Patent EP-0214772-A1 (EP)
Inventor: KING FRANCIS DAVID
IPC: A61P1/08
Filed: 1986-08-12
Abstract: Compounds of formula (I) and pharmaceutically acceptable salts thereof:wherein:n is 1, or 3; and m and p are independently 1 or 2 such that m + n + p 1≥4;X is NH; or O when Ar is offormula (a) and R<sub>4</sub> is hydrogen or when Ar is a group of formula (b);R<sub>1</sub>, R<sub>2</sub> and R<sub>3</sub> are independently hydrogen, C<sub>1-6</sub> alkyl, phenyl or phenyl-C<sub>1-6</sub> alkyl, which phenyl moieties may be substituted by C<sub>1-6</sub> alkyl, C<sub>1-6</sub> alkoxy or halogen;Ar is a group of formula (a):wherein either R<sub>4</sub> is C<sub>1-6</sub> alkoxy and one of R<sub>5</sub>, R<sub>6</sub> and R<sub>7</sub> is hydrogen and the other two are selected from hydrogen, halogen, CF<sub>3</sub>, C<sub>1-6</sub> alkylthio, C<sub>1-7</sub> acyl, C<sub>1-10</sub> carboxylic acylamino, C<sub>1-6</sub>alkyl S(O)n wherein n is 0,1 or 2, nitro or amino, aminocarbonyl or aminosulphonyl optionally substituted by one or two groups selected from C<sub>1-6</sub> alkyl, C<sub>3</sub>-<sub>8</sub> cycloalkyl, C<sub>3-8</sub> cycloalkyl C<sub>1-4</sub> alkyl or phenyl C<sub>1-4</sub> alkyl groups any of which phenyl moieties may be substituted by one or two groups selected from halogen, CF<sub>3</sub>, C<sub>1-6</sub> alkyl or C<sub>1-6</sub> alkoxy; or R<sub>4</sub> is hydrogen and R<sub>s</sub>, R<sub>6</sub> and R<sub>7</sub> are independently selected from hydrogen, C<sub>1-6</sub> alkyl, hydroxy, C<sub>1-6</sub> alkoxy, C<sub>1-6</sub> alkylthio or halo; or any two on adjacent carbon atoms together are C<sub>1-2</sub> alkylenedioxy and the third is hydrogen, C<sub>1-6</sub> alkyl, C<sub>1-6</sub> alkoxy or halo;or Ar is a group of formula (b):wherein Z is CH<sub>2</sub>, 0, S or NR<sub>9</sub> wherein R<sub>9</sub> is hydrogen, C<sub>1-6</sub> alkyl, C<sub>2-7</sub> alkenyl, phenyl or phenyl C<sub>1-4</sub> alkyl either of which phenyl moieties may be substituted by one or two of halogen, CF<sub>3</sub>, C<sub>1-6</sub> alkoxy or C<sub>1-6</sub> alkyl; and Y is CH or N; or Z is CH or N and Y is NR<sub>a</sub> or CHR<sub>a</sub> where R<sub>a</sub> is as defined for R<sub>9</sub> above;R<sub>b</sub> is present when the COX linkage is attached at the phenyl ring, and is selected from hydrogen, halogen, CF<sub>3</sub>, hydroxy, C<sub>1-6</sub> alkoxy or C<sub>1-6</sub> alkyl; R, is hydrogen, CF<sub>3</sub>, C<sub>1-6</sub> alkyl, C<sub>1-6</sub> alkoxy, C<sub>1-6</sub> alkylthio, C<sub>1-7</sub> acyl, C<sub>1-7</sub> acylamino, C<sub>1-6</sub>alkylsulphonytamino, N-(C<sub>1-6</sub>alsulphonyl)-N-C<sub>1-4</sub> alkylamino, C<sub>1-6</sub> alkylsulphinyl, hydroxy, nitro or amino, aminocarbonyl, aminosulphonyl, aminosulphonylamino or N-(aminosulphonyl)-C<sub>1-4</sub> alkylamino optionally N-substituted byone or two groups selected from C<sub>1-6</sub> alkyl, C<sub>3</sub>.<sub>8</sub> cycloalkyl, C<sub>3-8</sub> cycloalkyl C<sub>1-4</sub> alkyl, phenyl or phenyl C<sub>1-4</sub> alkyl groups or optionally N-disubstituted by C<sub>4-5</sub> polymethylene; having gastric motility enchancing activity and/or anti-emetic activity and/or 5-HT antagonist activity, a process for their preparation and their use as pharmaceuticals.