Publications by authors named "Kirsten L Morton"

5 Publications

  • Page 1 of 1

Novel benzamide-based histamine h3 receptor antagonists: the identification of two candidates for clinical development.

ACS Med Chem Lett 2015 Apr 13;6(4):450-4. Epub 2015 Mar 13.

Janssen Pharmaceutical Company, a division of Johnson & Johnson Pharmaceutical Research & Development L.L.C. , 3210 Merryfield Row, San Diego, California 92121, United States.

The preclinical characterization of novel phenyl(piperazin-1-yl)methanones that are histamine H3 receptor antagonists is described. The compounds described are high affinity histamine H3 antagonists. Optimization of the physical properties of these histamine H3 antagonists led to the discovery of several promising lead compounds, and extensive preclinical profiling aided in the identification of compounds with optimal duration of action for wake promoting activity. This led to the discovery of two development candidates for Phase I and Phase II clinical trials.
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http://dx.doi.org/10.1021/ml5005156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4394347PMC
April 2015

Synthesis and Pharmacological Characterization of Two Novel, Brain Penetrating P2X7 Antagonists.

ACS Med Chem Lett 2013 Apr 12;4(4):419-22. Epub 2013 Mar 12.

Janssen Research and Development, LLC , 3210 Merryfield Row, San Diego, California 92121-1126, United States.

The synthesis and preclinical characterization of two novel, brain penetrating P2X7 compounds will be described. Both compounds are shown to be high potency P2X7 antagonists in human, rat, and mouse cell lines and both were shown to have high brain concentrations and robust receptor occupancy in rat. Compound 7 is of particular interest as a probe compound for the preclinical assessment of P2X7 blockade in animal models of neuro-inflammation.
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http://dx.doi.org/10.1021/ml400040vDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027403PMC
April 2013

Indole- and benzothiophene-based histamine H3 antagonists.

Bioorg Med Chem Lett 2010 Nov 27;20(21):6226-30. Epub 2010 Aug 27.

Johnson & Johnson Pharmaceutical Research & Development, L.L.C., 3210 Merryfield Row, San Diego, CA 92121-1126, United States.

Previous research on histamine H(3) antagonists has led to the development of a pharmacophore model consisting of a central phenyl core flanked by two alkylamine groups. Recent investigation of the replacement of the central phenyl core with heteroaromatic fragments resulted in the preparation of novel 3,5-, 3,6- and 3,7-substituted indole and 3,5-substituted benzothiophene analogs that demonstrate good to excellent hH(3) affinities. Select analogs were profiled in a rat pharmacokinetic model.
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http://dx.doi.org/10.1016/j.bmcl.2010.08.103DOI Listing
November 2010

Pre-clinical characterization of aryloxypyridine amides as histamine H3 receptor antagonists: identification of candidates for clinical development.

Bioorg Med Chem Lett 2010 Jul 16;20(14):4210-4. Epub 2010 May 16.

Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, USA.

The pre-clinical characterization of novel aryloxypyridine amides that are histamine H(3) receptor antagonists is described. These compounds are high affinity histamine H(3) ligands that penetrate the CNS and occupy the histamine H(3) receptor in rat brain. Several compounds were extensively profiled pre-clinically leading to the identification of two compounds suitable for nomination as development candidates.
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http://dx.doi.org/10.1016/j.bmcl.2010.05.041DOI Listing
July 2010

Novel substituted pyrrolidines are high affinity histamine H3 receptor antagonists.

Bioorg Med Chem Lett 2010 May 20;20(9):2755-60. Epub 2010 Mar 20.

Johnson & Johnson Pharmaceutical Research & Development L.L.C., 3210 Merryfield Row, San Diego, CA 92121, United States.

Pre-clinical characterization of novel substituted pyrrolidines that are high affinity histamine H(3) receptor antagonists is described. These compounds efficiently penetrate the CNS and occupy the histamine H(3) receptor in rat brain following oral administration. One compound, (2S,4R)-1-[2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(3-fluoro-phenoxy)-pyrrolidin-1-yl]-ethanone, was extensively profiled and shows promise as a potential clinical candidate.
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http://dx.doi.org/10.1016/j.bmcl.2010.03.071DOI Listing
May 2010