4,6-dimethyl-7-acetoxycoumarin | 90370-17-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 4,6-dimethyl-7-acetoxycoumarin
• 英文别名: 7-acetoxy-4,6-dimethyl benzopyran-2(H)-one；7-acetoxy-4,6-dimethyl-coumarin；7-Acetoxy-4,6-dimethyl-cumarin；(4,6-Dimethyl-2-oxochromen-7-yl) acetate
• CAS: 90370-17-5
• 化学式: C₁₃H₁₂O₄
• 分子量: 232.236
• InChiKey: TZCWEZGQPBVQDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-dimethyl-7-acetoxycoumarin 在 盐酸 、 三氯化铝 、 amalgamated zinc 、 硫酸 、 甲苯 作用下， 生成 8-ethyl-7-hydroxy-4,6-dimethyl-coumarin
  参考文献：
  名称：

  Yanagita, