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Effect of chronic treatment with lead compound from this series (I) at 30 and 60 mg/kg showed significant reduction in body weight, serum triglyceride and leptin levels. In continuation of these efforts, we have designed a novel series of rigidized 3-aminoalkoxy indoles (II). The preliminary molecular modeling studies indicated that the proposed compounds retain the pharmacophoric arrangements required for the binding at the receptor. Many of the synthesized compounds are potent and selective 5-HT6R antagonists.

Wickenden3, and J. com. (1) Department of Chemistry, Johnson & Johnson Pharmaceutical Research and Development LLC, 3210 Merryfield Row, San Diego, CA 92121, (2) Computer Aided Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121, (3) Pain & Related Disorders Biology, Johnson & Johnson Pharmaceutical Research and Development LLC, San Diego, CA 92121, (4) Pain & Related Disorders Biology, Johnson & Johnson Pharmaceutical Resaerch and Development LLC, San Diego, CA 92121, (5) Department of Chemistry, Johnson & Johnson Pharmaceutical Resaerch and Development LLC, San Diego, CA 92121 The transient receptor potential vanilloid 1 (TRPV1 or VR1) receptor is a ligand-gated, non-selective cation channel that is primarily expressed in nocieptive fibers.

Mills1, Malcolm MacCoss1, Julia M. Ayala2, Pasquale P. Vicario2, and Margaret A. Cascieri2. (1) Department of Medicinal Chemistry, Merck Research Laboratories, RY121-252, PO Box 2000, Rahway, NJ 07065, Fax: 732-594-2210, (2) Department of Immunology, Merck Research Laboratories, Rahway, NJ 07065-0900 Monocyte Chemotactic Protein-1 (MCP-1) is a member of the chemokine family of pro-inflammatory proteins that are involved in recruitment, chemo-trafficking and activation of leucocytes (monocytes, lymphocytes, esinophils, basophiles, NK cells) by the activation of CCR2 receptors.

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