N⁶-benzoyl-5'-deoxy-5'-(nitromethyl)-2',3'-O-isopropylideneadenosine | 84757-71-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: N⁶-benzoyl-5'-deoxy-5'-(nitromethyl)-2',3'-O-isopropylideneadenosine
• 英文别名: N-[9-[(3aR,4R,6R,6aR)-2,2-dimethyl-6-(2-nitroethyl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl]purin-6-yl]benzamide
• CAS: 84757-71-1
• 化学式: C₂₁H₂₂N₆O₆
• 分子量: 454.442
• InChiKey: HNKGHKDQSQIDBO-KHTYJDQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  33.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  143.53
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  N⁶-benzoyl-5'-deoxy-5'-(nitromethyl)-2',3'-O-isopropylideneadenosine 在 吡啶 、 sodium tetrahydroborate 、 titanium(III) chloride 、 potassium tert-butylate 、 sodium methylate 作用下， 以 甲醇 、 乙醇 、 叔丁醇 为溶剂， 反应 21.37h， 生成 5'-deoxy-5'-(-L-homocystein-S-yl(RS)-hydroxyethyl)-2',3'-O-isopropylideneadenosine
  参考文献：
  名称：

  Toward the synthesis of isozyme-specific enzyme inhibitors. Potent inhibitors of rat methionine adenosyltransferases. Effect of one-atom elongation of the ribose-P.alpha. bridge in two covalent adducts of L-methionine and .beta.,.gamma.-imido-ATP

  摘要：

  With 2',3'-O-isopropylideneadenosine or its N6-benzoyl derivative as starting material, synthetic routes to two novel adducts of L-methionine and beta,gamma-imido-ATP have been devised. One adduct, 14 (2:3 mixture of 6' epimers), had a P alpha OCH(R1)CH2 system [R1 = CH2-L-SCH2CH2CH2CH(NH2)CO2H] in place of the P alpha OC(5')H2 system of ATP, while the other, 16 (2:3 mixture of 5' epimers), had a P alpha OCH2CH2CH(R2) system [R2 = L-SCH2CH2CH(NH2)CO2H]. The ribose-P alpha bridge in 14 and 16 contained one more methylene group than in two homologous methionine-ATP adducts studied previously. Adduct 14 was a potent inhibitor of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase and gave competitive kinetics vs MgATP (Ki = 0.39 and 0.63 microM, respectively) or vs L-methionine (Ki = 2.2 and 2.7 microM). Adduct 16 was likewise a potent inhibitor competitive vs MgATP (Ki = 0.44 and 0.81 microM, respectively) or L-methionine (Ki = 2.1 and 1.5 microM). The kinetic data indicate that 14 and 16 inhibit by binding simultaneously to the MgATP and L-methionine substrate sites and that the extra methylene group facilitates the interaction of their methionine residues with these methionine sites.

  DOI：

  10.1021/jm00397a020

文献信息

• Isozyme-specific enzyme inhibitors. 13. S-[5'(R)-['N-triphosphoamino)methyl]adenosyl]-L-homocysteine, a potent inhibitor of rat methionine adenosyltransferases
  作者：Vivekananda M. Vrudhula、Francis Kappler、Alexander Hampton

  DOI：10.1021/jm00388a024

  日期：1987.5

  A synthesis is described of the title compound and its 5'S epimer, which are two-substrate adducts of adenosine 5'-triphosphate (ATP) and L-methionine (Met) in which the C(5')H2OP system in ATP is replaced by CH(R)CH2NHP [R = L-S(CH2)2CH(NH2)CO2H]. The 5'R epimer was a potent nonselective competitive inhibitor [averaged Ki = 0.32 microM; KM(ATP)/Ki = 440] vs. ATP of the rat M-2 (normal tissue) and M-T (Novikoff ascitic hepatoma) variants of methionine adenosyltransferase. It produced simple noncompetitive inhibition (averaged Ki = 2.7 microM) vs. Met with both variants. The 5'S epimer inhibited M-T competitively vs. ATP, but was 74-fold less effective than the 5'R epimer. Replacement of the homocysteine moiety in the 5'R epimer by hydrogen markedly reduced inhibitory potency, as indicated by Ki values of 14 microM for competitive inhibition vs. ATP and 580 microM for noncompetitive inhibition vs. Met with M-2. The data suggest that the 5'R epimer can interact simultaneously with two enzymic sites. Information on the kinetic mechanism of a human counterpart of M-2 and inhibitor properties of a previously studied Met-ATP adduct are consistent with the view that the two sites might resemble those that interact with the initial products of the reaction, S-adenosylmethionine and triphosphate.
• KAPPLER, FRANCIS;VRUDHULA, VIVEKANANDA M.;HAMPTON, ALEXANDER, J. MED. CHEM., 31,(1988) N 2, 384-389
  作者：KAPPLER, FRANCIS、VRUDHULA, VIVEKANANDA M.、HAMPTON, ALEXANDER

  DOI：——

  日期：——