31332-88-4Relevant academic research and scientific papers
ETHYNYLBENZENE DERIVATIVES
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Page/Page column 45, (2012/03/26)
Disclosed are compounds of formulae (I), (II), and (II)I: and pharmaceutically acceptable salts thereof, wherein the variables, R, R1, R2, R3, R101, L, D, Q, Y, X, and Z are defined herein. These compounds are useful for treating Gram-negative bacteria infections.
Novel synthesis of [1-11C]γ-vinyl-γ-aminobutyric acid ([1-11C]GVG) for pharmacokinetic studies of addiction treatment
Zhang, Zongren,Ding, Yu-Shin,Studenov, Andrei R.,Gerasimov, Madina R.,Ferrieri, Richard A.
, p. 199 - 211 (2007/10/03)
γ-Vinyl-γ-aminobutyric acid (GVG, Vigabatrin), a suicide inhibitor of GABA-transaminase (GABA-T), has been suggested as a new drug for the treatment of substance abuse. In order to better understand its pharmacokinetics and potential side effects, we have developed a radiosynthesis of carbon-11 (t1/2=20min) labeled GVG for positron emission tomographic (PET) studies. We report here a novel synthetic strategy to prepare the precursor and to efficiently label GVG with C-11. 5-Bromo-3-(carbobenzyloxy)amino-1-pentene was synthesized in five steps from homoserine lactone, including reduction and methylenation. This was used in a one-pot, two-step radiosynthesis. Displacement of bromide with no-carrier-added [11C]cyanide followed by acid hydrolysis afforded [1-11C]GVG with decay corrected radiochemical yields of 27 ± 9% (n=6, not optimized) with respect to [11C]cyanide in a synthesis time of 45 min. Copyright
Synthesis and in vitro enzyme activity of aza, oxa and thia derivatives of bacterial cell wall biosynthesis intermediates
Cox,Wang
, p. 2022 - 2034 (2007/10/03)
Mechanism based inhibitors of diaminopimelate aminotransferase (DAP-AT) were designed using knowledge of its substrate specificity and mechanism. Synthesis of thiolester and amide substrate analogues was achieved prior to in vitro inhibition studies, but ester analogues proved too unstable to isolate. Thia substrate analogues showed no inhibitory properties, but the aza substrate analogue 12a showed reversible inhibition vs. DAP-AT and time dependent inhibition in the absence of the natural substrate 4. Substrate analogue 12a is thefirst example of an amide inhibitor of PLP dependent enzymes. Antibiotic properties of 12a were also briefly assessed.
New synthetic routes to α-amino acids and γ-oxygenated α-amino acids. Reductive denitration and oxidative transformations of γ-nitro-α-amino acids
Crossley, Maxwell J.,Fung, Yik M.,Kyriakopoulos, Efstathia,Potter, Jeffrey J.
, p. 1123 - 1130 (2007/10/03)
Transformation of γ-nitro-α-amino acid derivatives into α-amino acids by reductive denitration, into the γ-oxo-α-amino acids by ozonolysis of the corresponding amino acid ester nitronate derivatives, and into γ-hydroxy-α-amino acid derivatives by subsequent reduction of the oxo functionality, can be achieved in good yields. As the γ-nitro-α-amino acid derivatives are prepared from N,O-protected dehydroalanines derivable from the corresponding alanine, serine and cysteine derivatives by specific routes, the overall procedures provide a means for selective conversion of these simple α-amino acids into more complex ones.
Design and Synthesis of &γ-Oxygenated Phosphinothricins as Inhibitors of Glutamine Synthetase
Walker, Daniel M.,McDonald, John F.,Franz, John E.,Logusch, Eugene W.
, p. 659 - 666 (2007/10/02)
The ability of L-γ-hydroxyglutamic acids to act as substrates of the enzyme glutamine synthetase (GS) was exploited as a rationale for the synthesis of γ-oxygenated analogues of the naturally occurring GS inhibitor phosphinothricin (PPT).The potent new in
Synthesis of D,L-&γ-Hydroxyphosphinothricin, a Potent New Inhibitor of Glutamine Synthetase
Walker, Daniel M.,McDonald, John F.,Logusch, Eugene W.
, p. 1710 - 1711 (2007/10/02)
A flexible synthesis of D,L-γ-hydroxyphosphothricin (GHPPT), a potent inhibitor of the enzyme glutamine synthetase, is described which features silicon-mediated addition of ethyl methylphosphinate to benzyl 2-benzyloxycarbonylamino-4-oxobutyrate; selectiv
Synthesis of (Z)-4-(acylamino)- and 4-(alkylamino)-α-oximinophenylacetic acids: properties and stereochemical determination
Domagala, John M.,Haskell, Theodore H.
, p. 134 - 140 (2007/10/02)
The preparation, properties, and stereochemical determinations of a series of 4-substituted α-oximinophenylacetic acids are described.The 4-acetamino and 4-amino>-α-oxophenylacetic acids 7 and 19 were synthesized from the corresponding acetophenones with selenium dioxide.The oximes were then prepared and their stereochemistry determined as Z (syn), through the chemical properties of the methoxyimino derivatives.A key intermediate was (Z)-methyl 4-amino>-α-imino>phenylacetate (24), which was synthesized from the free oxime or from the keto acid by using O-(tetrahydropyran-2-yl)hydroxylamine.Deprotection of this compound at nitrogen gave the 4-amino-α-oximino ester, 25, which was acylated with a variety of acid chlorides and hydrolyzed to the 4-(acylamino)-α-oximinophenylacetic acids.By employment of methyl 4-amino-α-oxophenylacetate dimethyl ketal (9), a general reductive amination process was developed, leading to the 4-(alkylamino)-α-oximinophenylacetic acids.
