- KRAS G12D INHIBITORS
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The present invention relates to compounds that inhibit KRas G12D. In particular, the present invention relates to compounds that inhibit the activity of KRas G12D, pharmaceutical compositions comprising the compounds and methods of use therefor.
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Paragraph 0938
(2021/03/05)
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- METHODS AND FORMULATIONS TO TREAT MITOCHONDRIAL DYSFUNCTION
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Methods of treatment and pharmaceutical formulations configured to treat primary and secondary mitochondrial dysfunction are provided. The methods and treatments use an agonist of AMPK. The agonist activates AMPK to activate ATP-producing pathways and inhibiting ATP-consuming pathways, thus allowing for the alleviation of symptoms associated with mitochondrial dysfunctions.
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Paragraph 00182
(2020/07/21)
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- Preparation method of high-purity 1,4-dibromonaphthalene
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The invention relates to a preparation method of high-purity 1,4-dibromonaphthalene and belongs to the technical field of organic synthesis. The provided preparation method of high-purity 1,4-dibromonaphthalene aims to solve the problems that preparation methods of 1,4-dibromonaphthalene in the prior art are complicated, the reaction conditions are high, the product purity is low, the yield is low, and the product quality is unstable. The method comprises the four steps of a one-pot acetylation protection and selective bromination process, a hydrolysis deprotection process, a diazotization coupling reaction process and a recrystallization purification process to obtain high-purity 1,4-dibromonaphthalene. The provided preparation method has the advantages that the synthesis route is short,the reaction conditions are mild and easy to control, and the production cost is low. The organic synthesis reaction site is monotonous, the selectivity is high, the product purity is up to 99.0%, andthe total yield can reach 71.7%. Industrial production is easily realized, the need for large-scale production of 1,4-dibromonaphthalene can be effectively met, and the method has a broad applicationprospect.
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Page/Page column 6-12
(2019/10/01)
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- Synthesis of Arylamides via Ritter-Type Cleavage of Solid-Supported Aryltriazenes
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A novel route for the synthesis of N-arylamides via the cleavage of aryltriazenes with alkyl or aryl nitriles is presented. We developed a variation of the Ritter reaction that allows the use of acetonitrile as solvent and reagent in reactions with solid-supported precursors. The reaction was optimized for the generation of N-aryl acetamides using a diverse range of immobilized building blocks including o-, m-, and p-substituted aryltriazenes. The cleavage via the Ritter-type conversion was combined with an on-bead cross-coupling reaction of halogen-substituted aryltriazenes with pyrazoles. Additionally, the synthesis of on-bead generated arylboronic ester-substituted triazenes was shown. The developed procedure was further expanded to use other commercially available nitriles, such as acrylonitrile, benzonitrile, and chlorinated alkyl nitriles as suitable reagents for a Ritter-type cleavage of the prepared triazene linkers.
- Wippert, Nicolai A.,Jung, Nicole,Br?se, Stefan
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supporting information
p. 568 - 572
(2019/09/03)
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- Monna, a potent and selective blocker for transmembrane protein with unknown function 16/anoctamin-1
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Transmembrane protein with unknown function 16/anoctamin-1 (ANO1) is a protein widely expressed in mammalian tissues, and it has the properties of the classic calcium-activated chloride channel (CaCC). This protein has been implicated in numerous major physiological functions. However, the lack of effective and selective blockers has hindered a detailed study of the physiological functions of this channel. In this study, we have developed a potent and selective blocker for endogenous ANO1 in Xenopus laevis oocytes (xANO1) using a drug screening method we previously established (Oh et al., 2008). We have synthesized a number of anthranilic acid derivatives and have determined the correlation between biological activity and the nature and position of substituents in these derived compounds. A structure-activity relationship revealed novel chemical classes of xANO1 blockers. The derivatives contain a-NO2 group on position 5 of a naphthyl group-substituted anthranilic acid, and they fully blocked xANO1 chloride currents with an IC 5050 of 0.08 μM for xANO1. Selectivity tests revealed that other chloride channels such as bestrophin-1, chloride channel protein 2, and cystic fibrosis transmembrane conductance regulator were not appreciably blocked by 10~30 μM MONNA. The potent and selective blockers for ANO1 identified here should permit pharmacological dissection of ANO1/CaCC function and serve as potential candidates for drug therapy of related diseases such as hypertension, cystic fibrosis, bronchitis, asthma, and hyperalgesia.
- Oh, Soo-Jin,Hwang, Seok Jin,Jung, Jonghoon,Yu, Kuai,Kim, Jeongyeon,Choi, Jung Yoon,Hartzell, H. Criss,Roh, Eun Joo,Justin Lee
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supporting information
p. 726 - 735
(2013/11/06)
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- Studies on enamides. VI. An improvised methodology for orton rearrangement under neutral condition
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A highly efficient methodology in neutral medium has been developed for the synthesis of bromoanilides from the corresponding anilides using N-bromosuccinimide in carbon tetrachloride under irradiation with visible light. The products are obtained in highly pure crystalline state with an excellent yield.
- Ghosh,Baul
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p. 2783 - 2786
(2007/10/03)
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- A new mild and selective reagent for nuclear bromination
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Hexamethylene tetramine tribromide HMTAHBr3 - a new, mild and regioselective brominant is reported for bromination of aromatic hydrocarbons, substituted ethers, phenols and anilides in high yields.
- Bisarya,Rao
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p. 779 - 788
(2007/10/02)
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