94685-18-4

Upstream product

• 57000-49-4 (5-methoxy-1H-indol-3-yl)acetic acid ethyl ester 
• 100-44-7 benzyl chloride 
• 104-94-9 4-methoxy-aniline 
• 1006-94-6 5-methoxylindole 
• 100-39-0 benzyl bromide 
• 19501-58-7 4-methoxyphenylhydrazine hydrochloride 
• 858232-58-3 3-(carboxymethyl)-5-methoxy-1H-indole-2-carboxylic acid 
• 72963-98-5 ethyl 3-(2-ethoxy-2-oxoethyl)-5-methoxy-1H-indole-2-carboxylate 

Downstream Products

• 164083-04-9 2-bromo-5-methoxy-1-(phenylmethyl)-1H-indole-3-acetic acid ethyl ester 
• 164084-32-6 5-methoxy-2-(methylthio)-1-(phenylmethyl)-1H-indole-3-acetamide 
• 93879-42-6 1-benzyl-5-methoxy-1H-indole-3-acetamide 
• 94005-21-7 NSC₅₄₇₇₁ 
• 93871-13-7 5-methoxy-1-(phenylmethyl)-1H-indole-3-acetic acid hydrazide 

Relevant academic research and scientific papers

Tert-Butyl Iodide Mediated Reductive Fischer Indolization of Conjugated Hydrazones

A novel reductive Fischer indolization of readily available N-aryl conjugated hydrazones with tert-butyl iodide has been developed. In this reaction, tert-butyl iodide is used as anhydrous HI source, and the generated HI acts as a Br?nsted acid and a reducing agent. This operationally simple method allows access to various indole derivatives. Furthermore, the procedure can be applied to the synthesis of biologically active compounds.

New N-(pyridin-4-yl)-(indol-3-yl)acetamides and propanamides as antiallergic agents

A series of new N-(pyridin-4-yl)-(indol-3-yl)alkylamides 44-84 has been prepared in the search of novel antiallergic compounds. Synthesis of the desired ethyl (2-methyindol-3-yl)acetates 1-4 was achieved by indolization under Fischer conditions; Japp-Klingemann method followed by 2- decarboxylation afforded the ethyl (indol-3-yl)alkanoates 17-25. Amidification was successfully carried out by condensation of the corresponding acids or their N-aryl(methyl) derivatives with 4-aminopyridine promoted by 2-chloro-1-methylpyridinium iodide. Efforts to improve the antiallergic potency of the title series by variation of the indole substituents (R1, R2, R) and the length of the alkanoic chain (n = 1, 2, 3) led to the selection of N-(pyridin-4-yl)-[1-(4-fluorobenzyl)indol-3- yl]acetamide 45, out of 41 compounds. This amide was 406-fold more potent than astemizole in the ovalbumin-induced histamine release assay, using guinea pig peritoneal mast cells, with an IC50 = 0.016 μM. Its inhibitory activity in IL-4 production test from Th-2 cells was identical to that of the reference histamine antagonist (IC50 = 8.0 μM) and twice higher in IL-5 assay: IC50 = 1.5 and 3.3 μM, respectively. In vivo antiallergic activity evaluation confirmed efficiency of 45 in sensitized guinea pig late phase eosinophilia inhibition, after parenteral and oral administration at 5 and 30 mg/kg, respectively. Its efficiency in inhibition of microvascular permeability was assessed in two rhinitis models; ovalbumin and capsaicin- induced rhinorrhea could be prevented after topical application of submicromolar concentrations of 45 (IC50 = 0.25 and 0.30 μM); and it also exerted significant inhibitory effect in the first test after iv and oral administration, with ID50 = 0.005 and 0.46 mg/kg.

1H-INDOLE-3-ACETAMIDE SPLA2 INHIBITORS

A class of novel 1-indole-3-acetamides represented by the formula; is disclosed together with the use of such indole compounds for inhibiting sPLA2 mediated release of fatty acids.

Indole inhibitors of human nonpancreatic secretory phospholipase A2. 1. Indole-3-acetamides

Phospholipases (PLAs) produce rate-limiting precursors in the biosynthesis of various types of biologically active lipids involved in inflammatory processes. Increased levels of human nonpancreatic secretory phospholipase A2 (hnps-PLA2) have been detected in several pathological conditions. An inhibitor of this enzyme could have therapeutic utility. A broad screening program was carried out to identify chemical structures which could inhibit hnps-PLA2. One of the lead compounds generated by the screening program was 5-methoxy-2-methyl-1-(phenylmethyl)-1H-indole-3-acetic acid (13a). We describe the syntheses, structure-activity relationships, and pharmacological activities of a series of indole-3-acetamides and related compounds derived from this lead. This SAR was undertaken with the aid of X- ray crystal structures of complexes between the inhibitors and hnps-PLA2 which were of great value in directing the SAR.