259143-04-9Relevant articles and documents
Design, synthesis and biological evaluation of Tozadenant analogues as adenosine A2A receptor ligands
Renk, Dana R.,Skraban, Marcel,Bier, Dirk,Schulze, Annette,Wabbals, Erika,Wedekind, Franziska,Neumaier, Felix,Neumaier, Bernd,Holschbach, Marcus
, (2021/02/09)
With the aim to obtain potent adenosine A2A receptor (A2AR) ligands, a series of eighteen derivatives of 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide (SYN-115, Tozadenant) were designed and synthesized. The target compounds were obtained by a chemical building block principle that involved reaction of the appropriate aminobenzothiazole phenyl carbamates with either commercially available or readily synthesized functionalized piperidines. Their affinity and subtype selectivity with regard to human adenosine A1-and A2A receptors were determined using radioligand binding assays. Ki values for human A2AR ranged from 2.4 to 38 nM, with more than 120-fold selectivity over A1 receptors for all evaluated compounds except 13k which had a Ki of 361 nM and 18-fold selectivity. The most potent fluorine-containing derivatives 13e, 13g and 13l exhibited Ki values of 4.9 nM, 3.6 nM and 2.8 nM for the human A2AR. Interestingly, the corresponding values for rat A2AR were found to be four to five times higher. Their binding to A2AR was further confirmed by radiolabeling with 18F and in vitro autoradiography in rat brain slices, which showed almost exclusive striatal binding and complete displacement by the A2AR antagonist ZM 241385. We conclude that these compounds represent potential candidates for the visualization of the A2A receptor and open pathways to novel therapeutic treatments of neurodegenerative disorders or cancer.
Design and Synthesis of Novel N-(2-aminophenyl)benzamide Derivatives as Histone Deacetylase Inhibitors and Their Antitumor Activity Study
La, Minh Thanh,Jeong, Byung-Hoon,Kim, Hee-Kwon
, p. 740 - 743 (2021/03/16)
Histone deacetylases (HDACs) are promising therapeutic targets for cancer therapy because inhibition of HDACs triggers growth arrest or apoptosis of tumor cells. In the present study, a new series of fluorinated N-(2-aminophenyl)benzamide derivatives were synthesized to investigate potential inhibition of HDACs and associated anticancer activity. Among the synthesized derivatives, compound 24a showed potent inhibitory activity of HDACs and higher antitumor efficacy in human cancer cell lines (HCT-116, MCF-7, and A549) compared with SAHA. Moreover, animal studies demonstrated that compound 24a showed potent in vivo antitumor efficacy in an HCT-116 colon cancer xenograft mouse model.
Synthesis of [18F]FA-4 and [11C]pipzA-4 as radioligands for the high affinity choline uptake system
Gilissen,Bormans,De Groot,Verbruggen
, p. 1289 - 1300 (2007/10/03)
We have prepared two radiolabelled analogues of hemicholinium-3 (HC-3) as potential in vivo tracers of the sodium dependent high affinity choline uptake (SDHAChU) system. Thus, 4-[1-hydroxy-2-(4-[18F]fluoromethylpiperidinyl)ethyl]-4'-[1-hydroxy-2-(4 -methylpiperidinyl)ethyl]biphenyl ([18F]FA-4) and 4-[1-hydroxy-2-(4-11C]methylpiperazinyl)ethyl]-4'-[1-hydroxy-2-(4 -methylpiperidinyl)]biphenyl ([11C]pipzA-4) have been synthesized. [18F]FA-4 was prepared by reaction of 4-[18F]fluoromethylpiperidine with 4-(α-bromoacetyl)-4'-(4-methylpiperidinylacetyl)biphenyl followed by reduction of the keto groups to alcohols with NaBH4. The total synthesis time was 300 minutes and [18F]FA-4 was obtained with a specific activity of 5.6 GBq/μmol (EOS) and an overall decay corrected radiochemical yield of 3.1 ± 0.6%. [11C]pipzA-4 was prepared by reaction of [11C]methyl triflate with 4-[1-hydroxy-2-piperazinyl)ethyl]-4'-[1-hydroxy-2-(4 -methylpiperidinyl)ethyl]biphenyl. The total synthesis time was 25 minutes and [11C]pipzA-4 was obtained with a specific activity of 13.7 GBq/μmol (EOS) and an overall decay corrected radiochemical yield of 19.5 ± 2.2%.
