Antipsychotic benzothiopyranylamines

• US 5,071,858 A
• Filed: 10/12/1990
• Issued: 12/10/1991
• Est. Priority Date: 03/22/1989
• Status: Expired due to Fees

• Current Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Original Assignee: Ciba-Geigy Corporation (Novartis Ag)
• Inventors: Hutchison, Alan J.
• Primary Examiner(s): Lee, Mary C.
• Assistant Examiner(s): Haley, Jacqueline
• Application Number:
  US07/597,299
• Time in Patent Office: 424 Days
• Field of Search: 514/212, 514/324, 514/422, 514/443, 540/596, 546/202, 548/525, 549/23
• US Class Current: 514/324
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/12 Antihypertensives
• CPC Class Codes: C07D 335/06 Benzothiopyrans; Hydrogenated benzothiopyrans
• CPC Class Codes: C07D 409/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

Disclosed are 3,4-dihydro-2H-1-benzothiopyran-3-yl-methyl- and ethylamines useful as antipsychotics, processes for the preparation of said compounds, pharmaceutical compositions containing same, and a method of treating psychotic disorders by administering said compounds.

Claims

1. A compound of the formula ##STR8## wherein n is one or two, X represents hydrogen, halogen, lower alkyl, hydroxy or lower alkoxy, R¹ is lower alkyl, R² is lower alkyl, substituted by A, or R¹ and R² together represent alkylene of 4 to 6 carbon atoms substituted by A, and A is hydroxymethyl, hydroxy-arylmethyl, hydroxy-diarylmethyl, lower alkoxymethyl, aryl-lower alkoxymethyl, lower alkanoyloxymethyl, aryl-lower alkanoyloxymethyl, aroyloxymethyl, lower alkanoyl, aryl-lower alkanoyl, aroyl, lower alkoxycarbonyl, or aryl-lower alkoxycarbonyl, or a salt thereof.

2. A compound according to claim 1 wherein n is one, X represents hydrogen, halogen, lower alkyl or lower alkoxy, R¹ is lower alkyl, R² is aroyl-lower alkyl, or R¹ and R² together represent straight, chain alkylene of 4 to 6 carbon atoms substituted by A, wherein A is hydroxymethyl, hydroxy-arylmethyl, hydroxy-diarylmethyl, lower alkoxymethyl, aryl-lower alkoxymethyl, lower alkanoyloxymethyl, aryl-lower alkanoyloxymethyl, aroyloxymethyl, lower alkanoyl, aryl-lower alkanoyl, aroyl, lower alkoxycarbonyl or aryl-lower alkoxycarbonyl;

or an acid addition salt thereof.

3. A compound according to claim 1 of the formula ##STR9## wherein n is one or two, X represents hydrogen, halogen, lower alkyl or lower alkoxy, R¹ is lower alkyl and R² is aroyl-lower alkyl or a pharmaceutically acceptable acid addition salt thereof.

4. A compound according to claim 3 wherein n is one, X represents hydrogen, halogen, lower alkyl or lower alkoxy, R¹ is lower alkyl and R² is aroyl-lower alkyl;

or a pharmaceutically acceptable acid addition salt thereof.

5. A compound according to claim 3 wherein n is one, X represents fluoro and is located in the 6-position, and R¹ is lower alkyl and R² is p-fluorobenzoyl-lower alkyl, or a pharmaceutically acceptable acid addition salt thereof.

6. A compound according to claim 1 of formula ##STR10## wherein X represents hydrogen, halogen, lower alkyl or lower alkoxy, and A is hydroxymethyl, alpha-hydroxybenzyl, alpha-hydroxydiphenylmethyl, lower alkoxymethyl, phenyl-lower alkoxymethyl, lower alkanoyloxymethyl, phenyl-lower alkanoyloxymethyl, benzoylmethyl, lower alkanoyl, phenyl-lower alkanoyl, benzoyl, lower alkoxycarbonyl or phenyl-lower alkoxycarbonyl, and wherein the phenyl group in phenyl, benzyl and benzoyl is unsubstituted or substituted by halogen in o-, m- or p-position;

or a pharmaceutically acceptable acid addition salt thereof.

7. A compound according to claim 6 wherein X represents hydrogen, halogen, lower alkyl or lower alkoxy, and A is hydrogen, hydroxymethyl, alpha-hydroxydi(p-fluorophenyl)methyl, lower alkoxymethyl, p-fluorobenzyloxymethyl, p-fluorobenzoyloxymethyl, p-fluorobenzoyl, or lower alkoxycarbonyl;

or a pharmaceutically acceptable acid addition salt thereof.

8. A compound according to claim 6 wherein X represents fluoro and is located in 6-position, and A represents alpha-hydroxydi(p-fluorophenyl)methyl, p-fluorobenzyloxymethyl, p-fluorobenzoyloxymethyl, or p-fluorobenzoyl;

or a pharmaceutically acceptable acid addition salt thereof.

9. A compound according to claim 6 wherein X represents fluoro and is located in 6-position, and A represents p-fluorobenzoyl;

or a pharmaceutically acceptable acid addition salt thereof.

10. A pharmaceutical preparation for the treatment of psychotropic, gastrointestinal and cardiovascular disorders responsive to serotonin-2 receptor antagonist activity comprising an effective amount of a compound of formula I as claimed in claim 1 or a pharmaceutically acceptable salt thereof together with a pharmaceutical carrier.

11. A pharmaceutical preparation for the treatment in mammals of psychotic disorders responsive to serotonin-2 receptor antagonist activity comprising an effective amount of a compound of claim 9 together with a pharmaceutical carrier.

12. A method of treating mammals suffering from anxiety, psychotic, gastrointestinal or cardiovascular disorders responsive to serotonin-2-receptor antagonist activity which comprises administering to a said mammal a therapeutically effective amount of a compound of formula I according to claim 1 or a pharmaceutically acceptable salt thereof.

13. A method of treating mammals suffering from psychotic disorders or anxiety responsive to serotonin-2-receptor antagonist activity which comprises administering to a said mammal in need thereof a therapeutically effective amount of a compound of claim 8.

14. A method of treating mammals suffering from psychotic disorders responsive to serotonin-2 receptor antagonist activity which comprises administering to a said mammal in need thereof a therapeutically effective antipsychotic amount of a compound of claim 9.

15. A method of treating mammals suffering from psychotic disorders or anxiety responsive to serotonin-2-receptor antagonist activity which comprises administering to a said mammal in need thereof a therapeutically effective amount of a compound of claim 3.