Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-04-07
1995-03-21
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540526, 540527, 540580, 540521, A61K 3155, C07D48704
Patent
active
053995570
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel pyrroloazepine compounds, and more specifically to novel pyrroloazepine compounds and salts thereof, said compounds and salts being useful as therapeutics for circulatory diseases such as ischemic heart diseases and hypertension, their preparation processes and therapeutics for circulatory diseases, said therapeutics containing them as active ingredients.
BACKGROUND ART
It is known that serotonin is contained abundantly in platelets, a blood component, and that upon stimulation by thromboxane A.sub.2, ADP, collagen or the like, it is released to synergistically act on the release of various platelet aggregation factors through activation of the serotonin-2 receptor in platelets and vascular smooth muscle cells and on vasoconstriction by norepinephrine through the .alpha..sub.1 receptor, thereby inducing strong platelet aggregation and vasoconstriction [P. M. Vanhoutte, "Journal of Cardiovascular Pharmacology", Vol. 17 (Supple. 5), S6-S12 (1991)].
With the foregoing in view, there is hence an outstanding desire for the development of a serotonin-2 receptor antagonist as a circulatory disease therapeutic for preventing thrombus formation and vasoconstriction so that the serotonin-2 receptor antagonist can be used for hypertension and ischemic heart diseases such as angina pectoris, myocardial infarction, heart failure and post-PTCA restenosis. It is however the present situation that no drug has been obtained yet with sufficient antagonism and selectivity. Pharmaceuticals having .alpha..sub.1 -blocking action in combination with anti-serotonin action are expected to reduce side effects caused by hypotensive action based on .alpha..sub.1 -blocking action, such as orthostatic disorder and reflex tachycardia, so that some drugs having both actions have been developed. However, none of them have been provided with sufficient hypotensive action.
DISCLOSURE OF THE INVENTION
In view of the foregoing circumstances, the present inventors have carried out an extensive investigation, resulting in the finding of certain pyrroloazepine compounds which have strong anti-serotonin action without significant side effects and toxicity and are useful as therapeutics for ischemic heart diseases based on their antagonism against serotonin receptors. Some of the compounds according to the present invention have also been found to have .alpha..sub.1 -blocking action too, whereby they are useful as hypotensive drugs with reduced side effects and can be used in a wide variety of therapeutics for circulatory diseases.
The present invention has been completed based on the above described findings and provides a pyrroloazepine compound represented by the following formula (I) or (II): ##STR2## wherein the dashed line indicates the presence or absence of a bond and when the bond indicated by the dashed line is present, Z.sub.1 represents a hydrogen atom but, when the bond indicated by the dashed line is absent, Z.sub.1 represents a hydrogen atom and Z.sub.2 represents a hydroxyl group or Z.sub.1 and Z.sub.2 are taken together to form an oxygen atom or a group NOR.sub.1, in which R.sub.1 represents a hydrogen atom, an alkyl group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group; R represents an alkyl group, a cycloalkyl group, a cycloalkyl-alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group; A represents an alkylene, alkenylene or alkynylene group; and Y represents a substituted or unsubstituted heterocyclic group or a group: ##STR3## in which R.sub.2 and R.sub.3 may be the same or different and individually represent a hydrogen atom, an alkyl group which may be substituted by a lower alkoxy group or a substituted or unsubstituted aryloxy group, a substituted or unsubstituted aryl group or a substituted or unsubstituted aralkyl group; or a salt thereof; a preparation process thereof; and a therapeutic for circulatory diseases, said therapeutic containing as an active ingredient the py
REFERENCES:
patent: 3563979 (1971-02-01), Hester, Jr.
patent: 3573323 (1971-03-01), Hester, Jr.
patent: 3573324 (1971-03-01), Hester, Jr.
patent: 5206239 (1993-04-01), Mizuno et al.
Aust. J. Chem., vol. 43, 1990, pp. 355-365, B. Kasum, et al., "Dihydroindol-7(6H)-Ones and 6,7-Dihydropyrrolo[2,3-C]Azepine-4,8(1H,5H)-Dione".
Chemical Abstracts, vol. 102, 1985, AN-146334h, N. K. Utkina, et al., "Nitrogen-Containing Metabolites of the Marine Sponge Acanthella Carteri".
Tetrahedron, vol. 41, No. 24, pp. 6019-6033, 1985, G. De Nanteuil, et al., "Invertebres Marins Du Lagon Neo-Caledonien-V1", (With English Abstract).
Journal of The Chemical Society, pp. 435 & 436, Jan. 3, 1980, G. Sharm, et al., "Characterization of a Yellow Compound Isolated from the Marine Sponge Phakellia Flabellata".
Journal of Natural Products, vol. 48, No. 1, pp. 47-53 (1985).
Inomata Norio
Ishihara Takafumi
Miya Mikiko
Mizuno Akira
Tatsuoka Toshio
Grumbling Matthew V.
Shah Mukund J.
Suntory Limited
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