Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1994-10-17
1997-04-29
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514259, 514267, 514245, 544237, 544250, 544284, 544212, 544234, 544233, 544247, 544245, C07D40114, A61K 31505, A61K 3150
Patent
active
056249268
DESCRIPTION:
BRIEF SUMMARY
This is a 371 application of PCT/JP94/00229, filed Feb. 16, 1994.
TECHNICAL FIELD
The present invention relates to a drug containing a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative or a pharmaceutically acceptable salt thereof as an active ingredient, which inhibits nucleoside uptake of the cells to increase an extracellular adenosine concentration and is therefore useful for the protection of myocardium against myocardosis due to anoxemia or hypoxia, such as ischemia and reperfusion disorders, and for the prevention or treatment of inflammation, such as leg and foot edema.
BACKGROUND ART
With respect to 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivatives having a 1-(6,7-dimethoxy-4-quinazolinyl)-4-piperidinyl group at the 3-position, those having a hydrogen atom, a chlorine atom or a nitro group at the 6-position are described in Chem. Pharm. Bull., 38, 1591-1595 (1990). Further, it is known that a compound having adenosine uptake inhibitory activity exhibits myocardium protecting activity [Circul., 80, 1400-1411 (1989); Am. J. Physiol., H1570-1577 (1991); J. Cardiovasc. Pharmacol., 20, 173-178 (1992)].
DISCLOSURE OF THE INVENTION
The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema which contain as an active ingredient a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR2## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C--R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen), or a pharmaceutically acceptable salt thereof.
The present invention also relates to a method for protecting myocardium or preventing or treating inflammatory edema and a method for preventing or treating diseases caused by adenosine uptake, which comprise administering an effective amount of a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I) or a pharmaceutically acceptable salt thereof.
The present invention further relates to the use of a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I) or a pharmaceutically acceptable salt thereof for the preparation of a pharmaceutical composition which is useful for the protection of myocardium, the prevention or treatment of inflammatory edema, and the prevention or treatment of diseases caused by adenosine uptake.
Furthermore, the present invention relates to the use of a 1,2,3,4-tetrahydro-2, 4-dioxoquinazoline derivative represented by formula (I) or a pharmaceutically acceptable salt thereof for the protection of myocardium, the prevention or treatment of inflammatory edema, and the prevention or treatment of diseases caused by adenosine uptake.
The present invention also provides a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I-a): ##STR3## wherein R.sup.1a represents substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; and R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, Y and Z have the same meanings as defined above, and a pharmaceutically acceptable salt thereof.
The compounds represented by formula (I) and the compounds represented by formula (I-a) are hereinafter referred to as Compounds (I) and Compounds (I-a), respectively. The same applies to t
REFERENCES:
patent: 4166117 (1979-08-01), Vincent et al.
patent: 4668683 (1987-05-01), Takai et al.
Young, M.A. et al. Am. J. Physiol. 261, H1570-H1577 (1991).
Dorion, M. et al. J. Cardiovasc. Pharmacol. 19, 69-77 (1992).
Nomoto, Y. et al. Chem. Pharm. Bull. 38, 1591-1595 (1990).
Swinyard, E.A. et al. Remington's Pharmaceutical Sciences, Gennaro, A.R. et al. ed. (Philadelphia College of Pharmacy, Philadelphia), pp. 1286-1992 (1990).
Fujiwara Shigeki
Karasawa Akira
Kase Hiroshi
Kawakage Michiyo
Kusaka Hideaki
Kyowa Hakko Kogyo Co. Ltd.
Shah Mukund J.
Wong King Lit
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