contribution map analysis identified a number of positions that are promising for the development of receptor isoform specific ligands.

[1]  Mary E. McGrath,et al.  A structural role for hormone in the thyroid hormone receptor , 1995, Nature.

[2]  A. Tropsha,et al.  Beware of q2! , 2002, Journal of molecular graphics & modelling.

[3]  Johan Malm,et al.  Thyroid receptor ligands. Part 5: novel bicyclic agonist ligands selective for the thyroid hormone receptor beta. , 2006, Bioorganic & medicinal chemistry letters.

[4]  Peter Brandt,et al.  Thyroid receptor ligands. 6. A high affinity "direct antagonist" selective for the thyroid hormone receptor. , 2006, Journal of medicinal chemistry.

[5]  L. Ye,et al.  Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. , 2003, Journal of medicinal chemistry.

[6]  Marcelo Santos Castilho,et al.  Classical and Hologram QSAR Studies on a Series of Tacrine Derivatives as Butyrylcholinesterase Inhibitors , 2007 .

[7]  M. Lazar.  Thyroid hormone receptors: multiple forms, multiple possibilities. , 1993, Endocrine reviews.

[8]  G. Grover,et al.  Selective thyroid hormone agonists: A strategy for treating metabolic syndrome , 2005 .

[9]  J. Sutherland,et al.  A comparison of methods for modeling quantitative structure-activity relationships. , 2004, Journal of medicinal chemistry.

[10]  Adriano D Andricopulo,et al.  Hologram quantitative structure-activity relationships for a series of farnesoid X receptor activators. , 2005, Bioorganic & medicinal chemistry letters.

[11]  Johan Malm,et al.  Thyroid receptor ligands. Part 2: Thyromimetics with improved selectivity for the thyroid hormone receptor beta. , 2004, Bioorganic & medicinal chemistry letters.

[12]  Grazia Chiellini,et al.  Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Subhash C. Basak,et al.  Topological Indices: Their Nature and Mutual Relatedness , 2000, J. Chem. Inf. Comput. Sci..

[14]  Johan Malm,et al.  Thyroid receptor ligands. Part 4: 4'-amido bioisosteric ligands selective for the thyroid hormone receptor beta. , 2006, Bioorganic & medicinal chemistry letters.

[15]  Glaucius Oliva,et al.  Two- and three-dimensional quantitative structure-activity relationships for a series of purine nucleoside phosphorylase inhibitors. , 2006, Bioorganic & medicinal chemistry.

[16]  Ovidiu Ivanciuc,et al.  Design of Topological Indices. Part 10.1 Parameters Based on Electronegativity and Covalent Radius for the Computation of Molecular Graph Descriptors for Heteroatom-Containing Molecules , 1998, J. Chem. Inf. Comput. Sci..

[17]  Grazia Chiellini,et al.  Synthesis and biological activity of novel thyroid hormone analogues: 5'-aryl substituted GC-1 derivatives. , 2002, Bioorganic & medicinal chemistry.