N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate

Details N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate

1999-06-14

2000-11-14

Ambrose, Michael G.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

544382, A61K 31495, C07D24104, A61P 2528

Patent

active

061470791

DESCRIPTION:

BRIEF SUMMARY
TECHNICAL FIELD

This invention relates to N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate which is useful as a medicament.


BACKGROUND ART

N-(4-Acetyl-1-piperazinyl)-4-fluorobenzamide having The following chemical formula: ##STR1## was first described by the applicant of the instant application in WO 91/01979 and is a per se known compound. This compound has the potentiation of the cholinergic activity and is known to have excellent antidementia and antiamnesic actions.


DISCLOSURE OF INVENTION

This invention relates to N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate.
One object of this invention is to provide N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide in a form easy to handle under ordinary interior humidity conditions and resistant to stress testings, i.e. N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate.
Another object of this invention is to provide an agent and a pharmaceutical composition comprising, as an active ingredient, said hydrate.
A further object of this invention is to provide a therapeutical method for the treatment and/or prevention of disorders in the central nervous system For human beings, and more particularly in the treatment and/or prevention of amnesia, dementia, senile dementia and the like.
More particularly, the inventors of this invention endeavored in earnest to accomplish the above object and discovered the hydrate form of N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide which can be handled with ease under ordinary interior humidity conditions and stable even under accelerated heat, humidity, and light exposure test conditions. This invention has been accomplished on the basis of the above finding.
Thus, N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide free of water of crystallization undergoes change in water content by absorbing moisture under ordinary interior humidity conditions and the rate of its moisture absorption also varies with the ambient relative humidity, thus offering the disadvantage that it cannot be easily handled in the laboratory room and the pharmaceutical manufacturing room. Therefore, the inventors explored for a stable form of N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide which would show little change in water content under ordinary interior humidity conditions and could, therefore, be easily handled in both the laboratory room and the pharmaceutical manufacturing room and discovered that the hydrate, preferably the monohydrate (theoretical water content 6.36%), of the above compound shows substantially no change in water content in addition to the advantage that it can be easily handled. Furthermore, this N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate, preferably monohydrate thereof, is chemically stable even under accelerated heat, humidity, and light exposure test conditions. It was also confirmed that N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate, preferably monohydrate thereof, remains chemically stable without undergoing crystallographic change in the accelerated heat, humidity, and light exposure tests. The following are experimental findings substantiating the above description.
In this invention, it is to be noted that N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate may include all hydrate containing one or more water molecule(s) such as monohydrate, dihydrate, trihydrate, etc., in which preferable one is monohydrate.
About 0.2 g of N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide monohydrate was accurately weighed into a weighing bottle about 3 cm in diameter and placed in a desiccator controlled at a relative humidity (R.H.) value of 43% with a saturated potassium carbonate solution. This test sample was stored in a constant-temperature room at 25.degree. C. for 24 hours and the change in water content was sequentially monitored.


TABLE 1 ______________________________________ Time (Hr) 0 1 2 3 4 5 6 24 ______________________________________ Water content 6.23 6.23 6.23 6.27 6.23 6.27 6.23 6.18 (%) ______________________________________
The above results indicate that N-4(-acetyl-1-piperaz

REFERENCES:
patent: 5250528 (1993-10-01), Oku, et al.
Yamazaki, M. et al. The Journal of Pharmacology and Experimental Therapeutics. vol. 279, No. 3, Dec. 1996, pp. 1157-1173.

Affiliated with

Also associated with

Rating

N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and N-(4-acetyl-1-piperazinyl)-4-fluorobenzamide hydrate will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2065675