28792-97-4

Upstream product

• 3192-10-7 phenyl(vinylsulfonyl)amine 
• 77-78-1 dimethyl sulfate 
• 141-52-6 sodium ethanolate 
• 74-88-4 methyl iodide 
• 1622-32-8 2-Chloroethanesulfonyl chloride 
• 100-61-8 N-methylaniline 
• 62-53-3 aniline 
• 579-10-2 N-acetyl-N-methylaniline 
• 103-84-4 Acetanilid 

Downstream Products

• 2628-53-7 2-Aethoxy-aethan-sulfonyl- 
• 33718-40-0 N-methyl-ethanesulfonic acid anilide 
• 100-61-8 N-methylaniline 

Relevant academic research and scientific papers

H2O-Regulated Chemoselectivity in Oxa- Versus Aza-Michael Reactions

A H2O-regulated chemoselective addition in oxa- and aza-Michael reactions for aminoalcohols and mixtures of structurally similar alcohols and amines was reported. The oxa-Michael reactions might be kinetically controlled, and the reactions to produce O-selective products were slowed by the addition of water. The electrophilicity of Michael acceptors and the steric hindrance of Michael donors also affect the ratios of O/N products. This method offers novel ideas over conventional metal-catalyzed or ligand-induced strategies.

Novel hybrid conjugates with dual estrogen receptor α degradation and histone deacetylase inhibitory activities for breast cancer therapy

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.

Visible-Light-Promoted Radical Cyclization of N -Arylvinylsulfonamides: Synthesis of CF 3/CHF 2/CH 2CF 3-Containing 1,3-Dihydrobenzo[ c ]isothiazole 2,2-Dioxide Derivatives

A photocatalyzed and highly efficient trifluoromethylation of N-arylvinylsulfonamides using commercially available CF3SO2Cl as the trifluoromethyl radical source under blue LEDs is reported. The reaction proceeds through radical cyclization under mild con

Exploring the PROTAC degron candidates: OBHSA with different side chains as novel selective estrogen receptor degraders (SERDs)

As the mutant estrogen receptor (ER) continues to be characterized, breast cancer is becoming increasingly difficult to cure when treated with hormone therapy. In this regard, a strategy to selectively and effectively degrade the ER might be an effective alternative to endocrine therapy for breast cancer. In a previous study, we identified a novel series of 7-oxabicyclo[2.2.1]heptene sulfonamide (OBHSA) compounds as full ER antagonists while lacking the prototypical ligand side chain that has been widely used to induce antagonism of ERα. Further crystal structure studies and phenotypic assays revealed that these compounds are selective estrogen receptor degraders (SERDs) with a new mechanism of action. However, from a drug discovery point of view, there still is room to improve the potency of these OBHSA compounds. In this study, we have developed new classes of SERDs that contain the OBHSA core structure and different side chains, e.g., basic side chains, long alkyl acid side chains, and glycerol ether side chains, to simply mimic the degrons of proteolysis targeting chimera (PROTAC) and then investigated the structure-activity relationships of these PROTAC-like hybrid compounds. These novel SERDs could effectively inhibit MCF-7 cell proliferation and demonstrated good ERα degradation efficacy. Among the SERDs, compounds 17d, 17e and 17g containing a basic side chain with a N-trifluoroethyl substituent and a para methoxyl group at the phenyl group of the sulfonamide turned out to be the best candidates for ER degraders. A further docking study of these compounds with ERα elucidates their structure-activity relationships, which provides guidance to design new PROTAC degrons targeting ER for breast cancer therapy. Lastly, easy modification of these PROTAC-like SERDs enables further fine-tuning of their pharmacokinetic properties, including oral availability.

N-Phenyl-N-aceto-vinylsulfonamides as Efficient and Chemoselective Handles for N-Terminal Modification of Peptides and Proteins

A number of vinylsulfonamides were synthesized and screened to identify reagents that can be used to modify octreotide under biological pH and room temperature with improved efficiency. N-Phenyl-N-aceto-vinylsulfonamide exhibits higher reactivity and has emerged as an efficient reagent that has the ability to realize the selective modification of peptides and proteins at the N-terminus via aza-Michael addition. We showed that, after conjugation of peptides and proteins with the reagent containing a bioorthogonal functional group, the derivatives could be further labelled by functionalities, including fluorescent tags, modified drugs and polyethylene glycol (PEG) polymers without the need for prior treatment. Somatostatin, lysozyme, and RNaseA were selectively modified at the N-terminus, which illustrated the application of the method.

Selective lysine modification of native peptides: Via aza-Michael addition

A series of vinylsulfonamides were synthesized and screened for site-selective modification of the ?-amino group of lysine-bearing free α-amine residues. N-Methyl-N-phenylethenesulfonamide has emerged as an applicable reagent and has been developed for efficient and highly selective modification of the lysine residue of native peptides in the presence of a free N-terminus via aza-Michael addition. We demonstrated that functional N-phenylvinylsulfonamide derivatives with a fluorescent moiety or drug could also be conjugated to the lysine residue of octreotide and insulin with high specificity, without modifying the N-terminus. Our method provides a promising strategy for site-selective lysine functionalization in native peptides with a free N-terminus.

2-(Phenylseleno)ethanesulfon-amide as a novel protecting group for aniline that can be deprotected by a radical reaction

Anilines were protected as 2-(phenylseleno)ethanesulfonanilide (SeES anilide) via sulfonylation by 2-chlorosulfonyl chloride followed by the conjugate addition of benzeneselenol. The SeES anilide was deprotected by radical reduction using tributyltin hydride in the presence of AIBN. The corresponding anilines were obtained in high yields when the hydride and AIBN were added to the system slowly. Since the radical reaction proceeds under neutral conditions, chemoselective deprotection of the SeES group was accomplished. The SeES anilide was stable under various conditions, including some severe conditions.

Bicyclic core estrogens as full antagonists: Synthesis, biological evaluation and structure-activity relationships of estrogen receptor ligands based on bridged oxabicyclic core arylsulfonamides

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.

A new approach for the ortho-substitution of anilines and for the synthesis of indolines

Intermolecular radical addition of a xanthate to a vinyl sulfanilide is followed by ring closure to the aromatic ring to give a dihydrobenzoisothiazole dioxide structure, which upon heating loses sulfur dioxide to give a 2-substituted aniline; in some exa