Claims
- 1. A compound of formula I ##STR5## wherein R.sup.1 and R.sup.2 are independently hydrogen, trifluoromethyl or halogen;
- R.sup.3 is trifluoromethyl, methoxy or halogen;
- R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl; or R.sup.4 is C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl or C.sub.3-8 -cycloalkyl optionally substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl; or R.sup.4 is Y--R.sup.5, wherein Y is --O--or --N(R.sup.6)--;
- R.sup.5 and R.sup.6 are independently straight or branched C.sub.1-12 -alkyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl or C.sub.3-8 -cycloalkyl optionally substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, heteroaryl, heteroarylalkyl, aryloxy or aryl, wherein the aryl or heteroaryl is optionally substituted with halogen or trifluoromethyl; or R.sup.5 and R.sup.6 together with the nitrogen atom form a 3-12 membered mono- or bicyclic system, in which one or more of the carbon atoms may be substituted with nitrogen, oxygen or sulfur, wherein each of these ring systems is optionally mono- or polysubstituted with halogen. C.sub.1-6 -alkyl, hydroxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkoxy-C.sub.1-6 -alkyl, nitro, amino, cyano, trifluoromethyl, C.sub.1-6 -monoalkyl- or dialkylamino or oxo;
- X is N--CN;
- or a pharmaceutically acceptable salt thereof, or an optical isomer or mixture of optical isomers thereof, or a tautomeric form thereof.
- 2. A compound of claim 1, wherein R.sup.1 is hydrogen, R.sup.2 is hydrogen or trifluoromethyl and R.sup.3 is trifluoromethyl.
- 3. A compound of claim 2, wherein R.sup.2 is hydrogen.
- 4. A compound of claim 2, wherein R.sup.2 is trifluoromethyl.
- 5. A compound of claim 1, wherein R.sup.1 is hydrogen and R.sup.2 and R.sup.3 are chloro.
- 6. A compound of claim 1, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl; or R.sup.4 is C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl or C.sub.3-8 -cycloalkyl optionally substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl.
- 7. A compound of claim 6, wherein the heteroarylalkyl is (2-furyl)methyl, (3-furyl)methyl, (2-thienyl)methyl, (3-thienyl)methyl, (2-pyridyl)methyl or 1-methyl-1-(2-pyrimidyl)ethyl.
- 8. A compound of claim 6, wherein the heteroaryl is 4-pyridinyl.
- 9. A compound of claim 6, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl.
- 10. A compound of claim 9, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl or aryl.
- 11. A compound of claim 10, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl, heteroaryl or aryl.
- 12. A compound of claim 11, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl.
- 13. A compound of claim 11, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with aryl or heteroaryl.
- 14. A compound of claim 6, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl or aryl.
- 15. A compound of claim 14, wherein R.sup.4 is straight or branched C.sub.1-12 -alkyl substituted with aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl or aryl.
- 16. A compound of claim 6, wherein R.sup.4 is C.sub.3-8 -cycloalkyl optionally substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl.
- 17. A compound of claim 16, wherein R.sup.4 is C.sub.3-8 -cycloalkyl substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, heteroarylalkyl or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl.
- 18. A compound of claim 19, wherein R.sup.4 is C.sub.3-8 -cycloalkyl substituted with C.sub.3-8 -cycloalkyl, aryloxy, arylalkoxy, C.sub.1-6 -alkoxy, C.sub.1-6 -alkylthio, arylthio, C.sub.1-6 -alkylamino, C.sub.1-6 -dialkylamino, heteroaryl, or aryl, wherein the heteroaryl is optionally substituted with halogen or trifluoromethyl.
- 19. A compound of claim 17, wherein R.sup.4 is C.sub.3-8 -cycloalkyl or straight or branched C.sub.1-12 -alkyl substituted with C.sub.3-8 -cycloalkyl.
- 20. A compound of claim 19, wherein R.sup.4 is cyclopentyl, 3-cyclopentylpropyl or 2-cyclopropylethyl.
- 21. A compound of claim 6, wherein R.sup.5 and R.sup.6 are independently straight or branched C.sub.1-12 -alkyl, C.sub.2-12 -alkenyl, C.sub.2-12 -alkynyl or C.sub.3-8 -cycloalkyl optionally substituted with C.sub.3-8 -cycloalkyl, halogen, hydroxy, heteroaryl, heteroarylalkyl, aryloxy or aryl.
