Patent GB-1414363-A (GB)
Title: Indeno-pyran and- thiopyran derivatives
IPC: C07C33/38
Filed: 1973-07-02
Abstract: 1414363 Indenopyran- and indenothiopyranalkylamines AYERST McKENNA & HARRISON Ltd 2 July 1973 [12 Oct 1972 (2)] 31351/73 Heading C2C Novel indenopyran- and indenothiopyranalkylamines of the general formula wherein R<SP>1</SP> is a straight chain C 1-6  alkyl or branched chain C 3  or C 4  alkyl group, each of R<SP>2</SP>, R<SP>3</SP>, R<SP>4</SP> and R<SP>5</SP> is as R<SP>1</SP> or a hydrogen atom, R<SP>6</SP> is as R<SP>1</SP>, a hydrogen or halogen atom, or a hydroxy, nitro, C 1-4  alkoxy or C 2-6  alkanoyloxy group, R<SP>7</SP> is as R<SP>1</SP> or a hydrogen atom, X is O or S, and Y is -Alk-NR<SP>8</SP>R<SP>9</SP> in which Alk is CR<SP>10</SP>R<SP>11</SP>, CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>, CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>- R<SP>15</SP> or CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>R<SP>15</SP>CR<SP>16</SP>R<SP>17</SP> (each of R<SP>10</SP>, R<SP>11</SP>, R<SP>12</SP>, R<SP>13</SP>, R<SP>14</SP>, R<SP>15</SP>, R<SP>16</SP> and R<SP>17</SP> is as R<SP>1</SP> or a hydrogen atom) and each of R<SP>8</SP> and R<SP>9</SP> is as R<SP>1</SP> or a hydrogen atom or NR<SP>8</SP>R<SP>9</SP> is pyrrolidino, piperidino, morpholino, piperazino, 4-R<SP>1</SP>-piperazino or 4-(hydroxy-R<SP>1</SP>)-piperazino, and pharmaceutically acceptable acid addition salts thereof are prepared (i) by treating an indene of the general formula wherein X<SP>1</SP> is -OH, -SH, -S-SO 3 Na or -S-SO 3 K, with a compound of the general formula R<SP>1</SP>-CO-Y<SP>1</SP>, wherein Y<SP>1</SP> is (a) -COOR<SP>19</SP> or -Alk<SP>1</SP>-COOR<SP>19</SP>, in which R<SP>19</SP> is as R<SP>1</SP> or a hydrogen atom and Alk<SP>1</SP> is CR<SP>20</SP>R<SP>11</SP>, CR<SP>10</SP>R<SP>11</SP>-CR<SP>12</SP>R<SP>13</SP> or CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>R<SP>15</SP>, (b) -CONR<SP>8</SP>R<SP>9</SP> or -Alkl-CONR<SP>8</SP>R<SP>9</SP>, (c) -CH 2 OCOR<SP>20</SP> or -Alk<SP>1</SP>-CH 2 OCOR<SP>20</SP>, in which R<SP>20</SP> is as R<SP>1</SP> or a hydrogen atom, (d) -Alk<SP>2</SP>-L. in which Alk<SP>2</SP> is CR<SP>10</SP>R<SP>11</SP>CHR<SP>12</SP>, CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>- R<SP>13</SP>CHR<SP>14</SP> or CR<SP>10</SP>R<SP>11</SP>CR<SP>12</SP>R<SP>13</SP>CR<SP>14</SP>R<SP>15</SP>CHR<SP>16</SP> and L is a halogen atom, (e) -Alk-NR<SP>20</SP>- COR<SP>21</SP>, in which R<SP>21</SP> is a hydrogen atom or C 1-5  alkyl group, (f) -Alk-NO 2  or (g) -Alk- NR<SP>8</SP>R<SP>9</SP>, in the presence of an acid catalyst to form a compound of the general formula and where necessary, transforming this compound (optionally via other compounds of the same general formula) into the desired product by a method known per se. Indenes of the second general formula above wherein X<SP>1</SP> is -SH are prepared by reacting the corresponding compound in which X<SP>1</SP> is -Br with Na 2 S 2 O 3 , heating the resulting thiosulphate (Na salt) with aqueous ethanolic NaOH and reducing the resulting bis-indenylalkyl disulphide with LiAlH 4 . Pharmaceutical compositions having antidepressant activity comprise, as active ingredient, an indenopyran- or indenothiopyranalkyl-amine of the first general formula above or a pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier.