Name: 3-(4-methoxy-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

2,6-Piperidinedione, 3-(1,3-dihydro-7-methoxy-1-oxo-2H-isoindol-2-yl)-

Boiling Point

581.5±50.0 °C at 760 mmHg

Density

1.376±0.06 g/cm3

InChI Key

WQBYRVHGTFSBTA-UHFFFAOYSA-N

InChI

InChI=1S/C14H14N2O4/c1-20-10-4-2-3-8-7-16(14(19)12(8)10)9-5-6-11(17)15-13(9)18/h2-4,9H,5-7H2,1H3,(H,15,17,18)

Canonical SMILES

COC1=CC=CC2=C1C(=O)N(C2)C3CCC(=O)NC3=O

Background Introduction

3-(4-methoxy-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione is a synthetic derivative structurally related to thalidomide, a well-documented immunomodulatory imide drug. This compound features an isoindoline core with a 4-methoxy substituent, making it a valuable component as a CRBN (Cereblon) E3 ligase ligand. As a building block in the rapidly advancing field of targeted protein degradation, it plays a vital role in facilitating the development of novel PROTAC (Proteolysis Targeting Chimera) molecules that harness the body's natural protein disposal machinery.

Mechanism

Functioning as a CRBN-binding ligand, 3-(4-methoxy-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione interacts with the Cereblon subunit of the CUL4 E3 ubiquitin ligase complex. This specific binding enables the recruitment of the E3 ligase to a target protein when tethered via an appropriate linker and target-binding moiety. The CRBN-ligand-target complex triggers ubiquitination, marking the target protein for degradation by the proteasome. The 4-methoxy functional group provides unique chemical handle properties, supporting further linker derivatization and tailored PROTAC design.

Applications

3-(4-methoxy-3-oxo-1H-isoindol-2-yl)piperidine-2,6-dione is widely applied in the rational design of CRBN-based PROTACs and molecular glues. Its adaptable structure makes it ideal for constructing bifunctional molecules that induce selective protein degradation for research and therapeutic development. Key applications include:

• Serving as a core CRBN ligand in PROTAC synthesis to enable targeted protein degradation in diverse disease models
• Use in structure-activity relationship (SAR) studies for optimizing CRBN-targeted degraders
• Supporting the development of molecular glues for modulating protein-protein interactions
• Facilitating chemoproteomic studies and drug discovery programs involving the CRBN pathway
• Custom synthesis projects by CROs and academic labs seeking innovative E3 ligase recruiting warheads

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Specifically designed for CRBN E3 ligase recruitment, enabling high-efficiency PROTAC synthesis.
• Features robust phthalimide core structure, providing enhanced binding affinity and reliable degradation of target proteins.

1. Synthesis and asymmetric hydrogenation of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione

Alexander A Bisset, Akira Shiibashi, Jasmine L Desmond, Allan Dishington, Teyrnon Jones, Guy J Clarkson, Takao Ikariya, Martin Wills Chem Commun (Camb). 2012 Dec 21;48(98):11978-80.doi: 10.1039/c2cc36807b.

The synthesis of (3E)-1-benzyl-3-[(2-oxopyridin-1(2H)-yl)methylidene]piperidine-2,6-dione 5 from N-benzylglutarimide was achieved in three steps. The asymmetric hydrogenation of 4 gave either the product of partial reduction (10) or full reduction (13), depending on the catalyst which was employed, in high ee in each case. Attempts at asymmetric transfer hydrogenation (ATH) of resulted in formation of a racemic product.

2. A First-in-Human Study of Novel Cereblon Modulator Avadomide (CC-122) in Advanced Malignancies

Drew W Rasco, Kyriakos P Papadopoulos, Michael Pourdehnad, Anita K Gandhi, Patrick R Hagner, Yan Li, Xin Wei, Rajesh Chopra, Kristen Hege, Jorge DiMartino, Kent Shih Clinical TrialClin Cancer Res. 2019 Jan 1;25(1):90-98.doi: 10.1158/1078-0432.CCR-18-1203.Epub 2018 Sep 10.

Purpose:Avadomide is a novel, small-molecule therapeutic agent that modulates cereblon E3 ligase activity and exhibits potent antitumor and immunomodulatory activities. This first-in-human phase I study (NCT01421524) evaluated the safety and clinical activity of avadomide in patients with advanced solid tumors, non-Hodgkin lymphoma (NHL), and multiple myeloma.Patients and methods:Thirty-four patients were treated with avadomide in 7 dose-escalation cohorts using a 3 + 3 design (0.5-3.5 mg, 28-day continuous dosing cycles). The primary objectives were to determine the dose-limiting toxicity (DLT), nontolerated dose (NTD), maximum tolerated dose (MTD), recommended phase II dose, and pharmacokinetics of avadomide. The secondary objective was to determine preliminary avadomide efficacy. Exploratory objectives included evaluation of pharmacodynamic effects of avadomide. Results:DLTs were reported in 2 patients, and grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 14 patients (41%). The most common TEAEs (≥15%) were fatigue, neutropenia, and diarrhea. The NTD and MTD were 3.5 and 3.0 mg, respectively. Of 5 patients with NHL, 1 achieved a complete response, and 2 had partial responses. Although no objective responses were observed in patients with solid tumors, 5 of 6 patients with brain cancer experienced nonprogression of ≥6 months. A dose-dependent relationship between Aiolos degradation in peripheral B and T cells occurred within 5 hours of the first dose of avadomide administered, starting at 0.5 mg.Conclusions:Avadomide monotherapy demonstrated acceptable safety and favorable pharmacokinetics in patients with solid tumors, NHL, and multiple myeloma. In addition, 3 objective responses were observed in NHL.

3. Crystallographic and molecular modeling studies on 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione and its butyl analogue, inhibitors of mammalian aromatase. Comparison with natural substrates: prediction of enantioselectivity for N-alkyl derivatives

C A Laughton, R McKenna, S Neidle, M Jarman, R McCague, M G Rowlands Comparative StudyJ Med Chem. 1990 Sep;33(9):2673-9.doi: 10.1021/jm00171a052.

Inhibitors of the cytochrome P450 enzyme aromatase, which is involved in the biosynthesis of estrogens from androgens, are of proven utility in the treatment of hormone-dependent breast cancer. The determination of the crystal structure of one such inhibitor, 3-ethyl-3-(4-pyridyl)piperidine-2,6-dione (2) and its 3-butyl analogue (3) is described. In the absence of three-dimensional structural information for the enzyme, conformational analysis and comparison with natural substrates has been performed in order to define possible "active" conformations. The enhanced inhibitory activity of 3 may be linked to hydrophobic interactions between the side chain and that portion of the enzyme that normally interacts with the B and C rings of a steroid substrate. Information gained from this study and previous studies by other workers has been combined in order to produce a hypothesis to explain the pattern of activity of N(1)-alkyl derivatives of 2. The successful application of this hypothesis to the prediction of the relative aromatase inhibitory activities of the two enantiomers of the N-octyl derivative (4) is described.

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