US 4,308,270 A · 1,2,4-Oxadiazine derivatives, process for their preparation and pharmaceutical compositions containing them

Abstract

The invention concerns new compounds of the general formula (I) ##STR1## wherein R.sup.1 is hydrogen or phenyl optionally substituted by one or more of the following substituents: alkyl having 1 to 4 carbon atoms, halogen, alkoxy having 1 to 4 carbon atoms or nitro; R.sup.2 is alkyl having 1 to 4 carbon atoms, cycloalkyl having 5 to 7 carbon atoms or phenyl, optionally substituted with one or more of the following groups: alkyl having 1 to 4 carbon atoms, halogen, alkoxy having 1 to 4 carbon atoms or nitro; or R.sup.2 is a naphthyl group; R.sup.3 is alkyl having 1 to 4 carbon atoms, acyl or hydrogen; R.sup.4 hydrogen or alkyl having 1 to 4 carbon atoms; R.sup.5 is cycloalkyl having 5 to 7 carbon atoms, alkyl having 1 to 6 carbon atoms, phenyl-(C.sub.1-4 -alkyl) in which the phenyl moiety may optionally be substituted with alkoxy having 1 to 4 carbon atoms, halogen or nitro; or R.sup.4 and R.sup.5 together represent a group of the general formula (V) ##STR2## wherein R.sup.6 is hydrogen or alkoxy having 1 to 4 carbon atoms, m and n stand for 0, 1 or 2 and acid addition and quaternary salts thereof. The compounds of the general formula (I) are potent peripheral vasodilators and hypotensive agents. They increase the coronary blood flow and in addition to their slight antiinflammatory and diuretic acidivity possess strong antiarrhythmic properties. A process for the preparation of these compounds and pharmaceutical compositions containing them are also within the scope of the invention.

Claims19

Dependent claims

A compound of the formula (I) ##STR10## wherein R.sup.1 is hydrogen or phenyl optionally substituted by one or more of the following substituents:

alkyl having 1 to 4 carbon atoms, halogen, alkoxy having 1 to 4 carbon atoms or nitro;
R.sup.2 is alkyl having 1 to 4 carbon atoms, cycloalkyl having 5 to 7 carbon atoms or phenyl, optionally substituted with one or more of the following groups:
alkyl having 1 to 4 carbon atoms, halogen, alkoxy having 1 to 4 carbon atoms or nitro;
or R.sup.2 is naphthyl group;
R.sup.3 is alkyl having 1 to 4 carbon atoms, alkanoyl having 1 to 4 carbon atoms, tosyl or benzoyl which may be optionally substituted by alkyl having 1 to 4 carbon atoms, nitro or halogen, or hydrogen;
R.sup.4 is hydrogen or alkyl having 1 to 4 carbon atoms;
R.sup.5 is cycloalkyl having 5 to 7 carbon atoms, alkyl having 1 to 6 carbon atoms, phenyl-(C.sub.1-4 -alkyl) in which the phenyl moiety may optionally be substituted with alkoxy having 1 to 4 carbon atoms, halogen or nitro;
or
R.sup.4 and R.sup.5 together represent a group of the formula (V) ##STR11## wherein R.sup.6 is hydrogen or alkoxy having 1 to 4 carbon atoms,
m and n are each 0, 1 or 3, or a pharmaceutically acceptable acid-addition or quaternary salt thereof.

7 more elements

A process for the preparation of a compound of the formula (I) ##STR12## wherein R.sup.1 is hydrogen or phenyl optionally substituted by one or more of the following substituents:

alkyl having 1 to 4 carbon atoms, halogen, alkoxy having 1 to 4 carbon atoms or nitro;
R.sup.2 is alkyl having 1 to 4 carbon atoms, cycloalkyl having 5 to 7 carbon atoms or phenyl, optionally substituted with one or more of the following groups:
alkyl having 1 to 4 carbon atoms, halogen alkoxy having 1 to 4 carbon atoms or nitro;
or R.sup.2 is a naphthyl group;
R.sup.3 is alkyl having 1 to 4 carbon atoms, acyl or hydrogen;
R.sup.4 is hydrogen or alkyl having 1 to 4 carbon atoms;
R.sup.5 is cycloalkyl having 5 to 7 carbon atoms, alkyl having 1 to 6 carbon atoms, phenyl-(C.sub.1-4 -alkyl) in which the phenyl moiety may optionally be substituted with alkoxy having 1 to 4 carbon atoms, halogen or nitro;
or
R.sup.4 and R.sup.5 together are a group of the formula (V) ##STR13## wherein R.sup.6 is hydrogen or alkoxy having 1 to 4 carbon atoms,
m and n are each 0, 1 or 2 or a pharmaceutically acceptable acid-addition or quaternary salt thereof, which comprises
(a) reacting a compound of the formula (II) ##STR14## wherein R.sup.7 is hydrogen or alkyl having 1 to 4 carbon atoms,
Z is halogen or sulfonyloxy,
with a compound of the formula (III) ##STR15## to prepare compounds of the formula (I), in which R.sup.3 is identical with an R.sup.7 group, wherein
R.sup.7 is hydrogen or alkyl having 1 to 4 carbon atoms;
or
(b) reacting a compound of the formula (IV) ##STR16## wherein Y is halogen, with a base, to prepare a compound of the formula (I), in which R.sup.3 is hydrogen;
or
(c) acylating a compound of the formula (I), in which R.sup.3 is hydrogen, in a manner known per se, to prepare a compound of the formula (I), in which R.sup.3 is acyl;
or
(d) hydrolyzing a compound of the formula (I), in which R.sup.3 is acyl, in a manner known per se, to prepare a compound of the formula (I), in which R.sup.3 is hydrogen,
and optionally converting a compound of the formula (I) obtained into a pharmaceutically acceptable acid-addition or quaternary salt thereof.

18 more elements

Dependencies are inferred from the claim text.

1,2,4-Oxadiazine derivatives, process for their preparation and pharmaceutical compositions containing them

Life of this patent

1,2,4-Oxadiazine derivatives, process for their preparation and pharmaceutical compositions containing them

Life of this patent

Abstract

Claims19