1214341-16-8Relevant articles and documents
Surprisingly High Selectivity and High Affinity in Mercury Recognition by H-Bonded Cavity-Containing Aromatic Foldarands
Shen, Jie,Ren, Changliang,Zeng, Huaqiang
, p. 5387 - 5396 (2017)
In the absence of macrocyclic ring constraints, few synthetic systems, possessing a mostly solvent-independent well-folded conformation that is predisposed for highly selective and high affinity recognition of metal ions, have been demonstrated. We report here such a unique class of conformationally robust modularly tunable folding molecules termed foldarands that can recognize Hg2+ ions surprisingly well over 22 other metal ions. Despite the lack of sulfur atoms and having only oxygen-donor atoms in its structure, the best foldarand molecule, i.e., tetramer 4, exhibits a selectivity factor of at least 19 in differentiating the most tightly bound Hg2+ ion from all other metal ions, and a binding capacity that is ≥18 times that of thio-crown ethers. These two noteworthy binding characters make possible low level removal of Hg2+ ions. With a [4]:[Hg2+] molar ratio of 5:1 and a single biphasic solvent extraction, the concentration of Hg2+ ions could be reduced drastically by 98% (from 200 to 4 ppb) in pure water. 4 could also effect a highly efficient reduction in mercury content by 98% (from 500 to 10 ppb) in artificial groundwater via multiple successive extractions with an overall consumption of 4 being 9:1 in terms of [4]:[Hg2+] molar ratio.
New cysteine protease inhibitors: Electrophilic (Het)arenes and unexpected prodrug identification for the trypanosoma protease rhodesain
Barthels, Fabian,Distler, Ute,Engels, Bernd,Hellmich, Ute A.,Johe, Patrick,Jung, Sascha,Kühlborn, Jonas,Klein, Philipp,Opatz, Till,Schirmeister, Tanja,Tenzer, Stefan,Wagner, Annika,Waigel, Waldemar
, (2020)
Electrophilic (het)arenes can undergo reactions with nucleophiles yielding π- or Meisenheimer (σ-) complexes or the products of the SNAr addition/elimination reactions. Such building blocks have only rarely been employed for the design of enzyme inhibitors. Herein, we demonstrate the combination of a peptidic recognition sequence with such electrophilic (het)arenes to generate highly active inhibitors of disease-relevant proteases. We further elucidate an unexpected mode of action for the trypanosomal protease rhodesain using NMR spectroscopy and mass spectrometry, enzyme kinetics and various types of simulations. After hydrolysis of an ester function in the recognition sequence of a weakly active prodrug inhibitor, the liberated carboxylic acid represents a highly potent inhibitor of rhodesain (Ki = 4.0 nM). The simulations indicate that, after the cleavage of the ester, the carboxylic acid leaves the active site and re-binds to the enzyme in an orientation that allows the formation of a very stable π-complex between the catalytic dyad (Cys-25/His-162) of rhodesain and the electrophilic aromatic moiety. The reversible inhibition mode results because the SNAr reaction, which is found in an alkaline solvent containing a low molecular weight thiol, is hindered within the enzyme due to the presence of the positively charged imidazolium ring of His-162. Comparisons between measured and calculated NMR shifts support this interpretation.
