Pharmaceutical compositions, 2-benzothiazolamine derivatives, and their preparation

• US 5,236,940 A
• Filed: 09/03/1991
• Issued: 08/17/1993
• Est. Priority Date: 12/15/1988
• Status: Expired due to Fees

• Current Assignee: Rhone-Poulenc Sante (Sanofi )
• Original Assignee: Rhone-Poulenc Sante (Sanofi )
• Inventors: Audiau, Francois, James, Claude
• Primary Examiner(s): Gerstl, Robert
• Application Number:
  US07/758,378
• Time in Patent Office: 714 Days
• Field of Search: 548/164, 514/367
• US Class Current: 514/367
• CPC Class Codes: C07D 277/82 Nitrogen atoms

Abstract

Pharmaceutical compositions are disclosed. They are useful for the treatment of medical conditions associated with the effects of glutamate, comprise as active principle, at least one compound of formula: ##STR1## or a salt thereof, in which either R₁ represents polyfluoroalkoxy, 2,2,2-trifluoroethyl, pentafluoroethyl, tert-butyl, trimethylsilyl or trifluoromethylthio and R₂ and R₃ represent hydrogen,

or R₁ represents polyfluoroalkoxy, R₂ represents hydrogen and R₃ represents alkyl, amino, alkoxy, phenyl, phenylalkyl, dimethylamino or dialkylaminoakylthio,

or R₁ represents polyfluoroalkoxy, R₂ represents amino and R₃ represents hydrogen, with the exception of 6-trifluoromethoxy-2-benzothiazolamine.

Claims

1. A compound of formula:

##STR5## in which either;

(1) - R₁ represents polyfluoroalkoxy, tert-butyl, or trimethylsilyl, and R₂ and R₃ represent hydrogen, with the proviso that, when R₁ represents trifluoromethoxy, R₂ and R₃ are not both hydrogen;

(2) - or R₁ represents polyfluoroalkoxy, R₂ represents hydrogen, and R₃ represents amino or phenylalkyl;

(3) - or R₁ represents polyfluoroalkoxy, R₂ represents amino and R₃ represents hydrogen, provided that said alkyl and alkoxy radicals or portions contain 1to 4 carbon atoms each in a straight or branched chain, or a pharmaceutically acceptable salt of a said compound with an inorganic or organic acid.

2. A compound as claimed in claim 1, in which either:

(1) - R₁ represents pentafluoroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, or 2,2,3,3,3-pentafluoropropoxy, and R₂ and R₃ represent hydrogen;

(2) - R₁ represents trifluoromethoxy, R₂ represents hydrogen, and R₃ represents amino;

(3) - R₁ represents trifluoromethoxy, R₂ represents amino, and R₃ represents hydrogen.

3. A compound as claimed in claim 1 which is 6-pentafluoroethoxy-2-benzothiazolamine and its acid addition salts.

4. A compound as claimed in claim 1 which is 6-tertbutyl-2-benzothiazolamine, and its acid addition salts.

5. A compound as claimed in claim 1 which is 6-trifluoromethoxy-2,5-benzothiazolediamine and its acid addition salts.

6. A compound as claimed in claim 1 which is 6-trifluoromethoxy-2,4-benzothiazolediamine and its acid addition salts.

7. A pharmaceutical composition comprising, as active principle, in association with a compatible pharmaceutically acceptable carrier, an effective amount of at least one compound of formula:

##STR6## in which either (1) - R₁ represents polyfluoroalkoxy, tert-butyl, or trimethylsilyl and R₂ and R₃ represent hydrogen, with the proviso that, when R₁ represents trifluoromethoxy, R₂ and R₃ are not both hydrogen;

(2) - or R₁ represents polyfluoroalkoxy, R₂ represents hydrogen and R₃ represents amino or phenylalkyl;

(3) - or R₁ represents polyfluoroalkoxy, R₂ represents amino and R₃ represents hydrogen, provided that said alkyl and alkoxy radicals or portions contain 1 to 4 carbon atoms each in a straight or branched chain, or a pharmaceutically acceptable salt of a said compound with an inorganic or organic acid.

8. A pharmaceutical composition according to claim 7, in which either:

(1) - R₁ represents pentafluoroethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, or 2,2,3,3,3-pentafluoropropoxy, and R₂ and R₃ represent hydrogen;

(2) - or R₁ represents trifluoromethoxy, R₂ represents hydrogen, and R₃ represents amino;

(3) - or R₁ represents trifluoromethoxy, R₂ represents amino, and R₃ represents hydrogen.

9. A pharmaceutical composition according to claim 7 in which the active ingredient is 6-pentafluoroethoxy-2-benzothiazolamine, 6-tert-butyl-2-benzothiazolamine, 6-trifluoromethoxy-2,5-benzothiazolediamine, or 6-trifluoromethoxy-2,4-benzothiazolediamine.

10. A method for the treatment of a medical condition associated with the effects of glutamate which comprises administering to a subject in need of such treatment an amount of a compound of formula (I) as defined in claim 7 sufficient to inhibit such effects.

11. A method for the treatment of a medical condition associated with the effects of glutamate which comprises administering to a subject in need of such treatment an amount of a compound of formula (I) as defined in claim 8, sufficient to inhibit such effects.