Use of beta-sheet mimetics as protease and kinase inhibitors and as inhibitors of transcription factors

摘要

The specification describes sheet mimetics and the use thereof, including use for the manufacture of a medicament for achieving therapeutic effects in a warm-blooded animal through one or more of protease inhibition, kinase inhibition, and/or regulation of a transcription factor. The therapeutic effects result from administering to the warm-blooded animal a therapeutically effective amount of a sheet mimetic including a bicyclic ring system, wherein the sheet mimetic has the formula (I) (including pharmaceutically acceptable salts thereof) wherein A is selected from -C (=O)-, -(CH2)0-4-, -C(=O) (CH2)13-, -(CH2)1-20- and -(CH2)1-2S-; B is selected from N and CH; C is selected from -C(=O)-, -C(=O) (CH2) 1-3, -(CH2)0-3-, -O-, -S-, -O-(CH2)1-2- and -S(CH2)1-2-; D is selected from N and C(R4); E is selected from see figure (II) F is an optional carbonyl moiety; R1, R2, and R4 are independently selected from amino acid side chain moieties and derivatives thereof; R2 is selected from an amino acid side chain moiety and derivatives thereof, or taken together with C forms a fused substituted or unsubstituted homocyclic or heteocyclic ring; R3 is selected from an amino acid side chain moiety and derivatives thereof, or taken together with C forms a bridging moiety selected from -(CF12)12-, -0- and -S-; Y and Z represent the remainder of the molecule; and any two adjacent CH groups of the bicyclic ring may form a double bond.