60252-77-9Relevant academic research and scientific papers
Synthesis of 4-Trifluoromethylated 1,3-Butadienes via Palladium Catalyzed Heck Reaction
Li, Yang,Hao, Meng,Chang, Yu-Chen,Liu, Yuan,Wang, Wen-Fei,Sun, Ning,Zhu, Wen-Qing,Gao, Ziwei
supporting information, p. 2962 - 2966 (2021/08/23)
1,3-Butadiene plays a key role in modern synthetic chemistry and biochemistry because it is a key intermediate in the synthesis of many drugs. A new and effective method for the synthesis of 4-trifluoromethylated 1,3-butadiene through the fluorinated Heck reaction catalyzed by Pd(0) is described. Without additives, 1-chloro-3,3,3-trifluoropropene (an inexpensive CF3 structural unit that is harmless to ozone) reacts with enamide to synthesize 4-trifluoromethylated 1,3-butadienes with good yield, high regioselectivity and chemical selectivity, and strong tolerance of substrate functional groups such as alkynes, aldehyde, and ester groups.
An efficient approach for the synthesis of new (±)-coixspirolactams
Nascimento, Vinicius R.,Suenaga, Melissa L. S.,Andrade, Leandro H.
, p. 5458 - 5465 (2020/08/03)
Coixspirolactams, spiro[oxindole-γ-lactones], are found in adlay seeds and exhibit anticancer activity. A novel synthetic methodology was developed to enable an easy access to (±)-coixspirolactam A and a large number of new coixspirolactams in excellent overall yields. The exquisite exploitation of formamide reactivity was essential for the construction of oxindole and lactone scaffolds. This journal is
Rh(i)-Catalyzed regioselective arylcarboxylation of acrylamides with arylboronic acids and CO2
Cai, Lei,Fu, Lei,Gao, Yuzhen,Li, Gang,Li, Shangda,Zhou, Chunlin
supporting information, p. 7328 - 7332 (2020/11/19)
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.
Metal-Free C–S Bond Cleavage to Access N-Substituted Acrylamide and β-Aminopropanamide
Yang, Ke,Li, Yi,Ma, Zhiyan,Tang, Long,Yin, Yue,Zhang, Hao,Li, Zhengyi,Sun, Xiaoqiang
, p. 5812 - 5814 (2019/08/27)
Metal-free and Selectfluor-mediated C–S bond cleavage is described. This novel strategy provides a facile and efficient method to access important N-substituted acrylamide and β-aminopropanamide derivatives with good functional group tolerance and yields.
COMPOSITONS AND METHODS FOR MODULATING UBA5
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Paragraph 0633; 0634; 0636; 0691, (2018/08/26)
Disclosed herein, inter alia, are compositions and methods useful for inhibiting ubiquitin-like modifier activating enzyme 5.
COMPOSITIONS AND METHODS FOR MODULATING PPP2R1A
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Paragraph 0599; 0600; 0607; 0669, (2018/08/26)
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
Bateman,Nguyen,Roberts,Miyamoto,Ku,Huffman,Petri,Heslin,Contreras,Skibola,Olzmann,Nomura
supporting information, p. 7234 - 7237 (2017/07/11)
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.
Systematic study of the glutathione (GSH) reactivity of N-arylacrylamides: 1. Effects of aryl substitution
Cee, Victor J.,Volak, Laurie P.,Chen, Yuping,Bartberger, Michael D.,Tegley, Chris,Arvedson, Tara,McCarter, John,Tasker, Andrew S.,Fotsch, Christopher
, p. 9171 - 9178 (2015/12/23)
Success in the design of targeted covalent inhibitors depends in part on a knowledge of the factors influencing electrophile reactivity. In an effort to further develop an understanding of structure-reactivity relationships among N-arylacrylamides, we determined glutathione (GSH) reaction rates for a family of N-arylacrylamides independently substituted at ortho-, meta-, and para-positions with 11 different groups common to inhibitor design. We find that substituent effects on reaction rates show a linear Hammett correlation for ortho-, meta-, and para-substitution. In addition, we note a correlation between 1H and 13C NMR chemical shifts of the acrylamide with GSH reaction rates, suggesting that NMR chemical shifts may be a convenient surrogate measure of relative acrylamide reactivity. Density functional theory calculations reveal a correlation between computed activation parameters and experimentally determined reaction rates, validating the use of such methodology for the screening of synthetic candidates in a prospective fashion.
Promiscuity and selectivity in covalent enzyme inhibition: A systematic study of electrophilic fragments
J?st, Christian,Nitsche, Christoph,Scholz, Therese,Roux, Lionel,Klein, Christian D.
supporting information, p. 7590 - 7599 (2014/12/11)
Covalent ligand-target interactions offer significant pharmacological advantages. However, off-target reactivity of the reactive groups, which usually have electrophilic properties, must be minimized, and the selectivity of irreversible inhibitors is a crucial requirement. We therefore performed a systematic study to determine the selectivity of several electrophilic groups that can be used as building blocks for covalently binding ligands. Six reactive groups with modulated electrophilicity were combined with 11 nonreactive moieties, resulting in a small combinatorial library of 72 fragment-like compounds. These compounds were screened against a group of 11 enzyme targets to assess their selectivity and their potential for promiscuous binding to proteins. The assay results showed a considerably lower degree of promiscuity than initially expected, even for those members of the screening collection that contain supposedly highly reactive electrophiles.
Ligand-free CuTC-catalyzed N-arylation of amides, anilines and 4-aminoantipyrine: Synthesis of N-arylacrylamides, 4-amido-N-phenylbenzamides and 4-amino(N-phenyl)antipyrenes
Quan, Zheng-Jun,Xia, Hai-Dong,Zhang, Zhang,Da, Yu-Xia,Wang, Xi-Cun
, p. 81 - 85 (2014/02/14)
N-Arylation of amides and anilines with aryl iodides was efficiently catalyzed by copper thiophenecarboxylate under ligand-free conditions with good to excellent yields. A variety of substituted aryl iodides, amides, anilines and 4-aminoantipyrine were found to be applicable to the simple catalytic system. Furthermore, some practical, unique secondary amides, such as N-arylacrylamides and 4-amido-N-phenylbenzamides, and 4-amino(N-phenyl)antipyrenes, which are difficult to obtain by the classical methods, were prepared.
