202271-89-4

Usage

Uses

Used in Pharmaceutical Industry:
(-)-4-Amino-2-[2,6-dioxopiperidin-3(S)-yl]-1,2-dihydroisoindole-1,3-dione is used as an anti-inflammatory agent for its ability to inhibit TNF-α production, which is a key mediator of inflammation. This property makes it a valuable compound in the development of treatments for various inflammatory conditions.
Used in Oncology:
(-)-4-Amino-2-[2,6-dioxopiperidin-3(S)-yl]-1,2-dihydroisoindole-1,3-dione is used as an antitumor agent for its therapeutic effects against multiple myeloma, a type of blood cancer. It is employed in the treatment of this disease due to its ability to modulate immune responses and target cancer cells, leading to the inhibition of tumor growth and progression.
Used in Drug Development:
(-)-4-Amino-2-[2,6-dioxopiperidin-3(S)-yl]-1,2-dihydroisoindole-1,3-dione is used as a lead compound in the development of new drugs targeting inflammation and cancer. Its unique properties and mechanisms of action make it a valuable starting point for the design and synthesis of novel therapeutic agents with improved efficacy and reduced side effects.

Upstream product

• 603-62-3 4-nitro-1H-isoindole-1,3(2H)-dione 
• 2650-64-8 Cbz-L-Gln 
• 22785-43-9 (S)-benzyl (2,6-dioxopiperidin-3-yl)carbamate 
• 118061-00-0 (3S)-3-aminopiperidine-2,6-dione hydrobromide 
• 641-70-3 3-nitrophthalic acid anhydride 
• 24666-55-5 3-(benzyloxycarbonyl)-amino-2,6-dioxopiperidine 
• 24666-56-6 rac-α-aminoglutarimide hydrochloride 
• 6946-22-1 3-aminophthalic acid hydrochloride 
• 2635-64-5 2-(4-amino-1,3-dioxoisoindolin-2-yl)-4-carbamoylbutanoic acid 
• 19171-18-7 4-NT 
• 67-64-1 acetone 
• 530-62-1 1,1'-carbonyldiimidazole 
• 603-11-2 3-nitrophthalic acid 
• 617-65-2 Glutamic acid 

Downstream Products

• 444287-84-7 2‐chloro‐N‐(2‐(2,6‐dioxopiperidin‐3‐yl)‐1,3‐dioxoisoindolin‐4‐yl)acetamide 

Relevant academic research and scientific papers

Rational Design and Synthesis of HSF1-PROTACs for Anticancer Drug Development

PROTACs employ the proteosome-mediated proteolysis via E3 ligase and recruit the natural protein degradation machinery to selectively degrade the cancerous proteins. Herein, we have designed and synthesized heterobifunctional small molecules that consist of different linkers tethering KRIBB11, a HSF1 inhibitor, with pomalidomide, a commonly used E3 ligase ligand for anticancer drug development.

The tale of proteolysis targeting chimeras (PROTACs) for Leucine-Rich Repeat Kinase 2 (LRRK2)

Here we present the rational design and synthetic methodologies towards proteolysis-targeting chimeras (PROTACs) for the recently-emerged target leucine-rich repeat kinase 2 (LRRK2). Two highly potent, selective, brain-penetrating kinase inhibitors were selected, and their structure was appropriately modified to assemble a cereblon-targeting PROTAC. Biological data show strong kinase inhibition and the ability of the synthesized compounds to enter the cells. However, data regarding the degradation of the target protein are inconclusive. The reasons for the inefficient degradation of the target are further discussed.

Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties.

Chemical degradation of androgen receptor (Ar) using bicalutamide analog–thalidomide protacs

A series of PROTACs (PROteolysis-TArgeting Chimeras) consisting of bicalutamide analogs and thalidomides were designed, synthesized, and biologically evaluated as novel androgen receptor (AR) degraders. In particular, we found that PROTAC compound 13b could successfully demonstrate a targeted degradation of AR in AR-positive cancer cells and might be a useful chemical probe for the investigation of AR-dependent cancer cells, as well as a potential therapeutic candidate for prostate cancers.

PHOTO INDUCED CONTROL OF PROTEIN DESTRUCTION

By hijacking endogenous E3 ligase to degrade protein targets via the ubiquitin-proteasome system, PROTACs (PRoteolysis TArgeting Chimeras) provide a new strategy to inhibit protein targets that were previously regarded as undruggable. The compounds described herein comprise a photolabile group on PROTACs, enabling the degradation of protein targets in a spatiotemporally controlled manner. By adding a photolabile caging group on ubiquitin recruiting moieties, light-inducible protein degradation was acheived. These opto-PROTACs display no activity in the dark, while restricted degradation can be induced at a specific time and rate by UVA-irradiation. Accordingly, these compounds provide light-controlled PROTACs and methods of using such compounds.

Synthesis process for continuously preparing pomalidomide by using microchannel reactors

The invention discloses a synthesis process for continuously preparing pomalidomide by using microchannel reactors. The synthesis process comprises the following steps tha (1) 3-nitrophthalic acid isdissolved in acetic anhydride, and a reaction is performed to obtain 3-nitrophthalic anhydride; (2) 3-nitrophthalic anhydride is dissolved in formic acid to prepare a homogeneous solution A; (3) 3-aminopiperidine-2,6-dione is dissolved in ammonium formate and formic acid to prepare a homogeneous solution B; (4) palladium on carbon and methanol are prepared into suspension C; (5) the homogeneous solution A and the homogeneous solution B are simultaneously pumped into a microstructured mixer I in a microchannel reaction device separately, and after mixing, the mixture is introduced into a microstructured reactor I; (6) the suspension C and an effluent from the microstructured reactor I are simultaneously pumped into a microstructured mixer II in the microchannel reaction device separately while the step (5) is carried out, and after mixing, the mixture is introduced into a microstructured reactor II; and (7) an effluent from the microstructured reactor II is collected to obtain pomalidomide.

Selective degradation of CDK6 by a palbociclib based PROTAC

Development of selective kinase inhibitors that target the ATP binding site continues to be a challenge largely due to similar binding pockets. Palbociclib is a cyclin-dependent kinase inhibitor that targets the ATP binding site of CDK4 and CDK6 with similar potency. The enzymatic function associated with the kinase can be effectively probed using kinase inhibitors however the kinase-independent functions cannot. Herein, we report a palbociclib based PROTAC that selectively degrades CDK6 while sparing the homolog CDK4. We used competition studies to characterize the binding and mechanism of CDK6 degradation.

PYRIDAZINE DERIVATIVES AS SMARCA2/4 DEGRADERS

The present invention provides pyridazine derivatives of formula (I), which are therapeutically useful as SMARCA2/4 degraders. These compounds are useful in the treatment and/or prevention of diseases or disorders dependent upon SMARCA2/4 in a mammal. The present invention also provides preparation of the compounds and pharmaceutical compositions comprising at least one of the pyridazine derivatives of formula (I) or a pharmaceutically acceptable salt, or a stereoisomer thereof.

SUBSTITUTED 4-AMINOISOINDOLINE-1,3-DIONE COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH

Provided herein are 4-aminoisoindoline-1,3-dione compounds having the following structure: wherein R, Ring A, and n are as defined herein, compositions comprising an effective amount of a 4-aminoisoindoline-1,3-dione compound, and methods for treating or preventing disorders.

IMIDE-BASED MODULATORS OF PROTEOLYSIS AND METHODS OF USE

The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.