947331-05-7

Usage

Clinical Use

Allisartan isoproxil, a member of a new class of selective angiotensin II-1 receptor antagonists, was approved by the Chinese Food and Drug Administration (CFDA) for the treatment of hypertension in July 2012.19 At time of publication, there is no trade name associated with this drug. Allisartan was discovered and developed by the Chinese biomedical company Allist Pharmaceuticals. Allisartan isoproxil is a prodrug which is readily hydrolyzed to active metabolite EXP3174, which is also the active metabolite of losartan (des-triphenylmethyl-9).

Synthesis

Although several synthetic routes have been reported within two patents, the most likely scalable process route is described in the scheme. Commercial 2-butyl-4-chloro-5-(hydroxymethyl)-imidazole (7) was alkylated with Ntriphenylmethyl- 5-(4'-bromomethylbiphenyl-2-yl)tetrazole (8) under basic conditions in warm DMF, providing alcohol 9 in 90% yield. This alcohol was then oxidized to the corresponding carboxylic acid 10 with KMnO4 in 88% yield. Etherification of acid 10 with isopropyl chloromethyl carbonate (11) followed by de-tritylation of the tetrazole group under acidic contidions gave allisartan isoproxil (II) in 69% yield.

Upstream product

• 947331-22-8 2-butyl-4-chloro-1-[(2'-(1-triphenylmethyl-1H-tetrazol-5-yl)(1,1'-biphenyl)-4-yl)methyl]imidazole-5-carboxylic acid 1-[(isopropoxy)carbonyloxy]methyl ester 
• 35180-01-9 chloromethyl isopropyl carbonate 
• 124750-92-1 2-butyl-4-chloro-1-((2'-(1H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-1H-imidazole-5-carboxylic acid 

Relevant academic research and scientific papers

ALLISARTAN ISOPROXIL POLYMORPH, ITS PREPARATION METHOD AND PHARMACEUTICAL

Disclosed are polymorph of allisartan isoproxil and a pharmaceutical composition thereof. The polymorph is non-electrostatic, highly flowable and highly stable, and can be used for treating hypertension and complications thereof.

CRYSTALLINE IMIDAZOL-5-CARBOXYLIC ACID DERIVATE

The invention discloses the crystalline imidazole-5-carboxylic acid derivative (I, the chemical name: 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl) 1,1'-biphenyl-methyl]-imidazole-5-carboxylic acid, 1-[(isopropoxy)-carbonyloxy] methyl ester), its preparation

THE THERAPEUTIC USES OF IMIDAZOL-5-CARBOXYLIC ACID DERIVATIVES

The invention discloses the use of 2-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)1,1'-biphenyl-methyl]-imidazole-5-carboxylic acid, 1-[(isopropoxycarbonyl)oxy] methyl ester and the pharmaceutically acceptable salts thereof in the manufacture of a medicament for the treatment of the damage of a target organ caused by hypertension. It particularly discloses the use of this compound in the manufacture of a medicament for the treatment of left ventricular hypertrophy, renal dysfunction, aorta thickening caused by hypertension, which provides an effective drug and method for the treatment of the damage of target organs for hypertension patients.

NEW PHARMACEUTICAL COMPOSITION

The invention provides a new pharmaceutical compositions for treating cardiovascular disease, which contains the active component 2-butyl-4-chloro-1-[2'-(1H-tetrazot-5-yl)1,1'-biphenyl-methyl]imidazole-5-carboxylic acid, 1-[(isopropoxy)carbonyloxy]methyl

Imidazole-5-Carboxylic Acid Derivatives, The Preparation Method Therefor and The Uses Thereof

The invention discloses imidazole-5-carboxylic acid derivatives, and their preparation methods. The derivatives of the invention are Angiotensin II receptor antagonists with angiotensin II antagonistic activity and antihypertensive activity, and thereby can be used as a therapeutical agent to treat hypertension.

THE SALTS OF IMIDAZOL-5-CARBOXYLIC ACID DERIVATIVES, PREPARATION METHODS AND USE THERROF

The present invention provides pharmaceutically acceptable salts of imidazole-5-carboxylic acid derivatives, methods for preparing same and pharmaceutical compositions comprising same. The salts obtained by the present invention can be easily dissolved in

SALTS OF IMIDAZOLE-5-CARBOXYLIC ACID DERIVATIVES, A METHOD FOR PREPARING SAME AND PHARMACEUTICAL COMPOSITIONS COMPRISING SAME

The present invention provides pharmaceutically acceptable salts of imidazole-5-carboxylic acid derivatives, methods for preparing same and pharmaceutical compositions comprising same. The salts obtained by the present invention can be easily dissolved in

IMIDAZOL-5-CARBOXYLIC ACID DERIVATIVES, PREPARATION METHODS AND USE THERROF

The invention discloses imidazole-5-carboxylic acid derivatives, and their preparation methods. The derivatives of the invention are Angiotensin II receptor antagonists with angiotensin II antagonistic activity and antihypertensive activity, and thereby can be used as a therapeutical agent to treat hypertension.