Potent, elective human beta3 adrenergic receptor agonists containing a substituted indoline-5-sulfonamide pharmacophore.

R J Mathvink, A M Barritta, M R Candelore, M A Cascieri, L Deng, L Tota, C D Strader, M J Wyvratt, M H Fisher, A E Weber

Department of Medicinal Chemistry and Biochemistry, Merck Research Laboratories, Rahway, NJ 07065, USA.

Bioorganic & medicinal chemistry letters 1999 Jul 5

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A series of compounds possessing an N-substituted indoline-5-sulfonamide pharmacophore was prepared and evaluated for their human beta3 adrenergic receptor agonist activity. The SAR of a wide range of urea and heterocyclic substituents is discussed. 4-Octyl thiazole compound 8c was the most potent and selective compound in the series, with 2800-fold selectivity over beta1 binding and 1400-fold selectivity over beta2 binding.

Citation

R J Mathvink, A M Barritta, M R Candelore, M A Cascieri, L Deng, L Tota, C D Strader, M J Wyvratt, M H Fisher, A E Weber. Potent, elective human beta3 adrenergic receptor agonists containing a substituted indoline-5-sulfonamide pharmacophore. Bioorganic & medicinal chemistry letters. 1999 Jul 5;9(13):1869-74