- 22. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 together with one or more pharmaceutically acceptable carriers or diluents.
- 23. The pharmaceutical composition of claim 22 in the form of an oral dosage unit or parenteral dosage unit.
- 24. The pharmaceutical composition of claim 23 wherein the compound is administered as a dose in a range from about 0.05 to 1000 mg per day.
- 25. A method of treating or preventing diseases of the endocrinologic system comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.
- 26. A compound which is:
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(3-methylbutyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(1,2,2-trimethylpropyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(1,2-dimethylpropyl )guanidine,
- N-Cyano-N'-[3,5-bis(trifluoromethyl)phenyl]-N"-propyl-guanidine,
- N-Cyano-N'-[3,5-bis(trifluoromethyl)phenyl]-N"-(1,1-dimethylpropyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(1-methylethyl)-guanidine,
- N-Cyano-N'-(3-methoxy-5-trifluoromethylphenyl)-N"-(3-methylbutyl)guanidine;
- or a pharmaceutically acceptable salt thereof.
- 27. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 28 together with one or more pharmaceutically acceptable carriers or diluents.
- 28. The pharmaceutical composition of claim 29 in the form of an oral dosage unit or parenteral dosage unit.
- 29. The pharmaceutical composition of claim 28 wherein the compound is administered as a dose in a range from about 0.05 to 1000 mg per day.
- 30. A method of treating or preventing diseases of the endocrinologic system comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 26.
- 31. A compound which is:
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(2-chlorobenzyl )guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(3-chlorobenzyl)guanidine,
- N-Cyano-N'-(3,5-dichlorophenyl)-N"-(2-chlorobenzyl )guanidine,
- N-Cyano-N'-cyclopentyl-N"-(3,5-dichlorophenyl)guanidine,
- N-Cyano-N'-cyclopentyl-N"-(3-methyloxy-5-trifluoromethylphenyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(2-(4-pyridinyl)ethyl)guanidine;
- or a pharmaceutically acceptable salt thereof.
- 32. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 31 together with one or more pharmaceutically acceptable carriers or diluents.
- 33. The pharmaceutical composition of claim 32 in the form of an oral dosage unit or parenteral dosage unit.
- 34. The pharmaceutical composition of claim 33 wherein the compound is administered as a dose in a range from about 0.05 to 1000 mg per day.
- 35. A method of treating or preventing diseases of the endocrinologic system comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 31.
- 36. A compound which is:
- N-Cyano-N'-(3,5-dichlorophenyl)-N"-(3-cyclopentylpropyl)guanidine,
- N-Cyano-N'-(3,5-dichlorophenyl)-N"-(3-cyclopentyl)guanidine,
- N-Cyano-N'-(3,5-dichlorophenyl)-N"-(2-cyclopropylethyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(3-cyclopentylpropyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(2-cyclopropylethyl)guanidine,
- N-Cyano-N'-(3,5-bis(trifluoromethyl)phenyl)-N"-(cyclopentyl)guanidine,
- N-Cyano-N'-(3-trifluoromethylphenyl)-N"-cyclopentylguanidine;
- N-Cyano-N'-cyclopentyl-N"-(3-methyloxy-5-trifluoromethylphenyl)guanidine
- or a pharmaceutically acceptable salt thereof.
- 37. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 36 together with one or more pharmaceutically acceptable carriers or diluents.
- 38. The pharmaceutical composition of claim 37 in the form of an oral dosage unit or parenteral dosage unit.
- 39. The pharmaceutical composition of claim 38 wherein the compound is administered as a dose in a range from about 0.05 to 1000 mg per day.
- 40. A method of treating or preventing diseases of the endocrinologic system comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 36.
Priority Claims (1)
Number |
Date |
Country |
Kind |
00634/98 |
May 1998 |
DKX |
|
CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C. 119 of U.S. provisional application Ser. No. 60/085,885 filed May 18, 1998 and Danish application no. PA 1998 00634 filed May 11, 1998, the contents of which are fully incorporated herein by reference.
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