Publications by authors named "Shelly Aeron"

3 Publications

  • Page 1 of 1

Pharmacodynamic and pharmacokinetic profile of RBx 343E48F0: a novel, long acting muscarinic receptor antagonist.

Eur J Pharmacol 2011 May 1;658(2-3):219-28. Epub 2011 Mar 1.

Ranbaxy Research Laboratories Limited, Gurgaon, India.

RBx 343E48F0 is a novel, potent, selective and long acting muscarinic receptor antagonist with a potential for use in the treatment of Chronic Obstructive Pulmonary Disease (COPD). The aim of the present study was to describe the in vitro and in vivo profile of RBx 343E48F0 and to compare the results with the present day benchmark therapy, tiotropium. Radioligand binding and isolated tissue based functional assays were used to evaluate the affinity, potency and receptor subtype selectivity of RBx 343E48F0. Inhibition of carbachol-induced bronchoconstriction in the anaesthetized rat and acetylcholine-induced bronchoconstriction in the conscious rat were used to assess the extent and duration of the bronchospasmolytic activity of RBx 343E48F0. In vitro and in vivo pharmacokinetic studies were conducted to evaluate the pharmacokinetic and lung retention properties of the compound. In vitro radioligand binding studies using human recombinant muscarinic receptors showed that RBx 343E48F0 had a pKi of 9.6 at the M(3) receptor and a 60-fold selectivity for the M(3) receptor over the M(2) receptor. In isolated tissue bioassays, it exhibited surmountable antagonism at the guinea pig trachea with a pK(B) of 9.5. Intratracheal administration to anaesthetized rats demonstrated a dose-dependent inhibition of carbachol-induced bronchoconstriction with an ED(50) value of 110 ng/kg. RBx 343E48F0 also exhibited a fast onset of action and long duration of action of greater 24h.
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http://dx.doi.org/10.1016/j.ejphar.2011.02.024DOI Listing
May 2011

Synthesis and optimization of novel and selective muscarinic M(3) receptor antagonists.

Bioorg Med Chem Lett 2007 Sep 30;17(18):5256-60. Epub 2007 Jun 30.

Ranbaxy Research Laboratories, New Drug Discovery Research, Department of Medicinal Chemistry, Gurgaon, Haryana 122 001, India.

A series of constrained piperidine analogues were synthesized as novel muscarinic M(3) receptor antagonists. Evaluation of these compounds in binding assays revealed that they not only have high affinity for the M(3) receptor but also have high selectivity over the M(2) receptor.
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http://dx.doi.org/10.1016/j.bmcl.2007.06.081DOI Listing
September 2007

Design, synthesis and activity of novel derivatives of oxybutynin and tolterodine.

Bioorg Med Chem Lett 2005 Apr;15(8):2093-6

Ranbaxy Research Laboratories, New Drug Discovery Research, Department of Medicinal Chemistry, Gurgaon 122 001, Haryana, India.

Novel derivatives of Tolterodine (1) and Oxybutynin (2) have been designed using conformationally restricted azabicyclics as replacement for open-chain amines. The synthesis and structure-activity relationships are presented.
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http://dx.doi.org/10.1016/j.bmcl.2005.02.036DOI Listing
April 2005