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Identification of novel amino acid derived CCK-2R antagonists as potential Anti-Ulcer agent: Homology Modeling, Design, Synthesis, and Pharmacology

IR@CDRI: CSIR-Central Drug Research Institute, Lucknow


Field	Value

Creator	Gupta, A K Varshney, Kanika Singh, Neetu Mishra, Vaibhav Saxena, Mridula Palit, Gautam Saxena, A K

Date	2013-07-12T07:05:11Z 2013-07-12T07:05:11Z 2012

Identifier	Journal of Chemical Information and Modeling, 2012, 53(1), 176-87 http://hdl.handle.net/123456789/1085

Description	The present study revisited the three-dimensional (3D) homology model of CCK-2R using human A2a adenosine receptor and the resolved NMR based structure of the third extracellular loop of the CCK-2R as templates. Further in order to identify novel antiulcer agents, rational designing have been performed utilizing the sub structure of a well known CCK-2R antagonist benzotript as a lead molecule and submitted to the combined docking and simulation studies. This led to the understanding of the essential structure requirement as well as variation of binding mode among conformational isomers of small molecule CCK-2R antagonists. In the next step preparation of each configurational isomer of these molecules were carried out and submitted for their in vitro activity followed by in vivo screening into antiulcer rat model. The biological screening of these compounds has not only validated the developed homology model of CCK-2R but also led to the identification of highly potent CCK-2R antagonist 6a as orally active and safe candidate molecule having better antiulcer properties than the well known drug benzotript.

Format	3337123 bytes application/pdf

Language	en

Relation	CSIR-CDRI Communication No. 8373

Subject	Homology model Sub-structure based drug discovery CCK-2 receptor antagonists Synthesis Pharmacology

Title	Identification of novel amino acid derived CCK-2R antagonists as potential Anti-Ulcer agent: Homology Modeling, Design, Synthesis, and Pharmacology

Type	Article