69372-19-6

Usage

Originator

Alamast, Santen

Uses

Anti-allergic; inhibitor (mediator release).

Brand name

Alamast (Sanofi Winthrop).

Clinical Use

Pemirolast, with an acidic tetrazole isosteric replacement for a carboxylic acid functionality, is used topically in the eye to prevent itching associated with allergic conjunctivitis. It is an inhibitor of the release of histamine and other inflammatory mediators, including leukotrienes. Significant use as a systemic agent has been reported, and it has been shown to be of value in preventing restenosis after percutaneous coronary angiopathy.

Upstream product

• 1603-40-3 3-methylpyridin-2-ylamine 
• 122-51-0 orthoformic acid triethyl ester 
• 109-77-3 malononitrile 
• 102781-19-1 3-cyano-4-imino-9-methyl-4H-pyrido<1,2-a>pyrimidine 
• 132056-88-3 4-imino-9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido<1,2-a>pyrimidine 

Downstream Products

• 100299-08-9 Pemirolast potassium 

Relevant academic research and scientific papers

CRYSTALLINE FORM OF PEMIROLAST

There is provided a hemihydrate form of the sodium salt of pemirolast.

A facile and convenient synthesis of 9-methyl-3(1H-tetrazol-5-YL)-4H-pyrido[1,2-a]pyrimidin-4-one potassium

Two convenient synthetic methods of anti-allergy agent, 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one potassium (1a), are described. Heating of a mixture of malononitrile (2b), 2-amino-3-picoline (4), ethyl orthoformate, and sodium azide in acetic acid, followed by hydrolysis with hydrochloric acid gave 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (1b) which was led to 1a by treatment with potassium hydroxide. The use of ethyl cyanoacetate (2a) instead of 2b afforded ethyl 3-(3-methyl-2-pyridylamino)-2-(1H-tetrazol-5-yl)acrylate (8) which was also led to 1a by treatment with potassium hydroxide. 1. The generic name is pemirolast potassium.

A facile and practical synthesis of 9-Methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one

A facile and practical synthesis of 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (4), the potassium salt of which is used clinically as an anti-asthma agent, is described. Treatment of a key intermediate (6b), prepared from 2-amino-3-methylpyridine (1) and 2-ethoxymethylene-1,3-propanedinitrile, with sodium azide in N,N-dimethylformamide gave predominantly the cyanotetrazole (7a), while in acetic acid it gave exclusively the iminotetrazole (7b), which was easily converted into 4 by acid hydrolysis. A one-pot process starting from 6b to give 4, avoiding the use of explosive aluminum azide, was established.

Process for producing 3-tetrazolyl pyrido[1,2-a]pyrimidine derivatives

3-Tetrazolylpyrido[1,2-a]pyrimidin-4-one derivatives useful as an antiallergy agent are produced by reacting a cyano derivative of pyrido[1,2-a]pyrimidin-4-one compound with (i) hydrazoic acid, followed by hydrolysis, or with (ii) a salt of hydrazoic acid

3-TETRAZOLO-5,6,7,8-SUBSTITUTED PYRIDO[1,2-a]PYRIMIDIN-4-ONES

A novel series of optionally substituted 3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-ones is provided for use as inhibitors of allergic reactions. The compounds exhibit antiallergy activity by both oral and parenteral routes of administration