10219-10-0Relevant articles and documents
Copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagents
Xia, Qinqin,Liu, Xiaolong,Zhang, Yuejiao,Chen, Chao,Chen, Wanzhi
, p. 3326 - 3329 (2013)
The copper-catalyzed N-methylation of amides and O-methylation of carboxylic acids by using peroxides as the methylating reagent are described. Various amides and carboxylic acids were methylated affording N-substituted amides and esters. Tentative mechanistic studies suggest that this reaction is likely to involve a radical process.
Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy
Zhao, Chenxi,Tang, Chu,Li, Changhao,Ning, Wentao,Hu, Zhiye,Xin, Lilan,Zhou, Hai-Bing,Huang, Jian
, (2021/05/10)
Hormone therapy targeting estrogen receptors is widely used clinically for the treatment of breast cancer, such as tamoxifen, but most of them are partial agonists, which can cause serious side effects after long-term use. The use of selective estrogen receptor down-regulators (SERDs) may be an effective alternative to breast cancer therapy by directly degrading ERα protein to shut down ERα signaling. However, the solely clinically used SERD fulvestrant, is low orally bioavailable and requires intravenous injection, which severely limits its clinical application. On the other hand, double- or multi-target conjugates, which are able to synergize antitumor activity by different pathways, thus may enhance therapeutic effect in comparison with single targeted therapy. In this study, we designed and synthesized a series of novel dual-functional conjugates targeting both ERα degradation and histone deacetylase inhibiton by combining a privileged SERD skeleton 7-oxabicyclo[2.2.1]heptane sulfonamide (OBHSA) with a histone deacetylase inhibitor side chain. We found that substituents on both the sulfonamide nitrogen and phenyl group of OBHSA unit had significant effect on biological activities. Among them, conjugate 16i with N-methyl and naphthyl groups exhibited potent antiproliferative activity against MCF-7 cells, and excellent ERα degradation activity and HDACs inhibitory ability. A further molecular docking study indicated the interaction patterns of these conjugates with ERα, which may provide guidance to design novel SERDs or PROTAC-like SERDs for breast cancer therapy.
Method for promoting acylation of amine or alcohol by carbon dioxide
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Paragraph 0033-0034, (2021/05/29)
The invention relates to a method for promoting acylation of amine or alcohol by carbon dioxide, which comprises the following steps of: mixing an amine compound, carboxylate or thiocarboxylate compound and a reaction solvent under the action of carbon dioxide, and reacting to obtain an amide compound, or under the action of carbon dioxide, mixing the alcohol compound, the thiocarboxylate compound and the reaction solvent [gamma]-valerolactone, and reacting to obtain the ester compound. According to the invention, under the promotion action of carbon dioxide, carboxylate or thiocarboxylate is used as an acylation reagent, and amine and alcohol are converted into amide and ester compounds in the absence of a transition metal catalyst, so that acylation reagents such as acyl chloride or anhydride with irritation and corrosivity are avoided; and the method has the advantages of simple operation, mild reaction conditions, high tolerance of substrate functional groups, strong applicability and high yield, and provides an efficient, reliable and economical preparation method for synthesis of amide and ester compounds.
Selective Methylation of Amides, N-Heterocycles, Thiols, and Alcohols with Tetramethylammonium Fluoride
Cheng, Hong-Gang,Pu, Maoping,Kundu, Gourab,Schoenebeck, Franziska
supporting information, p. 331 - 334 (2019/12/30)
We herein disclose the use of tetramethylammonium fluoride (TMAF) as a direct and selective methylating agent of a variety of amides, indoles, pyrroles, imidazoles, alcohols, and thiols. The method is characterized by operational simplicity, wide scope, and ease of purification. Our computational studies suggest a concerted methylation-deprotonation as the preferred reaction pathway.
Cross-Coupling of Chloro(hetero)arenes with Thiolates Employing a Ni(0)-Precatalyst
Gehrtz, Paul H.,Geiger, Valentin,Schmidt, Tanno,Sr?an, Laura,Fleischer, Ivana
supporting information, p. 50 - 55 (2019/01/11)
A general and efficient Ni-catalyzed coupling of challenging aryl chlorides and in situ generated aliphatic and aromatic thiolates is described. The employed on-cycle, air-stable defined Ni precatalysts allow for transformation of a broad scope of substrates. A variety of functional groups and heterocyclic motifs as well as structurally varied thiols are tolerated at unprecedented moderate catalyst loadings and reaction temperatures. Depending on reaction conditions, aryl thiols can selectively undergo C-S or C-C couplings.
Thermolysis and radiofluorination of diaryliodonium salts derived from anilines
Linstad, Ethan J.,Vāvere, Amy L.,Hu, Bao,Kempinger, Jayson J.,Snyder, Scott E.,DiMagno, Stephen G.
supporting information, p. 2246 - 2252 (2017/03/17)
Aniline-derived diaryliodonium salts were synthesized and functionalized in good to excellent yields by judicious utilization of electron-withdrawing protecting groups. This simple approach opens another route to radiolabeling amino arenes in relatively complex molecules, such as flutemetamol.
