133075-99-7

Upstream product

• 95-54-5 1,2-diamino-benzene 
• 114772-38-2 Methyl 4'-(bromomethyl)biphenyl-2-carboxylate 
• 109-52-4 valeric acid 
• 5851-44-5 2-n-butylbenzimidazole 
• 947-84-2 2-Biphenylcarboxylic acid 
• 667457-40-1 4-acetamidomethylbiphenyl-2'-carboxylic acid 
• 667457-41-2 4-(chloromethyl)biphenyl-2'-carboxylic acid 
• 133224-94-9 tert.butyl 4'-[(2-n-butyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylate 
• 133052-50-3 methyl 4'-[(2-butyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylate 

Downstream Products

• 1022177-73-6 4'-[(2-butyl-5-chlorosulfonyl-1H-benzimidazol-1-yl)methyl]biphenyl-2-carboxylic acid 
• 133143-44-9 4'-[(2-n-Butyl-benzimidazol-1-yl)-methyl]biphenyl-2-carboxylic acid-(N-methanesulphonyl)-amide 

Relevant academic research and scientific papers

Design, synthesis, and evaluation of novelly substituted benzimidazole compounds as angiotensin II receptor antagonists

5-Nitrobenzimidazole derivatives with varying substituents at 2-position have been designed, synthesized, and evaluated for angiotensin II antagonistic activity. A drug-receptor interaction model has been proposed.

Benzimidazoles and medicaments containing these compounds

The invention relates to benzimidazoles of the formula STR1 in which R1 to R2 are as defined in claim 1, 1 and 3 isomer mixtures thereof and addition salts thereof which have valuable properties. In particular, the novel compounds ar

Biphenylmethane derivative and pharmacological use

The biphenylmethane derivative having the formula (I) is useful to prevent and treat hypertension and cardiac failure. STR1 in which R1 is hydrogen, an alkyl, a cycloalkyl, a halogenated alkyl, --S--R7, --SO2--R7, --C C--R7 or --(CH2)--OR7, R7 being hydrogen, an alkyl, a cycloalkyl or a halogenated alkyl, p being zero or 1, --A1=A2--A3=A4-- is CH=CH--CH=CH--, --N=CH--CH=CH--, --CH=N--CH=CH--, --CH=CH--N=CH--, --CH=CH--CH=N-- or --CH=N--CH=N--, R2 and R3 are each hydrogen, a halogen, a lower alkyl, a lower alkoxy, a carbamoyl or cyano, R4 is hydrogen or a lower alkyl, R5 is 1H-tetrazol-5-yl, carboxyl (--COOH) or a carboxylic ester and R6 is hydrogen, a halogen, hydroxyl or a lower alkoxy, or a pharmacologically acceptable salt thereof.

6-Substituted benzimidazoles as new nonpeptide angiotensin II receptor antagonists: Synthesis, biological activity, and structure-activity relationships

Starting from the recently reported nonpeptidic angiotensin II (AII) receptor antagonists DuP 753 (1) and Exp 7711 (2), we have designed and investigated novel substituted benzimidazoles. Systematic variation of several substituents at the benzimidazole ring positions 4-7 led to the finding that substitution in position 6 with acylamino groups results in highly active AII antagonists. Compounds with 6-membered lactam or sultam substituents in position 6 of benzimidazole showed receptor activities in the low nanomolar range but were only weakly active when given orally to rats. In contrast, analogous substitution of the benzimidazole moiety with basic heterocycles resulted in potent AII antagonists which were also well absorbed after oral application. The most active compound of this series, 33 (BIBR 277), was selected as a candidate for clinical development. On the basis of molecular modeling studies a binding model of this new class of AII antagonists to the AT1 receptor is proposed.

Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazoles

A series of substituted 2-butylbenzimidazoles bearing a biphenylylmethyl moiety at the 1-position was prepared via three synthetic routes and evaluated for angiotensin II (AII) receptor antagonistic activity (in vitro and in vivo). Binding affinity was determined using bovine adrenal cortical membrane. Substitution at the 4-, 5-, or 6-position reduced the affinity relative to that of the unsubstituted compound (13a). However, most of the compounds with a substituent at the 7-position showed binding affinity comparable to that of DuP 753 (losartan). In functional studies, a carboxyl group was found to be very important for antagonistic activity against AII. Comparison of 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-4-,-5-,-6-, and -7-carboxylic acids (15a-d) in an AII-induced rabbit aortic ring contraction assay clearly demonstrated the importance of the substitutional position of the carboxyl group. In an in vivo assay, oral administration of benzimidazole-7-carboxylic acids caused long-lasting inhibition of the AII-induced pressor response in rats. The optimum substituent at the 7-position of the benzimidazole ring was found to be a carboxyl or an ester group. The representative compound, 2-butyl-1-[[2'-(1H- tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylic acid (15d, CV-11194), inhibited the specific binding of [125I]AII to bovine adrenal cortical membrane with an IC50 value of 5.5 x 10-7 M. The AII-induced contraction of rabbit aortic strips was antagonized by CV-11194 (IC50 value, 5.5 x 10-11 M), while the compound had no effect on the contraction induced by norepinephrine or KCl. Orally administered CV-11194 at doses of 0.3-10 mg/kg dose-dependently inhibited the AII-induced pressor response in rats and dogs. CV-11194 at 1 mg/kg po reduced blood pressure in spontaneously hypertensive rats (SHR). The three-dimensional molecular structure of CV- 11194 was determined by X-ray diffraction.

New nonpeptide angiotensin II receptor antagonists. 1. Synthesis, biological properties, and structure-activity relationships of 2-alkyl benzimidazole derivatives

On the basis of an extension of the literature lead 1, a series of benzimidazoles have been synthesized and shown to be angiotensin II (AII) receptor antagonists. The structure-activity relationships of these new antagonists have been explored and the key

Benzimidazole derivatives and their use

Novel imidazole derivatives of the formula (I): STR1 wherein R1 is an optionally substituted alkyl group, R2 and R3 are independently a group capable of forming an anion or a group which can be changed thereinto, ring A is a benzene ring optionally having, besides the group shown by R2, further substituents, and X shows linkage of phenylene group and phenyl group directly or through a spacer whose atomic length is not more than 2 and a salt thereof, show antagonistic actions to angiotensin II, thus being useful as therapeutics for cardiovascular diseases.

Benz[4,5]imidazole-containing angiotensin antagonists

The invention concerns novel heterocyclic compounds of the formula I as defined herein and their physiologically acceptable salts, together with pharmaceutical compositions containing them. The heterocyclic compounds antagonize the actions of angiotensin II and are of value in treating diseases or medical conditions such as hypertension and congestive heart failure in warm-blooded animals. The invention further includes processes for the manufacture of the novel compounds and their use in medical treatment.