566200-63-3

Upstream product

• 20697-04-5 (R)-meta-chlorostyrene oxide 
• 179819-93-3 (+/-)-3-(2-aminopropyl)-7-benzyloxyindole 
• 115648-90-3 (S)-3-chlorostyrene oxide 
• 20289-27-4 7-benzyloxyindole 
• 92855-65-7 7-(benzyloxy)-1H-indole-3-carbaldehyde 
• 294178-11-3 7-benzyloxy-3-(2-nitro-1-propenyl)indole 

Downstream Products

• 566200-67-7 3-[(2S)-(7-benzyloxy-1H-indol-3-yl)propyl]-(5R)-(3-chlorophenyl)-1,3-oxazolidin-2-one 
• 566200-66-6 3-[(2R)-(7-benzyloxy-1H-indol-3-yl)propyl]-(5R)-(3-chlorophenyl)-1,3-oxazolidin-2-one 
• 566200-65-5 [2-(3-chloro-phenyl)-2-hydroxy-ethyl]-[2-(7-hydroxy-1H-indol-3-yl)-1-methyl-ethyl]-carbamic acid tert-butyl ester 
• 566200-64-4 methyl [3-[2-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetate 
• 244081-42-3 Rafabegron 
• 566200-68-8 [3-[(2S)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid 
• 853022-56-7 methyl [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetate 
• 853022-58-9 methyl [3-[[(2S)-[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetate 
• 853022-61-4 methyl [3-[(2R)-[(5R)-(3-chlorophenyl)-1,3-oxazolidin-2-one-3-yl]propyl]-1H-indol-7-yloxy]acetate 
• 853022-62-5 methyl [3-[(2S)-[(5R)-(3-chlorophenyl)-1,3-oxazolidin-2-one-3-yl]propyl]-1H-indol-7-yloxy]acetate 
• 853022-60-3 (5R)-(3-chlorophenyl)-3-[(2R)-(7-hydroxy-1H-indol-3-yl)propyl]-1,3-oxazolidin-2-one 
• 1027546-19-5 (R)-5-(3-Chloro-phenyl)-3-[(R)-2-(7-methoxy-1H-indol-3-yl)-1-methyl-ethyl]-oxazolidin-2-one 
• 1027260-26-9 (R)-5-(3-Chloro-phenyl)-3-[(S)-2-(7-methoxy-1H-indol-3-yl)-1-methyl-ethyl]-oxazolidin-2-one 

Relevant academic research and scientific papers

Novel and potent human and rat β3-adrenergic receptor agonists containing substituted 3-indolylalkylamines

A novel series of 2-(3-indolyl)alkylamino-1-(3-chlorophenyl)ethanols was prepared and evaluated for in vitro ability to stimulate cAMP production in Chinese hamster ovary cells expressing cloned human β3-AR. The optically active 30a was found to be the most potent and selective human β3-AR agonist in this series with an EC50 value of 0.062 nM. In addition, 30a selectivity for human β3-AR was 210-fold and 103-fold that for human β2-AR and β1-AR, respectively. Furthermore, 30a showed potent agonistic activity at rat β3-AR.

Discovery of a novel and potent human and rat β3-adrenergic receptor agonist, [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl] -1H-indol-7-yloxy]acetic acid

In search for potent and selective β3-adrenergic receptor (β3-AR) agonists as potential drugs for the treatment of type II diabetes and obesity, a novel series of 1-(3-chlorophenyl)-2-aminoethanol derivatives were prepared and evaluated for their biological activity at human β1-, β2-, and β3-ARs and rat β3-AR expressed in Chinese hamster ovary (CHO) cells. Replacement of the right-hand side (RHS, benzene ring) in the 'first generation' β3-AR agonists BRL 37344 and CL 316243 with a 1H-indole ring gave compound 31 with unique pharmacological properties among β3-AR agonists. Initial in vitro assays showed that 31 possesses modest rat and human β3-ARs agonistic activity. Introduction of various substituent into the indole nucleus of 31 afforded a number of compounds with good β3-ARs agonistic activity. In particular, 90 having a carboxylic acid functionality at the 7-position of the indole nucleus showed the most potent human β3-AR agonistic activity. Finally, optical resolution of 90 led to the identification of the most promising compound, [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H- indol-7-yloxy]acetic acid (96, AJ-9677). This compound exhibited potent human β3-AR agonistic activity (EC50 = 0.062 nM, IA = 116%) with 210- and 103-fold selectivity over human β2-AR and β1-AR, respectively. Compound 96 also exhibited potent rat β3-AR agonistic activity (EC50 = 0.016 nM, IA = 110%). Moreover, repeated oral administration of 96 inhibited body weight gain and significantly decreased glucose, insulin, free fatty acid, and triglyceride concentrations in plasma in KK-Ay/Ta mice. On the basis of this pharmacological profile, 96 entered clinical development as a drug for the treatment of type II diabetes and obesity.