Thiazinoindoles useful as antidepressants
AssigneeAyerst McKenna and Harrison Ltd.
InventorsChristopher A. Demerson, Leslie G. Humber, George Santroch, Thomas A. Dobson, Ivo Jirkovsky
Life of this patent
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Abstract
Thiazinoindole derivatives characterized by having an amino(lower)alkyl radical attached to the 1 position of a 1H-1,4-thiazino[4,3-a]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated in a heterocyclic amine radical. The derivatives are substituted further at positions 1 and 10 and may be optionally substituted at positions 3, 4, 6, 7, 8 and 9. The thiazinoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the use of these derivatives and compositions containing them are also disclosed.
Claims3
A compound of formula ##STR35## in which R.sup.1 is lower alkyl or lower cycloalkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different selected from the group consisting of hydrogen and lower alkyl;
- R.sup.6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo, R.sup.7 is lower alkyl;
- X is thio;
- and Alk--NR.sup.8 R.sup.9 is an amino(lower)alkyl radical in which Alk is an alkylene selected from the group consisting of CR.sup.10 R.sup.11, CR.sup.10 R.sup.11 CR.sup.12 R.sup.13, CR.sup.10 R.sup.11 CR.sup.12 R.sup.13 CR.sup.14 R.sup.15 and CR.sup.10 R.sup.11 CR.sup.12 R.sup.13 CR.sup.14 R.sup.15 CR.sup.16 R.sup.17 in which R.sup.10, R.sup.11 R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16 and R.sup.17 are hydrogen or lower alkyl, and R.sup.8 and R.sup.9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are joined from a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, piperazino, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl.
A method of treating depression in a mammal which comprise administering to said mammal an antidepressant effective amount from about 0.1 to about 50 milligrams per kilogram of mammal weight per day of a compound of formula ##STR36## in which R.sup.1 is lower alkyl or lower cycloalkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different selected from the group consisting of hydrogen and lower alkyl;
- R.sup.6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo, R.sup.7 is lower alkyl;
- X is thio;
- and Alk--NR.sup.8 R.sup.9 is an amino(lower)alkyl radical in which Alk is an alkylene selected from the group consisting of CR.sup.10 R.sup.11, CR.sup.10 R.sup.11 CR.sup.12 R.sup.13, CR.sup.10 R.sup.11 CR.sup.12 R.sup.13 CR.sup.14 R.sup.15 and CR.sup.10 R.sup.11 CR.sup.12 R.sup.13 CR.sup.14 R.sup.15 CR.sup.16 R.sup.17 in which R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16 and R.sup.17 are hydrogen or lower alkyl, and R.sup.8 and R.sup.9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, piperazino, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl, or a corresponding pharmaceutically acceptable acid addition salt thereof.
A pharmaceutical composition comprising a pharmaceutically acceptable carrier and about 0.1 to about 50 milligrams of a compound of formula ##STR37## in which R.sup.1 is lower alkyl or lower cycloalkyl;
- R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are the same or different selected from the group consisting of hydrogen and lower alkyl;
- R.sup.6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo, R.sup.7 is lower alkyl;
- X is thio;
- and Alk-NR.sup.8 R.sup.9 is an amino(lower)alkyl radical in which Alk is an alkylene selected from the group consisting of CR.sup.10 R.sup.11, CR.sup.10 R.sup.11 CR.sup.12 R.sup.13, CR.sup.10 R.sup.11 CR.sup.12 R.sup.13 CR.sup.14 R.sup.15 and CR.sup.10 R.sup.11 CR.sup.12 R.sup.13 CR.sup.14 R.sup.15 CR.sup.16 R.sup.17 in which R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.15, R.sup.16 and R.sup.17 are hydrogen or lower alkyl, and R.sup.8 and R.sup.9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R.sup.8 and R.sup.9 together with the nitrogen atom to which they are joined from a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, piperazino, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl, or a corresponding pharmaceutically acceptable acid addition salt thereof.
Dependencies are inferred from the claim text.