Room temperature C(sp2)-H oxidative chlorination: Via photoredox catalysis
Zhang, Lei,Hu, Xile
, p. 7009 - 7013 (2017/10/05)
Photoredox catalysis has been developed to achieve oxidative C-H chlorination of aromatic compounds using NaCl as the chlorine source and Na2S2O8 as the oxidant. The reactions occur at room temperature and exhibit exclusive selectivity for C(sp2)-H bonds over C(sp3)-H bonds. The method has been used for the chlorination of a diverse set of substrates, including the expedited synthesis of key intermediates to bioactive compounds and a drug.
Bicyclic core estrogens as full antagonists: Synthesis, biological evaluation and structure-activity relationships of estrogen receptor ligands based on bridged oxabicyclic core arylsulfonamides
Zhu, Manghong,Zhang, Chen,Nwachukwu, Jerome C.,Srinivasan, Sathish,Cavett, Valerie,Zheng, Yangfan,Carlson, Kathryn E.,Dong, Chune,Katzenellenbogen, John A.,Nettles, Kendall W.,Zhou, Hai-Bing
, p. 8692 - 8700 (2013/01/15)
Compounds that block estrogen action through the estrogen receptor (ER) or downregulate ER levels are useful for the treatment of breast cancer and endocrine disorders. In our search for structurally novel estrogens having three-dimensional core scaffolds, we found some compounds with a 7-oxabicyclo[2.2.1]heptene core that bound well to the ERs. The best of these compounds, a phenyl sulfonate ester (termed OBHS for oxabicycloheptene sulfonate), was a partial antagonist on both ERα and ERβ. Although OBHS bears no structural resemblance to other estrogen antagonists, it appears to achieve its partial antagonist character by stabilizing a novel conformation of the ER that involves a significant distortion of helix-11. To enhance the antagonist properties of these oxabicyclo[2.2.1]heptane core ligands, we expanded the functional diversity of OBHS by replacing the sulfonate with secondary or tertiary sulfonamides (-SO2NR-), isoelectronic and potentially isostructural molecular replacements. An array of 16 OBHS sulfonamide analogues were prepared through a Diels-Alder reaction of a 3,4-diarylfuran using various N-aryl vinyl sulfonamide dienophiles. While the more polar secondary sulphonamides were weak ligands, certain of the tertiary sulfonamides had very good ER binding affinity. In HepG2 cell reporter gene assays, the sulphonamides had moderate potency, but they showed lower intrinsic transcriptional activity on ERα than the selective estrogen receptor modulator (SERM) hydroxytamoxifen or OBHS, and they were inverse agonists on ERβ. Thus, the behaviour of these OBH-sulfonamides more closely mirrors the activity of full antagonists like the drug fulvestrant (ICI 182780), and their greater antagonist biocharacter appears to arise from an accentuated distortion of helix-11.
Oxidative Dealkylation of 4-Substituted N,N-Dialkylanilines with Molecular Oxygen in the Presence of Acetic Anhydride Promoted by Cobalt(II) or Copper(I) Chloride
Murata, Satoru,Suzuki, Kaoru,Tamatani, Akira,Miura, Masahiro,Nomura, Masakatsu
, p. 1387 - 1392 (2007/10/02)
The reaction of 4-substituted N,N-dimethylanilines 1a-d with acetic anhydride 5 proceeded efficiently in the presence of a catalytic amount of cobalt(II) or copper(I) chloride under oxygen to give the corresponding N-methylacetanilides 2a-d along with N-methylformanilides 3a-d.The reaction of N-alkyl-N-methyl-p-toluidines 1f-h with cobalt chloride revealed that the order of reactivity of the N-substituents follows the sequence allyl > benzyl >/= methyl > ethyl, while in the case of copper chloride the order was benzyl > allyl > methyl > ethyl.Aldehydes 18a-e and phenylglyoxylic acid derivatives 18f and 18g were obtained in fair to good yield from the reaction of n-substituted N-ethyl-p-toluidines 17a-g.
Cobalt(II) Chloride Catalyzed Oxidation of 4-Substituted N,N-Dialkylanilines with Molecular Oxygen in the Presence of Acetic Anhydride
Murata, Satoru,Tamatani, Akira,Suzuki, Kaoru,Miura, Masahiro,Nomura, Masakatsu
, p. 757 - 760 (2007/10/02)
The oxidation of 4-substituted N,N-dialkylanilines with molecular oxygen using a catalytic amount of cobalt(II) chloride efficiently proceeds in the presence of acetic anhydride to give N-alkylacetanilides in good yields along with N-alkylformanilides.
