139481-59-7

Candesartan (CAS 139481-59-7) is an angiotensin II receptor I (AT1) antagonist, IC50s=1.12 and 2.86 nM for bovine adrenal cortex and rabbit aorta respectively.1?Selectively inhibits angiotensin II-induced contraction of rabbit aortic strips with no effect on contraction induced by other agents such as norepinephrine, KCl, serotonin, PGF2αor endothelin. Prevents astrocyte and microglial activation and neuroinflammation and improves hippocampal neurogenesis.2?Attenuates angiogenesis in hepatocellular carcinoma.3?Clinically useful antihypertensive agent. Ameliorates brain inflammation associated with Alzheimer’s disease.4?Active?in vivo?and orally active.

Crystalline Solid

An angiotensin II type-1 receptor antagonist. Used in treatment of congestive heart failure. Antihypertensive

antihypertensive, angiotensin II inhibitor

Candesartan is a selective AT1 (angiotensin II receptor 1) antagonist. Antagonism of angiotensin receptors inhibits vasoconstriction and the production of aldosterone, leading to a decrease in water and sodium concentration in blood plasma. Exhibits antihypertensive effects in animal models. Used in treatment of congestive heart failure, as antihypertensive. Candesartan does not affect cell viability or proliferation but increases the expression of VEGF and interleukin-8 in the cultured medium of KU-19-19 cells. Candesartan (0.1 nM) could reduce the maximal contractile response to angiostensin II by approximately 50%.

ChEBI: A benzimidazolecarboxylic acid that is 1H-benzimidazole-7-carboxylic acid substituted by an ethoxy group at position 2 and a ({2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl}methyl) group at position 1. It is a angiotensin eceptor antagonist used for the treatment of hypertension.

Atacand (AstraZeneca).

Candesartan, (+)-1-[[(cyclohexyloxy)carbonyl]-oxy]ethyl 2- ethoxy-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-1H-benzimidazole-7-carboxylate(Atacand), like losartan, possesses the acidic tetrazole system,which most likely plays a role in binding to the angiotensin IIreceptor similarly to the acidic groups of angiotensin II. Also,the imidazole system has been replaced with a benzimidazolepossessing an ester at position. This ester must be hydrolyzedto the free acid. Fortunately, this conversion takesplace fairly easily because of the carbonate in the ester sidechain. This facilitates hydrolysis of the ester so much thatconversion to the free acid takes place during absorption fromthe gastrointestinal tract.

The general procedure for the synthesis of 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1-[[(2'-(1H-tetrazol-5-yl)biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid using 2-ethoxy-1-[[(2'-(1H-tetrazol-5-yl)biphenyl]-4-yl)methyl]-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid was performed as follows: the obtained in step A) was product (350 g) was dissolved in methanol (1.17 L), followed by addition of sodium hydroxide solution (93 g, dissolved in 1.17 L of water). The reaction mixture was heated to 78-80°C and refluxed for 1 hour. After completion of the reaction, methanol was removed under vacuum at 40-45°C. Ethyl acetate (2.8 L) and water (3.50 L) were added to the residue, stirred for 1 hour at room temperature and allowed to stand for 15 minutes. The organic and aqueous layers were separated, and the pH of the aqueous layer was adjusted to 4-5 with acetic acid (~450 g) at a controlled temperature of 10-15°C. The product was extracted by filtration. The precipitated product was filtered, washed twice with water (2 x 0.7 L) and blotted dry. The wet filter cake was air-dried at room temperature for 2 h and then dried at 50-55 °C to afford the target product 1-((2'-(2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-ethoxy-1H-benzo[d]imidazole-7-carboxylic acid in 323 g (95% yield).

Store at -20°C

1) Shibouta?et al.?(1993),?Pharmacological profile of a highly potent and long-acting angiotension II receptor antagonist, 2-ethoxy-1-[[2’-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazol-7-carboxylic acid (CV-11974), and its prodrug, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2’-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116); J. Pharmacol. Exp. Therap.,?266?114 2) Bhat?et al. (2017),?Angiotensin receptor Blockade by Inhibiting Glial Activation Promotes Hippocampal Neurogenesis Via Activation of Wnt/B-Catenin signaling in hypertension; Mol. Neurobiol.,?55 5282 3) Fan?et al.?(2016),?Candesartan attenuates angiogenesis in hepatocellular carcinoma via downregulating AT1R/VEGF pathway; Biomed. Pharmacother.,?83?704 4) Torika?et al.?(2018),?Candesartan ameliorates brain inflammation associated with Alzheimer’s disease; CNS Neurosci. Ther.?24?231