8-(4-Chlorophenyl)-8-methoxy-5-methyl-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-(4-Chlorophenyl)-8-methoxy-5-methyl-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one
• 化学式: C₁₃H₁₁ClN₂O₃S
• 分子量: 310.761
• InChiKey: BBMGMJVPBGHYGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  76.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(4-Chlorophenyl)-8-methoxy-5-methyl-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one 在 Chiralpak-IB column 作用下， 以 正己烷 、 异丙醇 为溶剂， 以99.9%的产率得到
  参考文献：
  名称：

  Absolute configuration and biological profile of two thiazinooxadiazol-3-ones with L-type calcium channel activity: a study of the structural effects

  摘要：

  我们对外消旋噻嗪并噁二唑-3-酮很感兴趣，因此测定了两种化合物的绝对构型和作为 L 型钙通道阻滞剂的生物活性，这两种化合物的缩醛链长度不同，可能会影响药理特征。我们观察到了一种有趣的立体选择性反转现象：短链化合物（n = 1）的活性在 R-形式上，而长链化合物（n = 12）的活性在 S-形式上。线性乙缩醛链的长度似乎能使这一类化合物的立体选择性发生反转，硅学模拟表明，这种不同的行为可能是由于与结合位点的亲水性和疏水性相互作用不同造成的。

  DOI：

  10.1039/c2ob25946j
• 作为产物：
  描述：

  8-(4-chlorophenyl)-8-hydroxy-5-methyl-8H-<1,4>thiazino<3,4-c><1,2,4>oxadiazol-3-one 、 原甲酸三甲酯 在 对甲苯磺酸 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 8-(4-Chlorophenyl)-8-methoxy-5-methyl-[1,2,4]oxadiazolo[3,4-c][1,4]thiazin-3-one
  参考文献：
  名称：

  Inhibition of MDR1 Activity in Vitro by a Novel Class of Diltiazem Analogues: Toward New Candidates

  摘要：

  The reversal of multidrug resistance by 22 molecules [8-aryl-8-hydroxy-5-R'-8H-[1,4]thiazino[3,4-c]-[1,2,4]oxadiazol-3-ones (1a-i) and 8-aryl-8-alkoxy-5-methyl-8H-[1,4]thiazino[3,4-c][1,2,4]oxadiazol-3-ones (2a-m)] related to myocardial-calcium-channel-modulator diltiazem was studied in multidrug resistant A2780/DX3 and their sensitive counterpart A2780 cells. MTT, cytofluorimetry assays, and fluorescence microscopy analyses were used to define activity and accumulation of doxorubicin with or without the diltiazem-like modulators. Of the 22 molecules, 1a, 2f, 2g, and 2m were able to overcome the established criteria for the selection in A2780/DX3 cells (IC50 reduction >= 25%), but only 2f, 2g, and 2m caused a significant increase of intracellular accumulation of doxorubicin. In conclusion, experiments lead to the identification of three diltiazem-like molecules able to increase the intracellular accumulation of doxorubicin by inhibiting the MDR1 function, thus potentiating its anti proliferative activity in multidrug resistant A2780/DX3 cells.

  DOI：

  10.1021/jm801195k

文献信息

• Cardiovascular Characterization of [1,4]Thiazino[3,4-<i>c</i>][1,2,4]oxadiazol-1-one Derivatives:  Selective Myocardial Calcium Channel Modulators
  作者：Roberta Budriesi、Barbara Cosimelli、Pierfranco Ioan、Camilla Zaira Lanza、Domenico Spinelli、Alberto Chiarini

  DOI：10.1021/jm020815d

  日期：2002.8.1

  As an extension of previous investigations (Tetrahedron 1999, 55, 5433-5440; J. Heterocycl. Chem. 2000, 37, 875-878), a series of 21 [1,4]thiazino[3,4-c][1,2,4]oxadiazolones, which has already been synthesized (except for compounds 5a, 5b, 6), was evaluated as calcium entry blockers by functional studies, namely, in isolated guinea-pig left and right atria and K+-depolarized aortic strips. With the aim of investigating the effect of a condensed benzene ring on the molecular structure and the influence of substituents on the 8-phenyl ring of 4a, ab initio computations (RHF/3-21*G) were performed on compounds 3, 4a-d, 4f, and 4k. The results obtained show that many of the compounds studied are potent and selective negative inotropic agents; in particular, compounds 4e and 4f are about 3- and 2-fold more potent than diltiazem, respectively.