Patent ID: 7962290
Filing Date: 2011-06-14
Classification: C12Q,G01N,G16B,G16C

Abstract:
1. A method of constructing a spleen tyrosine kinase (SYK) inhibitor pharmacophore comprising: (a) generating on a computer a set of three-dimensional conformers comprising a binding site of SYK and compounds from a training set comprising one or more SYK ligands for the binding site, wherein the three-dimensional conformers are generated by using the coordinates of the SYK binding site as set forth in any one of Tables 1 to 6 and the conformers comprise residues selected from the group consisting of Leu377, Gly378, Phe382, Val385, Ala400, Val433, Met448, Glu449, Met450, Ala451, Glu452, Gly454, Pro455, Lys458, Leu501, Asp512, Lys375, Ser379, Gly380, Gly383, Thr384, Lys402, Leu453, Arg498, Asn499, and Ser511 or any combinations thereof, wherein the amino acid numbering is of SEQ ID NO: 1; (b) using the conformers generated in (a) to identify on a computer one or more features on the ligands, wherein the features comprise groups that interact with the residues lining the binding site; (c) formulating (i) by chemical synthesis or (ii) on a computer a set of one or more pharmacophores from the conformers of (a), each of the pharmacophore comprising one or more features identified in (b); and (d) determining those pharmacophores that bind to SYK wherein the training set comprises one or more compounds having the structure: wherein