162269-79-6Relevant academic research and scientific papers
Synthesis and biological activity of novel 2-(α- alkoxyimino)benzylpyridine derivatives as K+ channel openers
Maekawa, Tsuyoshi,Yamamoto, Satoshi,Igata, Yumiko,Ikeda, Shota,Watanabe, Toshifumi,Shiraishi, Mitsuru
, p. 1994 - 2004 (1997)
The search for novel K+ channel openers with a non-benzopyran skeleton, unlike cromakalim, led to the discovery of a new series of (Z)-2-(α- alkoxyimino)benzylpyridine derivatives. Synthesis was achieved by using a (Z)-dominant condensation reaction of henzoylpyridines with O- alkylhydroxylamines, followed by m-chloroperhenzoic acid (m-CPBA) oxidation. The compounds were tested for their vasorelaxant activity in tetraethylammonium chloride (TEA) and BaCl2- and high KCl-induced contraction of rat aorta to identify potential K+ channel openers, and also for their effects on the coronary blood flow (CBF) after intracoronary injection in anesthetized dogs. A large number of the 2-(α- alkoxyimino)benzylpyridines strongly inhibited TEA and BaCl2-induced contraction, had no effect on 80 mM KCl-induced contraction, and increased the CBF to more than 200% of the basal flow at 10-30μg/dog. In particular, (Z)-2-[5-bromo-α-(tert-butoxyimino)-4-fluoro-2-hydroxybenzyl]-3- hydroxypyridine 1-oxide (7d) showed highly potent vasorelaxant activity (EC50=0.28μM) comparable to that of levcromakalim (EC50=0.17 μM), and gave a significantly longer-lasting increase (T ( 1/4 ) = 30 min) in the CBF compared to levcromakalim, nicorandil, nitroglycerin, or diltiazem (T( 1/4 )=5.2, 0.9, 0.4, and 2.2 min, respectively). It also exhibited a stable and long-lasting hypotensive effect (over 7h) upon oral administration of 1 mg/kg in spontaneously hypertensive rats (SHRs).
A yellowish-green-light-controllable nitric oxide donor based on: N -nitrosoaminophenol applicable for photocontrolled vasodilation
Okuno, Hana,Ieda, Naoya,Hotta, Yuji,Kawaguchi, Mitsuyasu,Kimura, Kazunori,Nakagawa, Hidehiko
, p. 2791 - 2796 (2017/04/03)
Nitric oxide (NO) has been known as a gaseous chemical mediator, which modulates several physiological functions. Spatial and temporal control of NO release facilitates further study and medical application of NO. Herein, we report design and synthesis of a novel NO donor, NO-Rosa. NO-Rosa has a rosamine moiety, which absorbs yellowish green light. Upon irradiation with yellowish green light (530-590 nm), NO is released from NO-Rosa, presumably via photoinduced electron transfer from the N-nitrosoaminophenol moiety to the rosamine moiety. NO release from NO-Rosa was detected by ESR spin trapping and a NO fluorescent probe. Cellular NO release control was achieved in HEK293 cells using a NO fluorescent probe, DAF-FM DA. Furthermore, temporally controlled NO-induced vasodilation was demonstrated by treatment of a rat aortic strip with NO-Rosaex vivo and irradiation by yellowish green light. NO-Rosa is expected to be utilized for further study of NO-related physiological functions, utilizing its ability of spatiotemporal release of NO as a photocontrollable compound with harmless yellowish-green light.
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.
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 (2007/10/03)
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.
