Tricyclic compounds in treating hyperalgesic conditions and NIDDM
AssigneeNovo Nordisk A/S
InventorsPeter Madsen, Knud Erik Andersen, Rolf Hohlweg, Florenzio Zaragossa Dorwald, Tine Krogh J.o slashed.rgensen, Uffe Bang Olsen, Henrik Sune Andersen
Life of this patent
Estimating the term…
Abstract
The present invention relates to novel N-substituted amino acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.
Claims8
A compound of formula I ##STR12## wherein R.sup.1 and R.sup.2 independently are hydrogen, halogen, trifluoromethyl, hydroxy, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
- Y is >N--CH.sub.2 -- wherein only the underscored atom participates in the ring system;
- X is --CH.sub.2 CH.sub.2 --, --CH.sub.2 --(C.dbd.O)-- or --(C.dbd.O)--CH.sub.2 --;
- r is 1, 2 or 3;
- and
- Z is ##STR13## wherein n is 0 or 1;
- R.sup.3 is --(CH.sub.2).sub.m OH or --(CH.sub.2).sub.s COR.sup.4 wherein m is 0, 1, 2, 3, 4, 5 or 6, s is 0 or 1, and R.sup.4 is --OH, --NH.sub.2, --NHOH or C.sub.1-6 -alkoxy;
- R.sup.5 is hydrogen, halogen, trifluoromethyl, hydroxy, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
- R.sup.10 is hydrogen or C.sub.1-6 -alkyl;
- A is C.sub.1-6 -alkylene, C.sub.2-6 -alkenylene or C.sub.2-6 -alkynylene;
- or a pharmaceutically acceptable salt thereof.
A compound of formula I ##STR14## wherein R.sup.1 and R.sup.2 independently are hydrogen, halogen, trifluoromethyl, hydroxy, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
- Y is >N--CH.sub.2 -- wherein only the underscored atom participates in the ring system;
- X is --CH.dbd.CH--;
- r is 1, 2 or 3;
- and
- Z is ##STR15## wherein n is 0 or 1;
- R.sup.3 is --(CH.sub.2).sub.m OH or --(CH.sub.2).sub.s COR.sup.4 wherein m is 0, 1, 2, 3, 4, 5 or 6, s is 0 or 1, and R.sup.4 is --OH, --NH.sub.2, --NHOH or C.sub.1-6 -alkoxy;
- R.sup.5 is hydrogen, halogen, trifluoromethyl, hydroxy, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
- R.sup.10 is hydrogen or C.sub.1-6 -alkyl;
- A is C.sub.1-6 -alkylene, C.sub.2-6 -alkenylene or C.sub.2-6 -alkynylene;
- or a pharmaceutically acceptable salt thereof.
A method of treating insulin resistance, neurogenic inflammation, migraine, diabetic neuropathy or rheumatoid arthritis in a subject in need thereof, comprising administering to the subject a compound of formula I ##STR16## wherein R.sup.1 and R.sup.2 independently are hydrogen, halogen, trifluoromethyl, hydroxy, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
- Y is >N--CH.sub.2 -- wherein only the underscored atom participates in the ring system;
- X is --CH.sub.2 CH.sub.2 --, --CH.sub.2 --(C.dbd.O)--, --(C.dbd.O)--CH.sub.2 --, or --CH.dbd.CH--;
- r is 1, 2 or 3;
- and
- Z is ##STR17## wherein n is 0 or 1;
- R.sup.3 is --(CH.sub.2).sub.m OH or --(CH.sub.2).sub.s COR.sup.4 wherein m is 0, 1, 2, 3, 4, 5 or 6, s is 0 or 1, and R.sup.4 is --OH, --NH.sub.2, --NHOH or C.sub.1-6 -alkoxy;
- R.sup.5 is hydrogen, halogen, trifluoromethyl, hydroxy, C.sub.1-6 -alkyl or C.sub.1-6 -alkoxy;
- R.sup.10 is hydrogen or C.sub.1-6 -alkyl;
- A is C.sub.1-6 -alkylene, C.sub.2-6 -alkenylene or C.sub.2-6 -alkynylene;
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.