Losartan, valsartan, candesartan, irbesartan, telmisartan and olmesartan all contain a biphenyl-methyl group.
Losartan is partly metabolized to its 5-carboxylic acid metabolite EXP 3174, which is a more potent AT receptor antagonist than its parent compound
and has been a model for the continuing development of several other ARBs.
Valsartan, candesartan and irbesartan were all developed in 1990.
Valsartan, first marketed by Novartis, is a nonheterocyclic ARB, where the imidazole of losartan has been replaced by an acylated amino acid.
Irbesartan was developed by Sanofi Research and is longer acting than valsartan and losartan and it has an imidazolinone ring where a carbonyl group functions as a hydrogen bond acceptor instead of the hydroxymethyl group in losartan. Irbesartan is a non-competitive inhibitor.
Candesartan cilexetil (TCV 116) is a benzimidazole which was developed at Takeda and is an ester carbonate prodrug. In vivo, it is rapidly converted to the much more potent corresponding 7-carboxylic acid, candesartan. In the interaction of candesartan with AT receptor the carboxyl group of the benzimidazole ring plays an important role. Candesartan and its prodrug have stronger blood pressure lowering effects than EXP 3174 and losartan.
Telmisartan, which was discovered and developed in 1991 by Boehringer Ingelheim, has carboxylic acid as the biphenyl acidic group. It has the longest elimination half-life of the ARBs or about 24 hours.
Olmesartan medoxomil was developed by Sankyo in 1995 and is the newest ARB on the market, marketed in 2002. It is an ester prodrug like candesartan cilexetil. In vivo, the prodrug is completely and rapidly hydrolyzed to the active acid form, olmesartan (RNH-6270). It has a hydroxyisopropyl group connected to the imidazole ring in addition to the carboxyl group.