448296-28-4Relevant academic research and scientific papers
Synthesis of the proton-ionizable lariat crown ether and chiral recognition of primary amines
Tsubaki, Kazunori,Tanaka, Hiroyuki,Kinoshita, Takayoshi,Fuji, Kaoru
, p. 1679 - 1684 (2002)
An optically active proton-ionizable lariat crown ether derivative 2 was prepared. Host 2 displays enantiomeric selectivity toward phenylglycinol (Klarge/Ksmall=3.2) and phenylalaninol (Klarge/Ksmall=1.7). The key intermediate 1 was synthesized in two steps from commercially available binaphthol in 30% yield.
Design and Synthesis of Janus Kinase 2 (JAK2) and Histone Deacetlyase (HDAC) Bispecific Inhibitors Based on Pacritinib and Evidence of Dual Pathway Inhibition in Hematological Cell Lines
Yang, Eugene Guorong,Mustafa, Nurulhuda,Tan, Eng Chong,Poulsen, Anders,Ramanujulu, Pondy Murugappan,Chng, Wee Joo,Yen, Jeffrey J. Y.,Dymock, Brian W.
, p. 8233 - 8262 (2016/10/03)
Blockage of more than one oncoprotein or pathway is now a standard approach in modern cancer therapy. Multiple inhibition is typically achieved with two or more drugs. Herein, we describe a pharmacophore merging strategy combining the JAK2/FLT3 inhibitor pacritnib with the pan-HDAC inhibitor, vorinostat, to create bispecific single molecules with both JAK and HDAC targeted inhibition. A preferred ether hydroxamate, 51, inhibits JAK2 and HDAC6 with low nanomolar potency, is 50-fold selective for JAK2 in a panel of 97 kinases. Broad cellular antiproliferative potency is supported by demonstration of JAK-STAT and HDAC pathway blockade in several hematological cell lines, inhibition of colony formation in HEL cells, and analysis of apoptosis. This study provides new tool compounds for further exploration of dual JAK-HDAC pathway inhibiton achieved with a single molecule.
