COMPOUNDS AND METHODS OF STRENGTHENING THE DEGRADATION OF TARGET TARGETS AND OTHER POLYPEPTIDES USING E3 UBQUITIN LIGASES

摘要

1. The compound represented by the chemical structure: L-ULM, where L is a linker group, and ULM is a small molecule of the binding fragment of the ubiquitin ligase, which has a -OH substituent or a group that can be metabolized in the patient or subject to -OH where the ULM optionally contains a prolyl group, and where the linker group, in addition, is optionally associated with a fragment of the target protein (PTM). 2. A compound represented by the chemical structure: ULM-L-PTM, containing a small molecule of a binding fragment of a ubiquitin ligase (ULM), a fragment of a target protein (PTM) and a linker (L), where: ULM contains a group substituted by hydroxyl or a functional group which may be metabolized in the patient's body or converted to hydroxyl; L is a bond or chemical linker; PTM is attached to a target protein or polypeptide that must be ubiquitinylated with a ubiquitin ligase; ULM is chemically bound to L; and L is chemically bound to PTM; or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph or prodrug thereof. 3. A compound according to claim 2, wherein the compound comprises a plurality of ULMs, a plurality of PTMs, a plurality of linkers, or any combination thereof. The compound of claim 1, wherein the ULM contains a group having a chemical structure: http: //patentimages.storage.googleapis.com/WO2013106643A2/imgf000312_0001.png, where R is —OH or a group that can be metabolized in the patient or subject. to —OH; X and X ′ each independently represent C = O, C = S, S (O), S (O); R is selected from the group consisting of: optionally substituted - (CH) - (C = O) (NR) (SO) (CC) alkyl group, optionally substituted group RR- (CH) - (C = O) (NR) (SO) NRR, optionally substituted - (CH) - (C = O) (NR) ( SO) aryl optionally substituted with - (CH) - (C = O) (NR) (SO) heteroaryl optionally substituted with - (CH) - (C = O) NR (SO) -ge terocycle optionally substituted