Substituted acyclic sulfonamides as human cannabinoid-1 receptor inverse agonists

Sulfonamide analogues of the potent CB1R inverse agonist 2 (Taranabant) were optimized for CB1R activity. Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2007-04, Vol.17 (8), p.2184-2187
Hauptverfasser:	Armstrong, Helen E., Galka, Amy, Lin, Linus S., Lanza, Thomas J., Jewell, James P., Shah, Shrenik K., Guthikonda, Ravi, Truong, Quang, Chang, Linda L., Quaker, Grace, Colandrea, Vincent J., Tong, Xinchun, Wang, Junying, Xu, Sherry, Fong, Tung M., Shen, Chun-Pyn, Lao, Julie, Chen, Jing, Shearman, Lauren P., Stribling, D. Sloan, Rosko, Kimberly, Strack, Alison, Ha, Sookhee, der Ploeg, Lex Van, Goulet, Mark T., Hagmann, William K.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Anti-Obesity Agents - chemical synthesis Anti-Obesity Agents - pharmacology Biological and medical sciences Brain Chemistry Cannabinoid Cannabinoid Receptor Modulators - chemical synthesis Cannabinoid Receptor Modulators - pharmacology CB-1R General and cellular metabolism. Vitamins Humans Hypothermia - drug therapy Inhibitory Concentration 50 Medical sciences Miscellaneous Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Obesity Pharmacokinetics Pharmacology. Drug treatments Rats Receptor, Cannabinoid, CB1 - agonists Receptor, Cannabinoid, CB1 - drug effects Structure-Activity Relationship Sulfonamide Sulfonamides - chemical synthesis Sulfonamides - pharmacology
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Zusammenfassung:	Sulfonamide analogues of the potent CB1R inverse agonist 2 (Taranabant) were optimized for CB1R activity. Sulfonamide analogues of the potent CB1R inverse agonist taranabant were prepared and optimized for potency and selectivity for CB1R. They were variably more potent than the corresponding amide analogues. The most potent representative 22 had good pharmacokinetic and brain levels, but was modestly active in blocking CB1R agonist-mediated hypothermia.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2007.01.087