Benzodiazepine derivatives

• US 4,115,574 A
• Filed: 06/01/1977
• 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:
  US05/802,381
• Time in Patent Office: 475 Days
• Field of Search: 260/243.3, 260/268 TR, 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[2,3-b][1,5]benzodiazepine compound of the formula ##STR31## or a pharmaceutically acceptable acid addition salt thereof, wherein R¹ and R² independently represent hydrogen, C_1-4 alkyl, halogen, C_1-4 haloakyl, 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 R⁶ is hydrogen, phenyl, halophenyl, 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 in the 2-position.

2. The compound of claim 1 which is 2-ethyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

3. The compound of claim 1 which is 2-ethyl-7-chloro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

4. The compound of claim 1 which is 2-ethyl-7-trifluoromethyl-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

5. The compound of claim 1 which is 2-ethyl-7-fluoro-10-(1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

6. The compound of claim 1 which is 2-methyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

7. The compound of claim 1 which is 2-isopropyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

8. A method of treating an animal suffering from, or susceptible to, disorder of the CNS, which comprises administering to the animal a chemotherapeutically effective amount of a thieno[2,3-b][1,5]benzodiazepine 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 akylthio or a group of the formula --SO₂ N(R⁴)₂ where R⁴ is C_1-4 alkyl;

wherein R⁶ is hydrogen, phenyl, halophenyl, 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 in the 2-position.

9. The method of claim 8 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

10. The method of claim 8 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-chloro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

11. The method of claim 8 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-trifluoromethyl-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

12. The method of claim 8 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-fluoro-10-(1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

13. The method of claim 8 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-methyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

14. The method of claim 8 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-isopropyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

15. A pharmaceutical formulation comprising as an active ingredient a chemotherapeutically effective amount of a thieno[2,3-b][1,5]benzodiazepine compound of the formula:

##STR33## 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 H(R⁴)₂ where R⁴ is C_1-4 alkyl;

wherein R⁶ is hydrogen, phenyl, halophenyl, C_1-4 alkyl, C_1-4 l 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 in the 2-position.

16. The formulation of claim 15 wherein the thieno[2,3-b]-[1,5]benzodiazepine is 2-ethyl-7fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

17. The formulation of claim 15 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-chloro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

18. The formulation of claim 15 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-trifluoromethyl-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.

19. The formulation of claim 15 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-ethyl-7-fluoro-10-(1-piperazinyl)-4H-thieno[2,3-b][1,5benzodiazepine.

20. The formulation of claim 15 wherein the thieno[2,3-b][1,5benzodiazepine is 2-methyl-7fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b[]1,5]benzodiazepine.

21. The formulation of claim 15 wherein the thieno[2,3-b][1,5]benzodiazepine is 2-isopropyl-7-fluoro-10-(4-methyl-1-piperazinyl)-4H-thieno[2,3-b][1,5]benzodiazepine.