117322-30-2Relevant articles and documents
Exploration of N-(2-aminoethyl)piperidine-4-carboxamide as a potential scaffold for development of VEGFR-2, ERK-2 and Abl-1 multikinase inhibitor
Jin, Feng,Gao, Dan,Wu, Qin,Liu, Feng,Chen, Yuzong,Tan, Chunyan,Jiang, Yuyang
, p. 5694 - 5706 (2013/09/12)
VEGFR, ERK and Abl had been respectively identified as good drug targets, and their crosstalk also had been well elaborated. Multitarget drugs were more advantageous for cancer treatment, however, no inhibitors simultaneously acting on the three proteins were developed due to their structural diversities. Herein, N-(4-((2-(2-(naphthaen-1-yl)acetamido)ethyl)carbamoyl)piperidin-4-yl)-6- (trifluoromethyl)nicotinamide (NEPT, 6a) was discovered as an active scaffold against VEGFR-2, ERK-2 and Abl-1 kinases through the combination of support vector machine, similarity searching and molecular docking. NEPT and its derivatives were synthesized by convenient routine, their in vitro anti-proliferative abilities against human liver cancer cell line HepG2 were preliminarily evaluated. A representative compound 6b showed an IC50 value of 11.3 μM and induced significant HepG2 cells apoptosis. Besides, these compounds displayed better anti-proliferative abilities against K562 cells (a cell line with typical hyperactivity of the above multikinases), for example compound 6b exhibited an IC50 value of 4.5 μM. Based on hepatotoxicity case reports of Abl inhibitors, cytotoxicity of synthetic compounds against normal liver cell lines (QSG7701 and HL7702) was studied, 6b had a similar toxic effect with positive control imatinib, and most compounds showed less than 35% inhibition activities at 100 μM. Molecular docking study disclosed interactions of 6b with VEGFR-2, ERK-2 and Abl-1 kinases, respectively. Our data suggested the biological activities of 6b may derived from collaborative effects of VEGFR-2, ERK-2 and Abl-1 inhibition.
Solid-phase synthesis and utilization of side-chain reactive unnatural amino acids
O'Donnell, Martin J.,Alsina, Jordi,Scott, William L.
, p. 8403 - 8406 (2007/10/03)
Alkylation of the benzophenone imine of glycine Wang resin with α,ω-dihaloalkanes yielded valuable reactive intermediates. These racemic ω-chloro or ω-bromo intermediates were converted to α-amino acids containing diverse side-chain functionalities (e.g.
Zinc promoted rapid and efficient synthesis of Fmoc- and Z-α,α-dialkylamino acids under neutral conditions
Babu, Vommina V. Suresh,Ananda, Kuppanna
, p. 70 - 74 (2007/10/03)
The introduction of Nα-9-fluorenylmethyloxycarbonyl (Fmoc) and benzyloxycarbonyl (Z) groups into α,α-dialkylamino acids is described at neutral pH using Fmoc-Cl or Z-Cl as an acylating agent respectively in the presence of activated zing powder. The reaction is simple, fast and clean. It also permits the scale up with high yields. It is completely free from protected oligomer formation, which is a known side-reaction when Schotten-Baumann procedure is followed. All the Fmoc- and Z-amino acids prepared have been fully characterized.
