Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Ketone doai
Patent
1997-07-30
1998-12-15
Burn, Brian M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Ketone doai
514506, 514646, 514579, 514428, 514317, 514212, 5142388, 514255, 514327, 514330, 514278, 514331, 540610, 544173, 544399, 548571, A61K 31135
Patent
active
058498010
DESCRIPTION:
BRIEF SUMMARY
THE DESCRIPTION
This application is a 35 U.S.C. 371 of PCT/JP96/01023 (Apr. 12, 1996).
TECHNICAL FIELD
The present invention relates to 4-amino-5-oxy-2,6,6-trimethyl-2-cycloheptene compounds which are useful as medicaments, and to their pharmacologically acceptable salts and solvates. More specifically, it relates to a remedy for hypertension, peripheral arterial occlusion or bronchial asthma whose effective components are 4-amino-5-oxy-2,6,6-trimethyl-2-cycloheptene compounds, their pharmacologically acceptable salts and their solvates.
BACKGROUND ART
The present inventors have isolated and identified 4,5-dihydroxy-2,6,6-trimethyl-2-cyclohepten-1-one (hereunder referred to as "Saishin N") from the crude drug Asarum Siebeldi, as a useful antiulcer substance, and have developed a method for its chemical production, filing a patent application therefor (Japanese Unexamined Patent Publication No. Hei-3-275640) as well as a patent application for various Saishin N compounds with antiulcer effects (Japanese Unexamined Patent Publication No. Hei-5-213811).
It was found that the Saishin N compounds are effective for the treatment of ischemic and reperfusion disorders and the improvement of microcirculatory blood flow, and patent applications were filed therefor (Japanese Unexamined Patent Publication Nos. Hei-7-17852, Hei-7-101858).
DISCLOSURE OF THE INVENTION
The present Inventors have diligently researched aminolysis reactions of eucarvone-4,5-oxide for the purpose of synthesizing Saishin N compounds with amino groups, and have completed the present invention based upon the finding that Saishin N compounds with an amino group selectively introduced at position 4 may be obtained by using the method of Marco resulting 4-amino-5-oxy-2,6,6-trimethyl-2-cyclohepten-1-one compounds and their oxime derivatives exhibit an effect against rat peripheral arterial occlusion models, spontaneous hypertensive rats, histamine-induced airway contraction models and passive sensitization models.
According to the present invention there are provided 4-amino-5-oxy-2,6,6-trimethyl-2-cycloheptene compounds represented by the following general formula: ##STR2## (wherein R.sup.1 and R.sup.2 each independently represent a hydrogen atom, an alkyl group, or a phenyl group which may have a hydroxyl group, lower alkoxy group, amino group, nitro group, carboxyl group, lower alkoxycarbonyl group or halogen atom, or R.sup.1, R.sup.2 and the nitrogen atom together represent a saturated nitrogen heterocyclic group; R.sup.3 represents a hydrogen atom, a lower alkyl group or a lower aliphatic acyl group; and W represents an oxo group, oxime group or oxime ether group); and their pharmacologically acceptable salts and their solvates, as well as pharmaceutical composition containing then as an effective ingredient.
The alkyl group is an acyclic or cyclic alkyl group of 1 to 10 carbon atoms, and preferably 1 to 8 carbon atoms, and it may be substituted with a hydroxyl group, lower alkoxy group, amino group, lower alkylamino group, lower dialkylamino group, or a phenyl group which may have a hydroxyl group, lower alkoxy group, amino group, nitro group, carboxyl group, lower alkoxycarbonyl group or halogen atom. Specific examples thereof include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, tert-pentyl, hexyl, isohexyl, heptyl, octyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, 2-hydroxyethyl, 2-methoxyethyl, 2-dimethylaminoethyl, benzyl, 4-ethoxycarbonylbenzyl, phenethyl and 4-phenylbutyl groups.
The halogen atom may be fluorine, chlorine, bromine or iodine.
The saturated nitrogen heterocyclic group is pyrrolidine, piperidine, homopiperidine, piperazine, homopiperazine or morpholine which may have a lower alkyl group, hydroxyl group, lower alkoxy group, carboxyl group, lower alkoxycarbonyl group, oxo group or an acetal group thereof on its ring.
The oxime ether is a lower alkyloxime ether or benzyloxime ether.
The term "lower" here refers to an acyclic or cyclic
REFERENCES:
Chini et al., 1990, Metal Salts as New Catalysts . . . Tetrahedron Letters.
Corey et al., 1986, A New Synthetic Route To Prostaglandins, Tetrahedron Letters.
Iwamoto et al., Dec. 1986, Prophylactic Effect Of . . . Japanese Pharmacology & Therapeutics.
Minami et al., 1983, Japanese Journal of Thoracic Diseases.
Ishibashi et al., 1983, Folia Pharmacologica Japonica.
Suzuki et al., Sep. 1987, The Clinical Report vol. 21 No. 13.
Matsunaga Kouichi
Murakami Kiyokazu
Yajima Masao
Yokura Susumu
Burn Brian M.
Tokyo Tanabe Company Limited
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