- BIM-46174 fragments as potential ligands of G proteins
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The 5,6,7,8-Tetrahydroimidazo[1,2-A]pyrazine derivative BIM-46174 has received attention as Gαq inhibitor. We conducted structural reductions to monocyclic and bicyclic substructures to explore the chemical space of BIM fragments and to gain insights into the pharmacophore of BIM-Type Gαq inhibitors. Two piperazin-2-one-containing fragments and a small library of bicyclic lactams featuring fused pyrazine and diazepine rings were synthesized and evaluated. The results of a second messenger-based cellular assay indicate that the entire BIM structure is required for efficient Gαq inhibition.
- Küppers, Jim,Benkel, Tobias,Annala, Suvi,Schnakenburg, Gregor,Kostenis, Evi,Gütschow, Michael
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Read Online
- Preparation method of 4AA
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The invention discloses a preparation method of 4AA. The preparation method comprises the following steps: S1, preparing a first intermediate from benzamide and a formaldehyde aqueous solution; S2, preparing a second intermediate from the first intermediate, thionyl chloride, toluene and n-heptane; S3, preparing a third intermediate from the second intermediate, methyl acetoacetate, sodium methoxide, toluene, diluted hydrochloric acid and isopropanol; S4, preparing a fourth intermediate from the third intermediate, reductase, ethyl acetate, saturated sodium bicarbonate and saturated salt water; S5, preparing a fifth intermediate from the fourth intermediate, imidazole, TBSCL and methylbenzene; S6, preparing a sixth intermediate from the fifth intermediate, ethanolamine, methanol and n-heptane; S7, preparing a seventh intermediate by using the sixth intermediate, a Grignard reagent and n-heptane; and S8, preparing 4AA from the seventh intermediate, ruthenium trichloride, potassium acetate, ethyl acetate, acetic acid and a peracetic acid solution.
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Paragraph 0016; 0018; 0021; 0024
(2021/07/28)
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- Asymmetric synthesis of optically active methyl-2-benzamido-methyl-3-hydroxy-butyrate by robust short-chain alcohol dehydrogenases from Burkholderia gladioli
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Three short-chain alcohol dehydrogenases from Burkholderia gladioli were discovered for their great potential in the dynamic kinetic asymmetric transformation of methyl 2-benzamido-methyl-3-oxobutanoate, and their screening against varied organic solvents and substrates. This is the first report of recombinant enzymes capable of achieving this reaction with the highest enantio- and diastereo-selectivity.
- Chen, Xiang,Liu, Zhi-Qiang,Huang, Jian-Feng,Lin, Chao-Ping,Zheng, Yu-Guo
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supporting information
p. 12328 - 12331
(2015/07/27)
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- Outer-sphere coordination chemistry: Amido-ammonium ligands as highly selective tetrachloridozinc(II)ate extractants
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Eight new amido functionalized reagents, L1-L8, have been synthesized containing the sequence of atoms R2N-CH 2-NR′-CO-R″, which upon protonation forms a six-membered chelate with a hydrogen bond between the ter
- Turkington, Jennifer R.,Cocalia, Violina,Kendall, Katrina,Morrison, Carole A.,Richardson, Patricia,Sassi, Thomas,Tasker, Peter A.,Bailey, Philip J.,Sole, Kathryn C.
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p. 12805 - 12819
(2013/02/22)
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- 3-(Hydroxy(phenyl)methyl)azetidin-2-ones obtained via catalytic asymmetric hydrogenation or by biotransformation
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The catalytic asymmetric reduction of ethyl-2-(benzamidomethyl)-3-oxo- phenylpropanoate was realized with high enantiomeric and diastereoisomeric excesses via biotransformation using whole cells of different yeasts and asymmetric hydrogenation with Ru(II)
- Rimoldi, Isabella,Cesarotti, Edoardo,Zerla, Daniele,Molinari, Francesco,Albanese, Domenico,Castellano, Carlo,Gandolfi, Raffaella
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scheme or table
p. 597 - 602
(2011/06/21)
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- Mechanism of Hydrolysis of Benzamidomethyl Derivatives of Phenols and Its Implications for Prodrug Design
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A series of O-benzamidomethyl derivatives of phenols was synthesized, and their rates of hydrolysis were investigated.The hydrolyses of the compounds follow pseudo-first-order kinetics resulting in quantitative and rapid regeneration of the phenol.The rates of hydrolysis were shown to be dependent on phenol nucleofugicity as well as the pKa of the amide.The mechanism of hydrolysis apparently involves as elimination of the phenol anion from the conjugate base of the amide (E1cB-like).
- Getz, John J.,Prankerd, Richard J.,Sloan, Kenneth B.
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p. 1702 - 1706
(2007/10/02)
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