104902-94-5

Usage

Uses

Used in Pharmaceutical Industry:
1H-Indole, 2,3-dihydro-1-(1-oxo-2-propenyl)is used as a chemical intermediate for the preparation of acrylamide-functionalized indolines and indoles. These compounds act as mTORC1 modulators, which are crucial in the development of therapeutic agents for the treatment of cancer, neurodegenerative, and metabolic diseases. The modulation of mTORC1 pathways can help regulate cellular processes and offer potential therapeutic benefits in managing these conditions.

Upstream product

• 496-15-1 1-indoline 
• 814-68-6 acryloyl chloride 

Downstream Products

• 314284-69-0 1-(indolin-1-yl)-3-phenylpropan-1-one 
• 1353779-72-2 C₃₃H₄₁NO₃Si 

Relevant academic research and scientific papers

Total synthesis of (±)-mersicarpine

(Chemical Equation Presented) The first total synthesis of the indole alkaloid mersicarpine is reported. Key steps include a β-dicarbonyl radical cyclization, as well as an oxidation of the benzopyrrole moiety to establish the masked 1,2-dicarbonyl functionality. An X-ray crystal structure and discussion of the 1H NMR behavior of the natural product are also presented.

Rh(i)-Catalyzed regioselective arylcarboxylation of acrylamides with arylboronic acids and CO2

The first Rh(i)-catalyzed regioselective arylcarboxylation of electron-deficient acrylamides with arylboronic acids under atmospheric pressure of CO2 has been developed. A range of acrylamides and arylboronic acids were compatible with this reaction under redox-neutral conditions, leading to a series of malonate derivatives that are versatile building blocks in organic syntheses.

mTORC1 MODULATORS

Provided herein, inter alia, are methods and compounds for inhibiting mTORC1 and for treating diseases associated with mTORC1 activity.

COMPOSITONS AND METHODS FOR MODULATING UBA5

Disclosed herein, inter alia, are compositions and methods useful for inhibiting ubiquitin-like modifier activating enzyme 5.

COMPOSITIONS AND METHODS FOR INHIBITING RETICULON 4

Disclosed herein, inter alia, are compositions and methods useful for inhibiting reticulon 4(RTN4).

COMPOSITIONS AND METHODS FOR MODULATING PPP2R1A

Disclosed herein, inter alia, are compositions and methods useful for modulating PPP2R1 A and for the treatment of cancer.

Chemoproteomics-enabled covalent ligand screen reveals a cysteine hotspot in reticulon 4 that impairs ER morphology and cancer pathogenicity

Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, a major bottleneck of this approach is identifying the targets of lead compounds that arise from screens. Here, we coupled the synthesis and screening of fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify compounds that impair colorectal cancer pathogenicity and map the druggable hotspots targeted by these hits. Through this coupled approach, we discovered a cysteine-reactive acrylamide DKM 3-30 that significantly impaired colorectal cancer cell pathogenicity through targeting C1101 on reticulon 4 (RTN4). While little is known about the role of RTN4 in colorectal cancer, this protein has been established as a critical mediator of endoplasmic reticulum tubular network formation. We show here that covalent modification of C1101 on RTN4 by DKM 3-30 or genetic knockdown of RTN4 impairs endoplasmic reticulum and nuclear envelope morphology as well as colorectal cancer pathogenicity. We thus put forth RTN4 as a potential novel colorectal cancer therapeutic target and reveal a unique druggable hotspot within RTN4 that can be targeted by covalent ligands to impair colorectal cancer pathogenicity. Our results underscore the utility of coupling the screening of fragment-based covalent ligands with isoTOP-ABPP platforms for mining the proteome for novel druggable nodes that can be targeted for cancer therapy.

Efficient cu-catalyzed atom transfer radical addition reactions of fluoroalkylsulfonyl chlorides with electron-deficient alkenes induced by visible light

Fluoroalkylsulfonyl chlorides, RfSO2Cl, in which Rf=CF3, C4F9, CF2H, CH2F, and CH2CF3, are used as a source of fluorinated radicals to add fluoroalkyl groups to electron-deficient, unsaturated carbonyl compounds. Photochemical conditions, using Cu mediation, are used to produce the respective α-chloro-β-fluoroalkylcarbonyl products in excellent yields through an atom transfer radical addition (ATRA) process. Facile nucleophilic replacement of the α-chloro substituent is shown to lead to further diverse functionalization of the products.

One-pot condensation-oxidation of glyoxamide with 1,2-diamines providing imidazolines and benzimidazoles

A novel method for the preparation of imidazolines and benzimidazoles bearing an amide at the 2-position, is described. The reactions of the glyoxamide with aliphatic and aromatic 1,2-diamines were found to form five-membered imidazolines and benzimidazoles by a one-pot condensation-oxidation procedure.