162358-41-0Relevant articles and documents
Development of novel PP2A activators for use in the treatment of acute myeloid leukaemia
Toop, Hamish D.,Dun, Matthew D.,Ross, Bryony K.,Flanagan, Hayley M.,Verrills, Nicole M.,Morris, Jonathan C.
supporting information, p. 4605 - 4616 (2016/06/09)
AAL(S), the chiral deoxy analog of the FDA approved drug FTY720, has been shown to inhibit proliferation and apoptosis in several cancer cell lines. It has been suggested that it does this by activating protein phosphatase 2A (PP2A). Here we report the synthesis of new cytotoxic analogs of AAL(S) and the evaluation of their cytotoxicity in two myeloid cell lines, one of which is sensitive to PP2A activation. We show that these analogs activate PP2A in these cells supporting the suggested mechanism for their cytotoxic properties. Our findings identify key structural motifs required for anti-cancer effects.
Efficient chromatography-free synthesis of the oxy-analogue of fingolimod
Zivkovic, Aleksandra,Stark, Holger
supporting information; experimental part, p. 3769 - 3771 (2010/08/20)
Fingolimod (FTY720) and its analogue derivatives are not only promising therapeutics in sphingolipid signaling but also valuable tools for understanding the roles of sphingolipids in (patho)physiological conditions. A practical method for the synthesis of the ether analogue of FTY720 is described. Our final synthetic approach allows high yield and efficient synthesis of O-FTY in only four steps without chromatographic purifications.
Synthesis and immunosuppressive activity of 2-substituted 2- aminopropane-1,3-diols and 2-aminoethanols
Kiuchi, Masatoshi,Adachi, Kunitomo,Kohara, Toshiyuki,Minoguchi, Masanori,Hanano, Tokushi,Aoki, Yoshiyuki,Mishina, Tadashi,Arita, Masafumi,Nakao, Noriyoshi,Ohtsuki, Makio,Hoshino, Yukio,Teshima, Koji,Chiba, Kenji,Sasaki, Shigeo,Fujita, Tetsuro
, p. 2946 - 2961 (2007/10/03)
A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)- hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4- octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.
