Triazolopyridine derivatives as inhibitors of lipases and phospholipases

1. A compound of the formula I:

wherein:

X is identically or differently ═C(—R)— or ═N—, where only one X is ═N— and the remaining are ═C(—R)—;

W is —(C═O)—, —(S═O)— or —(SO 2 )—;

R is identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-alkyloxy -(C 1 -C 3 )-alkylene, hydroxy, phenoxy, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, cyano, nitro, COOR3, mono-(C 1 -C 6 )-alkylaminocarbonyl, di(C 2 -C 8 )-alkylaminocarbonyl, (C 1 -C 6 )-alkylmercapto, (C 1 -C 6 )-alkylsulfinyl, (C 1 -C 6 )-alkylsulfonyl, aminosulfonyl, pentafluorosulfanyl, aryl, heteroaryl, (C 3 -C 12 )-cycloalkyl, (C 1 -C 6 )-alkylcarbonyl, O—CO—NR3R3a, O—CO—(C 1 -C 6 )-alkylene-CO—O—(C 1 -C 6 )-alkyl, O—CO—(C 1 -C 6 )-alkylene-CO—OH, O—CO—(C 1 -C 6 )-alkylene-CO—NR3R3a or unsubstituted or mono- or poly-F-substituted (C 1 -C 6 )-alkyloxy;

R1 is (C 5 -C 16 )-alkyl, (C 5 -C 12 )-cycloalkyl, Y-aryl, Y-heteroaryl, Y—(C 5 -C 12 )-cycloalkyl, or bicycle, where aryl, heteroaryl, cycloalkyl or bicycle are optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 1 -C 6 )-alkylaminocarbonyl, (C 1 -C 6 )-alkyloxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl, aminosulfonyl;

Y is (C 1 -C 3 )-alkylene which is optionally substituted one or more times by halogen, (C 1 -C 2 )-alkyl or hydroxy;

R2 is hydrogen or (C 4 -C 12 )-alkyl; or

R1 and R2 together with the nitrogen atom carrying them form a monocyclic, saturated or partly unsaturated 4- to 7-membered ring system or a bicyclic saturated or partly unsaturated 8- to 14 membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the series —CHR4-, , —CR4R5-, ═(C—R4)-, —NR5-, —C(═O)—, —O—, —S—, —SO—or —SO 2 —, with the proviso that two units from the series —O—, —S—, —SO— or —SO 2 — are not adjacent to each other;

R3, R3a are identically or differently hydrogen, (C 1 -C 6 )-alkyl or benzyl; and

R4, R5 are identically or differently (C 1 -C 12 )-alkyl, (C 1 -C 6 )-alkyloxy, halogen, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-haloalkyloxy, COOR3, nitro, cyano, aryl, heterocycle, (C 3 -C 12 ) -cycloalkyl, (C 1 -C 3 )-alkylene -aryl, (C 1 -C 3 )-alkylene-heterocycle or (C 1 -C 3 )-alkylene-cycloalkyl, where aryl, heterocycle or cycloalkyl are optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, O—(C 1 -C 3 )-alkylene-aryl, trifluoromethyl, trifluoromethoxy, hydroxy, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, CO—(C1-06)-alkyl, CO—O—(C 1 -C 6 )-alkyl or NR3R3a; or

a tautomer thereof or a physiologically tolerated salt thereof,

with the proviso that the compound with the meanings of X in position 4, 5 and 6=C(—R)— and in position 7=N—, W is —(C═O)—, R is H and R1 and R2 form a morpholine, is excluded; and

with the proviso that the compounds with the meanings of X in position 4 and 6=C(—R)—, and in position 5 and 7=N—, W is —(C═O)—, and R is aryl, heteroaryl or phenoxy, are excluded.

2. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R)— or ═N—, where one X is ═N—; and

W is —(C═O)—.

3. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R)— or ═N—, where one X is ═N—;

W is —(C═O)—;

R is identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, (C 1 -C 3 )-alkyloxy -(C 1 -C 3 )-alkylene, hydroxy, phenoxy, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, cyano, nitro, COOR3, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkyl-aminocarbonyl, (C 1 -C 6 )-alkylsulfonyl, aminosulfonyl, pentafluorosulfanyl, phenyl,(C 1 -C 6 )-alkylcarbonyl, O—CO—NR3R3a, O—CO—(C 1 -C 6 )-alkylene-CO—O—(C 1 -C 6 )-alkyl, O—CO—(C 1 -C 6 )-alkylene-CO—OH, O—CO—(C 1 -C 6 )-alkylene-CO—NR3R3a or unsubstituted or mono- or poly-F-substituted (C 1 -C 6 )-alkyloxy;

R1 is (C 6 -C 12 )-alkyl, (C 5 -C 12 )-cycloalkyl, Y-phenyl, Y-heteroaryl or bicycle, where phenyl, heteroaryl, cycloalkyl or bicycle are optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkylmercapto, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, (C 1 -C 6 )-alkyloxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl;

