Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1991-10-16
1993-04-13
Daus, Donald G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514212, 514247, 514252, 540598, 544114, 544238, 544240, A61K 3150, C07D23716
Patent
active
052023230
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel 3(2H)-pyridazinone derivatives and their pharmaceutically acceptable salts having an inhibitory activity of platelet aggregation, a cardiotonic activity, a vasodilating activity and an anti-SRS-A activity, processes for their preparation and pharmaceutical compositions containing them as active ingredients.
BACKGROUND ART
1) Field of anti-thrombotic agent
It is known that platelet aggregation plays an important role for thrombus formation in connection with a disease state. Various thrombotic diseases caused by thrombus formation mainly include cerebral thrombosis, pulmonal thrombosis, myocardial infarction, angina pectoris, occlusion of peripheral artery and the like, and all of these diseases require development for useful drugs. As a prophylactic or therapeutic drug, an anti-thrombotic agent having an inhibitory activity of platelet aggregation draws public tension. Heretofore, the effect of aspirin has been widely studied, and more recently ticlopidine and cilostazol have been clinically developed. However, a more strongly effective drug is demanded in respect of its effects.
In addition to the above-mentioned various thrombotic diseases, there are enumerated various diseases in relation to platelets. Examples for these diseases include nephritis, cancer cell metastasis and the like, and recently various studies have been conducted with regard to prophylactic or therapeutic effects for these diseases achieved mainly by an anti-thrombotic agent having an activity for controlling platelet function ("Journal of Royal College of Physicians", Vol. 7, No. 1, p. 5-18, 1972; "Japan Clinics (Nihon Rinsho)", Vol. 4, No. 6, p. 130-136, 1988; Anticancer Research, Vol 6, p. 543-548, 1986).
2) Field of cardiotonic agent
A cardiotonic agent to enhance myocardial contractive force have been used as a therapeutic drug for congestive heart failure from old times. However, conventional cardiotonic agents such as cardiac glycosides represented by digitalis, aminophylline and catecholamines have strong side effects, and therefore drugs such as milrinone and denopamine are recently clinically developed.
3) Field of vasodilator
There are many known vasodilators, but at present there are few drugs which have beneficial pharmacologic properties for circulatory system such as a satisfactory inhibitory activity of platelet aggregation.
4) Field of anti-SRS-A agent
SRA-A (Slow Reacting Substances of Anaphylaxis) is a chemical mediator released together with histamine, etc. by an allergic reaction and has pharmacological activity to cause a strong and prolonged contraction of tracheal smooth muscle. Their existence has long been known from such a phenomenal aspect.
It was found in 1979 that SRS-A itself is a mixture of leukotriene C.sub.4 (hereinafter referred to as LTC.sub.4), leukotriene D.sub.4 (hereinafter referred to as LTD.sub.4) and leukotriene E.sub.4 (hereinafter referred to as LTE.sub.4) [generally called peptide leukotriene].
Extensive researches have been conducted on SRS-A for its relationship with a disease state. As a result, the relationship of SRS-A with immediate type allergic diseases such as bronchial asthma, allergic rhinitis, urticaria and hay fever, has become clear.
Further, the relationship of SRS-A with various inflammatory diseases, ischemic heart diseases, etc., has been suggested.
Therefore, a compound which exhibits inhibition against SRS-A, is expected to be useful as a prophylactic or therapeutic drug against the disorders caused by either LTC.sub.4, LTD.sub.4 or LTE.sub.4, or by a mixture thereof.
As the SRS-A antagonists, many medicinal substances have been reported. ("Drugs of the Future", Vol. 12, p. 453-474 (1987); "Annual Reports in Medicinal Chemistry", Vol. 22, p. 73-84 (1987) and "Annual Reviews in Pharmacological Toxicology", Vol. 29, p. 123-143 (1989)).
However, no instance of their practical clinical application has been reported.
Now, the relationship of 6-.omega.-substituted alkyloxy3(2H)-pyridazinones of the formula [I] and th
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Matsumoto Takashi
Saito Akira
Sakoda Ryozo
Shikada Ken-ichi
Tanikawa Keizo
Daus Donald G.
Nissan Chemical Industries Ltd.
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