Publications by authors named "Jang B Gupta"

7 Publications

  • Page 1 of 1

Tetrahydro-naphthols as orally available TRPV1 inhibitors.

Bioorg Med Chem Lett 2012 May 6;22(10):3408-11. Epub 2012 Apr 6.

Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto, Japan.

Starting from a naphthol-based lead series with low oral bioavailability, we have identified potent TRPV1 antagonists with oral bioavailability in rats. These compounds emerged from SAR studies aimed at replacing the lead's phenol structure whilst maintaining potency. Compound rac-6a is an orally available TRPV1 antagonist with single-digit nanomolar activity. The enantiomers show a low eudismic ratio at the receptor level.
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http://dx.doi.org/10.1016/j.bmcl.2012.03.108DOI Listing
May 2012

Naphthol derivatives as TRPV1 inhibitors for the treatment of urinary incontinence.

Bioorg Med Chem Lett 2011 Jun 9;21(11):3354-7. Epub 2011 Apr 9.

Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan.

We have identified naphthol derivatives as inhibitors of the vanilloid receptor TRPV1 by high throughput screening. The initial lead showed high clearance in rats and has been optimized by enhancing the acidity of the phenol group. Compound 6b has reduced clearance, improved potency and is active in rat cystometry models of urinary incontinence after intravenous administration.
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http://dx.doi.org/10.1016/j.bmcl.2011.04.013DOI Listing
June 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

Benzimidazole derivatives as novel nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 2: Benzimidazole-5-sulfonamides.

Bioorg Med Chem Lett 2005 Feb;15(3):805-7

Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan.

The 2-cyclopropyl substituted benzimidazole 2 has been used as a starting point for further optimization of an LHRH antagonist series. SAR studies revealed that a tert-butyl urea fragment connected through a simple carbon chain would improve activity. Further modification of the benzylsulfonamide moiety led to the discovery of 23 (IC(50): 4.2 nM).
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http://dx.doi.org/10.1016/j.bmcl.2004.10.090DOI Listing
February 2005

Benzimidazole derivatives as novel nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Part 1: Benzimidazole-5-sulfonamides.

Bioorg Med Chem Lett 2005 Feb;15(3):799-803

Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd, Kizu, Soraku, Kyoto 619-0216, Japan.

A new class of benzimidazole-5-sulfonamides has been identified as nonpeptide luteinizing hormone-releasing hormone (LHRH) antagonists. Initial structure-activity relationships are presented resulting in compounds 19 and 28 with submicromolar dual functional activity on human and rat receptors.
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http://dx.doi.org/10.1016/j.bmcl.2004.10.089DOI Listing
February 2005

Relaxant effect of oxygen free radicals on rabbit tracheal smooth muscle.

Pulm Pharmacol Ther 2002 ;15(4):375-84

Department of Physiology, College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan S7N 5E5, USA.

We investigated the effect of exogenously generated superoxide anions (O(2)(-)), hydrogen peroxide (H(2)O(2)) and hydroxyl radicals (.OH) on isolated rabbit tracheal smooth muscle suspended in Krebs-Ringer solution. The ability of oxygen free radicals (OFRs) to affect acetyicholine (Ach)-induced contraction in these muscles was also investigated. OFRs, in general, produced a concentration-dependent relaxation of the tracheal smooth muscle in the doses used. However, in large concentrations, O(2)(-) and H(2)O(2) produced effects which were smaller than those obtained with lower concentrations. The relaxant effects of these oxyradicals were progressive and lasted throughout the 20min observation period. At all concentrations used, the OFRs tended to abolish or reduce Ach-induced contraction in a concentration-dependent manner. O(2)(-) was more potent than H(2)O(2) or DHF in relaxing the Ach-precontracted muscle and in inhibiting the response of the muscle to Ach. OFR-induced relaxation of the Ach-contracted muscle was not due to inactivation of the Ach by OFRs. Relaxation produced by OFRs was greater in preparations with intact epithelium than in those denuded of epithelium. The relaxant effects were blocked by indomethacin, a cyclooxygenase inhibitor. OFRs in the presence of indomethacin produced contraction only in the preparations with intact epithelium, suggesting a release of contractile factor(s) from epithelium. These results suggest that OFRs relax rabbit tracheal smooth muscle. The relaxation appears to be mediated through the synthesis and release of prostaglandins from the epithelium and smooth muscles.
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http://dx.doi.org/10.1006/pupt.2002.0370DOI Listing
November 2002