Publications by authors named "Jag P Heer"

5 Publications

  • Page 1 of 1

Importance of Rigidity in Designing Small Molecule Drugs To Tackle Protein-Protein Interactions (PPIs) through Stabilization of Desired Conformers.

J Med Chem 2018 05 28;61(10):4283-4289. Epub 2017 Nov 28.

UCB , 216 Bath Road , Slough SL1 3WE , United Kingdom.

Tackling PPIs, particularly by stabilizing clinically favored conformations of target proteins, with orally available, bona fide small molecules remains a significant but immensely worthwhile challenge for the pharmaceutical industry. Success may be more likely through the application of nature's learnings to build intrinsic rigidity into the design of clinical candidates.
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http://dx.doi.org/10.1021/acs.jmedchem.7b01120DOI Listing
May 2018

Total synthesis of rapamycin.

Chemistry 2009 ;15(12):2874-914

Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.

For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.
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http://dx.doi.org/10.1002/chem.200801656DOI Listing
April 2009

The discovery of a selective, small molecule agonist for the MAS-related gene X1 receptor.

J Med Chem 2009 Feb;52(3):818-25

GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Third Avenue, Harlow, Essex CM19 5AW, United Kingdom.

The novel 7-transmembrane receptor MrgX1 is located predominantly in the dorsal root ganglion and has consequently been implicated in the perception of pain. Here we describe the discovery and optimization of a small molecule agonist and initial docking studies of this ligand into the receptor in order to provide a suitable lead and tool compound for the elucidation of the physiological function of the receptor.
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http://dx.doi.org/10.1021/jm800962kDOI Listing
February 2009

Discovery and optimization of highly ligand-efficient oxytocin receptor antagonists using structure-based drug design.

Bioorg Med Chem Lett 2009 Feb 24;19(3):990-4. Epub 2008 Nov 24.

GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Coldharbour Road, Harlow, Essex CM19 5AD, England, United Kingdom.

A novel oxytocin antagonist was identified by 'scaffold-hopping' using Cresset FieldScreen molecular field similarity searching. A single cycle of optimization driven by an understanding of the key pharmacophoric elements required for activity led to the discovery of a potent, selective and highly ligand-efficient oxytocin receptor antagonist. Selectivity over vasopressin receptors was rationalized based on differences in the structure of the natural ligands.
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http://dx.doi.org/10.1016/j.bmcl.2008.11.064DOI Listing
February 2009

Discovery and optimisation of a potent and selective tertiary sulfonamide oxytocin antagonist.

Bioorg Med Chem Lett 2009 Jan 12;19(2):528-32. Epub 2008 Nov 12.

GlaxoSmithKline Pharmaceuticals, New Frontiers Science Park (North), Coldharbour Road, Harlow, Essex CM19 5AD, England, UK.

The optimisation of a tertiary sulfonamide high-throughput screening hit is described. A combination of high-throughput chemistry, pharmacophore analysis and in silico PK profiling resulted in the discovery of potent sulfonamide oxytocin receptor antagonists with oral exposure and good selectivity over vasopressin receptors.
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http://dx.doi.org/10.1016/j.bmcl.2008.11.018DOI Listing
January 2009