Y is —CH 2 —, which is optionally substituted once by fluorine, methyl or hydroxy;

R2 is hydrogen or (C 5 -C 10 )-alkyl; or

R1 and R2 together with the nitrogen atom carrying them form a monocyclic, saturated or partly unsaturated 5- to 6-membered ring system or a bicyclic saturated or partly unsaturated 9- to 10-membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the series —CHR4—, —CR4R5-, ═(C—R4)-, —NR5-, —C(═O)—, —O—, —S— or —SO 2 —, with the proviso that two units from the series —O—, —S— or —SO 2 — are not adjacent to each other;

R3, R3a are identically or differently hydrogen, (C 1 -C 6 )-alkyl or benzyl; and

R4, R5 are identically or differently (C 1 -C 10 )-alkyl, (C 1 -C 6 )-alkyloxy, halogen, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-haloalkyloxy, COOR3, nitro, cyano, aryl, heterocycle, (C 3 -C 7 )-cycloalkyl, (C 1 -C 3 )-alkylene -aryl, or (C 1 -C 3 )-alkylene-heteroaryl, where aryl, heterocycle or cycloalkyl are optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, O—(C 1 -C 3 )-alkylene-aryl, trifluoromethyl, trifluoromethoxy, hydroxy, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, CO—(C 1 -C 6 )-alkyl, CO—O—(C 1 -C 6 )-alkyl or NR3R3a; or

a tautomer thereof or a physiologically tolerated salt thereof.

4. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R)— or ═N—, where one X is ═N—;

W is —(C═O)—;

R is identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxy, amino, cyano, COOR3, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, (C 1 -C 6 )-alkylsulfonyl, aminosulfonyl, pentafluorosulfanyl, (C 1 -C 6 )-alkylcarbonyl, O—CO—NR3R3a, O—CO—(C 1 -C 6 )-alkylene-CO—O—(C 1 -C 6 )-alkyl or unsubstituted or mono- or poly-F-substituted (C 1 -C 6 )-alkyloxy;

R1 is (C 6 -C 12 )-alkyl, Y-phenyl, Y-heteroaryl or bicycle, where aryl, heteroaryl or bicycle are optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, amino, (C 1 -C 6 )-alkylamino, di-(C 2 -C 12 )-alkylamino, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, (C 1 -C 6 )-alkyloxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl;

Y is —CH 2 —;

R2 is hydrogen or (C 5 -C 10 )-alkyl; or

R1 and R2 together with the nitrogen atom carrying them form a monocyclic, saturated or partly unsaturated 5- to 6-membered ring system or a bicyclic saturated or partly unsaturated 9- to 10-membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the series —CHR4-, —CR4R5-, ═(C—R4)-, —NR5-, —C(═O)—, —O— or —S—, with the proviso that two units from the series —O— or —S—, are not adjacent to each other;

R3, R3a are identically or differently hydrogen, (C 1 -C 6 )-alkyl or benzyl; and

R4, R5 are identically or differently (C 1 -C 10 )-alkyl, (C 1 -C 6 )-alkyloxy, halogen, (C 1 -C 3 )-haloalkyl, (C 1 -C 3 )-haloalkyloxy, COOR3, nitro, cyano, aryl, heteroaryl, (C 3 -C 7 )-cycloalkyl, (C 1 -C 3 )-alkylene-aryl or (C 1 -C 3 )-alkylene-heteroaryl, where aryl, heteroaryl or cycloalkyl are optionally substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, O—(C 1 -C 3 )-alkylene-aryl, trifluoromethyl, trifluoromethoxy, hydroxy, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, CO—(C 1 -C 6 )-alkyl, CO—O—(C 1 -C 6 )-alkyl or amino; or

a tautomer thereof or a physiologically tolerated salt thereof.

5. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R)— or ═N, where one X is ═N—;

W is —(C═O)—;

R is identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxy, amino, cyano, COOR3, (C 1 -C 6 )-alkylsulfonyl, aminosulfonyl, (C 1 -C 6 )-alkylcarbonyl or unsubstituted or mono- or poly-F-substituted (C 1 -C 6 )-alkyloxy;

R1 is (C 6 -C 12 )-alkyl or Y-phenyl, where phenyl may be substituted one to three times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, amino, (C 1 -C 6 )-alkyloxycarbonyl, (C 1 —C 6 )-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl, aminosulfonyl;

Y is —CH 2 —;

R2 is hydrogen or (C 5 -C 10 )-alkyl; or

R1 and R2 together with the nitrogen atom carrying them may form a monocyclic, saturated 5- to 6-membered ring system or a bicyclic saturated or partly unsaturated 9- to 10-membered ring system whose individual members of the ring systems may be replaced by one to three atoms or atomic groups from the series —CHR4-, —CR4R5-, ═(C—R4)-, —NR5-, —C(═O)—, —O— or —S—, with the proviso that two units from the series —O— or —S— may not be adjacent;

