- Discovery of Cyclic Boronic Acid QPX7728, an Ultrabroad-Spectrum Inhibitor of Serine and Metallo-β-lactamases
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Despite major advances in the β-lactamase inhibitor field, certain enzymes remain refractory to inhibition by agents recently introduced. Most important among these are the class B (metallo) enzyme NDM-1 of Enterobacteriaceae and the class D (OXA) enzymes
- Hecker, Scott J.,Reddy, K. Raja,Lomovskaya, Olga,Griffith, David C.,Rubio-Aparicio, Debora,Nelson, Kirk,Tsivkovski, Ruslan,Sun, Dongxu,Sabet, Mojgan,Tarazi, Ziad,Parkinson, Jonathan,Totrov, Maxim,Boyer, Serge H.,Glinka, Tomasz W.,Pemberton, Orville A.,Chen, Yu,Dudley, Michael N.
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p. 7491 - 7507
(2020/08/21)
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- A convenient and efficient H2SO4-promoted regioselective monobromination of phenol derivatives using N-bromosuccinimide
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A convenient, rapid H2SO4-promoted regioselective monobromination reaction with N-bromosuccinimide was developed. The desired para-monobrominated or ortho-monobrominated products of phenol derivatives were obtained in good to excellent yields with high selectivity. Regioselective chlorination and iodination were also achieved in the presence of H2SO4 using N-chlorosuccinimide and N-iodosuccinimide, respectively.
- Wu, Yong-Qi,Lu, Hai-Jia,Zhao, Wen-Ting,Zhao, Hong-Yi,Lin, Zi-Yun,Zhang, Dong-Feng,Huang, Hai-Hong
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p. 813 - 822
(2020/02/15)
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- A new process to prepare 3,6-dichloro-2-hydroxybenzoic acid, the penultimate intermediate in the synthesis of herbicide dicamba
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Glyphosate [N-(phosphonomethyl)glycine] is a broad spectrum, post-emergent herbicide that is among the most widely used agrochemicals globally. Over the past 30 years, there has been a development of glyphosate-resistant weeds, which pose a significant challenge to growers and crop scientists, resulting in lower crop yields and increased costs. 3,6-Dichloro-2-methoxybenzoic acid (dicamba) is the active ingredient in XtendiMax a standalone herbicide developed by Bayer Crop Science to control broadleaf weeds, including glyphosate-resistant species. 3,6-Dichloro-2-hydroxybenzoic acid (3,6-DCSA) is the penultimate intermediate in the synthesis of dicamba. Existing dicamba manufacturing routes utilize a high temperature, high pressure Kolbe-Schmitt carboxylation to prepare 3,6-DCSA. Described in this Letter is a new, non-Kolbe-Schmitt process to prepare 3,6-DCSA from salicylic acid in four chemical steps.
- Walker, Daniel P.,Harris, G. Davis,Carroll, Jeffery N.,Boehm, Terri L.,McReynolds, Matthew D.,Struble, Justin R.,van Herpt, Jochem,van Zwieten, Don,Koeller, Kevin J.,Bore, Mangesh
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supporting information
p. 1032 - 1036
(2019/03/17)
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- BORONIC ACID DERIVATIVES AND THERAPEUTIC USES THEREOF
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Disclosed herein are antimicrobial compounds, compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use a therapeutic agents.
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Paragraph 0174; 0177
(2019/11/12)
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- BORONIC ACID DERIVATIVES AND THERAPEUTIC USES THEREOF
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Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the method of use and preparation thereof. Some embodiments relate to boronic acid derivatives and their use as therapeutic agents, for example, β-lactamase inhibitors (BLIs).
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- Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines
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The synthesis of 6-aryl, 8- aryl, and 8-aryl-6-chloro-2-morpholino-1,3-benzoxazines with potent activity against PI3K and DNA-PK is described. Synthesis of thirty one analogues was facilitated by an improved synthesis of 3-bromo-2-hydroxybenzoic acid 13 by de-sulphonation of 3-bromo-2-hydroxy-5-sulfobenzoic acid 12 en route to 2-methylthio-substituted-benzoxazine intermediates 17-19. From this series, compound 20k (LTURM34) (dibenzo[b,d]thiophen-4-yl) (IC50 = 0.034 μM) was identified as a specific DNA-PK inhibitor, 170 fold more selective for DNA-PK activity compared to PI3K activity. Other compounds of the series show markedly altered selectivity for various PI3K isoforms including compound 20i (8-(naphthalen-1-yl) a potent and quite selective PI3Kδ inhibitor (IC50 = 0.64 μM). Finally, nine compounds were evaluated and showed antiproliferative activity against an NCI panel of cancer cell lines. Compound 20i (8-(naphthalen-1-yl) showed strong anti-proliferative activity against A498 renal cancer cells that warrants further investigation.
