145303-67-9

Upstream product

• 2417-73-4 methyl 2-bromomethylbenzoate 
• 145303-54-4 3-<(5-indolyl)methyl>-5,7-dimethyl-2-ethyl-3H-imidazo<4,5-b>pyridine 
• 89-71-4 2-Methyl-benzoic acid methyl ester 
• 614-96-0 5-methyl-1H-indole 
• 145303-52-2 (5-(bromomethyl)-1H-indol-1-yl)(phenyl)methanone 
• 145303-51-1 (5-methyl-1H-indol-1-yl)(phenyl)methanone 
• 145303-53-3 3-(N-Benzoyl-5-indolyl)methyl-5,7-dimethyl-2-ethyl-3H-imidazo[4,5-b]pyridin 

Relevant academic research and scientific papers

Non-peptide angiotensin II receptor antagonists. 1. Design, synthesis, and biological activity of N-substituted indoles and dihydroindoles

A series of N-acylated indoles (12-18), N-alkylated indoles (19-24), N- acylated dihydroindoles (26-30), and N-alkylated dihydroindoles (31-34) were synthesized and evaluated in the in vitro AT1 (rabbit aorta) and AT2 (rat midbrain) binding assay. The carboxylic acid 3-[[N-(2-carboxy-3,6- dichlorobenzoyl)-5-indolyl]methyl]-5,7-dimethyl-2-ethyl-3H-imidazo[4,5- b)pyridine (14b) was found to be the most potent AT1 (IC50 = 0.8 nM) antagonist in the N-acylated indole series and displayed a 25-fold higher potency than the parent unsubstituted derivative 14a (AT1 IC50 = 20 nM) and a 22-fold greater potency than the corresponding dihydroindole analog 27 (AT1 IC50 = 18 nM). Replacement of the terminal carboxyl (COOH) of 14a with the bioisostere tetrazole in 16 (AT1 IC50 = 5 nM, AT2 IC50 = 130 nM) not only improved the AT1 potency by 4-fold but also resulted in a 50- fold increase in AT2 activity. In the N-alkylated indole series, the tetrazole 3-[[N-(2-tetrazol-5-yl-6-chlorobenzyl)-5-indolyl]methyl]-5,7- dimethyl-2-ethyl-3H-imidazo[4,5,-b]pyridine (24) exhibited the highest AT1 (IC50 = 1 nM) activity, revealing a 230-fold increase in AT1 activity as a result of the incorporation of the isosteric tetrazole for the carboxyl (COOH) of 20 and a nearly 9-fold increase over the corresponding deschloro analog 22 (AT1 IC50 = 8.7 nM). Tetrazole 34 was identified as the most potent (AT1 IC50 = 18 nM) AT1 receptor antagonist in a structurally distinct series of compounds derived from N-alkylation of dihydroindole 25. A new class of highly potent (14b, AT1 IC50 = 0.8 nM; 24, AT1 IC50 = 1 nM) AT1-selective non-peptide AII receptor antagonists derived from N- substituted indoles and dihydroindoles is disclosed. Tetrazole 24 of the N- alkylated indole series displayed good in vivo activity by blocking the AII- induced pressor response for 5.5 h after intravenous administration in conscious normotensive rats at a 1.0 mg/kg dose level.

ANGIOTENSIN II ANTAGONISTS INCORPORATING AN INDOLE OR DIHYDROINDOLE

There are disclosed substituted indoles and dihydroindoles of Formula I which are useful as angiotensin II antagonists. STR1