13990-98-2Relevant academic research and scientific papers
Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents
Cheng, Jianjun,Qin, Jihong,Guo, Sihua,Qiu, Hangdeng,Zhong, Yun
, p. 4768 - 4772 (2015/01/09)
Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules.
Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: Synthesis, biological evaluation and structure-activity relationships. Part 2
Horiuchi, Takao,Nagata, Motoko,Kitagawa, Mayumi,Akahane, Kouichi,Uoto, Kouichi
experimental part, p. 7850 - 7860 (2010/04/02)
The design, synthesis and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitor are described. Focusing on the optimization of the heteroaryl moiety at the hydrazone with substituted phenyl group
Inhibitors of acyl-CoA:cholesterol O-acyl transferase (ACAT) as hypocholesterolemic agents. 8. Incorporation of amide or amine functionalities into a series of disubstituted ureas and carbamates. Effects of ACAT inhibition in vitro and efficacy in vivo
O'Brien,Sliskovic,Blankley,Roth,Wilson,Hamelehle,Krause,Stanfield
, p. 1810 - 1822 (2007/10/02)
A series of disubstituted ureas containing amide or amine groups was prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O- acyl transferase in vitro and to lower plasma total cholesterol in a variety of cholesterol-fed rat models in vivo. The presence of polar or ionizable functionalities within this class of compounds may impart greater aqueous solubility to those compounds and thus allow improved transport to the enzyme location within the intestinal enterocyte. Compounds from this class exhibit good cholesterol lowering in a chronic cholesterol-fed rat model of hypercholesterolemia even when dosed in an aqueous vehicle. In general, the amine-containing compounds were more potent and efficacious than the amides in the acute rat model of hypercholesterolemia. Further structure-activity relationship studies showed that the preferred position of the amide/amine group was β to the urea moiety and not α, and that in this series, the presence of a secondary amine (or amide) proton is required for good in vitro potency. One of these compounds, 9n(-), lowered plasma total cholesterol (- 47%) and elevated high-density lipoprotein cholesterol (+256%) when dosed in an aqueous vehicle to rats with preestablished hypercholesterolemia.
Chemical Ionization Mass Spectrometry of Bifunctional Compounds. The Behaviour of Bifunctional Compounds on Protonation
Nakata, Hisao,Suzuki, Yumi,Shibata, Miyuki,Takahashi, Konomi,Konishi, Hideyuki,et al.
, p. 649 - 654 (2007/10/02)
Positive-ion chemical ionization mass spectra were measured for simple bifunctional aromatic compounds of the type p-XCH2C6H4CH2Y, where X = NH2, NH(CH3) and N(CH3)2 and Y = OH and OCH3.For each compound, essentially only three peaks of ions, (1+), (1+) and (1+), appeared.The B/E constant linked-scan spectra showed that the stable non-decomposing (1+) had the proton only on the nitrogen-containing functional group.From these data, the relative amounts of total protonation, the ratio of N- and O-protonation and the fraction of fragmenting (1+) can be calculated.The ease of protonation (protonation sus ceptibility) and the reactivity (fragmentation capability) of the respective functional groups are discussed.
