Carbamoylbenzotriazole derivatives as inhibitors of lipases and phospholipases

1. A compound of the formula I

wherein:

W is —(C═O)—, —SO— or —SO 2 —;

R1 is X-aryl, X-heteroaryl, X—(C 5 -C 12 )-cycloalkyl or (C 8 -C 14 ) -bicycle, where aryl, heteroaryl, cycloalkyl or bicycle may be 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 ) -alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl, or aminosulfonyl, and may be substituted once by Y-aryl, Y-heteroaryl or Y—(C 3 -C 12 )-cycloalkyl, in which aryl, heteroaryl or cycloalkyl may be substituted one to three 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 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 ) -alkylsulfonyl or aminosulfonyl;

X is CH 2 , which may be substituted once by halogen, methyl or hydroxy;

Y is a bond, (C 1 -C 3 )-alkylene, —O— or —NH—;

R2, R3, R4, R5 are 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, NR6R7, cyano, nitro, COOR6, CO—NR6R7, —S—R6, —SO—R6, —SO 2 —R6, aminosulfonyl, pentafluorosulfanyl, aryl, heteroaryl, O-heteroaryl, (C 3 -C 12 ) -cycloalkyl, CO—R6, CO—NR6R7, O—CO—NR6R7, O—CO—(C 1 -C 6 )-alkylene-CO—O—(C1-C 6 )-alkyl, O—CO—(C 1 -C 6 )-alkylene-CO—OH, O—CO—(C 1 -C 6 )-alkylene -CO—NR6R7 or unsubstituted or mono- or poly-F-substituted (C 1 -C 6 )-alkyloxy; and

R6, R7 are identically or differently hydrogen, (C 1 -C 6 )-alkyl or benzyl; or

a tautomer thereof or a physiologically tolerated salt thereof.

2. The compound of the formula I as claimed in claim 1 , wherein W is —(C═O)—.

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

W is —(C═O)—;

R1 is X-aryl, X-heteroaryl or (C 8 -C 14 )-bicycle, where aryl, heteroaryl, cycloalkyl or bicycle may be 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 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 ) -alkylsulfonyl, or aminosulfonyl, and may be substituted once by Y-aryl, Y-heteroaryl, or Y—(C 3 -C 12 )-cycloalkyl, in which aryl, heteroaryl or cycloalkyl may be substituted once or twice 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, (C 1 -C 6 ) -alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, or trifluoromethyloxy;

X is —CH 2 —, which may be substituted once by halogen, methyl or hydroxy;

Y is a bond, —O— or —NH—; and

R2, R3, R4, R5 are identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxy, amino, cyano, phenoxy, (C 1 -C 6 )-alkylcarbonyl, (C 1 -C 6 ) -alkylsulfonyl, pentafluorosulfanyl, or unsubstituted or mono- or poly-F-substituted (C 1 -C 3 )-alkyloxy; or

a tautomer thereof or a physiologically tolerated salt thereof.

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

W is —(C═O)—;

R1 is X-phenyl, X-heteroaryl, or bicycle, where aryl, heteroaryl or bicycle may be substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl, and may be substituted once by Y-phenyl or Y-heteroaryl, in which phenyl or heteroaryl may be substituted once or twice by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 ) -alkyloxy, hydroxy, amino, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 ) -alkylcarbonyl, cyano, trifluoromethyl or trifluoromethyloxy;

X is —CH 2 —, which may be substituted by fluorine, methyl or hydroxy;

Y is a bond; and

R2, R3, R4, R5 are identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxy, amino, cyano, phenoxy, (C 1 -C 6 )-alkylcarbonyl or unsubstituted or mono- or poly-F-substituted (C 1 -C 3 )-alkyloxy; or

a tautomer thereof or a physiologically tolerated salt thereof.

