Condensed heterocyclic compounds, their production and use

Details Condensed heterocyclic compounds, their production and use Condensed heterocyclic compounds, their production and use

1995-06-26

1998-11-10

Berch, Mark L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Heterocyclic carbon compounds containing a hetero ring...

514221, 540517, 540518, 540495, 540557, 540567, A61K 3155, C07D24312

Patent

active

058344632

DESCRIPTION:

BRIEF SUMMARY
This application is a 371 of PCT/JP 95/00829, filed Apr. 26, 1995.


TECHNICAL FIELD

This invention relates to a novel condensed heterocyclic compound or a salt thereof having an excellent gonadotropin releasing hormone (GnRH) receptor antagonistic action and/or an excellent action to improve sleeping disturbances, a process for producing it, and a pharmaceutical composition containing it.
GnRH is a decapeptide consisting of 10 amino acids produced in hypothalamus, and controls secretion of, for example, luteinizing hormone or follicle stimulating hormone through a receptor considered to exist in an anterior lobe of pituitary gland, and, as a result, GnRH has been known as showing various physiological activities including induction of ovulation. Therefore, specific and selective antagonistic or agonistic agents for these receptors control an action of hormone produced from hypothalamus and suppress the secretion of anterior pipuitary hormone, thus these agents are expected to serve as prophylaxis or therapy of diseases dependent on anterior lobe of hypophysis.
Since 1971 when GnRH was discovered, a number of its analogues have been synthesized expecting their agonistic or antagonistic activities. For example, leuprorelin, which is a peptide, has a higher affinity to GnRH receptor than GnRH obtained from natural sources, and, is hardly susceptible to metabolism.
Leuprorelin acetate, which has 20 to 50 times as much activity as natural-type GnRH, by its repeated administration, reduced the release and production of gonadotropin, causing, for example, decreased reactivity to gonadotropin in testicle to reduce the productivity of testosterone to the level of castration. As a result, it has been known that leuprorelin acetate shows anti-tumor activity against such hormone-dependent cancers, for example, prostatic cancer. In practice, leuprorelin acetate has been widely used as a therapeutic agent of, for example, prostatic cancer and endometriosis in the clinical field.
However, these GnRH agonists are peptide and poor in oral absorbability, thus the administration forms are necessarily restricted, and, showing a transient agonistic activity, increasing the concentration of serum steroid hormone, and, in some cases, a transient aggravation such as osseus pain is observed.
On the other hand, in the modern society, those who have various mental disturbances and complain of sleeping disturbances, accompanied with social structure becoming more and more complicated and with increase of number of aged people, have increased. Sleeping disturbances include, for example, insomnia caused by stress, poriomania at night and depression of activity in day time due to abnormal circadian rhythm, jet lag caused by overseas travel and abnormal physical conditions caused by a three-shift system. Those who complain of these symptoms are, in general, administered with hypnotics such as 1,4-benzodiazepine type drugs, and all of these drugs have 1,4-benzodiazepine structure. This basic structure is thus considered to be essential for the action to induce sleeping.
While benzodiazepine-type drugs have been considered relatively safe, several problematic points are still found in them. More specifically, so-far known benzodiazepine-type hypnotics increase, among two fundamental sleeping conditions, i.e. REM sleep and non-REM sleep, increase REM-sleep latent period (time elapsing between the start of sleeping and the occurrence of the first episode), and decrease the REM-sleep period. Besides, suppression of REM sleep known as relating to fixation of memory is considered to possibly cause anterograde amnesia. Therefore, administration of such drugs as above to patients readily suffering from defects of memory such as senile dementia is not desirable. Further more, it has also been known that conventional benzodiazepine-type drugs, if the administration of them is discontinued, there may be considerable rebound in the amount and density of REM sleep, thus these drugs are not necessarily satisfactory from the practical viewpoints.


BA

REFERENCES:
patent: 3312689 (1967-04-01), Schmutz et al.
patent: 3347849 (1967-10-01), Schmutz et al.
Puodziunate, Chem Abs 110, 192788x (1988).
Essassi, Heterocycles 23, 799(1985.
Bauer, Archiv. Pharm. 305(8), 557 (1972).
Vernin Chemica Scripta 16, 157-162 (1980).

Affiliated with

Also associated with

Rating

Condensed heterocyclic compounds, their production and use does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Condensed heterocyclic compounds, their production and use, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Condensed heterocyclic compounds, their production and use will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1516945