1066-52-0Relevant articles and documents
Ion-molecule reactions of O,S-dimethyl methylphosphonothioate: Evidence for intramolecular sulfur oxidation during VX perhydrolysis
McAnoy, Andrew M.,Williams, Jilliarne,Paine, Martin R. L.,Rogers, Michael L.,Blanksby, Stephen J.
, p. 9319 - 9327 (2009)
(Chemical Equation Presented) The alkaline perhydrolysis of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) was investigated by studying the ion-molecule reactions of HOO- with O,S-dimethyl methylphosphonothioate in a modified linear ion-trap mass spectrometer. In addition to simple proton transfer, two other abundant product ions are observed at m/z 125 and 109 corresponding to the S-methyl methylphosphonothioate and methyl methylphosphonate anions, respectively. The structure of these product ions is demonstrated by a combination of collision-induced dissociation and isotope-labeling experiments that also provide evidence for their formation by nucleophilic reaction pathways, namely, (i) SN2 at carbon to yield the S-methyl methylphosphonothioate anion and (ii) nucleophilic addition at phosphorus affording a reactive pentavalent intermediate that readily undergoes internal sulfur oxidation and concomitant elimination of CH3SOH to yield the methyl methylphosphonate anion. Consistent with previous solution phase observations of VX perhydrolysis, the toxic P-O cleavage product is not observed in this VX model system and theoretical calculations identify P-O cleavage to be energetically uncompetitive. Conversely, intramolecular sulfur oxidation is calculated to be extremely exothermic and kinetically accessible explaining its competitiveness with the facile gas phase proton transfer process. Elimination of a sulfur moiety deactivates the nerve agent VX and thus the intramolecular sulfur oxidation process reported here is also able to explain the selective perhydrolysis of the nerve agent to relatively nontoxic products.
Asymmetric synthesis of a cyclopropanecarboxylic acid derivative–the potential agonist/antagonist of GABA receptors
Krysiak, Jerzy,Mikina, Maciej,Rzewnicka, Aneta,Sobczak, Agata,?urawiński, Remigiusz,Sieroń, Les?aw
, (2022/01/20)
The synthesis of enantiomerically pure (1S,2S,S P)-1-[hydroxy(methyl)phosphonyl]-2-aminocyclopropanecarboxylic acid (1) (a potential agonist/antagonist of GABA receptors) was accomplished in six steps based on optically inactive methyl 2-[metho
Discovery of phosphonamidate IDO1 inhibitors for the treatment of non-small cell lung cancer
Du, Qianming,Feng, Xi,Wang, Yinuo,Xu, Xi,Zhang, Yan,Qu, Xinliang,Li, Zhiyu,Bian, Jinlei
, (2019/08/26)
Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as an attractive approach for the development of cancer immunotherapy. In this study, a series of phosphonamidate ester containing compounds were designed, synthesized and evaluated for their inhibitory activities against IDO1. Among them, compounds 16, 17, and 26 with good IDO1 inhibitory (HeLa IDO1 IC50 = 10–21 nM, hIDO1 IC50 = 78–121 nM) activities were selected for further investigation and showed good physicochemical properties. Furthermore, based on comparable PK profile and excellent IDO2/TDO inhibitory potency, representative compound 16 was selected for further bio-evaluation and characterized with good efficacy in suppressing lung metastasis (77% inhibition rate) of Lewis cells in vivo. Thus, compound 16 could be a potential and efficacious agent for further evaluation.
