15647-47-9Relevant articles and documents
Synthetic studies towards N-substituted 3-vinyl-4-piperidineacetic acid derivatives
Johnson, David A.,Gribble, Gordon W.
, p. 178 - 195 (2019/05/15)
The synthesis and full characterization of two new (E)-2-butenyl)-5-amino-2-pentenoates, (Z)-4-[N-(3-buten-1-yl)benzamido]-2-buten-1-ol, and (Z)-1-chloro-4-[N-(3-buten-l-yl)benzamido]-2-butene are reported. These were designed as substrates for a projected thermal ene cyclization leading to the N-substituted 3-vinyl-4-piperidineacetic acid scaffold. Although conditions for this ene-cyclization have not yet been uncovered, the ease of preparation of these ene-cyclization substrates gives promise for their future use.
A metabolic screening study of trichostatin A (TSA) and TSA-like histone deacetylase inhibitors in rat and human primary hepatocyte cultures
Elaut,Laus,Alexandre,Richert,Bachellier,Tourwe,Rogiers,Vanhaecke, Tamara
, p. 400 - 408 (2008/02/05)
Hydroxamic acid (HA)-based histone deacetylase (HDAC) inhibitors, with trichostatin A (TSA) as the reference compound, are potential antitumoral drugs and show promise in the creation of long-term primary cell cultures. However, their metabolic properties have barely been investigated. TSA is rapidly inactivated in rodents both in vitro and in vivo. We previously found that 5-(4-dimethylaminobenzoyl)aminovaleric acid hydroxyamide or 4-Me2N-BAVAH (compound 1) is metabolically more stable upon incubation with rat hepatocyte suspensions. In this study, we show that human hepatocytes also metabolize TSA more rapidly than compound 1 and that similar pathways are involved. Furthermore, structural analogs of compound 1 (compounds 2-9) are reported to have the same favorable metabolic properties. Removal of the dimethylamino substituent of compound 1 creates a very stable but 50% less potent inhibitor. Chain lengthening (4 to 5 carbon spacer) slightly improves both potency and metabolic stability, favoring HA reduction to hydrolysis. On the other hand, Cα-unsaturation and spacer methylation not only reduce HDAC inhibition but also increase the rate of metabolic inactivation approximately 2-fold, mainly through HA reduction. However, in rat hepatocyte monolayer cultures, compound 1 is shown to be extensively metabolized by phase II conjugation. In conclusion, this study suggests that simple structural modifications of amide-linked TSA analogs can improve their phase I metabolic stability in both rat and human hepatocyte suspensions. Phase II glucuronidation, however, can compensate for their lower phase I metabolism in rat hepatocyte monolayers and could play a yet unidentified role in the determination of their in vivo clearance. Copyright
Composition containing a penem or carbapenem antibiotic and the use of the same
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, (2008/06/13)
Administration of an N-acylated amino acid in association with a penem or carbapenem antibiotic relieves or eliminates the renal problems associated with administration of the antibiotic alone. The amino acid derivative and antibiotic may be formulated together as a composition or administered separately, either simultaneously or sequentially.
