57688-34-3Relevant academic research and scientific papers
Discovery of Biphenyl-Sulfonamides as Novel β- N-Acetyl- d -Hexosaminidase Inhibitors via Structure-Based Virtual Screening
Chen, Tao,Li, Wen-Qin,Liu, Zheng,Jiang, Wen,Liu, Tian,Yang, Qing,Zhu, Xiao-Lei,Yang, Guang-Fu
, p. 12039 - 12047 (2021/10/20)
Novel insecticidal targets are always in demand due to the development of resistance. OfHex1, a β-N-acetyl-d-hexosaminidase identified in Ostrinia furnacalis (Asian corn borer), is involved in insect chitin catabolism and has proven an ideal target for insecticide development. In this study, structure-based virtual screening, structure simplification, and biological evaluation are used to show that compounds with a biphenyl-sulfonamide skeleton have great potential as OfHex1 inhibitors. Specifically, compounds 10k, 10u, and 10v have Ki values of 4.30, 3.72, and 4.56 μM, respectively, and thus, they are more potent than some reported nonglycosyl-based inhibitors such as phlegmacin B1 (Ki = 26 μM), berberine (Ki = 12 μM), 2 (Ki = 11.2 μM), and 3 (Ki = 28.9 μM). Furthermore, inhibitory kinetic assessments reveal that the target compounds are competitive inhibitors with respect substrate, and based on toxicity predictions, most of them have potent drug properties. The obtained results indicate that the biphenyl-sulfonamide skeleton characterized by simple chemical structure, synthetic tractability, potent activity, and low toxicity has potential for further development in pest management targeting OfHex1.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 00472; 00473; 001131; 001132, (2021/01/22)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with a defect in glyoxylate metabolism, for example a disease or disorder associated with the enzyme glycolate oxidase (GO) or alterations in oxalate metabolism. Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
GLYCOLATE OXIDASE INHIBITORS FOR THE TREATMENT OF DISEASE
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Paragraph 00514; 00515; 00516; 001173; 001174; 001175, (2019/07/17)
Described herein are compounds, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or disorders associated with the enzyme glycolate oxidase (GO). Such diseases or disorders include, for example, disorders of glyoxylate metabolism, including primary hyperoxaluria, that are associated with production of excessive amounts of oxalate.
Novel 5-methyl-2-phenylphenanthridium derivatives as FtsZ-targeting antibacterial agents from structural simplification of natural product sanguinarine
Liu, Jingru,Ma, Ruxin,Bi, Fangchao,Zhang, Fa,Hu, Chaoyu,Venter, Henrietta,Semple, Susan J.,Ma, Shutao
supporting information, p. 1825 - 1831 (2018/04/16)
A novel series of 5-methyl-2-phenylphenanthridium derivatives were displayed outstanding activity against a panel of antibiotic-sensitive and -resistant bacteria strains compared with their precursor sanguinarine, ciprofloxacin and oxacillin sodium. Compounds 7 l, 7m and 7n were found to display the most effective activity against five sensitive strains (0.06–2 μg/mL) and three resistant strains (0.25–4 μg/mL). The kinetic profiles indicated that compound 7l possessed the strongest bactericidal effect on S. aureus ATCC25923, with the MBC value of 16 μg/mL. The cell morphology and the FtsZ polymerization assays indicated that these compounds inhibited the bacterial proliferation by interfering the function of bacterial FtsZ. The SARs showed that all the 4-methyl-substituted 5-methyl-2-phenylphenanthridium subseries could be further investigated as the FtsZ-targeting antibacterial agents.
A terphenyl structure containing between the diamine compound and its synthetic method and application
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Paragraph 0036; 0037, (2017/04/19)
The invention discloses a diamine compound with a meta-terphenyl structure as well as a synthetic method and application thereof. An amino group is introduced by using an aryl halide through Suzuki reaction, and the functional diamine compound with the meta-terphenyl structure is obtained by virtue of bromination, diazotization, Suzuki coupling and reduction. The synthetic method for the diamine compound is simple and relatively high in yield, and the synthesized compound has certain fluorescence property. The diamine compound can be used for synthesizing high-performance and functional polymers such as polyamide, polyimide, polyamideimide and polyesterimide, and is especially suitable for preparing a soluble, colorless and transparent high-performance functional polyimide material with certain fluorescence property.
