Description

Pemirolast potassium, also known as 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one potassium, is a potent antiallergic mast cell stabilizer. It is a yellow, water-soluble powder and is considered an analog of one portion of the cromolyn structure, with the carboxyl group replaced by an isosteric tetrazole moiety. Pemirolast potassium is primarily indicated for the prevention of itching in the eyes caused by allergic conjunctivitis and is also being investigated for its potential as a gastroprotective agent.

Uses

1. Used in Pharmaceutical Industry:
Pemirolast potassium is used as an antiallergic agent for the prevention of itching in the eyes caused by allergic conjunctivitis. It acts as a histamine H1 antagonist and mast cell stabilizer, inhibiting the release of chemical mediators from tissue mast cells.
2. Used in Ophthalmic Applications:
Pemirolast potassium is used as an ophthalmic solution for topical administration to the eyes. The commercial preparation is available as a 0.1% sterile ophthalmic solution, which contains 1 mg of pemirolast potassium, along with preservatives, buffers, and other components to maintain the solution's pH and osmolality.
3. Used in Respiratory Applications:
Pemirolast potassium is used as a potent antiallergic mast cell stabilizer for the treatment of bronchial asthma. Its mechanism is similar to that of sodium cromoglycate, making it a valuable option for managing asthma symptoms.
4. Used in Gastroprotective Applications (Under Investigation):
Pemirolast potassium is being investigated for its potential as a gastroprotective agent, which could provide additional therapeutic benefits in the treatment of gastrointestinal disorders.
Chemical Properties:
Pemirolast potassium is a crystalline solid with potent antiallergic properties.
Brand Names:
Alamast (Sanofi Winthrop), Pemilaston, and Alegysal.

Originator

Bristol-Myers Squibb (U.S.A.)

Manufacturing Process

Ferrous nitrate hexahydrate (60 mg) followed by sodium (4.5 g, 0.196 gatom) were added to liquid ammonia. To this mixture was added a solution of 3-methylpyridine (10.0 g, 0.093 mole) in N,N-dimethylaniline (21 ml) over a period of 5 min. The ammonia was allowed to evaporate and the residue heated under nitrogen by means of an oil bath maintained at 180°C for 18 h. The cooled residue was treated with ice (50 g) followed by 2 N sodium hydroxide (50 ml). The mixture was triturated for 2 h and then filtered. The collected solid was washed with boiling toluene (2 times 100 ml). The toluene layer was separated from the combined filtrate and washings, concentrated to about 50 ml and extracted with 5% aqueous acetic acid (5 times 20 ml). The combined extracts were filtered and reduced to dryness. The residue was recrystallized from methylcyclohexane to give 2-amino-3-methylpyridine acetate (4.9 g, 29%), melting point 85°-95°C. The acetate (2.5 g, 1.37 mmoles) was briefly suspended in 1 N sodium hydroxide (50 ml). The mixture was extracted with methylene chloride. The extract was washed with water, dried, and concentrated to give 2-amino-3-methylpyridine as an oil. A solution of 2-amino-3-methylpyridine (5.0 g, 0.0462 mole) and ethyl ethoxymethylenecyanoacetate (7.82 g, 0.0462 mole) in toluene (4 ml) was heated for 15 min by means of an oil bath maintained at 100°C. The solution was cooled and the crude product (9.1 g, 85%) collected by filtration. The product was recrystallized from 2-propanol to give an analytical sample of ethyl 2-cyano-3-(3-methyl-2-pyridylamino)acrylate, melting point 144°146°C. Aluminum chloride (3.51 g, 0.0263 mole) was added to cold (-30°C) tetrahydrofuran (180 ml). Sodium azide (5.12 g, 0.0788 mole) was added and the mixture heated under reflux for 30 min. The mixture was cooled to 5°C. Ethyl 2-cyano-3-(3-methyl-2-pyridylamino)acrylate (5.0 g, 0.0216 mole) was added and the mixture heated under reflux for 18 h. The tetrahydrofuran was removed under reduced pressure. The residue was treated with ice water (100 ml) and acidified to pH 3 with 6 N hydrochloric acid. The mixture was filtered and the collected solid recrystallized from N,N-dimethylformamide to give the 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one (2.5 g, 50.7%). Melting point 310°-311°C, dec. Potassium hydroxide was added dropwise to a stirred mixture of 9-methyl-3(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]pyrimidin-4-one in water .The mixture was diluted with water to a volume of about 300 ml and was then heated to a temperature of 50°C during 2 min. The mixture was filtered and the water removed from the filtrate by lyophilization. The residue was recrystallized from water:ethanol to give the 9-methyl-3-(1H-tetrazol-5-yl)-4H-pyrido[1,2 2632 a]pyrimidin-4-one potassium salt

Therapeutic Function

Antiallergic, Antiulcer

Check Digit Verification of cas no

The CAS Registry Mumber 100299-08-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,0,2,9 and 9 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 100299-08:
(8*1)+(7*0)+(6*0)+(5*2)+(4*9)+(3*9)+(2*0)+(1*8)=89
89 % 10 = 9
So 100299-08-9 is a valid CAS Registry Number.

InChI:InChI=1/C10H7N6O.K/c1-6-3-2-4-16-9(6)11-5-7(10(16)17)8-12-14-15-13-8;/h2-5H,1H3;/q-1;+1