Computational Analysis of CRTh2 receptor antagonist: A Ligand-based CoMFA and CoMSIA approach

Birkinshaw, 2006, Discovery of potent CRTh2 (DP2) receptor antagonists, Bioorg. Med. Chem. Lett., 16, 4287, 10.1016/j.bmcl.2006.05.062 Bonafoux, 2011, Thienopyrrole acetic acids as antagonists of the CRTH2 receptor, Bioorg. Med. Chem. Lett., 21, 1861, 10.1016/j.bmcl.2011.01.008 Doweyko, 2004, 3D QSAR illusions, J. Comput. Aided Mol. Des., 18, 587, 10.1007/s10822-004-4068-0 Gervais, 2011, Pharmacological characterization of MK-7246, a potent and selective CRTH2 (chemoattractant receptor-homologous molecule expressed on T-helper type 2cells) antagonist, Mol. Pharmacol., 79, 69, 10.1124/mol.110.068585 Gallant, 2011, Discovery of MK-7246, a selective CRTH2 antagonist for the treatment of respiratory diseases, Bioorg. Med. Chem. Lett., 21, 288, 10.1016/j.bmcl.2010.11.015 Hirai, 2001, Prostaglandin D2 selectively induces chemotaxis in T helper type 2cells, eosinophils, and basophils via seven-transmembrane receptor CRTH2, J. Exp. Med., 193, 255, 10.1084/jem.193.2.255 Huang, 2004, Sequence variants of the gene encoding chemoattractant receptor expressed on Th2 cells (CRTH2) are associated with asthma and differentially influence mRNA stability, Hum. Mol. Genet., 13, 2691, 10.1093/hmg/ddh279 Hata, 2005, Identification of determinants of ligand binding affinity and selectivity in the prostaglandin D2 receptor CRTH2, J. Biol. Chem., 280, 32442, 10.1074/jbc.M502563200 Hata, 2004, Pharmacology and signaling of prostaglandin receptors: multiple roles in inflammation and immune modulation, Pharmacol. Ther., 103, 147, 10.1016/j.pharmthera.2004.06.003 Hong, 2003, Comparative molecular field analysis (CoMFA) model using a large diverse set of natural, synthetic and environmental chemicals for binding to the androgen receptor, SAR QSAR Environ. Res., 14, 373, 10.1080/10629360310001623962 Iwasaki, 2002, Association of a new-type prostaglandin D2 receptor CRTH2 with circulating T helper 2cells in patients with atopic dermatitis, J. Invest. Dermatol., 119, 609, 10.1046/j.1523-1747.2002.01862.x Jain, 2008, Three-dimensional QSAR study of 2,4-disubstituted-phenoxy acetic acid derivatives as a Crth2 receptor antagonist: using the K-nearest neighbor method Digest, J. Nanomater. Biostructures, 3, 147 Mathiesen, 2005, Identification of indole derivatives exclusively interfering with a G protein-independent signaling pathway of the prostaglandin D2 receptor CRTH2, Mol. Pharmacol., 68, 393, 10.1124/mol.104.010520 Nagata, 1999, Selective expression of a novel surface molecule by human Th2cells in vivo, J. Immunol., 162, 1278, 10.4049/jimmunol.162.3.1278 Nagata, 1999, CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s), Fed. Eur. Biochem. Soc., 459, 195, 10.1016/S0014-5793(99)01251-X Nagata, 2003, The second PGD2 receptor CRTH2: structure, properties, and functions in leukocytes, Prostaglandins Leukotrienes Essent. Fatty Acids, 69, 169, 10.1016/S0952-3278(03)00078-4 Pettipher, 2012, Update on the development of antagonists of chemoattractant receptor-homologous molecule expressed on Th2cells (CRTH2). From lead optimization to clinical proof-of-concept in asthma and allergic rhinitis, J. Med. Chem., 55, 293, 10.1021/jm2013997 Pothier, 2012, Novel 2-(2-(benzylthio)-1H-benzo[d]imidazol-1-yl) acetic acids: discovery and hit-to-lead evolution of a selective CRTh2 receptor antagonist chemotype, Bioorg. Med. Chem. Lett., 22, 4660, 10.1016/j.bmcl.2012.05.087 Pettipher, 2008, The roles of the prostaglandin D2 receptors DP1 and CRTH2 in promoting allergic responses, Br. J. Pharmacol., 153, 191, 10.1038/sj.bjp.0707488 Puzyn, 2010, 8, 103 Shimono, 2012, Isoquinoline derivatives as potent CRTH2 receptor antagonists: synthesis and SAR, Bioorg. Med. Chem. Lett., 22, 3305, 10.1016/j.bmcl.2012.03.009 Schroder, 2012, PGH1, the precursor for the anti-inflammatory prostaglandins of the 1-series, is a potent activator of the pro-inflammatory receptor CRTH2/DP2, PLoS One, 7, e33329, 10.1371/journal.pone.0033329 Sykes, 2012, Chemoattractant receptor homologous to the T helper 2cell (CRTH2) is not expressed in human amniocytes and myocytes, PLoS One, 7, 10.1371/journal.pone.0050734 Sandham, 2009, 7-Azaindole-3-acetic acid derivatives: potent and selective CRTh2 receptor antagonists, Bioorg. Med. Chem. Lett., 19, 4794, 10.1016/j.bmcl.2009.06.042 Takeshita, 2004, CRTH2 is a prominent effector in contact hypersensitivity-induced neutrophil inflammation, Int. Immunol., 16, 947, 10.1093/intimm/dxh096 Tumey, 2010, 3-Indolyl sultams as selective CRTh2 antagonists, Bioorg. Med. Chem. Lett., 20, 3287, 10.1016/j.bmcl.2010.04.046 Ulven, 2010, Novel CRTH2 antagonists: a review of patents from 2006 to 2009, Expert Opin. Ther. Patents, 20, 1505, 10.1517/13543776.2010.525506 Ulven, 2007, Synthesis and in vitro evaluation of a selective antagonist and the corresponding radioligand for the prostaglandin D2 receptor CRTH2, Bioorg. Med. Chem. Lett., 17, 5924, 10.1016/j.bmcl.2007.07.080 Uller, 2007, Antagonism of the prostaglandin D2 receptor CRTH2 attenuates asthma pathology in mouse eosinophilic airway inflammation, Respir. Res., 8, 16, 10.1186/1465-9921-8-16 Zhao, 2011, Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) studies on alpha 1A-adrenergic receptor antagonists based on pharmacophore molecular alignment, Int. J. Mol. Sci., 12, 7022, 10.3390/ijms12107022