192994-71-1

Upstream product

• 1074-86-8 4-formyl indole 
• 96258-56-9 4-trifluoromethylbenzyl methanesulfonate 
• 39830-66-5 methyl 1H-indole-4-carboxylate 
• 1074-85-7 (1H-indol-4-yl)methanol 

Relevant academic research and scientific papers

Optimization of alkylidene hydrazide based human glucagon receptor antagonists. Discovery of the highly potent and orally available 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6-tetramethylbenzyl)-1h-indol-4ylmethylene]hydrazide

Highly potent human glucagon receptor (hGluR) antagonists have been prepared employing both medicinal chemistry and targeted libraries based on modification of the core (proximal) dimethoxyphenyl group, the benzyl ether linkage, as well as the (distal) benzylic aryl group of the lead 2, 3-cyano-4-hydroxybenzoic acid (3,5-dimethoxy-4-isopropylbenzyloxybenzylidene)hydrazide. Electron-rich proximal aryl moieties such as mono- and dimethoxy benzenes, naphthalenes, and indoles were found to be active. The SAR was found to be quite insensitive regarding the linkage to the distal aryl group, since long and short as well as polar and apolar linkers gave highly potent compounds. The presence of a distal aryl group was not crucial for obtaining high binding affinity to the hGluR. In many cases, however, the affinity could be further optimized with substituted distal aryl groups. Representative compounds have been tested for in vitro metabolism, and structure - metabolism relationships are described. These efforts lead to the discovery of 74, NNC 25-2504, 3-cyano-4-hydroxybenzoic acid [1-(2,3,5,6tetramethylbenzyl)-1H-indol-4-ylmethylene]hydrazide, with low in vitro metabolic turnover. 74 was a highly potent noncompetitive antagonist of the human glucagon receptor (IC50 = 2.3 nM, KB = 760 pM) and of the isolated rat receptor (IC50 = 430 pM, KB = 380 pM). Glucagonstimulated glucose production from isolated primary rat hepatocytes was inhibited competitively by 74 (Ki = 14 nM). This compound was orally available in dogs (Fpo = 15%) and was active in a glucagon-challenged rat model of hyperglucagonemia and hyperglycemia.

Thiazolidinedione derivatives, method for preparing the derivatives and pharmaceutical compositions containing same

A thiazolidinedione derivative represented by the following general formula (I): STR1 ?wherein the dotted line represents a single bond or a double bond, the thiazolidinedione ring residue is linked to either of 2-, 3-, 4-, 5- and 6-positions on the indole ring and R represents a group selected from the group consisting of hydrogen atom and alkyl, alkenyl, alkynyl, phenyl, aralkyl, heterocycloalkyl, arylsulfonyl and arylaminocarbonyl groups! or a pharmaceutically acceptable salt thereof exhibits excellent effects of reducing the blood sugar level and of reducing the lipid concentration in blood and is accordingly useful as a therapeutic agent for treating diabates mellitus. These derivatives and pharmaceutically acceptable salt thereof are almost free of any side effect.