820216-46-4Relevant academic research and scientific papers
Discovery of 1,7-cyclized indoles as a new class of potent and highly selective human β3-adrenergic receptor agonists with high cell permeability
Mizuno, Kazuhiro,Sawa, Masaaki,Harada, Hiroshi,Taoka, Ikuko,Yamashita, Haruhisa,Oue, Mayumi,Tsujiuchi, Hiroshi,Arai, Yukiyo,Suzuki, Shinya,Furutani, Yasuji,Kato, Shiro
, p. 855 - 868 (2007/10/03)
The synthesis and evaluation of a novel series of 1,7-cyclized indole-based human adrenergic receptor (β3-AR) agonists are reported. The synthesis of a variety of 1,7-cyclized indole part was accomplished by the Mitsunobu reaction or a ring closing metathesis (RCM) reaction. SAR studies revealed that expansion of the ring size resulted in considerable selectivity against the β1- and β2-ARs. Compound 26, an eight-membered ring analogue with a double bond on its 1,7-linker portion, was found to be a potent β3-AR agonist (EC50 = 0.75 nM, IA = 90%) with extremely high selectivity for the β3-AR over the β1- and β2-ARs.
Tryptamine-based human β3-adrenergic receptor agonists. Part 1: SAR studies of the 7-position of the indole ring
Mizuno, Kazuhiro,Sawa, Masaaki,Harada, Hiroshi,Tateishi, Hirotaka,Oue, Mayumi,Tsujiuchi, Hiroshi,Furutani, Yasuji,Kato, Shiro
, p. 5959 - 5962 (2007/10/03)
The synthesis and biological evaluation of a series of tryptamine-based β3-adrenergic receptor (AR) agonists are described. The methanesulfonate 54 exhibited strong agonistic activity and excellent subtype selectivity for the β3-AR. A series of tryptamine-based 2-thiophenesulfonamide derivatives were prepared and their agonistic activity for the β-adrenergic receptors (ARs) was evaluated. Compound 54, containing 7-methanesulfonyloxy tryptamine, was found to be a highly potent β3-AR agonist (EC50 = 0.21 nM, IA = 97%) with excellent selectivity for the β3-AR over the β1- and β2-ARs (210- and 86-fold, respectively).
