Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-10-26
1997-11-11
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514215, A61K 3155, C07D48704, C07D51304
Patent
active
056864426
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP 94/02282, filed 28 Dec. 1994 which claims the priority of Japanese Applications 5/337189 filed 28 Dec. 1993 and 6/202349 filed 26 Aug. 1994.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel tricyclic benzazepine compounds, novel benzothiazepine compounds having anti-allergic activities, synthetic intermediates thereof, and processes for preparing them.
2. Background Art
It has been recently shown that allergic reactions such as immune responses caused by a variety of irritations include immediate type responses occurring just after irritation and delayed type responses occurring after several hours of irritation (see, for example "Late Asthmatic Responses", P. M. O'byrne, J. Dolovich and F. E. Hargreave, Am. Rev. Resppir. Dis., 1987, 136:740-751). The delayed responses, in particular, have been regarded as important to control.
In clinical aspects, there are few agents which have sufficient efficacy against the delayed allergy. It is thus desired to develop an agent which exhibits excellent therapeutic effects on either response of immediate type and delayed type.
There has hitherto been known sodium cromoglycate as a typical agent for suppressing allergic responses of immediate type and delayed type. However, this exhibits no effectiveness on oral administration and thus is clinically administered by inhalation.
However, it is sometimes difficult to administer properly to infants or little children by inhalation or to administer continuously to patients sensitive to inhalating irritation.
Because of these backgrounds, it has been desired to develop a compound which inhibits both immediate and delayed allergic responses, can be administered orally and has an excellent efficacy.
Furthermore, in recent years, a number of studies have been done on anti-allergic agents and anti-asthmatic therapeutics, among which tri-cyclic compounds containing a seven-membered ring have been reported. For instance, dibenzoxepin derivatives are disclosed in Japanese Patent Laid-Open Publication Nos. 10784/1988 and 78292/1993, and Chemical & Pharmaceutical Bulletin, 39 (10), 2724-2728 and 2729-2733 (1991), dibenzoxazepin derivatives in Japanese Patent Laid-Open Publication Nos. 184963/1991, 211071/1992 and 65257/1993, and European Patent EP 5180720, and dibenzocycloheptene derivatives in International Patent WO/93-13068.
Also, heterocyclic ring-containing compounds have been reported as anti-allergic agent. For instance, dibenzoxepinopyridine derivatives are disclosed in European Patent EP 515158, benzocycloheptathiophene derivatives in Japanese Patent Laid-Open Publication Nos. 294277/1991, and 226916/1992, benzocycloheptapyridine derivatives in Japanese Patent Laid-Open Publication No. 59040/1993, triazoloheptapyridine derivatives in Japanese Patent Laid-Open Publication No. 59040/1993, triazolobenzoxepine derivatives in Journal of Chemical Research (S), 400-401 (1984), thieno(pyrazolo-, thiazolo-)benzothiazepine derivatives in European Patent No. 547705.
Some of these derivatives have been reported to have side-effects on central or cardiovascular systems and thus to have a problem that the anti-allergic action be separated from the central actions including calmative, antidepressant or anxiolytic actions or the cardiovascular actions including hypotensive or anti-thrombotic actions. Among those compounds having similar structures, cyproheptadine hydrochloride is only available as an anti-allergic agent.
As for the additional similar compounds, there have been described pyridobenzoxazepine derivatives as HIV-1 reverse transcriptase inhibitors in Japanese Patent Laid-Open Publication No. 178390/1992, triazolobenzoxazepine derivatives as anti-depressant in Journal of Heterocyclic Chemistry, 22, 1693-1701 (1985), and triazolobenzodiazepine derivatives as anti-psychotic agents in Journal of Medicinal Chemistry, 32 (10), 2375-2381 (1989).
However, there has been described, as far as the present inventors know, no tricyclic benzazepine compound cont
REFERENCES:
patent: 4959361 (1990-09-01), Walser
Fushihara Kenichi
Hoshiko Shigeru
Imai Megumi
Iwasaki Takako
Kawaguchi Mami
Bond Robert T.
Meiji Seika Kabushiki Kaisha
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