Heterocyclic compounds

• US 4,678,793 A
• Filed: 04/01/1985
• Issued: 07/07/1987
• Est. Priority Date: 05/12/1982
• Status: Expired due to Fees

• Current Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Original Assignee: Hoffmann-La Roche Incorporated (Roche Holding AG)
• Inventors: Klaus, Michael, Loeliger, Peter
• Primary Examiner(s): Raymond, Richard L.
• Application Number:
  US06/718,674
• Time in Patent Office: 827 Days
• Field of Search: 546/165, 546/166, 514/311
• US Class Current: 514/311
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07D 215/06 having only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to the ring nitrogen atom
• CPC Class Codes: C07D 215/12 with substituted hydrocarbon radicals attached to ring carbon atoms
• CPC Class Codes: C07D 215/14 Radicals substituted by oxygen atoms
• CPC Class Codes: C07D 311/04 Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
• CPC Class Codes: C07D 311/58 other than with oxygen or sulphur atoms in position 2 or 4
• CPC Class Codes: C07D 335/06 Benzothiopyrans; Hydrogenated benzothiopyrans
• CPC Class Codes: C07F 9/60 Quinoline or hydrogenated quinoline ring systems
• CPC Class Codes: C07F 9/65522 condensed with carbocyclic rings or carbocyclic ring systems
• CPC Class Codes: C07F 9/655372 condensed with carbocyclic rings or carbocyclic ring systems

Abstract

Novel p-[2(4,4-dimethyl-6-heterophenyl)substituted phenyl derivatives and salts thereof which are useful for combatting neoplasms and dermatoses including oral and topical compositions containing said derivatives which are suitable for such uses.

Claims

1. A compound of the formula:

##STR11## wherein X is ##STR12## R¹ is methyl, ##STR13## R² is hydrogen or lower alkyl;

R³ is hydrogen or methyl;

R⁴ is hydrogen, lower alkyl or alkanoyl;

R⁵ is hydrogen, lower alkyl, amino, lower alkylamino, di(lower alkyl)-amino or OR⁶ ; and

R⁶ is hydrogen or lower alkyl;

or pharmaceutically acceptable salts thereof.

2. The compound of claim 1 wherein R¹ is carboxyl, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl or di(lower-alkyl)carbamoyl.

3. The compound of claim 2 wherein R¹ is lower alkoxycarbonyl.

4. The compound of claim 3 wherein said compound is ethyl p-[(E)-2-(4,4-dimethyl-1,2,3,4-tetrahydro-6-quinolinyl)propenyl]benzoate.

5. The compound of claim 3 wherein said compound is ethyl p-[(E)-2-(1,4,4-trimethyl-1,2,3,4-tetrahydro-6-quinolinyl)propenyl]benzoate.

6. A method for combatting acne or psoriasis comprising administering to a patient an effective amount of a compound of the formula ##STR14## wherein X is ##STR15## R¹ is methyl, ##STR16## R² is hydrogen or lower alkyl;

R³ is hydrogen or methyl;

R⁴ is hydrogen, lower alkyl or alkanoyl;

R⁵ is hydrogen, lower alkyl, amino, lower alkylamino, di(lower-alkyl)amino or OR⁶ ; and

R⁶ is hydrogen or lower alkyl;

or pharmaceutically acceptable salts thereof.

7. The method of claim 6 wherein said compound is administered orally.

8. The method of claim 6 wherein said amount is from 1 to 100 mg per day.

9. The method of claim 6 wherein said compound is administered topically.

10. The method of claim 9 wherein said preparation contains said compound in an amount of from 0.1 to 5% based upon the weight of said composition.

11. A method for combatting neoplasms comprising administering to a patient in an effective amount of a compound of the formula:

##STR17## wherein X is ##STR18## R¹ is methyl, ##STR19## R² is hydrogen or lower alkyl;

R³ is hydrogen or methyl;

R⁴ is hydrogen, lower alkyl or lower alkanoyl;

R⁵ is hydrogen, lower alkyl, amino, alkylamino, di(lower-alkyl)amino or OR⁶ ; and

R⁶ is hydrogen or lower alkyl;

or pharmaceutically acceptable salts thereof.

12. The method of claim 11 wherein said amoutn is from 0.5 to 100 mg per day administered orally.

13. The method of claim 12 wherein said compound is administered orally.

14. A composition in oral unit dosage form comprising from about 0.5 to about 100 mg of a compound of the formula:

##STR20## wherein X is ##STR21## R¹ is methyl, ##STR22## R² is hydrogen or lower alkyl;

R³ is hydrogen or methyl;

R⁴ is hydrogen, lower alkyl or alkanoyl;

R⁵ is hydrogen, lower alkyl, amino, lower alkylamino, di(lower-alkyl)amino or OR⁶ ; and

R⁶ is hydrogen or lower alkyl;

and an inert pharmaceutically acceptable carrier.

15. The composition of claim 14 wherein said compound is present in an amount of from 5 to 30 mg.

17. The compound of claim 14 wherein said composition is in the form of a shampoo, cream, lotion or salve.

16. A composition for topical administration comprising a therapeutically inert pharmaceutically acceptable carrier and from about 0.1 to 5% by weight based upon the weight of the composition of a compound of the formula:

##STR23## wherein X is ##STR24## R¹ is methyl, ##STR25## R² is hydrogen or lower alkyl;

R³ is hydrogen or methyl;

R⁴ is hydrogen, lower alkyl or alkanoyl;

R⁵ is hydrogen, lower alkyl, amino, lower alkylamino, di(lower-alkyl)amino or OR⁶ ; and

R⁶ is hydrogen or lower alkyl;

or pharmaceutically acceptable salts thereof.