244081-38-7

Upstream product

• 24424-99-5 di-tert-butyl dicarbonate 
• 244081-35-4 (R)-3-(2-aminopropyl)-7-benzyloxyindole 
• 244081-36-5 (R)-3-(2-aminopropyl)-7-benzyloxyindole oxalate 
• 20289-27-4 7-benzyloxyindole 

Downstream Products

• 776302-59-1 7-benzyloxy-3-[(2R)-2-(tert-butoxycarbonylamino)propyl]-1-[2-methoxycarbonylethyl]-1H-indole 
• 776302-55-7 7-benzyloxy-3-[(2R)-2-(tert-butoxycarbonylamino)propyl]-1-[2-hydroxypropyl]-1H-indole 
• 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 
• 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

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.

INDOLE, INDAZOLE, AND BENZAZOLE DERIVATIVE

The compound of the formula (I): wherein W is a group of the following formula (VIII) binding to any possible position on the Q: Q is, together with W, a group of the formula: -C(M=C(R3A)-N(R3)-, etc.; R3A is H or optionally substituted lower alkyl; R4, R5, R6, and R7 are independently H or optionally substituted lower alkyl; R1 is optionally substituted lower alkyl, etc.; R2 is H, etc.; R3 is H, etc.; Ar is phenyl, etc., or a pharmaceutically acceptable salt thereof, where these compounds exhibiting β3-adrenoceptor-stimulating activity and being useful as a medicament for treatment of obesity, etc.

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).

Process development of a scaleable route to (2R)-[3-(2-Aminopropyl)-1H- indol-7-yloxy]-N,N-diethylacetamide: A key intermediate for AJ-9677, a potent and selective human and rat β3-adrenergic receptor agonist

(2R)-[3-(2-Aminopropyl)-1H-indol-7-yloxy]acetic acid (2) is the left-hand side segment of AJ-9677, which is a potent and selective human and rat β3-adrenergic receptor agonist. Herein, we describe the process development of a scaleable synthetic route to the corresponding N,N-diethylacetamide derivative 3 of 2 from 7-benzyloxy-1H-indole (4). Reaction of the indole Grignard reagent 12 generated from 4 and methylmagnesium bromide with the N-Fmoc-D-alanyl chloride 22, followed by reduction of the resulting crude 3-acylindole 26 with NaBH4 in a mixture of MeCN and 2-PrOH at refluxing temperature and subsequent treatment with oxalic acid gave the oxalate of the N-deprotected product, (2R)-3-(2-aminopropyl)-7-benzyloxy-1H- indole [(R)-7] as a crystalline material in 60% yield. After N-protection of the (R)-7 by Boc group, the (2R)-3-[2-(Boc-amino)propyl]-1H-indole 30 was hydrogenated to provide the (2R)-3-(2-aminopropyl)-7-hydroxy-1H-indole 31, which was subsequently alkylated with ClCH2CONEt2 to give 32 in 91% yield. Finally, treatment of 32 with oxalic acid afforded the desired 3 in 79% in >99% ee.

Solid preparation

The present invention provides a solid preparation comprising a crystal of [3-[(2R)-[[(2R)-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1H-indol-7-yloxy]acetic acid (Compound A), especially a crystal of Compound A having a particle size of not larger tha