Claims
- 1. A compound of formula I ##STR88## wherein R1 is an unsaturated straight or branched C.sub.2-8 -hydrocarbon chain optionally substituted with one or more substituents,
- a saturated C.sub.3-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- an unsaturated C.sub.5-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- Q optionally substituted with one or more substituents or
- aryl optionally substituted with one or more substituents;
- R2 is a saturated C.sub.3-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- an unsaturated C.sub.5-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- aralkyl optionally substituted with one or more substituents or
- COR3 optionally substituted with one or more substituents;
- with the proviso that when R1 is aryl optionally substituted with one or more substituents R2 may not be aralkyl optionally substituted with one or more substituents;
- R3 is a saturated straight or branched C.sub.1-8 -hydrocarbon chain optionally substituted with one or more substituents,
- an unsaturated straight or branched C.sub.2-8 -hydrocarbon chain optionally substituted with one or more substituents,
- a saturated C.sub.3-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- an unsaturated C.sub.5-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- an aryl optionally substituted with one or more substituents,
- an aralkyl optionally substituted with one or more substituents or
- W optionally substituted with one or more substituents;
- Q and W are independently selected from the group consisting of ##STR89## X and Y are independently selected from the group consisting of NR4, O, S, >SO and >SO.sub.2 ;
- and R4 is selected from the group consisting of hydrogen,
- a saturated straight or branched C.sub.1-8 -hydrocarbon chain optionally substituted with one or more substituents,
- an unsaturated straight or branched C.sub.2-8 -hydrocarbon chain optionally substituted with one or more substituents,
- a saturated C.sub.3-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- an unsaturated C.sub.5-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents,
- C.sub.1-8 -acyl, C.sub.1-8 -alkoxycarbonyl, or mono- or dialkylcarbamoyl;
- R5, R6 and R7 are independently selected from amino-C.sub.1-6 -alkyl, hydroxy-C.sub.1-6 -alkyl, hydrogen, C.sub.1-6 -alkyl, aryl, aralkyl, aryloxy, aryloxy-C.sub.1-6 -alkyl, benzyl, halogen, hydroxy, mercapto, cyano, nitro, carboxy, carbamoyl, CONHC.sub.1-4 -alkyl, CON(C.sub.1-4 alkyl).sub.2, C.sub.1-4 -acyl, C.sub.1-4 -alkoxy, C.sub.1-4 -alkylthio, --SOC.sub.1-6 -alkyl, --SO.sub.2 C.sub.1-6 -alkyl, C.sub.1-4 -alkoxycarbonyl, C.sub.1-4 -alkanoyloxy, amino, optionally substituted mono- or di-C.sub.1-6 -alkylamino, acylamino, --NC.sub.1-4 -alkylCOC.sub.1-4 -alkyl, --SO3H, --SO2NH-C.sub.1-6 -alkyl, tetrazolyl, perhalomethyl, and perhalomethoxy,
- each of the above substituents being selected from the group consisting of halogen, hydroxyl, carboxy, carboxyalkenyl, 2-carboxyethenyl, cyano, nitro, carbamoyl, C.sub.1-8 -alkylcarbamoyl, C.sub.1-8 -acyl, acetamido, C.sub.1-8 -alkoxy, C.sub.1-8 -alkyl, C.sub.1-8 -alkoxycarbonyl, C.sub.1-8 -alkanoyloxy, C.sub.1-4 -alkylthio, C.sub.1-4 -alkylsulphinyl, C.sub.1-4 -alkylsulphonyl, C.sub.1-8 -alkylamino, C.sub.1-8 -dialkylamino, C.sub.2-6 -cycloamines, aminoalkyl, aminoalkoxy, aryl, aryloxy, aralkyloxy, hydroxyalkyl, perhaloalkoxy, alkoxyaryl, perhaloalkyl, oxo, C.sub.1-4 -alkanoylamino-C.sub.1-4 -alkyl, alkoxyoxoindanyl, dimethylhydrazidyl, methylendioxy, thioxothiazolyl, imidazolyl and 2-morpholin-4-ylethoxy;
- or a salt thereof with a pharmaceutically acceptable acid or base, or any optical isomer or mixture of optical isomers or any tautomeric form.
- 2. A compound of claim 1, wherein R5, R6 and R7 are hydrogen.
- 3. A compound of claim 1, wherein R2 is COR3.
- 4. A compound of claim 1 wherein R1 is Q optionally substituted with one or more substituents and Q is ##STR90##
- 5. A compound of claim 4 wherein X is NR4 or O.
- 6. A compound of claim 1 wherein R1 is Q optionally substituted with one or more substituents and Q is
- 7. A compound of claim 6 wherein X is O.
- 8. A compound of claim 1 wherein R3 is a saturated straight or branched C.sub.1-8 -hydrocarbon chain optionally substituted with one or more substituents.
- 9. A compound of claim 1 wherein R3 is an unsaturated straight or branched C.sub.2-8 -hydrocarbon chain optionally substituted with one or more substituents.
- 10. A compound of claim 1 wherein R3 is a saturated C.sub.3-8 -alicyclic hydrocarbon group optionally substituted with one or more substituents.
- 11. A compound of claim 1 wherein R3 is an aryl optionally substituted with one or more substituents.
- 12. A compound of claim 1 wherein R3 is W optionally substituted with one or more substituents.
- 13. A compound of claim 12 wherein W is
- 14. A compound of claim 13 wherein X is NR4.
- 15. A pharmaceutical composition comprising, as an active ingredient, a therapeutically effective amount of a compound of claim 1, together with a pharmaceutically acceptable carrier or diluent.
- 16. The pharmaceutical composition of claim 15 in the form of an oral dosage unit or a parenteral dosage unit.
