947331-05-7

Basic information

• Product Name: Allisartan Isoproxil
• Synonyms: Allisartan Isoproxil
• CAS NO: 947331-05-7
• Molecular Formula: C₂₇H₂₉ClN₆O₅
• Molecular Weight: 553.01
• Mol File: 947331-05-7.mol
• Article Data: 8

Chemical Properties

• Boiling Point: 745.0±70.0 °C(Predicted)
• Appearance: /
• Density: 1.35±0.1 g/cm3(Predicted)
• PKA: 4.16±0.10(Predicted)
• CAS DataBase Reference: Allisartan Isoproxil(CAS DataBase Reference)
• NIST Chemistry Reference: Allisartan Isoproxil(947331-05-7)
• EPA Substance Registry System: Allisartan Isoproxil(947331-05-7)

Safety Data

• Hazardous Substances Data: 947331-05-7(Hazardous Substances Data)

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

• 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 
• 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 

Relevant articles and documents

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.

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.

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.