95857-32-2Relevant articles and documents
Design and synthesis of boronic acid inhibitors of endothelial lipase
O'Connell, Daniel P.,Leblanc, Daniel F.,Cromley, Debra,Billheimer, Jeffrey,Rader, Daniel J.,Bachovchin, William W.
scheme or table, p. 1397 - 1401 (2012/03/26)
Endothelial lipase (EL) and lipoprotein lipase (LPL) are homologous lipases that act on plasma lipoproteins. EL is predominantly a phospholipase and appears to be a key regulator of plasma HDL-C. LPL is mainly a triglyceride lipase regulating (V)LDL levels. The existing biological data indicate that inhibitors selective for EL over LPL should have anti-atherogenic activity, mainly through increasing plasma HDL-C levels. We report here the synthesis of alkyl, aryl, or acyl-substituted phenylboronic acids that inhibit EL. Many of the inhibitors evaluated proved to be nearly equally potent against both EL and LPL, but several exhibited moderate to good selectivity for EL.
A Facile Alkylation of Aryl Aldehyde Tosylhydrazone with Trialkylboranes
Kabalka, George W.,Maddox, John T.,Bogas, Ekaterini
, p. 5530 - 5531 (2007/10/02)
Trialkylboranes readily alkylate aryl aldehyde tosylhydrazones to produce either the corresponding arylalkane or aryl alcohol in excellent yields.
Arylhydroxamic acid N,O-acyltransferase substrates. Acetyl transfer and electrophile generating activity of N-hydroxy-N-(4-alkenyl-, and 4-cyclohexylphenyl)acetamides
Mangold,Hanna
, p. 630 - 638 (2007/10/02)
Arylhydroxamic acid N,O-acyltransferase (AHAT) is an enzyme system that is capable of converting many N-arylhydroxamic acids into reactive electrophilic species. As part of an investigation into the influence of the structure of the aryl group upon the ability of N-arylhydroxamic acids to serve as substrates for AHAT, a series of N-hydroxy-N-(4-alkyl-, 4-alkenyl-, and 4-cyclohexylphenyl) acetamides was prepared and evaluated in vitro with partially purified rat and hamster hepatic AHAT. The nature of the 4-substituent markedly influenced the ability of the hydroxamic acids to serve as acetyl donors in the AHAT-catalyzed transacetylation of 4-aminoazobenzene (AAB). As the length of the 4-substituent was increased from methyl to pentyl, the compounds became increasingly more effective substrates. The compounds containing vinyl, propenyl, and 2-methylpropenyl 4-substituents were more effective acetyl donors than the corresponding compounds containing saturated 4-substituents. The three most effective AHAT substrates in the AAB transacetylation assay were N-hydroxy-N-(4-pentylphenyl)- (7), N-hydroxy-N-(4-propenylphenyl)- (10), and N-hydroxy-N-[4-(2-methylpropenyl)phenyl]acetamide (11), each of which was approximately as active as the standard compound, N-hydroxy-4-acetamidobiphenyl (1), with rat hepatic AHAT and approximately 60% as active as 1 with hamster hepatic AHAT. Both 1 and N-hydroxyl-N-(4-cyclohexylphenyl)acetamide (8) were activated by hamster hepatic AHAT to yield electrophilic intermediates that formed adducts with 2-mercaptoethanol. The 2-mercaptoethanol adducts were characterized by mass spectrometry and were identified as 4-phenyl-2-[(2-hydroxyethyl)thio]aniline (22) and 4-cyclohexyl-2-[(2-hydroxyethyl)thio]aniline (21). The structure of compounds 21 and 22 were confirmed by an unambiguous chemical synthesis. Both compounds 1 and 8 irreversibly inactivated hamster hepatic AHAT by a time-dependent process. The results of the inactivation experiments confirmed that 1 inactivates AHAT primarily via a suicide substrate mechanism and revealed that 8 inactivates the enzyme by a process consisting primarily of a pathway in which electrophiles are released into the medium and subsequently react with nucleophiles present on AHAT.
