42104-70-1

Upstream product

• 123-75-1 pyrrolidine 
• 814-68-6 acryloyl chloride 
• 625-36-5 2-chloropropionyl chloride 
• 74-86-2 acetylene 
• 92-84-2 10H-phenothiazine 
• 79-10-7 acrylic acid 
• 4553-05-3 1-pyrrolidin-1-yl-propan-1-one 

Downstream Products

• 72299-21-9 3-Cyclohexyl-1-pyrrolidin-1-yl-propan-1-one 
• 20681-51-0 methyl 3-cyclohexylpropionate 
• 119163-30-3 Oxiranyl-pyrrolidin-1-yl-methanone 
• 725697-51-8 [3-(4-chlorophenyl)-4,5-dihydro-isoxazol-5-yl]pyrrolidin-1-yl-methanone 
• 1009337-76-1 (3-phenyl-4,5-dihydroisoxazol-5-yl)(pyrrolidin-1-yl)methanone 
• 78910-33-5 sarmentine 
• 1353779-67-5 C₂₉H₄₁NO₃Si 

Relevant academic research and scientific papers

Potassium Base-Catalyzed Michael Additions of Allylic Alcohols to α,β-Unsaturated Amides: Scope and Mechanistic Insights

We report herein the first KHMDS-catalyzed Michael additions of allylic alcohols to α,β-unsaturated amides through allylic isomerization. The reaction proceeds smoothly in the presence of only 5 mol% of KHMDS to afford a variety of 1,5-ketoamides in high yields. Mechanistic investigations, including experimental and computational studies, reveal that the KHMDS-catalyzed in-situ generation of the enolate from the allylic alcohol through a tunneling-assisted 1,2-hydride shift is the key to the success of this transformation. (Figure presented.).

METHOD OF PRODUCING ACRYLOYL MONOMERS AND ACRYLOYL-BASED POLYMERS

Embodiments of the present disclosure are directed to a method of making a reaction inhibiting polymer having a formula of M-CO-NR. The method may comprise reacting PAA with an organic coupling reagent and at least one alicyclic amine to produce the reaction inhibiting polymer. In accordance with another embodiment of the present disclosure, a method of making an acryloyl monomer having a formula of R?a#191-CO-NR may comprise reacting an acrylic acid with an organic coupling reagent and an alicyclic amine to form the acryloyl monomer. R?a#191 may be an alkylene moiety, M may be a poly(acrylic) acid backbone. NR may be an alicyclic amine moiety coupled to the polymer backbone or coupled to the alkylene moiety.

Radical α,β-Dehydrogenation of Saturated Amides via α-Oxidation with TEMPO under Transition Metal-Free Conditions

A transition metal-free radical process for the selective α,β-dehydrogenation of saturated amides under mild conditions is developed. Utilizing radical activation strategy, the challenging issue associated with the low α-acidity of amides is resolved. For the first time, α,β-unsaturated Weinreb amides and acrylamides could be efficiently prepared directly from corresponding saturated amides. Mechanistic studies confirm the radical nature of this transformation. Two gram scale α,β-dehydrogenation have also been performed to demonstrate the utility of this method.

Asymmetric Diels-Alder Reaction of α,β-Unsaturated Oxazolidin-2-one Derivatives Catalyzed by a Chiral Fe(III)-Bipyridine Diol Complex

An asymmetric FeIII-bipyridine diol catalyzed Diels-Alder reaction of α,β-unsaturated oxazolidin-2-ones has been developed. Among various FeII/FeIII salts, Fe(ClO4)3·6H2O was selected as th

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 MODULATING PPP2R1A

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

COMPOSITIONS AND METHODS FOR INHIBITING RETICULON 4

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

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.

Visible-light-mediated generation of nitrile oxides for the photoredox synthesis of isoxazolines and isoxazoles

Visible-light photoredox catalysis enables the synthesis of biologically relevant isoxazolines and isoxazoles from hydroxyimino acids. The process shows broad functional group compatibility and mechanistic and computational studies support a visible-light-mediated generation of nitrile oxides by two sequential oxidative single electron transfer processes.

Discovery and SAR of N-(1-((substituted piperidin-4-yl)methyl)-3-methoxypiperidin-4-yl)-2-methoxybenzamide derivatives: 5-Hydroxytryptamine receptor 4 agonist as a potent prokinetic agent

A series of novel benzamide derivatives, altering the 4-fluorophenylalkyl moiety in cisapride, were synthesized as 5-HT4 receptor agonists, and SAR of these analogs was examined on in vitro and in vivo prokinetic activities. These compounds were synthesized for high 5-HT4 receptor binding affinities and low hERG affinities. Several types of analogs were obtained and screened for 5-HT4 binding, hERG blocking, agonism, and gastric emptying assessment. Among the analogues, compound 23g showed promising results compared with the other analogs with respect to gastric emptying rates in rats. Therefore, we suggest that it may be a clinical candidate for the development of a potent prokinetic agent to treat GI disorders.