Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1993-08-30
1995-04-25
Dees, Jose G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514510, 514601, 514602, 514603, 514604, 514605, 560 10, 562428, A01N 3712, C07C31100
Patent
active
054099560
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel indan derivatives or salts thereof which are capable of potently antagonizing the action of thromboxane A.sub.2 (hereinafter may be referred to as TXA.sub.2) and are significant in the medical field. More particularly, the present invention relates to indan derivatives or salts thereof which are useful for the treatment and prevention of diseases or diseased states caused by TXA.sub.2, such as thrombosis, vasospasm or asthma, and also to thromboxane antagonists containing the compounds.
BACKGROUND ART
TXA.sub.2 is a metabolite of arachidonic acid widely found in organs of creatures, such as the liver, kidney, lung and the brain, and it is known to have function of strongly coagulating the platelets and contracting the blood vessel ("Cascade of Arachidonic Acid and Drug" by Shozo YAMAMOTO, 1985).
Moreover, it is known that TXA.sub.2 is associated with various diseases such as cardiac infarction, angina pectoris, thrombosis, transient cerebral ischemia, hemicrania, cerebral hemorrhage, cerebral infarction, arteriosclerosis, peripheral circulatory insufficiency or failure, high blood pressure, pulmonary embolism, bronchial asthma, bronchitis, pneumonia, nephritis, hepatitis, and shocks because it strongly contracts the bronchi and the tracheal smooth muscles.
Accordingly, it is expected that effective treatments against the above-mentioned diseases may be obtained by suppressing the action of TXA.sub.2, and many studies have already been reported. For example, Japanese patent publication (Kokoku) 57-35910 discloses 4-(2-phenylsulfonylaminoethyl)phenoxy acetic acid derivatives as compounds which antagonize the action of TXA.sub.2. These compounds, however, are not necessarily satisfactory in terms of the efficacy as pharmaceuticals, lasting ability of the action, adverse side effects and so on.
Under these circumstances, the present inventors have carried out careful studies toward solving the above-mentioned problems, and have found that certain indan derivatives or their salts have a much stronger. TXA.sub.2 antagonizing activity than the above-described 4-(2-phenylsulfonylaminoethyl)phenoxy acetic acid derivatives, leading to the completion of the invention.
DISCLOSURE OF THE INVENTION
According to the present invention, there are provided indan derivatives represented by the formula (1) or pharmaceutically acceptable salts thereof: ##STR3## wherein R.sup.1 represents C1 to C12 alkyl, benzyl, styryl, naphthyl, optionally substituted phenyl or optionally substituted thienyl; R.sup.2 represents carboxyl, C1 to C4 alkoxycarbonyl, ##STR4## Y represents --(CH.sub.2).sub.p -- (wherein p represents an integer of 0 to 5), --CO--(CH.sub.2).sub.q .about., --CH(OH)--(CH.sub.2).sub.q .about., (wherein q represents an integer of 1 to 4, and the symbol .about. represents a linkage to R.sup.2), oxymethylene or ethylene; and n represents an integer of 1 to 4.
Moreover, the present invention provides thromboxane antagonists containing, as their active ingredients, the indan derivative of formula (1) above or pharmaceutically acceptable salts thereof.
The term "optionally substituted phenyl" means a phenyl group substituted by C1 to C8 alkyl, C1 to C4 alkoxy, trifluoromethyl, trifluoromethoxy, nitro, amino, nitrile or by a halogen atom at one or two positions, or a phenyl group having no substituent. The term "optionally substituted thienyl" means a thienyl group substituted by C1 to C4 alkyl, C1 to C4 alkoxy, phenylsulfonyl, trifluoromethyl or by a halogen atom at one or two positions, or a thienyl group having no substituent.
BEST MODE FOR CARRYING OUT THE INVENTION
The indan derivatives (1) according to the present invention can be prepared as follows:
First, indan-2-ylalkylcarboxylic acid, which can be prepared by or based on a known method, is converted to indan-2-ylalkylamine by a known method such as a Curtius rearrangement of acylazide or the reduction of carboxylic amide, and is subsequently condensed with a sulfonating agent such as sulfonyl chloride
REFERENCES:
patent: 4820705 (1989-04-01), Nickl et al.
patent: 4929754 (1990-05-01), Nickl et al.
patent: 5030652 (1991-07-01), Iwakuma et al.
patent: 5190975 (1993-03-01), Iwakuma et al.
Kurimoto Tadashi
Sato Ryuichi
Torizuka Motoki
Yamaji Yoshiaki
Yoshida Kiyoshi
Dees Jos,e G.
Jones Dwayne C.
Zeria Pharmaceutical Co. Ltd.
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