- 17. A compound of claim 1 characterized by having a glucose-6-phosphatase inhibitory activity corresponding to an IC.sub.50 value of less than 100 .mu.M.
- 18. 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.
- 19. A method of treating or preventing hyperglycemia or diabetes in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of claim 1.
- 20. A compound of claim 1 wherein R1 is N-methylpiperidinyl, tetrahydrofuryl or tetrahydropyranyl.
- 21. A compound of claim 1 wherein R1 is optionally substituted phenyl, thienyl, furanyl, Benzo[1,3]dioxol, pyridyl or cyclohexyl.
- 22. A compound of claim 21 wherein the substituents of R1 are selected from the group consisting of halogen, perhaloalkyl, perhaloalkoxy, C.sub.1-6 -alkoxy, C.sub.1-8 -alkyl, C.sub.1-8 -alkylamino, C.sub.1-8 -dialkylamino and C.sub.2-5 -cycloalkylamino.
- 23. A compound of claim 1 wherein R1 is selected from the group consisting of phenyl, 4-chlorophenyl, 3-fluorophenyl, 2,4-chlorophenyl, 3,5-chlorophenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2,4-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 4-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-dimethylaminophenyl, 4-pyridyl, 2-thienyl, 5-chloro-2-thienyl, 3-chloro-2-thienyl, Benzo[1,3]dioxol-5yl, cyclohexyl and 4-methoxycyclohexyl.
- 24. A compound of claim 1 wherein R3 is cyclohexyl, phenyl, alkoxyphenyl, dialkoxyphenyl, hydroxyphenyl, indanyl, imidazolyl, pyridyl, benzofuranyl, indolyl, benzimidazolyl, thienyl, furanyl, or pyranyl, each of which is optionally substituted with one or more substituents.
- 25. A compound of claim 14 wherein R4 is methyl or methanoyl.
- 26. A compound of claim 1 wherein R2 is COR3 and R3 is selected from the group consisting of phenyl, 3-methoxyphenyl, 4-methoxyphenyl 4-chlorophenyl, 4-trifluoromethylphenyl, 4-methylphenyl, 3,4-dimethoxyphenyl, 4-ethoxyphenyl, 4-fluorophenyl, 4-trifluoromethoxyphenyl, 4-dimethylaminophenyl, 4-bromophenyl, 4-hydroxyphenyl, 4-hydroxymethylphenyl, 4-nitrophenyl, 4-cyanophenyl, 4-methylthiophenyl, 4-methylsulfonylphenyl, 4-acetylphenyl, 4-acetamidophenyl, 4-acetoxyphenyl, 3,4-methylenedioxyphenyl, 3,4-dimethoxyphenyl, 3-chloro-4-methoxyphenyl, indolyl, 1H-indol-5-yl, and 1H-benzimidazol-5-yl, 2-(4-methoxyphenyl)-ethenyl, 2-(3-methoxyphenyl)-ethenyl, 2-(4-chlorophenyl)-ethenyl, 2-(4-fluorophenyl)-ethenyl, 2-(4-trifluoromethylphenyl)-ethenyl, 2-(4-methoxyphenyl)-ethyl, 2-(4-chlorophenyl)-ethyl, 4-chlorobenzyl, 4-methoxybenzyl, 2-(2-furyl)-ethenyl, 2-(4,5-dimethyl-2-furyl)-ethenyl, 2-(5-methyl-2-furyl)-ethenyl, 2-(3-furyl)-ethenyl, 2-(2-thienyl)-ethenyl, 2-(3-thienyl)-ethenyl, 4-methoxyphenyl-2-ethenyl, 4-pyridyl, 5-hydroxypyrazin-2-yl, 5-chloro-6-hydroxypyridin-3-yl, 2-chloropyridin-3-yl, benzofuran-2-yl, benzothiophen-2-yl-, 7-methoxybenzofuran-2-yl, furyl, thienyl, chlorothienyl, 5-chlorothiophen-2-yl, benzimidazol, 1 H-benzimidazol-5-yl, 4-methoxycyclohexyl, 4-oxycyclohexyl, N-methylpiperidinyl, tetrahydrofuryl, tetrahydropyranyl, 4-(2-carboxyethenyl)phenyl, 4-(2-dimethylaminoethoxy)phenyl and 4-(2-morpholin-4-ylethoxy)phenyl.
Priority Claims (1)
Number |
Date |
Country |
Kind |
1998 01108 |
Sep 1998 |
DKX |
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CROSS-REFERENCE TO RELATED APPLICATIONS
This application claims priority under 35 U.S.C. 119 of U.S. provisional application Ser. No. 60/099,930 filed Sep. 11, 1998 and Danish application no. PA 1998 01108 filed Sep. 2, 1998, the contents of which are fully incorporated herein by reference.
US Referenced Citations (5)
Foreign Referenced Citations (3)
Number |
Date |
Country |
WO 9215592 |
Sep 1992 |
WOX |
WO 9634870 |
Nov 1996 |
WOX |
WO 9840385 |
Sep 1998 |
WOX |
Non-Patent Literature Citations (12)
Entry |
CA 112:158190, 1990. |
CA 111:39219, 1989. |
CA 85:160017, 1976. |
CA 79:49080, 1973. |
CA 72:100743, 1970. |
Gray et al, J. Med. Chem., 32, pp. 1242-1248, 1989. |
Dressler et al, J. Het. Chem., 7(6), pp. 1257-1268, 1970. |
Chem Abstract No. 99:175627 (1983). |
Chem Abstract No 111:39219 (1989). |
Chem Abstract No. 79:49080 (1973). |
Chem Abstract No. 114:122254 (1991). |
Chem Abstract No. 85:160017 (1976). |