dimethyl <(methylsulfonyl)methyl>phosphonate | 25508-33-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: dimethyl <(methylsulfonyl)methyl>phosphonate
• 英文别名: dimethyl ((methylsulfonyl)methyl)phosphonate；Dimethyl (methanesulfonylmethyl)phosphonate；dimethoxyphosphoryl(methylsulfonyl)methane
• CAS: 25508-33-2
• 化学式: C₄H₁₁O₅PS
• mdl: MFCD00014744
• 分子量: 202.168
• InChiKey: IVOKOLXLZBLDCG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dimethyl <(methylsulfonyl)methyl>phosphonate 、 (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 在 sodium t-butanolate 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 tert-butyl (2S)-2-(1-hydroxy-2-(methylsulfonyl)ethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  CHEMOKINE RECEPTOR MODULATORS AND USES THEREOF

  摘要：

  披露的内容包括但不限于，用于调节趋化因子受体活性的化合物及其使用方法。

  公开号：

  US20180072743A1

文献信息

• Carboxyl-modified amino acids and peptides as protease inhibitors
  作者：Stewart A. Thompson、Peter R. Andrews、Robert P. Hanzlik

  DOI：10.1021/jm00151a018

  日期：1986.1

  mM, and k2 = 0.015 and 0.010 s-1, respectively). Inhibition of DPP-I by 3d provides only the second example of a cysteine protease which is strongly inhibited by a nitrile analogue of a specific substrate. Further studies are needed to determine the generality and potential utility of this finding. Compounds 3e, 3f, and 4e exemplify a new class of specific affinity labels for cysteine proteases whose

  制备几种类型的羧基修饰的氨基酸和肽，它们具有适合于几种代表性蛋白酶之一的N末端修饰（载体片段），并评估了它们对这些酶的抑制作用。羧基修饰（抑制单元）包括（b）CONH 2，（c）CSNH 2，（d）CN，（e）反式-CH ＝ CHCO 2 Me和（f）反式-CH ＝ CHSO 2 Me。载体片段包括NH2（PhCH2）CHX（1），AcNH（PhCH2）CHX（2），H2NCH2CONH（PhCH2）CHX（3）和AcNH（PhCH2）CHCONHCH2X（4）。化合物1b，1d，1e和1f是微粒体和胞质亮氨酸氨基肽酶的竞争性抑制剂（前者的Ki分别为14.8、67、61和3.7 mM，后者分别为14.1、26.4、27.3和8.8 mM） 。化合物1c和亮氨酸硫代酰胺均对这两种酶均无任何可检测的作用。化合物2b-f还是胰凝乳蛋白酶的竞争性抑制剂（Ki分别为13.9、23.0、5.3、30.8和29
• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE GAMMA-SECRÉTASE
  申请人：SCHERING CORP

  公开号：WO2009061699A1

  公开（公告）日：2009-05-14

  This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (I). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).

  这项发明提供了一种新型化合物，可以调节γ-分泌酶。这些化合物的化学式为(I)。还披露了调节γ-分泌酶活性的方法以及使用化合物(I)治疗阿尔茨海默病的方法。
• Discovery of a Potent and Selective CCR4 Antagonist That Inhibits T_reg Trafficking into the Tumor Microenvironment
  作者：Jeffrey J. Jackson、John M. Ketcham、Ashkaan Younai、Betty Abraham、Berenger Biannic、Hilary P. Beck、Minna H. T. Bui、David Chian、Gene Cutler、Raymond Diokno、Dennis X. Hu、Scott Jacobson、Emily Karbarz、Paul D. Kassner、Lisa Marshall、Jenny McKinnell、Cesar Meleza、Abood Okal、Deepa Pookot、Maureen K. Reilly、Omar Robles、Hunter P. Shunatona、Oezcan Talay、James R. Walker、Angela Wadsworth、David J. Wustrow、Mikhail Zibinsky

  DOI：10.1021/acs.jmedchem.9b00506

  日期：2019.7.11

  the TME can potentiate antitumor immune responses. We developed a novel series of potent, orally bioavailable small molecule antagonists of CCR4. From this series, several compounds exhibited high potency in distinct functional assays in addition to good in vitro and in vivo ADME properties. The design, synthesis, and SAR of this series and confirmation of its in vivo activity are reported.

