- Synthesis and biological evaluation of pentanedioic acid derivatives as farnesyltransferase inhibitors
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Structure-based virtual screening of a commercial library identified pentanedioic acid derivatives (6 and 13b) as a kind of novel scaffold farnesyltransferase inhibitors (FTIs). Chemical modifications of the lead compounds, biological assays and analysis of the structure-activity relationships (SAR) were conducted to discover more potent FTIs. Some of them displayed excellent inhibition against FTase, and among them, the most active compound 13n with an IC50 value of 0.0029 μM and SAR analysis might be helpful to the discovery of more potent FTIs. This journal is
- Yang, Liuqing,Liu, Wei,Mei, Hanbing,Zhang, Yuan,Yu, Xiaojuan,Xu, Yufang,Li, Honglin,Huang, Jin,Zhao, Zhenjiang
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p. 671 - 676
(2015/04/27)
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- A one-pot synthesis of 3-arylglutaric anhydrides by reaction of ketene with aromatic aldehydes and ketones
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Aromatic aldehydes and ketones react with ketene under Lewis acid catalysis to produce β-lactones, which in situ react with another molecule of ketene to produce 3-arylglutaric anhydrides. The mechanism, scope, and limitation of this one-pot synthesis of 3-substituted glutaric anhydrides are discussed.
- Matsunaga, Hirokazu,Ikeda, Kiyoshi,Iwamoto, Ken-ichi,Suzuki, Yumiko,Sato, Masayuki
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experimental part
p. 2334 - 2336
(2009/09/06)
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- Enzymatic desymmetrization of 3-arylglutaric acid anhydrides
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Optically active (R)- and (S)-3-arylglutaric acid monoesters 3 were synthesized in quantitative yields and good stereoselectivities by lipase-catalyzed desymmetrization of the corresponding 3-arylglutaric anhydrides 2 with alcohols. It was observed that the stereochemical outcome of the reaction was influenced by the substituents present on the aromatic ring. The influence of the enzyme, alcohol, and solvent was systematically examined. Absolute configurations of the monoesters 3 were assigned by chemical correlation to corresponding lactones 4.
- Fryszkowska, Anna,Komar, Marta,Koszelewski, Dominik,Ostaszewski, Ryszard
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p. 2475 - 2485
(2007/10/03)
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- BENZO-FUSED 5-MEMBERED HETROCYCLE COMPOUNDS,PROCESS FOR PREPARATION OF THE SAME, AND USE THEREOF
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A compound represented by the formula: (wherein, R1 and R2 are the same or different and each represents a hydrogen atom, hydrocarbon group or heterocyclic group, or R1 and R2 may form, together with the adjacent carbon atom, a 3-8 membered iso- or heterocyclic group, R3 represents a cyclic group, a hydroxy group, a mercapto group that may have oxo, or an amino group, R4 represents a hydrogen atom, a hydrocarbon group, a hydroxy group, a mercapto group which may have oxo, or an amino group, or R2 and R4 may link together to form a double bond, X represents a bond or a linear hydrocarbon group, W represents an oxygen atom or a sulfur atom, ring B represents a 5-8 membered nitrogen-containing heterocyclic group, ring C represents a benzene ring, and --- represents a single bond or a double bond), or a salt or a prodrug thereof that has excellent neurodegenerative inhibitory activity and brain penetrability, and is useful as an agent for preventing/treating neurodegenerative diseases.
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- Solid-phase synthesis of a nonpeptide RGD mimetic library: New selective αvβ3 integrin antagonists
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The solid-phase synthesis of a low molecular weight RGD mimetic library is described. Activities of the compounds in inhibiting the interaction of ligands, vitronectin and fibrinogen, with isolated immobilized integrins αvβ3 and αIIbβ3 were determined in a screening assay. Highly active and selective nonpeptide αvβ3 integrin antagonists with regard to orally bioavailability were developed, based on the aza-glycine containing lead compound 1. An important variation is the substitution of the aspartic amide of 1 by an aromatic residue. Furthermore, different guanidine mimetics have been incorporated to improve the pharmacokinetic profile. Exchange of the β-amino acid NH by a methylene moiety in one set of RGD mimetics leads to the azacarba analogue compounds representing a novel peptidomimetic approach, which should increase the metabolic stability.
- Sulyok,Gibson,Goodman,H?lzemann,Wiesner,Kessler
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p. 1938 - 1950
(2007/10/03)
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