Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1994-02-18
1996-11-19
Grumbling, Matthew V.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
544291, 544284, 544285, 544286, 544287, 544288, 544289, 544290, 544292, 544293, 514259, 514258, A61K 31505, A61K 31445, C07D23995, C07D23994
Patent
active
055763227
DESCRIPTION:
BRIEF SUMMARY
This is the national phase of PCT/JP92/01258, filed Sep. 30, 1991 and published as WO93/07214 Apr. 15, 1993.
FIELD OF THE INVENTION
The present invention relates to a nitrogeous heterocyclic compound having an excellent activity as a drug.
BACKGROUND OF THE INVENTION AND PRIOR ART
Angina pectoris which is one of ischemic heart diseases has been known as a disease which often attacks the aged. Although nitric and nitrous acid compounds, calcium antagonists and .beta.-blocker have been used as therapeutic agents therefor, the effect of such a therapeutic agent is far insufficient to treat angina pectoris or to prevent the evolution thereof into myocardial infarction. Recently, the age of a patient with angina pectoris has lowered and the symptom thereof has become complicated owing to change in the style of living, stress increased by the complication of society and so forth, so that a new type of more excellent drug has been desired eagerly.
It is believed that cyclic GMP (hereinafter abbreviated to "cGMP") which is one of cyclic nucleotides and is known as an intracellular second messenger participates in the action of the nitric and nitrous acid compounds among the above drugs which are now used. The relaxing effect of cGMP on the smooth muscle of vessel and bronchus is well known. Although the mechanism of action of these drugs are not always apparent, it is generally presumed that the activity of this cGMP results from the acceleration of the synthesis of cGMP which is caused by the activation of guanylate cyclase. However, the above-mentioned drugs exhibit a low bioavailability and a relatively short time of action. Further, it is reported that the drug resistance is induced, which is a problem in a clinical field.
Under these circumstances, the present inventors have started studies to develop a new type of more excellent drug.
That is, the present inventors have paid their attention to cGMP phosphodiesterase (hereinafter abbreviated to "cGMP-PDE")-inhibiting activity and have made extensive studies on compounds having such an activity for many years. As a result of the studies, they have found that a nitrogenous heterocyclic compound which will be described below has such an activity to be efficacious for various ischemic heart diseases and have accomplished the present invention.
Although quinazoline derivatives useful as drugs are included in, e.g., Publication of International Patent Application by Japanese No. 502462/1990, they are different from the compounds of the present invention in respect of both structure and activity.
DISCLOSURE OF THE INVENTION
The present invention provides a nitrogenous heterocyclic compound represented by the following general formula (1) or a pharmacologically acceptable salt thereof: ##STR1## [in formula (1), ring A represents a benzene ring, a pyridine ring or a cyclohexane ring; ring B represents a pyridine ring, a pyrimidine ring or an imidazole ring.
Provided that the ring A and the ring B are combined sharing two atoms and the atoms shared may be either a carbon atom or a nitrogen atom.
In the case where the ring A is a pyridine ring and that except the case where the ring B shares the nitrogen atom of this pyridine ring to combine therewith, the ring A is represented by ##STR2##
R.sup.1, R.sup.2, R.sup.3 and R.sup.4, each of which may be the same or different from one another, represent each a hydrogen atom, a halogen atom, a lower alkyl group which may be substituted with a halogen atom, a cycloalkyl group which may be substituted, a lower alkoxy group, a hydroxyalkyl group, a nitro group, a cyano group, an acylamino group, a carboxyl group which may be protected, a group represented by the formula ##STR3## (wherein R.sup.7 represents a lower alkyl group, and n represents 0 or an integer of 1 to 2), or a group represented by the formula ##STR4## (wherein R.sup.45 and R.sup.46, each of which may be the same or different from each other, represent each a hydrogen atom or a lower alkyl group; or R.sup.45 and R.sup.46 can form a ring which may contain a
REFERENCES:
patent: 3511836 (1970-05-01), Hess
patent: 3541094 (1970-11-01), Lutz
patent: 3560619 (1971-02-01), Harrison et al.
patent: 3635979 (1972-01-01), Hess
patent: 3669968 (1972-06-01), Hess
patent: 3833587 (1974-09-01), Gabel
patent: 3971783 (1976-07-01), Barnish et al.
patent: 3980650 (1976-09-01), Nauta
patent: 4098788 (1978-07-01), Crenshaw et al.
patent: 4323680 (1982-04-01), Nakagami et al.
patent: 4331667 (1982-05-01), Schneider
patent: 4341893 (1982-07-01), Manoury
patent: 4343940 (1982-08-01), Kreighbaum et al.
patent: 4376858 (1983-03-01), Colbry
patent: 4377581 (1983-03-01), Hess et al.
patent: 4749705 (1988-06-01), Tomiyama et al.
patent: 4795750 (1989-01-01), Schlager
patent: 4808715 (1989-02-01), Boyle et al.
patent: 4818753 (1989-04-01), Colwell et al.
patent: 4880804 (1989-11-01), Carini et al.
patent: 5064833 (1991-11-01), Ife et al.
patent: 5227387 (1993-07-01), Dreikorn et al.
patent: 5326766 (1994-07-01), Dreikorn et al.
Adachi Hideyuki
Akita Yasunori
Ikuta Hironori
Kimura Teiji
Matsui Makoto
Eisai Co. Ltd.
Grumbling Matthew V.
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