Amide compound as well as preparation method and application thereof
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Paragraph 0155-0159; 0195-0199, (2021/04/17)
The invention provides an amide compound as well as a preparation method and application thereof. The amide compound has a structure as shown in a formula I in the specification. The amide compound disclosed by the invention can have high insecticidal act
AMIDE COMPOUNDS AND PREPARATION METHOD THEREFOR AND USE THEREOF
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Page/Page column 23; 27, (2021/04/23)
Provided are amide compounds and a preparation method therefor and the use thereof. The amide compounds have a structure represented by formula (I). The amide compounds of the present invention have high insecticidal activity at a low dosage and have a go
Novel pyrimidine sulfonamide derivatives and a mite controlling composition comprising thereof
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Paragraph 0048-0057, (2021/06/01)
The present invention relates to a novel amide derivative and a composition for controlling an acaricide comprising the same. By introducing a heterocyclic substituent into the amide derivative, a composition for controlling an acaricide activity can be p
Preparation method and application of tetrahydrobenzothiophene compound and pharmaceutical composition
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Paragraph 0151; 0154-0155; 0277; 0280-0281, (2021/10/16)
The invention belongs to the field of medicines, and particularly relates to a tetrahydrobenzothiophene compound as well as a pharmaceutical composition and a preparation method and application thereof. The tetrahydrobenzothiophene compound is a compound I as shown I. In-flight R1 And R2 The C1 -4 is a saturated/unsaturated hydrocarbon group. - OCH3 , OCH2 CH3 Phenyl, substituted phenyl, NO2 One - COR of - OH - F, Cl - Br. I - H R1 AND R2 Or different. R3 It is-F. - Cl, Br, I, OH, Amino, C1 -4 saturated/unsaturated hydrocarbon group, OCH3 , OCH2 CH3 , H, Wherein one of them is, n ≥ 5, n Being an integer. The compound effectively inhibits salmonella by inhibiting the synthesis of ATP-dependent transporter in the lipopolysaccharide synthesis pathway. Aeruginosa, escherichia coli and staphylococcus aureus.
Berotralstat (BCX7353): Structure-Guided Design of a Potent, Selective, and Oral Plasma Kallikrein Inhibitor to Prevent Attacks of Hereditary Angioedema (HAE)
Babu, Yarlagadda S,Chambers-Wilson, Ramanda,Chen, Xilin,Chintareddy, Venkat,Davis Parker, Cynthia,Juarez, Luis,Kellogg-Yelder, Debra,Kotian, Pravin L,Lu, Pengcheng,Muppa, Saritha,Polach, Kevin J,Raman, Krishnan,Vadlakonda, Satish,Williams, Jason,Wu, Minwan,Zhang, Weihe
supporting information, p. 12453 - 12468 (2021/09/13)
Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50000 individuals worldwide. Until recently, prophylactic HAE treatment options were limited to injectables, a burdensome administration route that has driven the need for an oral treatment. A substantial body of evidence has shown that potent and selective plasma kallikrein inhibitors that block the generation of bradykinin represent a promising approach for the treatment of HAE. Berotralstat (BCX7353, discovered by BioCryst Pharmaceuticals using a structure-guided drug design strategy) is a synthetic plasma kallikrein inhibitor that is potent and highly selective over other structurally related serine proteases. This once-daily, small-molecule drug is the first orally bioavailable prophylactic treatment for HAE attacks, having successfully completed a Phase III clinical trial (meeting its primary end point) and recently receiving the U.S. Food and Drug Administration's approval for the prophylactic treatment of HAE attacks in patients 12 years and older.
POLYCYCLIC COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF RAPIDLY ACCELERATED FIBROSARCOMA POLYPEPTIDES
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Paragraph 1588; 1589, (2020/03/29)
The present disclosure relates to bifunctional compounds, ULM— L—PTM, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A- RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
Development of an Efficient Synthetic Process for Broflanilide
Huang, Chaoqun,Huang, Geng,Luo, Chunyan,Luo, Liangming,Xu, Qiong,Yin, Dulin,Zhang, Rong,Zhu, Jintao
, p. 1024 - 1031 (2020/07/15)
This article describes the development of an efficient and scalable synthetic route to the novel insecticide broflanilide (1). This redesigned synthetic sequence starts from 2-fluoro-3-nitrobenzoic acid and 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) ani
PIPERONYLIC ACID DERIVATIVE AND PREPARATION AND APPLICATION THEREOF
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Paragraph 0098-0099, (2020/07/05)
The present invention belongs to the fields of insecticides, acaricides and fungicides, and particularly relates to a piperonylic acid derivative, and preparation and application thereof. The structure is shown in a general formula I, and the definition o