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

W is —(C═O)—;

R1 is X-phenyl, X-heteroaryl, or bicycle of the formula Ia

 wherein n=1 or 2, where phenyl, heteroaryl or bicycle of the formula Ia may be substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C1-C6)-alkyloxy, hydroxy, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl, and may be substituted once by Y-phenyl or Y-heteroaryl, in which phenyl or heteroaryl may be substituted once or twice by halogen, (C 1 -C 6 ) -alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, amino, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 ) -alkylcarbonyl, cyano, trifluoromethyl or trifluoromethyloxy;

X is —CH 2 —, which may be substituted by fluorine, methyl or hydroxy;

Y is a bond; and

R2, R3, R4, R5 are identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxy, amino, cyano, phenoxy, (C 1 -C 6 )-alkylcarbonyl or unsubstituted or mono- or poly-F-substituted (C 1 -C 3 )-alkyloxy; or

a tautomer thereof or a physiologically tolerated salt thereof.

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

W is —(C═O)—;

R1 is X-phenyl, X-heteroaryl, or bicycle of the formula Ia

 wherein n=1 or 2, where phenyl, heteroaryl or bicycle of the formula Ia may be substituted one or more times by halogen, (C 1 -C 6 )-alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 )-alkylcarbonyl, cyano, nitro, trifluoromethyl, trifluoromethyloxy, (C 1 -C 6 )-alkylsulfonyl or aminosulfonyl, and may be substituted once by Y-phenyl or Y-heteroaryl, in which phenyl or heteroaryl may be substituted once or twice by halogen, (C 1 -C 6 ) -alkyl, (C 1 -C 6 )-alkyloxy, hydroxy, amino, (C 1 -C 6 )-alkoxycarbonyl, (C 1 -C 6 ) -alkylcarbonyl, cyano, trifluoromethyl or trifluoromethyloxy;

X is —CH 2 — which may be substituted by methyl;

Y is a bond;

R2, R3, R4, R5 are identically or differently hydrogen, halogen, (C 1 -C 6 )-alkyl, trifluoromethyl, hydroxy, amino, cyano, phenoxy, (C 1 -C 6 )-alkylcarbonyl or unsubstituted or mono- or poly-F-substituted (C 1 -C 3 )-alkyloxy.

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

W is —(C═O)—;

R1 is X-phenyl, X-thienyl, X-furan, X-benzothienyl, indanyl or tetrahydronaphthyl, where phenyl, thienyl, furan, benzothienyl, indanyl or tetrahydronaphthyl may be substituted once, twice or three times by F, Cl, Br, methyl, ethyl, isopropyl, methoxy, ethoxy, hydroxy, CO—OCH 3 , CO—CH 3 , cyano, nitro, trifluoromethyl or trifluoromethyloxy and may be substituted once by Y-phenyl, Y-thienyl, Y-pyridyl or Y-pyrazolyl, in which phenyl, thienyl, pyridyl or pyrazolyl may be substituted once or twice by F, Cl, Br, methyl, methoxy, hydroxy, amino, CO—OCH 3 , CO—CH 3 , cyano, trifluoromethyl or trifluoromethyloxy;

X is —CH 2 — which may be substituted by methyl;

Y is a bond;

R2, R3, R4, R5 are identically or differently hydrogen, F, Cl, methoxy, trifluoromethyl, cyano or phenoxy.

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

W is —(C═O)—;

R1 is X-phenyl, X-thienyl, X-furan, X-benzothienyl or indanyl, where phenyl, thienyl, X-furan, X-benzothienyl may be substituted once or twice by F, Cl, Br, methyl, isopropyl, methoxy, cyano or trifluoromethyl and may be substituted once by Y-phenyl, Y-thienyl, Y-pyridyl or Y-pyrazolyl, in which phenyl may be substituted by Cl;

X is —CH 2 —, which may be substituted by methyl;

Y is a bond;

R2 is hydrogen, F or Cl;

R3 is hydrogen, F, Cl, methoxy, trifluoromethyl, cyano or phenoxy;

R4 is hydrogen, F, Cl, methoxy, trifluoromethyl, cyano or phenoxy;

R5 is hydrogen, F or Cl.

9. The compound of the formula I as claimed in claim 1 , wherein R2, R3, R4, R5 are hydrogen.

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

R2, R3, R5 are hydrogen;

and

R4 is not hydrogen; or

R2, R4, R5 are hydrogen;

and

R3 is not hydrogen.

11. 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.