474020-88-7Relevant articles and documents
N-alkyl-hydroxybenzoyl anilide hydroxamates as dual inhibitors of HDAC and HSP90, downregulating IFN-γ induced PD-L1 expression
Mehndiratta, Samir,Lin, Mei-Hsiang,Wu, Yi-Wen,Chen, Chun-Han,Wu, Tung-Yun,Chuang, Kuo-Hsiang,Chao, Min-Wu,Chen, Yi-Ying,Pan, Shiow-Lin,Chen, Mei-Chuan,Liou, Jing-Ping
, (2019/10/28)
Novel dual inhibitors of histone deacetylase (HDAC) and heat-shock protein 90 (HSP90) are synthesized and evaluated. These compounds are endowed with potent HDAC and HSP90 inhibitory activities with IC50 values in nanomolar range with Compound 20 (HDAC IC50 = 194 nM; HSP90α IC50 = 153 nM) and compound 26 (HDAC IC50 = 360 nM; HSP90α IC50 = 77 nM) displaying most potent HDAC and HSP90α inhibitory activities. Both of these compounds induce HSP70 expression and down regulate HSP90 client proteins which play important roles in the regulation of survival and invasiveness in cancer cells. In addition, compounds 20 and 26 induce acetylation of α-tubulin and histone H3. Significantly, compounds 20 and 26 could effectively reduce programmed death-ligand 1 (PD-L1) expression in IFN-γ treated lung H1975 cells in a dose dependent manner. These findings suggest that dual inhibition of HDAC and HSP90 that can modulate immunosuppressive ability of tumor area may provide a better therapeutic strategy for cancer treatment in the future.
nepal reaches Neeb process and intermediates for the synthesis of (by machine translation)
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Paragraph 0039; 0078, (2016/11/02)
The invention discloses a method for synthesizing nepal reaches Neeb and intermediates thereof, the synthesis method comprises: under acidic conditions, the compound of formula (II) reaction of a compound of the formula (I) compound of formula (III); compound (III) of the detached with acid uncle Ding Zhiji carbonate, adding alkali reaction of the compound of formula (V); the compound of formula (V) reaction with chloroacetic acid derivatives of formula (VI) the activation of the compound, then the reaction-methyl piperazine N, obtain nepal reaches Neeb. The present invention provides a mild reaction conditions of a new method for synthesizing nepal reaches Neeb, the invention also provides synthetic intermediates nepal reaches Neeb. (by machine translation)
Targeting metal-Aβ aggregates with bifunctional radioligand [11C]L2-b and a fluorine-18 analogue [18F]FL2-b
Cary, Brian P.,Brooks, Allen F.,Fawaz, Maria V.,Shao, Xia,Desmond, Timothy J.,Carpenter, Garrett M.,Sherman, Phillip,Quesada, Carole A.,Albin, Roger L.,Scott, Peter J. H.
, p. 112 - 116 (2015/03/04)
Interest in quantifying metal-Aβ species in vivo led to the synthesis and evaluation of [11C]L2-b and [18F]FL2-b as radiopharmaceuticals for studying the metallobiology of Alzheimer's disease (AD) using positron emission tomography (PET) imaging. [11C]L2-b was synthesized in 3.6% radiochemical yield (nondecay corrected, n = 3), >95% radiochemical purity, from the corresponding desmethyl precursor. [18F]FL2-b was synthesized in 1.0% radiochemical yield (nondecay corrected, n = 3), >99% radiochemical purity, from a 6-chloro pyridine precursor. Autoradiography experiments with AD positive and healthy control brain samples were used to determine the specificity of binding for the radioligands compared to [11C]PiB, a known imaging agent for β-amyloid (Aβ) aggregates. The Kd for [11C]L2-b and [18F]FL2-b were found to be 3.5 and 9.4 nM, respectively, from those tissue studies. Displacement studies of [11C]L2-b and [18F]FL2-b with PiB and AV-45 determined that L2-b binds to Aβ aggregates differently from known radiopharmaceuticals. Finally, brain uptake of [11C]L2-b was examined through microPET imaging in healthy rhesus macaque, which revealed a maximum uptake at 2.5 min (peak SUV = 2.0) followed by rapid egress (n = 2).
