820216-60-2

Upstream product

• 18162-48-6 tert-butyldimethylsilyl chloride 
• 193761-55-6 (R)-2-bromo-1-(3-nitrophenyl)ethan-1-ol 
• 2227-64-7 3'-nitro-2-bromoacetophenone 
• 776302-69-3 (R)-2-bromo-1-(tert-butyldimethylsilyloxy)-1-(3-nitrophenyl)ethane 

Downstream Products

• 776302-68-2 (R)-N-{3-[2-bromo-1-(tert-butyldimethylsilyloxy)ethyl]phenyl}(2-thiophene)sulfonamide 
• 820216-51-1 thiophene-2-sulfonic acid {3-[1-(tert-butyl-dimethyl-silanyloxy)-2-(2-{7-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxy]-1H-indol-3-yl}-1-methyl-ethylamino)-ethyl]-phenyl}-amide 
• 820216-59-9 4-[3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yloxysulfonyl]-benzoic acid ethyl ester 
• 820216-54-4 octane-1-sulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 
• 820216-50-0 2-[3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yloxy]-N,N-diethyl-acetamide 
• 776301-50-9 Thiophene-2-sulfonic acid {3-[(R)-2-((R)-2-{7-[2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-ethoxy]-1H-indol-3-yl}-1-methyl-ethylamino)-1-hydroxy-ethyl]-phenyl}-amide 
• 820216-57-7 pyridine-3-sulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 
• 776302-21-7 4-[3-((R)-2-{(R)-2-Hydroxy-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yloxysulfonyl]-benzoic acid ethyl ester 
• 820216-53-3 butane-1-sulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 
• 820216-58-8 thiophene-2-sulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 
• 820216-56-6 benzenesulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 
• 776302-74-0 thiophene-2-sulfonic acid {3-[2-[2-(7-benzyloxy-1H-indol-3-yl)-1-methyl-ethylamino]-1-(tert-butyl-dimethyl-silanyloxy)-ethyl]-phenyl}-amide 
• 820216-55-5 propane-2-sulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 
• 820216-52-2 methanesulfonic acid 3-(2-{2-(tert-butyl-dimethyl-silanyloxy)-2-[3-(thiophene-2-sulfonylamino)-phenyl]-ethylamino}-propyl)-1H-indol-7-yl ester 

Relevant academic research and scientific papers

Tryptamine-based human β3-adrenergic receptor agonists. Part 3: Improved oral bioavailability via modification of the sulfonamide moiety

The continued SAR investigation of tryptamine-based human β3-adrenergic receptor (AR) agonists is reported. Prior efforts resulted in the identification of 2 as a potent β3-AR agonist. Further modification of the left side arylsulfonamide portion in 2 provided compounds with good cell permeability, which have potent agonistic activity for β3-AR. Cinnamylamine analog 16i exhibited an excellent agonistic profile in vitro and good oral bioavailability in rats.

Discovery of 1,7-cyclized indoles as a new class of potent and highly selective human β3-adrenergic receptor agonists with high cell permeability

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

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).

Tryptamine-based human β3-adrenergic receptor agonists. Part 2: SAR of the methylene derivatives

In an effort to reduce the cost of production, we conducted further optimization of tryptamine-based β3-adrenergic receptor (AR) agonists. Optimization of the left-hand side aryl moiety led to the identification of a series of potent β3/s