Piperazine-substituted pyrroloanthracenes

• US 5,409,932 A
• Filed: 12/09/1993
• Issued: 04/25/1995
• Est. Priority Date: 12/09/1993
• Status: Expired due to Fees

• Current Assignee: Bayer AG
• Original Assignee: Bayer AG
• Inventors: Ladouceur, Gaetan, Aune, Thomas M., Kabbe, Hans-Joachim, Schwenner, Eckhard
• Primary Examiner(s): TSANG, CECILIA J
• Application Number:
  US08/164,499
• Time in Patent Office: 502 Days
• Field of Search: 544/373, 514/253
• US Class Current: 514/254.08
• CPC Class Codes: C07D 209/58 [b]- or [c]-condensed

Abstract

The piperazine-substituted pyrroloanthracenes are prepared by reacting either furanoanthracenes with piperazinalkylamines or reacting unsubstituted pyrroloanthracenes first with dihalogenoalkyl compounds and then with appropriately substituted piperazines or by reacting furan derivatives first with piperazinalkylamines and then condensing with anthracenes. The new compounds can be employed as active ingredients in medicaments, in particular in immunomodulators.

Claims

1. A piperazine-substituted pyrroloanthracene of the formula (I) ##STR27## in which A and D are identical or different and represent hydrogen, hydroxyl, halogen, cyano, carboxyl, nitro, trifluoromethyl or trifluoromethyloxy, or represent straight-chain or branched alkyl or alkoxy in each case having up to 8 carbon atoms,

R¹ and R² are identical or different and represent hydrogen, halogen, cyano, formyl, phenyl or hydroxyl, or represent straight-chain or branched alkoxy having up to 8 carbon atoms, or represent straight-chain or branched alkyl or alkenyl in each case having up to 8 carbon atoms, each of which is optionally substituted up to 2 times by identical or different hydroxyl, nitro, phenyl or halogen, by straight-chain or branched alkoxy having up to 6 carbon atoms or by a group of the formula --NR³ R⁴,

in which

R³ and R⁴ are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 6 carbon atoms or phenyl,

E and L together form a heterocyclic radical of the formula ##STR28## in which R⁵ and R⁶ are identical or different and denote hydrogen, halogen, phenyl or straight-chain or branched alkyl having up to 8 carbon atoms, which is optionally substituted by carboxyl or by straight-chain or branched alkoxycarbonyl having up to 6 carbon atoms,

R⁷, R⁸, R⁹ and R¹⁰ are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 6 carbon atoms, or

R⁷ and R⁸ and/or R⁹ and R¹⁰ in each case together form the radical of the formula=O,

a denotes a number 0, 1, 2, 3, 4, 5 or 6,

R¹¹ denotes aryl having 6 to 10 carbon atoms, which is optionally substituted up to 3 times by identical or different halogen, hydroxyl, nitro, cyano, trifluoromethyl, trifluoromethoxy or by straight-chain or branched alkyl or alkoxy in each case having up to 8 carbon atoms,

or a pharmaceutically acceptable salt thereof.

2. A piperazine-substituted pyrroloanthracene or salt thereof as claimed in claim 1

in which

A and D are identical or different and represent hydrogen, hydroxyl, fluorine, chlorine, bromine, carboxyl, nitro, trifluoromethyl, trifluoromethoxy or represent straight-chain or branched alkyl or alkoxy in each case having up to 6 carbon atoms,

R¹ and R² are identical or different and represent hydrogen, fluorine, chlorine, bromine, cyano, formyl, phenyl or hydroxyl, or represent straight-chain or branched alkoxy having up to 6 carbon atoms, or represent straight-chain or branched alkyl or alkenyl in each case having up to 6 carbon atoms, each of which is optionally substituted up to 2 times by identical or different hydroxyl, nitro, phenyl, fluorine, chlorine or bromine, by straight-chain or branched alkoxy having up to 4 carbon atoms or by a group of the formula --NR³ R⁴,

in which

R³ and R⁴ are identical or different and denote hydrogen, straight-chain or branched alkyl having up to 4 carbon atoms or phenyl,

