((S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutyl)phosphinic acid | 864682-69-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ((S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutyl)phosphinic acid
• 英文别名: [(3S)-4-methoxy-4-oxo-3-(phenylmethoxycarbonylamino)butyl]phosphinic acid
• CAS: 864682-69-9
• 化学式: C₁₃H₁₈NO₆P
• 分子量: 315.263
• InChiKey: SCIHCYPVHVTBOU-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ((S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutyl)phosphinic acid 在 三氟化硼乙醚 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 methyl [(3S)-3-(N-benzyloxycarbonyl)amino-3-methoxycarbonylpropyl][(3-nitrophenyl)(N-benzylamino)methyl]phosphinate
  参考文献：
  名称：

  Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites

  摘要：

  A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an L-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu(4) subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber-Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties that are markedly different from typical CNS drugs, they hold significant therapeutic potential.

  DOI：

  10.1021/acs.jmedchem.7b01438
• 作为产物：
  描述：

  methyl (2S)-2-(benzyloxycarbonylamino)-4-bromobutanoate 在 吡啶 、 sodium tetrahydroborate 、 次磷酸铵 、 三乙基硼 、 双氧水 、 氧气 作用下， 以 甲醇 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 ((S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutyl)phosphinic acid
  参考文献：
  名称：

  对应于谷氨酰胺-γ-谷氨酸的膦酸磷酸肽的立体选择性合成及其掺入有效的多聚-γ-谷氨酰合成酶抑制剂

  摘要：

  将H 3 PO 2自由基加到N- / C-保护的乙烯基甘氨酸中可得到相应的H-次膦酸，产率极高。将非亲核性H-次膦酸转化为亲核性的P III物种RP（OTMS）2，该物质以两种方法用于含有伪肽的目标次膦酸。开发了一种新的方法，可导致RP（OTMS）2与未活化的亲电试剂（包括无环均烯丙基溴）的反应获得优异的收率。然而，途中目标假肽，RP（OTMS）的阿尔布蜀夫反应2与环状高烯丙基溴，（ř）-3-（溴甲基）-环戊-1-烯导致重排的烯丙基次膦酸而不是所需的均烯丙基衍生物，即假定的谷氨酸替代物。将RP（OTMS）2共轭添加到含有手性助剂的α-亚甲基戊二酸酯中只会导致适度的非对映选择性。通过快速色谱纯化提供假肽的两种非对映异构体的保护衍生物。整体脱保护后，（S）-H-Glu-γ-[Ψ（P（O）（OH）（CH 2））]-（S）-Glu-OH与（S）-H-Glu-γ偶联-[Ψ（P（O）（OH）（CH 2

  DOI：

  10.1021/jo0507439

文献信息

• [EN] HYPOPHOSPHOROUS ACID DERIVATIVES HAVING ANTIHYPERALGIC ACTIVITY AND BIOLOGICAL APPLICATIONS THEREOF<br/>[FR] DÉRIVÉS DE L'ACIDE HYPOPHOSPHOREUX AYANT UNE ACTIVITÉ ANTIHYPERALGIQUE ET LEURS APPLICATIONS BIOLOGIQUES
  申请人：UNIV PARIS DESCARTES

  公开号：WO2012156931A1

  公开（公告）日：2012-11-22

  The invention relates to hypophosphorous acid derivatives of formula (I) wherein - X is H or OH, - R represents one or several radicals R1-R5, identical or different, two of R1-R5 optionally occupying the same position on the phenyl group, one to four of R1-R5 being H and the others being selected in the group comprising - 0-(CH2)n-COOH; - S-(CH2)n-COOH; -NH-(CH2)n-COOH; - 0-(CH,R') -COOH; -O- (CH2)n-OH; OR', -R' being a C1 -C3 alkyl radical;-OH; --COOH; halogen, particularly -F, - CI, -Br, -I, -CF3; -OCF3; -N02; -CH=CH-COOH; - -(CH2)n-COOH; O - (CH2)n- P03H2; O - (CF2)n- P03H2; O - (CH2)n- S03H; O - (CH2)n- CONHOH; O - (CH2)n-tetrazol; O - (CH2)n-hydroxyisoxazol - n = 1 to 5, preferably 1-3; said hypophosrous acid derivatives being diastereoisomers or enantiomers.

  该发明涉及式(I)的次磷酸衍生物，其中- X为H或OH，- R代表一个或几个基团R1-R5，相同或不同，R1-R5中的两个可以选择占据苯基上的同一位置，R1-R5中的一到四个为H，其余的选择自-0-(CH2)n-COOH；-S-( )n-COOH；-NH-( )n-COOH；-0-(CH,R')-COOH；-O-( )n-OH；OR'，其中-R'为C1-C3烷基基团；-OH；-COOH；卤素，特别是-F，-Cl，-Br，-I，-CF3；-O ；-NO2；-CH=CH-COOH；-( )n-COOH；O-( )n-P03H2；O-(CF2)n-P03H2；O-( )n-S03H；O-( )n-CONHOH；O-( )n-四唑；O-( )n-羟基异噁唑-n=1至5，优选1-3；所述的次磷酸衍生物为对映异构体或对映体。
• Determination of the absolute configuration of phosphinic analogues of glutamate
  作者：Bruno Commare、Delphine Rigault、Isabelle A. Lemasson、Patrick Deschamps、Alain Tomas、Pascal Roussel、Isabelle Brabet、Cyril Goudet、Jean-Philippe Pin、Frédéric R. Leroux、Françoise Colobert、Francine C. Acher

  DOI：10.1039/c4ob01960a

  日期：——

  promising in vivo activity. However, so far all were synthesized and tested as a mixture of two diastereomers whose absolute and relative configurations are not known. In this study, the stereomers were separated on a Crownpack CR(+) column and their absolute configuration was assessed by means of a diastereoselective synthesis. Both separated L-stereomers activated the mGlu4 receptor with EC50's of 0.72

  已证明一系列次膦谷氨酸衍生物（例如LSP1-2111）是促代谢型谷氨酸（mGlu）受体的有效激动剂，并显示出有希望的体内活性。但是，到目前为止，所有化合物都是作为两种非对映异构体的混合物进行合成和测试的，其绝对和相对构型尚不清楚。在这项研究中，在Crownpack CR（+）色谱柱上分离了立体异