One-Pot Palladium-Catalyzed Cross-Coupling Treble of Borylation, the Suzuki Reaction and Amination
Jong, Howard,Eey, Stanley T.-C.,Lim, Yee Hwee,Pandey, Sangeeta,Iqbal, Nurul Azmah Bte,Yong, Fui Fong,Robins, Edward G.,Johannes, Charles W.
supporting information, p. 616 - 622 (2017/02/23)
A methodology for a sequential palladium-catalyzed cross-coupling procedure consisting of borylation, the Suzuki reaction and amination has been developed for the assembly of molecules with multi-aryl backbones. The linchpin of this development is the meta-terarylphosphine ligand, Cy*Phine, which has been employed as an air- and moisture-stable precatalyst, Pd(Cy*Phine)2Cl2, to improve the efficiency of one-pot borylation–Suzuki reactions. Additionally, the reactivity of the Pd-Cy*Phine system could be tuned to furnish a one-pot, borylation–Suzuki reaction–amination (BSA) cross-coupling treble. The methodology successfully integrated complementary conditions for three distinctly different and modular reactions. Average yields of 74–94% could be achieved for each segment that cumulatively afforded 50–84% yield over the entire three-step sequence in a single pot. (Figure presented.).
3-Hydroxypyrimidine-2,4-diones as Selective Active Site Inhibitors of HIV Reverse Transcriptase-Associated RNase H: Design, Synthesis, and Biochemical Evaluations
Tang, Jing,Liu, Feng,Nagy, Eva,Miller, Lena,Kirby, Karen A.,Wilson, Daniel J.,Wu, Bulan,Sarafianos, Stefan G.,Parniak, Michael A.,Wang, Zhengqiang
, p. 2648 - 2659 (2016/04/10)
Human immunodeficiency virus (HIV) reverse transcriptase (RT) associated ribonuclease H (RNase H) remains an unvalidated antiviral target. A major challenge of specifically targeting HIV RNase H arises from the general lack of selectivity over RT polymerase (pol) and integrase (IN) strand transfer (ST) inhibitions. We report herein the synthesis and biochemical evaluations of three novel 3-hydroxypyrimidine-2,4-dione (HPD) subtypes carefully designed to achieve selective RNase H inhibition. Biochemical studies showed the two subtypes with an N-1 methyl group (9 and 10) inhibited RNase H in low micromolar range without siginificantly inhibiting RT polymerase, whereas the N-1 unsubstituted subtype 11 inhibited RNase H in submicromolar range and RT polymerase in low micromolar range. Subtype 11 also exhibited substantially reduced inhibition in the HIV-1 INST assay and no significant cytotoxicity in the cell viability assay, suggesting that it may be amenable to further structure-activity relationship (SAR) for identifying RNase H inhibitors with antiviral activity.
Nickel-catalyzed monoarylation of ammonia
Borzenko, Andrey,Rotta-Loria, Nicolas L.,Macqueen, Preston M.,Lavoie, Christopher M.,McDonald, Robert,Stradiotto, Mark
supporting information, p. 3773 - 3777 (2015/03/18)
Structurally diverse (hetero)aryl chloride, bromide, and tosylate electrophiles were employed in the Ni-catalyzed monoarylation of ammonia, including chemoselective transformations. The employed JosiPhos/[Ni(cod)2] catalyst system enables the use of commercially available stock solutions of ammonia, or the use of ammonia gas in these reactions, thereby demonstrating the versatility and potential scalability of the reported protocol. Proof-of-principle experiments established that air-stable [(JosiPhos)NiCl2] precatalysts can be employed successfully in such transformations. Lighten Up: The substrate scope of the title reaction includes (hetero)aryl chloride, bromide, and tosylate electrophiles. The versatility and potential scalability of the reported method is demonstrated by the use of either commercially available stock solutions of ammonia or ammonia gas.
Structure-activity relationship study of E6 as a novel necroptosis inducer
Mou, Jianfeng,Park, Ann,Cai, Yu,Yuan, Junying,Yuan, Chengye
supporting information, p. 3057 - 3061 (2015/06/22)
Necroptosis inducers represent a promising potential treatment for drug-resistant cancer. We herein describe the structure modification of E6, which was identified recently as a potent and selective necroptosis inducer. The studies described herein demonstrate for the first time that functionalized biphenyl derivatives possess necroptosis inducer activity. Furthermore, these studies have led to the identification of two promising compounds (5h and 5j) that can be used for further optimization studies as well as mechanism of action investigations.
A novel 4-aminoantipyrine-Pd(II) complex catalyzes Suzuki-Miyaura cross-coupling reactions of aryl halides
Contreras-Celedn, Claudia A.,Mendoza-Rayo, Daro,Rincn-Medina, Jos A.,Chacn-Garca, Luis
supporting information, p. 2821 - 2826 (2015/02/19)
A simple and efficient catalytic system based on a Pd complex of 4-aminoantipyrine, 4-AAP-Pd(II), was found to be highly active for Suzuki-Miyaura cross-coupling of aryl iodides and bromides with phenylboronic acids under mild reaction conditions. Good to excellent product yields from the cross-coupling reaction can be achieved when the reaction is carried out in ethanol, in the open air, using low loading of 4-AAP-Pd(II) as a precatalyst, and in the presence of aqueous K2CO3 as the base. A variety of functional groups are tolerated.
