Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-01-30
1997-01-14
Ivy, C. Warren
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
5142225, 5142338, 514255, 514256, 514300, 514302, 514318, 514330, 546113, 546114, 546115, 546193, 546225, A61K 31435, C07D21134, C07D21162, C07D47104
Patent
active
055940048
DESCRIPTION:
BRIEF SUMMARY
This application is the National phase of PCT/JP94/00437 filed on Mar. 17, 1994 and published as WO94/21599 on Sep. 29, 1994.
FIELD OF THE INVENTION
The present invention relates to a cyclohexene and a nitrogen-containing heterocyclic derivative for inhibiting the aggregation of platelets, and a pharmaceutical composition for the treatment and prophylaxis of thrombotic diseases comprising as effective ingredient at least one of these derivatives.
BACKGROUND TECHNOLOGIES
Caldiovascular diseases are increased along with the change of dietary habits and the increase of advanced ages. Almost fifty percent of these diseases may be caused by thrombus.
Platelets in plasma are mainly associated with the formation of thrombus in organisms. For the purpose of the treatment and prophylaxis of thrombotic diseases in clinical practice, there have been used a medicine which suppresses the functions of platelet or inhibits the aggregation of platelets, for example, aspirin which inhibits cyclooxygenase and ticlopidine which activates adenylcyclase.
In recent years, glycoproteins on platelet membrane have been progressively analyzed. As the results, it has been elucidated that the glycoprotein called GPIIb/IIIa is a receptor of fibrinogen. This has therefore led to the expectation that a GPIIb/IIIa antagonists would become an inhibitor of platelet aggregation having a novel action mechanism effectively used for the treatment and prophylaxis of the thrombotic diseases (Trends in Pharmacological Science, 13, 413, 1992). The compounds as the GPIIb/IIIa antagonist include a monoclonal antibody (Ann. New York Acad. Sci., 614, 193, 1991), a tripeptide derivative comprising arginine-glycine-aspartic acid (J. Med. Chem., 35, 2040, 1992), amidinophenyl derivative (J. Med. Chem., 35, 4393, 1992; Japanese Patent Laid-Open Publication Nos. 264068/1992 and 334351/1992), and a tyrosine derivative (J. Med. Chem., 35, 4640, 1992).
It is also desired to be developed a medicine having no side effects such as hemorrhage and a highly selective function as a therapeutic or prophylactic agent of thrombotic diseases.
SUMMARY OF THE INVENTION
The present inventors have now found that a certain kind of a compound becomes a GPIIb/IIIa antagonist.
Thus, an object of the present invention is to provide a novel compound inhibiting the aggregation of platelets.
Another object of the present invention is to provide a pharmaceutical composition comprising a novel compound having the aforementioned effect.
Further object of the present invention is to provide a therapeutic or prophylactic method of thrombotic diseases which comprises administering a novel compound having the above activity.
Further object of the present invention is to provide the use of the novel compound having the above activity for preparing a pharmaceutical composition used for the therapy or prophylaxis of thrombotic disorders.
The compound according to the present invention is represented by the formula (I): ##STR3## or a pharmaceutically accetptable salt ans solvate thereof wherein
R.sup.1 represents a group --W--(CH.sub.2).sub.i -COOR.sub.3 where W represents O- or a bond, R.sup.3 represents hydrogen lower alkyl, C.sub.5 _.sub.7 cycloalkyl or an ester moiety which may be removed under a physiological condition and i is an integer from 1 to 4,
R.sup.2 represents hydrogen or a group --W--(CH.sub.2).sub.i --COOR.sup.3 where W, R.sup.3 and i have the same meanings as defined above, or a group OR.sup.4, where R.sup.4 represents hydrogen lower alkyl mono-lower alkylaminocarbonyl or phenyl-lower alkyl, atoms may be substituted by hydroxyl, halogen, amino, carboxyl, lower alkoxy, lower alkylamino, or lower alkoxycarbonyl; phenyl-lower alkyl in which one or more hydrogen atoms in the phenyl moiety may be substituted by hydroxyl, halogen, amino, carboxyl, lower alkoxy, lower alkylamino, lower alkoxycarbonyl or halo-lower alkyl; or acyl, --(CH.sub.2).sub.m --CHR.sup.6 --, where m is an integer from 1 to 3 and R.sup.6 represents hydrogen or hydroxyl, and R.sup.5 have the same meani
REFERENCES:
Jain PC, Paul B, Anand N. Indian J. Chem. 10(5), 455-60 (abstract) 1972.
Merck Manual. Eleventh Edition (1966). p. 1574 Merck USA.
Asai Kenji
Hatsushiba Emiko
Iida Hiroyuki
Ishikawa Midori
Isomura Yasuko
Huang Evelyn
Ivy C. Warren
Meiji Seika Kabushiki Kaisha
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