- Morrison, Rick,Al-Rawi, Jasim M.A.,Jennings, Ian G.,Thompson, Philip E.,Angove, Michael J.
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p. 326 - 339
(2016/02/18)
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- 3,6-DICHLOROSALICYLIC ACID COMPOUNDS AND RELATED SYNTHETIC PROCESSES
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The present disclosure relates, in general, to 5-halo-3,6-dichlorosalicylic acid compounds, 5-halo-3,6-dichlorosalicyaldehyde compounds, processes for preparing 5-halo-3,6-dichlorosalicylic acid compounds, processes for preparing 5-halo-3,6- dichlorosalicyaldehyde compounds, processes for preparing 3,6-dichlorosalicylic acid compounds, and processes that employ such compounds as intermediates in the preparation of the herbicide dicamba.
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Paragraph 0133
(2016/01/26)
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- Mono- and disalicylic acid derivatives: PTP1B inhibitors as potential anti-obesity drugs
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A series of compounds containing one or two salicylic acid moieties were synthesized, and their efficacy to inhibit the phosphohydrolase activity of PTP1B examined. Some of the methylenedisalicylic acid derivatives were potent inhibitors of PTP1B. Of those derivatives, 3c exhibited about a 14-fold selectivity against TC-PTP, and this compound was tested in a mouse model for its efficacy to prevent diet-induced obesity. It effectively suppressed the increases in body weight and adipose mass, without any noticeable toxic effect. The compound also prevented increases in the plasma triglyceride, cholesterol, and nonesterified fatty acid concentrations; thus, expanding its therapeutic potential to other related metabolic diseases, such as hyperlipidemia and hypercholesterolemia.
- Shrestha, Suja,Bhattarai, Bharat Raj,Lee, Keun-Hyeung,Cho, Hyeongjin
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p. 6535 - 6548
(2008/04/12)
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- A short and efficient preparation of methyl-[1,2,4]oxadiazolium derivatives with plant-inducing activity
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A short and efficient preparation of methyl-[1,2,4]oxadiazolium derivatives with plant-inducing activity is discussed. A concise and efficient synthetic method leading to structurally diverse array of oxadiazolium derivatives, starting from halogenated phenols is also developed. The starting point of the synthesis is the Lewis acid mediated addition of isocyanates to phenols. The strategy also involves a new and rapid access to all meta-halogenated salicylic acids, compounds of high synthetic value.
- Dobler, Markus R.
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p. 963 - 964
(2007/10/03)
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- A highly efficient strategy for the synthesis of 3-substituted salicylic acids by either directed ortho-lithiation or halogen-metal exchange of substituted mom protected phenols followed by carboxylation
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A highly efficient synthesis of various 3-substituted salicylic acids is described starting from inexpensive starting materials and requiring no special apparatus.
- Lau, Stephen Y.W.,Keay, Brian A.
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p. 1541 - 1545
(2007/10/03)
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- Electrophilic Catalysis of Sulphate (-SO3-) Group Transfer: Hydrolysis of Salicyl Sulphates assisted by Intramolecular Hydrogen Bonding
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The hydrolysis of substituted salicyl sulphates has been measured over a range of pH values at 70 deg C to obtain kinetic parameters for hydronium ion (kH) and carboxylic acid (kp) calalysis.A Jaffe treatment of the carboxy-catalysis parameter for a range of nuclear substituents yields ρphenol 1.51; ρcarboxy 0 indicates that the carboxy-function does not ionise on going from the ground- to the transition-state, consistent with hydrogen bonding rather than catalysis through proton transfer.The change in 'effective' charge on the phenol oxygen on going from the ground- to the transition-state confirms less build up of negative charge than in the uncatalysed hydrolysis of aryl sulphates.
- Hopkins, Andrew Ramsay,Green, Adam Llywellyn,Williams, Andrew
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p. 1279 - 1284
(2007/10/02)
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- Benzamide derivatives
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Benzamide derivatives of the formula:- STR1 wherein R1 represents a fluorine, chlorine or bromine atom, or an alkyl, alkoxy, alkylthio, alkylsulphonyl, alkanoylamino, alkylamino or alkylsulphamoyl group, each such group containing from 1 to 6 carbon atoms, a dialkylsulphamoyl, dialkylamino or dialkylcarbamoyl group (wherein the two alkyl groups may be the same or different and each contains from 1 to 4 carbon atoms), an alkanoyl, alkoxycarbonyl, alkoxycarbonylamino or alkylcarbamoyl group containing from 2 to 6 carbon atoms, or a hydroxy, formyl, nitro, trifluoromethyl, aryl, benzyloxycarbonylamino, amino, sulphamoyl, cyano, tetrazol-5-yl, carboxy, carbamoyl or aroyl group, and n represents an integer 1, 2 or 3, are new compounds possessing pharmacological properties, in particular properties of value in the treatment of respiratory disorders manifested by the interaction of tissue-fixed antibodies with specific antigens.
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