Thieno[3,2-b]-[1,5]benzodiazepines

• US 4,115,568 A
• Filed: 04/13/1977
• Issued: 09/19/1978
• Est. Priority Date: 11/26/1974
• Status: Expired due to Term

• Current Assignee: Lilly Industries Limited
• Original Assignee: Lilly Industries Limited
• Inventors: Tupper, David Edward, Chakrabarti, Jiban Kumar
• Primary Examiner(s): Tovar, Jose
• Application Number:
  US05/787,197
• Time in Patent Office: 524 Days
• Field of Search: 260/268 TR, 260/243.3, 424/250
• US Class Current: 514/220
• CPC Class Codes: C07C 323/00 Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/68 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Abstract

Thieno[1,5]benzodiazepines having useful CNS activity containing the novel tricyclic ring system: ##STR1## the 10-position being substituted by an amino, preferably a piperazino, group.

Claims

1. A thieno[3,2-b][1,5]benzodiazepine of the formula ##STR30## or an acid addition salt thereof, wherein R¹ and R² independently represent hydrogen, C_1-4 alkyl, halogen, C_1-4 haloalkyl, nitro, amino, C_1-4 alkoxy, C_1-4 alkylthio or a group of the formula --SO₂ N(R⁴)₂ where R⁴ is C_1-4 alkyl;

wherein R⁵ is a group of the formula ##STR31## wherein R⁶ is hydrogen, phenyl, halo phenyl, C_1-4 alkyl, C_1-4 carbalkoxy or --(CH₂)_n OH where n is 2 or 3; and

wherein the thiophene ring is unsubstituted or is substituted by a C_1-4 alkyl group.

2. A thieno[3,2-b][1,5]benzodiazepine of claim 1 wherein R¹ and R² are optional substituents at the 6- or 7-positions of the thieno[1,5]benzodiazepine system.

3. A thieno[3,2-b][1,5]benzodiazepine of claim 1, wherein R¹ is a 6- or 7-halo or trifluoromethyl substituent when R² is hydrogen.

4. A thieno[3,2-b][1,5]benzodiazepine of claim 1 wherein R⁶ is methyl.

5. An acid addition salt according to claim 1 which is pharmaceutically-acceptable.

9. The compound of claim 1 which is 7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[3,2-b][1,5]benzodiazepine or a pharmaceutically-acceptable salt thereof.

7. A pharmaceutical formulation comprising as an active ingredient a chemotherapeutically effective amount of a compound of the formula:

##STR32## or a pharmaceutically-acceptable salt thereof, wherein R¹ and R² independently represent hydrogen, C_1-4 alkyl, halogen, C_1-4 haloalkyl, nitro, amino, C_1-4 alkoxy, C_1-4 alkylthio or a group of the formula --SO₂ N(R⁴)₂ where R⁴ is C_1-4 alkyl;

wherein R⁵ is a group of the formula;

##STR33## wherein R⁶ is hydrogen, phenyl, halo phenyl, C_1-4 alkyl, C_1-4 carbalkoxy or --(CH₂)_n OH where n is 2 or 3; and

wherein the thiophene ring is unsubstituted or is substituted by a C_1-4 alkyl group.

6. A pharmaceutical formulation according to claim 7 in the form of a capsule, tablet or injection solution.

8. A method of treating an animal suffering from, or susceptible to, disorders of the CNS, which comprises administering to the animal a chemotherapeutically effective amount of a compound of the formula:

##STR34## or a pharmaceutically-acceptable salt thereof, wherein R¹ and R² independently represent hydrogen, C_1-4 alkyl, halogen, C_1-4 haloalkyl, nitro, amino, C_1-4 alkoxy, C_1-4 alkylthio or a group of the formula --SO₂ N(R⁴)₂ where R⁴ is C_1-4 alkyl;

wherein R⁵ is a group of the formula;

##STR35## wherein R⁶ is hydrogen, phenyl, halo phenyl, C_1-4 alkyl, C_1-4 carbalkoxy or --(CH₂)_n OH where n is 2 or 3;

and wherein the thiophene ring is unsubstituted or is substituted by a C_1-4 alkyl group.