E and L together form a heterocyclic radical of the formula ##STR29## in which R⁵ and R⁶ are identical or different and denote hydrogen, fluorine, chlorine, bromine, phenyl or straight-chain or branched alkyl having up to 6 carbon atoms, which is optionally substituted by carboxyl or by straight-chain or branched alkoxycarbonyl having up to 4 carbon atoms,

R⁷, R⁸, R⁹ and R¹⁰ are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 4 carbon atoms, or

R⁷ and R⁸ and/or R⁹ and R¹⁰ in each case together form the radical of the formula=O,

a denotes a number 0, 1, 2, 3, 4 or 5,

R¹¹ denotes phenyl which is optionally substituted up to 3 times by identical or different fluorine, chlorine, bromine, hydroxyl, nitro, cyano, trifluoromethyl or trifluoromethoxy or by straight-chain or branched alkyl or alkoxy in each case having up to 6 carbon atoms.

3. A piperazine-substituted pyrroloanthracene or salt thereof as claimed in claim 1

in which

A and D are identical or different and represent hydrogen, hydroxyl, fluorine, chlorine, bromine or straight-chain or branched alkyl having up to 4 carbon atoms,

R¹ and R² are identical or different and represent hydrogen, fluorine, chlorine, bromine, cyano, formyl, phenyl or hydroxyl, or represent straight-chain or branched alkoxy having up to 4 carbon atoms, or represent straight-chain or branched alkyl or alkenyl in each case having up to 4 carbon atoms, each of which is optionally substituted up to 2 times by identical or different hydroxyl, nitro, phenyl, fluorine, chlorine or bromine, by straight-chain or branched alkoxy having up to 3 carbon atoms or by amino or aminomethyl,

E and L together form a heterocyclic radical of the formula ##STR30## in which R⁵ and R⁶ are identical or different and denote hydrogen, fluorine, chlorine, bromine, phenyl or straight-chain or branched alkyl having up to 4 carbon atoms, which is optionally substituted by carboxyl or by straight-chain or branched alkoxycarbonyl having up to 3 carbon atoms,

R⁷, R⁸, R⁹ and R¹⁰ are identical or different and denote hydrogen or straight-chain or branched alkyl having up to 3 carbon atoms, or

R⁷ and R⁸ and/or R⁹ and R¹⁰ in each case together form the radical of the formula=O,

a denotes a number 0, 1, 2, 3 or 4,

R¹¹ denotes phenyl which is optionally substituted up to 3 times by identical or different fluorine, chlorine, bromine, hydroxyl, nitro, cyano, trifluoromethyl or trifluoromethoxy or by straight-chain or branched alkyl or alkoxy in each case having up to 4 carbon atoms.

4. A compound according to claim 1, wherein such compound is ##STR31## or a pharmaceutically acceptable salt thereof.

5. A compound according to claim 1, wherein such compound is ##STR32## or a pharmaceutically acceptable salt thereof.

6. A composition for the treatment of rheumatoid arthritis, inflammatory gastric diseases or inflammations of the gastrointestinal tract, comprising an amount effective therefor of a compound or salt thereof according to claim 1 and a pharmaceutically acceptable carrier.

7. A method of treating rheumatoid arthritis, inflammatory gastric diseases and inflammations of the gastrointestinal tract in a patient afflicted therewith which comprises administering to such patient an amount effective therefor of a compound or salt thereof according to claim 1.

8. The method according to claim 7, wherein such compound is ##STR33## or a pharmaceutically acceptable salt thereof.

9. The method according to claim 7, wherein the patient is afflicted with rheumatoid arthritis.

10. The method according to claim 7, wherein the patient is afflicted with inflammatory gastric diseases.

11. The method according to claim 7, wherein the patient is afflicted with inflammations of the gastrointestinal tract.