Thalidomide-O-amido-C4-NH2 hydrochloride

• CAT Number: I015440
• CAS Number: 2245697-86-1
• Molecular Formula: C19H23ClN4O6
• Molecular Weight: 438.86
• Purity: ≥95%
• Synonyms: N-(4-aminobutyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetamide;hydrochloride
• InChI: InChI=1S/C19H22N4O6.ClH/c20-8-1-2-9-21-15(25)10-29-13-5-3-4-11-16(13)19(28)23(18(11)27)12-6-7-14(24)22-17(12)26;/h3-5,12H,1-2,6-10,20H2,(H,21,25)(H,22,24,26);1H
• InChIKey: UZDTXDUTMCCMDO-UHFFFAOYSA-N
• SMILES: C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)OCC(=O)NCCCCN.Cl

Thalidomide-O-amido-C4-NH2 hydrochloride, a synthesized E3 ligase ligand-linker conjugate that incorporates the Thalidomide based cereblon ligand and a linker, can be used in the synthesis of PROTACs[1].
Thalidomide-O-amido-C4-NH2 is an amine intermediate (Compound 41), which can be used as is a heterobifunctional PROTAC BET degrader. The bromodomain and extra-terminal (BET) family proteins, consisting of BRD2, BRD3, BRD4, and testis-specific BRDT members, are epigenetic “readers” and play a key role in the regulation of gene transcription. BET proteins are considered to be attractive therapeutic targets for cancer and other human diseases. Recently, heterobifunctional small-molecule BET degraders have been designed based upon the proteolysis targeting chimera (PROTAC) concept to induce BET protein degradation[1]. Thalidomide-O-amido-C4-NH2 is a degron-linker (refer to Compound DL6-TL). Degron-linker-targeting ligand, wherein the linker is covalently bound lo at least one degron and at least one targeting ligand, the degron is a compound capable of binding to an ubiquitin ligase such as an E3 ubiquitin ligase (e g, cereblon), and the targeting ligand is capable of binding to the targeted protein (s)[2].

Reference

[1]. Zhou B, et al. Discovery of a Small-Molecule Degrader of Bromodomain and Extra-Terminal (BET) Proteins withPicomolar Cellular Potencies and Capable of Achieving Tumor Regression.J Med Chem. 2018 Jan 25;61(2):462-481.
 [Content Brief]

[2]. James Bradner, et al. Methods to induce targeted protein degradation through bifunctional molecules. WO 2017024317 A2.