69807-81-4Relevant articles and documents
Discovery of novel heteroarylmethylcarbamodithioates as potent anticancer agents: Synthesis, structure-activity relationship analysis and biological evaluation
Li, Ying-Bo,Yan, Xu,Li, Ri-Dong,Liu, Peng,Sun, Shao-Qian,Wang, Xin,Cui, Jing-Rong,Zhou, De-Min,Ge, Ze-Mei,Li, Run-Tao
, p. 217 - 230 (2016/05/02)
A series of new analogs based on the structure of lead compound 10 were designed, synthesized and evaluated for their in vitro anti-cancer activities against four selected human cancer cell lines (HL-60, Bel-7402, SK-BR-3 and MDA-MB-468). Several synthesized compounds exhibited improved anti-cancer activities comparing with lead compound 10. Among them, 1,3,4-oxadiazole analogs 17o showed highest bioactivity with IC50 values of 1.23, 0.58 and 4.29 μM against Bel-7402, SK-BR-3 and MDA-MB-468 cells, respectively. It is noteworthy that 17o has potent anti-proliferation activity toward a panel of cancer cells with relatively less cytotoxicity to nonmalignant cells. The further mechanistic study showed that it induced apoptosis and cell cycle arrest through disrupting spindle assembly in mitotic progression, indicating these synthesized dithiocarbamates represented a novel series of anti-cancer compounds targeting mitosis.
Design, synthesis and biological evaluation of novel arachidonic acid derivatives as highly potent and selective endocannabinoid transporter inhibitors
López-Rodríguez,Viso,Ortega-Gutiérrez,Lastres-Becker,González,Fernández-Ruiz,Ramos
, p. 4505 - 4508 (2007/10/03)
In the present work, we have designed and synthesized a series of arachidonic acid derivatives of general structure I which have been characterized as highly potent and selective inhibitors of anandamide transporter (IC50 = 24-0.8 μM, Ki > 1000-5000 nM for CB1 and CB2 cannabinoid receptors and vanilloid VR1 receptor). Among them, N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide deserves special attention as being the most potent endocannabinoid transporter inhibitor (IC50 = 0.8 μM) described to date.
Piperazinylalkyl Heterocycles as Potential Antipsychotic Agents
Scott, Malcolm K.,Baxter, Ellen W.,Bennett, Debra J.,Boyd, Robert E.,Blum, Paul S.,et al.
, p. 4198 - 4210 (2007/10/03)
We recently reported on a series of pyrrole Mannich bases orally active in inhibiting the conditioned avoidance response (CAR) in rats.These compounds exhibit affinity for both D2 and 5-HT1A receptors, and some are noncataleptogenic.Such a profile suggest that they may be potential antipsychotic agents which lack the propensity for causing extrapyramidal side effects and tardive dyskinesias in humans.One of these compounds, 1--1-piperazinyl>methyl>-1H-pyrrol-2-yl>methyl>-2-piperidinone (RWJ 25730, 1), was chosen for further development but found to be unstable in dilute acid.In order to improve stability, we replaced the pyrrole methylene linkage to the piperazine ring with ethylene, employed ethylene and dicarbonyl as linkers between the lactam and the pyrrole ring, placed electron-withdrawing groups on the pyrrole ring, and substituted acyclic amide for lactam.In addition, we replaced the pyrrole segment with other heterocycles including thiophene, furan, isoxazole, isoxazoline, and pyridine.Generally, replacemcent of the N-methylpyrrole segment with thiophene, furan, isoxazoline, or pyridine afforded compounds equipotent with 1 in CAR, which were more stable in dilute acid.In the case of side chain or lactam modifications, CAR activity was significantly decreased or abolished, with the exception of 6.For the most part, the modifications to 1 resulted in the decrease or loss of D2 receptor binding.However, within this series, 5-HT1A receptor binding was greatly increased, with thiophene 40 exhibiting an IC50 of 0.07 nM.The CAR activities of pyrroles 6 and 12, thiophene 40, furans 44-47, isoxazolines 49 and 50, pyridine 54 coupled with their weak or nonexistent D2 binding and strong 5-HT1A binding suggest that they may be acting via a nondopaminergic mechanism or that dopaminergic active metabolites are responsible.Pyrrole 6 and furans 44 and 47 show promise as antipsychotic agents based on their CAR activity, receptor-binding profile, and solution stability.
