Chroman derivatives and analogues having antihypertensive activity.

摘要

Compounds of formula (I) and pharmaceutically acceptable salts thereof:
<Chemistry id="chema01" num="0001"><Image id="ia01" he="25" wi="70" file="IMGA0001.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry>wherein:
<UnorderedLists id="ula01" listStyle="none"><ListItem>either one of R<Sub>1</Sub> and R<Sub>2</Sub> is hydrogen and the other is selected from the class of C<Sub>1-6</Sub> alkylcarbonyl, C<Sub>1-6</Sub> alkoxycarbonyl, C<Sub>1-6</Sub> alkylcarbonyloxy, C<Sub>1-6</Sub> alkylhydroxymethyl, nitro, cyano, chloro, trifluoromethyl, C<Sub>1-6</Sub> alkylsulphinyl, C<Sub>1-6</Sub> alkylsulphonyl, C<Sub>1-6</Sub> alkoxysulphinyl, C<Sub>1-6</Sub> alkoxysulphonyl, C<Sub>1-6</Sub> alkylcarbonylamino, C<Sub>1-6</Sub> alkoxycarbonylamino, C<Sub>1-6</Sub> alkyl-thiocarbonyl, C<Sub>1-6</Sub> alkoxy-thiocarbonyl, C<Sub>1-6</Sub> alkyl-thiocarbonyloxy, 1-mercapto C<Sub>2-7</Sub> alkyl, formyl or aminosulphinyl, aminosulphonyl or aminocarbonyl, the amino moiety being optionally substituted by one or two C<Sub>1-6</Sub> alkyl groups, or C<Sub>1-6</Sub> alkylsulphinylamino, C<Sub>1-6</Sub> alkylsulphonylamino, C<Sub>1-6</Sub> alkoxysulphinylamino or C<Sub>1-6</Sub> alkoxysulphonylamino or ethenyl terminally substituted by C<Sub>1-6</Sub> alkylcarbonyl, nitro or cyano, or -(C<Sub>1-6</Sub> alkyl-(NOH) or -C(C<Sub>1-6</Sub> alkyl)NNH<Sub>2</Sub> or, when Y is oxygen, one of R<Sub>1</Sub> and R<Sub>2</Sub> is nitro, cyano or C<Sub>1-3</Sub> alkylcarbonyl and the other is methoxy or amino optionally substituted by C<Sub>2</Sub>-<Sub>7</Sub> alkanoyl;</ListItem><ListItem>one of R<Sub>3</Sub> and R<Sub>4</Sub> is hydrogen or C<Sub>1-4</Sub> alkyl and the other is C<Sub>1-4 </Sub>alkyl or R<Sub>2</Sub> and R<Sub>3</Sub> together are C<Sub>2</Sub>-<Sub>5</Sub> polymethylene;</ListItem><ListItem>R<Sub>5</Sub> is hydroxy, C<Sub>1-6</Sub> alkoxy or C<Sub>1-7</Sub> acyloxy;</ListItem><ListItem>R<Sub>6</Sub> is hydrogen or C<Sub>1-6</Sub> alkyl;</ListItem><ListItem>R<Sub>7</Sub> is NR<Sub>8</Sub>R<Sub>9</Sub> wherein R<Sub>8</Sub> and R<Sub>9</Sub> are independently C<Sub>1-8</Sub> alkyl, R<Sub>8</Sub> is hydrogen and R<Sub>9</Sub> is C<Sub>1-6</Sub> alkyl or R<Sub>8</Sub> and R<Sub>9</Sub> together are C<Sub>4</Sub>-<Sub>5</Sub> polymethylene; or R<Sub>6</Sub> and R<Sub>B</Sub> together are -(CH<Sub>2</Sub>)<Sub>2</Sub>- wherein n is 2 or 3, and R<Sub>9</Sub> is hydrogen or C<Sub>1-6</Sub> alkyl; or R<Sub>7</Sub> is CH<Sub>2</Sub>R<Sub>10</Sub> wherein R<Sub>10</Sub> is hydrogen or C<Sub>1-5</Sub> alkyl optionally substituted by halo, hydroxy or C<Sub>1-6</Sub> alkoxy; or R<Sub>6</Sub> and Rio are -(CH<Sub>2</Sub>)<Sub>m</Sub>- wherein m is 2 or 3;</ListItem><ListItem>X is oxygen or sulphur; and</ListItem><ListItem>Y is oxygen, CH<Sub>2</Sub> or NH;</ListItem></UnorderedLists>

the R<Sub>6</Sub>-CH-CX-R<Sub>7</Sub> group being trans to the R<Sub>5</Sub> group; having blood pressure lowering activity, a process for their preparation and their use as pharmaceuticals.