146650-76-2

Upstream product

• 18441-43-5 5-methylbenzofuran 
• 145824-18-6 3-[3-Bromo-2-(2-tert-butoxycarbonylamino-phenyl)-benzofuran-5-ylmethyl]-5-chloro-2-ethyl-3H-imidazole-4-carboxylic acid 
• 145824-16-4 1-[[3-Bromo-2-[2-[[(1,1-dimethylethoxy)carbonyl]amino]phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxaldehyde 
• 145824-11-9 1,1-dimethylethyl <2-(3-bromo-5-(bromomethyl)-2-benzofuranyl)phenyl>carbamate 
• 146624-44-4 1,1-dimethylethyl <2-(3-bromo-5-methyl-2-benzofuranyl)phenyl>carbamate 
• 143381-74-2 methyl 2-(3-bromo-5-methyl-2-benzofuranyl)benzoate 
• 143381-73-1 methyl 2-(5-methyl-2-benzofuranyl)benzoate 
• 146650-65-9 2-ethyl-4-chloro-5-(hydroxymethyl)-imidazole 
• 72993-43-2 2-ethyl-5-hydroxymethyl-1H-imidazole 
• 145066-95-1 2-(3-bromo-5-methyl-2-benzofuranyl)benzoic acid 
• 145824-12-0 4-chloro-2-ethyl-1H-imidazole-5-carboxaldehyde 
• 610-94-6 2-bromobenzoic acid methyl ester 
• 358-23-6 trifluoromethylsulfonic anhydride 
• 146650-73-9 ethyl 1-[[3-bromo-2-(2-aminophenyl)-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylate 

Downstream Products

• 146650-79-5 1-[[3-Bromo-2-[2-[[(trifluoromethyl)sulphonyl]amino]phenyl]-5-benzofuranyl]methyl]-4-chloro-2-ethyl-1H-imidazole-5-carboxylic acid 

Relevant academic research and scientific papers

Bromobenzofuran-based non-peptide antagonists of angiotensin II: GR138950, a potent antihypertensive agent with high oral bioavailability

We have identified GR138950, a potent antagonist of the angiotensin II receptor with high oral bioavailability, as our second drug candidate to GR117289. Using GR117289, a compound with moderate bioavailability (20%) in man as a lead, we pursued a strategy aimed at enhancing bioavailability. The strategy was based on SAR established around the diacid GR117289, and from this, it was proposed that a monoacid, in particular a trifluoromethanesulfonamide, should be better absorbed after oral administration and have enhanced oral bioavailability. This led to the identification of GR138950, a potent antihypertensive agent in the renal hypertensive rat, causing sustained falls in blood pressure after oral administration. Oral bioavailability of GR138950 in rats and dogs is high, confirming that GR138950 is well absorbed after oral administration. Moreover, the low plasma clearance and long plasma half-life suggest that this compound will be suitable for once a day administration. Furthermore, the preliminary data indicate that the high bioavailability of GR138950 seen in rats and dogs translates to man. These results demonstrate clearly that GR138950 has the potential to be a clinically effective antihypertensive agent. Further studies are in progress to evaluate GR138950 in the treatment of hypertension.

BENZOFURAN DERIVATIVES

The invention provides compounds of the general formula (I) STR1 and physiologically acceptable salts, solvates or non-toxic metabolically labile esters thereof where R 1 represents a halogen atom; Ar represents the group STR2 R 3 represents a C-linked tetrazolyl group; R 4 and R 5, which may be the same or different, each independently represent a hydrogen atom or a halogen atom or a C. sub.1-6 alkyl group; andHet represents an N-linked imidazolyl group optionally substituted at the 2-position.The compounds may be used in the treatment or prophylaxis of hypertension and diseases associated with cognitive disorders.