R3, R3a are identically or differently hydrogen or (C 1 -C 6 )-alkyl; and

R4, R5 are identically or differently (C 1 -C 10 )-alkyl, (C 1 -C 6 )-alkyloxy, halogen, trifluoromethyl, trifluoromethoxy, COOR3, cyano, aryl, cyclopropyl or (C 1 -C 3 )-alkylene-phenyl, where aryl may be substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, O—(C 1 —C 3 )-alkylene-phenyl, trifluoromethyl, trifluoromethoxy, hydroxy, mono-(C 1 -C 6 )-alkylaminocarbonyl, di-(C 2 -C 8 )-alkylaminocarbonyl, CO—(C 1 -C 6 )-alkyl or CO—O—(C 1 -C 6 )-alkyl, amino; or

a tautomer thereof or a physiologically tolerated salt thereof.

6. The compound of the formula I as claimed in claim 1 , wherein:

NR1R1 2 is a monocyclic saturated 5- to 6-membered ring system which comprises in position 4 an atom or atomic member from the series —CHR4-, —CR4R5-, —NR5-, —(C═O) or is a bicyclic saturated or partly unsaturated 9- to 10-membered ring system whose individual members of the ring system may be replaced by one or two atomic groups from the series —CHR4-, —(C═R4)-, ═(C—R4)-, —NR5- or —(C═O).

7. The compound of the formula I as claimed in claim 1 , wherein:

R1 and R1 2 together with the nitrogen atom carrying them form a monocyclic, saturated 5- to 6-membered ring system or a bicyclic saturated or partly unsaturated 9- to 10-membered ring system, whose individual members of the ring systems may be replaced by an atomic group from the series —CHR4- or —NR5.

8. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R)— or ═N—, where one X is ═N—;

R is identically or differently hydrogen or Cl;

NR1R2 is piperidine which comprises in position 4 the atomic member —CHR4-; or is piperazine which comprises in position 4 the atomic member —NR5; and

R4, R5 are (C 1 -C 8 )-alkyl, phenyl, —(C 1 -C 2 )-alkylene-phenyl, naphthyl, pyrrolidin-2-one or benzofuranyl, where phenyl may be substituted once, twice or three times by methyl, ethyl, t-butyl, methoxy, ethoxy, F, Cl, Br, OH, CF 3 , NH 2 , CO—OCH 3 , CO—CH 3 , phenyl or —O-benzyl.

9. The compound of the formula I as claimed in claim 1 , wherein:

NR1R2 is piperidine which comprises in position 4 the atomic member —CHR4-, or is piperazine which comprises in position 4 the atomic member —NR5; and

R4, R5 are methyl or phenyl which may be substituted once or twice by methyl, methoxy, ethoxy, F, Cl, Br, OH, CF 3 , NH 2 , CO—OCH 3 , CO—CH 3 , phenyl or —O-benzyl.

10. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R—)— or ═N—, where one X is ═N—;

R is identically or differently hydrogen or Cl;

NR1R1 2 is tetrahydroquinoline or tetrahydroisoquinoline which may be substituted once or twice by methoxy.

11. The compound of the formula I as claimed in claim 1 , wherein:

R2 is hydrogen.

12. The compound of the formula I as claimed in claim 1 , wherein:

R1 is (C 6 l-C 12 )-alkyl or Y-phenyl, where phenyl may be substituted one to three times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, amino, (C 1 -C 6 )-alkyloxycarbonyl, (C 1 —C 6 )-alkylcarbonyl, cyano, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl;

Y is —CH 2 —; and

R2 is hydrogen.

13. The compound of the formula I as claimed in claim 1 , wherein:

X is identically or differently ═C(—R)— or ═N—, where one X is ═N—;

R is identically or differently hydrogen or Cl;

R1 is hexyl or Y-phenyl, where phenyl is optionally substituted by methyl;

Y is —CH 2 —; and

R2 is hydrogen.

14. The compound of the formula I as claimed in claim 1 , wherein:

X in position 4, 5 and 6 is identically or differently ═C(—R)—, and in position 7 is ═N—.

15. The compound of the formula I, as claimed in claim 1 , wherein:

X optionally in position 4 or 7 is ═C(—R)— with R=hydrogen or ═N—, and in position 5 or 6 is ═C(—R)— wherein R is not hydrogen.

16. A pharmaceutical composition comprising one or more compounds of the formula I as claimed in claim 1 or a tautomer thereof or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.

17. A method for the treatment of disorders in which insulin resistance is involved comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of the formula I as claimed in claim 1 or a pharmaceutically acceptable salt thereof.

18. A method for the treatment of diabetes mellitus comprising administering to a patient in need of said treatment a therapeutically effective amount of a compound of the formula I as claimed in claim 1 or a pharmaceutically acceptable salt thereof.

19. A process for producing a medicament comprising one or more of the compounds of the formula I as claimed in claim 1 , which comprises mixing said compounds with a pharmaceutically suitable carrier to form a mixture and converting said mixture into a form suitable for administration.