Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1993-04-06
1995-03-14
Bond, Robert T.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540215, A61K 3155, C07D48704
Patent
active
053977807
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel pyrroloazepine derivatives, and more specifically to novel pyrroloazepine derivatives and salts thereof, said derivatives and salts having strong anti-.alpha..sub.1 action and anti-serotonin action moreover low toxicity and being useful as therapeutics for circulatory diseases such as hypertension and congestive heart failure, their preparation processes and therapeutics for circulatory diseases, said therapeutics containing them as active ingredients.
BACKGROUND ART
Numerous substances have heretofore been known as drugs which act on the circulatory system. Among these, a variety of substances have been developed as antihypertensive drugs.
Of such drugs as employed as circulatory drugs, .alpha..sub.1 -blockers are accompanied by the drawback that they generally have side effects such as orthostatic disorder and reflex tachycardia, tend to induce orthostatic hypotension especially when administered to aged people and hence require attention.
As drugs having less tendency of inducing such side effects of .alpha..sub.1 -blockers, on the other hand, certain drugs having both anti-serotonin action and anti-.alpha..sub.1 action have been developed as drugs effective for senile hypertension and the like. However, these drugs may not be able to exhibit, for example, sufficient hypotensive action in some instances, and their side effects to the central nervous system such as drowsiness and sedative action have posed problems.
DISCLOSURE OF THE INVENTION
In view of the foregoing circumstances, the present inventors synthesized numerous compounds and investigated their pharmacological effects with a view toward obtaining drugs having both anti-serotonin action and anti-.alpha..sub.1 action, strong hypotensive action, and low side effects and toxicity.
As a result, the compounds represented by the below-described formula (I) having the pyrroloazepine structure have been found to meet the above requirements, leading to the completion of the present invention.
This invention therefore provides a pyrroloazepine derivative represented by the following formula (I): ##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 a hydrogen atom, an alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted cycloalkyl-alkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted aralkyl group; A represents an alkylene, alkenylene or alkynylene group with one of hydrogen atoms being substituted or unsubstituted by a hydroxyl group; and Y represents 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, aryloxyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted aralkyl group or a partially-saturated naphthyl group, or a group: ##STR4## in which R.sub.4 and R.sub.5 may be the same or different and individually represent a hydrogen atom or an alkyl group, B represents a carbonyl group, a sulfonyl group, an alkylene group, an alkenylene group or a substituted or unsubstituted phenylmethylene group, m stands for 1 or 2, n stands for 0 or 1, and D represents an alkoxy group, a substituted or unsubstituted aromatic heterocyclic group, a substituted or unsubstituted aryl group or a 1,4-benzodioxanyl group, or a salt thereof; a preparation process thereof; and a therapeutic for circulatory diseases, said therapeutic containing as an acti
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.
Journal of Natural Products, vol. 48, No. 1, pp. 47-53 (1985), Schmitz 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. Sharma, et al., "Characterizaton of a Yellow Compound Isolated from the Marine Sponge Phakellia flabellata".
Cho Hidetsura
Ishihara Takafumi
Miya Mikiko
Mizuno Akira
Tatsuoka Toshio
Bond Robert T.
Suntory Limited
LandOfFree
Pyrroloazepine derivative does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pyrroloazepine derivative, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pyrroloazepine derivative will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-713871