Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-03-04
1998-06-09
Bernhardt, Emily
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514252, 544238, 544239, 544240, 544241, A61K 3150, C07D40112, C07D23722, C07D41712
Patent
active
057634394
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to novel pyridazinone derivatives or salts thereof, processes for their production and pharmaceutical compositions containing them as active ingredients. More particularly, it relates to anti-shock agents.
BACKGROUND ART
Japanese Unexamined Patent Publication No. 267560/1986 discloses that a 3-pyridazinone compound having C.sub.2-5 alkyl at the 2-position, H, C.sub.1-3 alkyl, Cl or Br at the 4-position and substituted phenylmethylamino at the 5-position is useful as an antiallergic agent.
WO91/16314 discloses that a pyridazinone derivative having Ce, Br, H or CN at the 4-position, --N(R.sup.3)CH(R.sup.4)Ar at the 5-position, and OR.sup.2 wherein R.sup.2 is A.sup.1 --Y.sup.1 (wherein A.sup.1 is alkylene, and Y.sup.1 is CO.sub.2 R.sup.5, CN, OR.sup.6, thienyl, pyridyl, etc.) or A.sup.2 --y.sup.2 (wherein A.sup.2 is alkylene, and y.sup.2 is phenyl), at the 6-position, is useful as a preventive or therapeutic agent for e.g. thrombotic diseases, congestive failure, hypertension, asthma or immediate allergy.
Japanese Unexamined Patent Publication No. 201994/1993 discloses that a pyridazinone derivative having a diphenylmethyl group at the 2-position is useful as a therapeutic agent for hypertension, congestive failure or chronic renal diseases.
J. Heterocycl. Chem. (1990) 27 (3) 471-477 discloses 5-benzylamino-6-methoxycarbonyl-2-phenylpyridazin-3(2H)-one at page 475, left column, lines 19-20.
Yakugaku Zasshi (Pharmacological Journal) (1978) 98 (10) 1421-1427 discloses at page 1425, lines 3-7, e (XIII) as an intermediate for the synthesis of urinary methabolites of 4-ethoxy-2-methyl-5-morpholino-3(2H)-pyridazinone having antiinflammatory effects.
However, the compounds of the present invention are different in the chemical structure from the compounds disclosed in the above-mentioned Japanese Unexamined Patent Publication No. 267560/1986, WO91/16314, Japanese Unexamined Patent Publication No. 201994/1993, J. Heterocycl. Chem. (1990) 27 (3) 471-477 and Yakugaku Zasshi (1978) 98 (10) 1421-1427.
In a broad sense, shock is regarded as an ischemic diseases, but it is caused by various diseases such as septic shock, hemorrhagic shock and cardiogenic shock. The septic shock occurs to a patient seriously diseased with a Gram negative bacteria infectious disease, and it is one of serious diseases, whereby the patient is likely to be killed when the symptom is really bad. There are many patients particularly in the field of emergency medical care. As an anti-shock agent, steroids or Miraclid has been used which is one of protease inhibitors. However, even then, the death rate is still high, and development of a more effective drug is desired.
DISCLOSURE OF THE INVENTION
It is an object of the present invention to provide a novel pyridazinone derivative or a salt thereof which is useful as an anti-shock agent, a process for its production and a pharmaceutical composition containing it as an active ingredient.
The present inventors have prepared shock models of small animals such as rats and mice and have conducted extensive researches with an aim to improve the survival rate. As a result, they have found that pyridazinone derivatives having a certain specific chemical structure exhibit excellent anti-shock effects. The present invention has been accomplished on the basis of this discovery.
That is, the present invention provides a pyridazinone derivative of the formula (I) or a pharmaceutically acceptable salt thereof: ##STR2## wherein Q is --CH.sub.2 -- or --CO--, A is a furanyl group which may be substituted, a thienyl group which may be substituted, a pyridyl group which may be substituted, a pyridyl N-oxide group which may be substituted, a thiazolyl group which may be substituted, or a phenyl group which may be substituted, R.sup.1 is a hydrogen atom, an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, or a phenyl group which may be substituted, R.sup.2 is a hydrogen atom, a cyano group, an a
REFERENCES:
patent: 5079261 (1992-01-01), Serhan et al.
patent: 5098900 (1992-03-01), Mutsukado et al.
Derwent Abstract for WO9013292 (Nov. 15, 1990), Serhan et al.
Takaya et al, Chemical Abstracts vol. 90, No. 152105 (1979).
Higuchi Rie
Kimura Hirohiko
Nakayama Hitoshi
Odawara Shinji
Okada Hiroshi
Bernhardt Emily
Ishihara Sangyo Kaisha Ltd.
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