40916-80-1Relevant articles and documents
Stereoselective synthesis of 1,4,2-oxazaphosphorines as precursors of chiral α-aminophosphonic acids by intramolecular heterocyclization of β-aldiminoalkylphosphites
Dimukhametov, Mudaris N.,Bajandina, Eugenija V.,Davydova, Elena Yu.,Litvinov, Igor A.,Gubaidullin, Aidar T.,Dobrynin, Alexey B.,Zyablikova, Tatyana A.,Alfonsov, Vladimir A.
, p. 56 - 61 (2003)
The intramolecular version of nucleophilic addison of phosphites to imines was carried out for the first time taking as an example β-aldimino-alkylphosphites, formed from chlorophosphites and β-aldiminoalcohols [N-(benzylidene)-2-aminoethanol and R-(+)-N-(benzylidene)-2-aminobutanol-1]. In these reactions, stereoisomeric 1,4,2-oxazaphospho-rines were obtained in good yields. R-(+)-N-(benzylidene)-2-aminobutanol-1 being used as a precursor, nucleophilic attack by P(III) atone on electrophilic C atom of the C=N group proceeds stereospecifically with participation of only re-face of the two possible diastereotopic faces of the imine double bond to give the epimeric at phosphorus (3R, 5R)-2-(β-chloroethyl)-2-oxo-3-phenyl-5-ethyl-1,4,2-oxazaphosphorines as precursors of nonracemic α-aminophosphonic acids.
Structure-based design of potent and selective 3-phosphoinositide-dependent kinase-1 (PDK1) inhibitors
Medina, Jesús R.,Becker, Christopher J.,Blackledge, Charles W.,Duquenne, Celine,Feng, Yanhong,Grant, Seth W.,Heerding, Dirk,Li, William H.,Miller, William H.,Romeril, Stuart P.,Scherzer, Daryl,Shu, Arthur,Bobko, Mark A.,Chadderton, Antony R.,Dumble, Melissa,Gardiner, Christine M.,Gilbert, Seth,Liu, Qi,Rabindran, Sridhar K.,Sudakin, Valery,Xiang, Hong,Brady, Pat G.,Campobasso, Nino,Ward, Paris,Axten, Jeffrey M.
experimental part, p. 1871 - 1895 (2011/05/30)
Phosphoinositide-dependent protein kinase-1(PDK1) is a master regulator of the AGC family of kinases and an integral component of the PI3K/AKT/mTOR pathway. As this pathway is among the most commonly deregulated across all cancers, a selective inhibitor of PDK1 might have utility as an anticancer agent. Herein we describe our lead optimization of compound 1 toward highly potent and selective PDK1 inhibitors via a structure-based design strategy. The most potent and selective inhibitors demonstrated submicromolar activity as measured by inhibition of phosphorylation of PDK1 substrates as well as antiproliferative activity against a subset of AML cell lines. In addition, reduction of phosphorylation of PDK1 substrates was demonstrated in vivo in mice bearing OCl-AML2 xenografts. These observations demonstrate the utility of these molecules as tools to further delineate the biology of PDK1 and the potential pharmacological uses of a PDK1 inhibitor.
Stereocontrolled synthesis of 3-substituted azetidinic amino acids
Sivaprakasam, Mangaleswaran,Couty, Fran?ois,Evano, Gwilherm,Srinivas,Sridhar,Rao, K. Rama
, p. 781 - 785 (2007/10/03)
A set of enantiomerically pure N-disubstituted β-amino alcohols was chlorinated by treatment with thionyl chloride. This reaction gave a mixture of regioisomeric chlorides that could be equilibrated to the more stable regioisomer by heating in DMF. The chlorides thus obtained were engaged in an intramolecular anionic ring-closure and gave access to fully protected enantio- and diastereomerically pure 2,3-cis-disubstituted azetidinic amino acids. One of the latter was deprotected and included in a short peptide sequence. Georg Thieme Verlag Stuttgart.