  将抑制性CD4 + FOXP3 +调节性T细胞（Treg）招募到肿瘤微环境（TME）可能会削弱接受免疫肿瘤学（IO）药物治疗的患者的抗肿瘤反应。人Treg表达CCR4，可以通过CC趋化因子配体CCL17和CCL22募集到TME。在某些癌症中，Treg积累与患者预后不良相关。临床前数据表明，防止Treg募集并增加TME中活化的效应T细胞（Teff）的数量可以增强抗肿瘤免疫反应。我们开发了一系列新颖的，有效的，口服生物利用的CCR4小分子拮抗剂。从该系列中，除了良好的体外和体内ADME特性外，几种化合物在独特的功能测定中还显示出强大的效用。设计，综合，
• The chemistry of substituted pyrazolidinones; applications to the synthesis of bicyclic derivatives
  作者：Robert J. Ternansky、Susan E. Draheim

  DOI：10.1016/s0040-4020(01)88183-7

  日期：——

  Methodology for the selective chemical derivatizations of substituted pyrazolidinones is described. The application of these methods to the preparation of [4.3.0] and [3.3.0] bicyclic systems is also discussed. The importance of these latter systems as nuclei of antibacterial agents with potential utility in the treatment of infectious disease provides the motivation for these investigations.

  描述了取代的吡唑烷酮的选择性化学衍生化的方法。还讨论了这些方法在制备[4.3.0]和[3.3.0]双环系统中的应用。后一种系统作为具有潜在用途的抗菌剂在传染病治疗中的重要性，为这些研究提供了动力。
• Structure-activity relationships for inhibition of papain by peptide Michael acceptors
  作者：Siming Liu、Robert P. Hanzlik

  DOI：10.1021/jm00084a012

  日期：1992.3

  Two series of peptidyl Michael acceptors, N-Ac-L-Phe-NHCH2CH = CH-E with different electron withdrawing groups (E = CO2CH3, 1a; SO2CH3, 1b; CO2H, 1c; CN, 1d; CONH2, 1e; and C6H4-p-NO2, 1f) and R-NHCH2CH = CHCOOCH3 with different recognition and binding groups (R = N-Ac-D-Phe, 2a; N-Ac-L-Leu, 3a; N-Ac-L-Met, 4a; PhCH2CH2CO, 5a; PhCO, 6a), were synthesized and evaluated as inactivators against papain. It was found that the inhibition of papain by peptidyl Michael acceptors is a general phenomenon and that the intrinsic chemical reactivity of the E group in the Michael acceptors has a direct effect on the kinetics of the inactivation process as reflected in k2/K(i). At pH 6.2, the reactivity of papain toward the Michael acceptors is about 283 000-fold higher than the reactivity of the model thiol 3-mercaptopropionate. This large increase in reactivity is attributable to at least 2 factors; one is the low apparent pK(a) of Cys-25 of papain, and the other is the recruitment of catalytic power by specific enzyme-substrate interactions. The unexpectedly high reactivity of 1c (E = COOH) was rationalized by proposing a direct interaction of the acid group with His-159 in the active site of papain. The unexpected inactivity of 1f (E = C6H4-p-NO2) as a Michael acceptor and its very powerful competitive inhibition of papain were rationalized by molecular graphics which showed the nitrophenyl moiety rotated out of conjugation with the olefin and interacting instead with the hydrophobic S1' region of papain. A plot of log (k2/K(i)) for 1a-6a vs log (k(cat)/K(m)) for analogous R-Gly-p-NA substrates was linear (r = 0.98) with slope of 0.83, suggesting that binding energy from specific enzyme-ligand interactions can be used to drive the self-inactivation reaction to almost the same extent as it is used to drive catalysis.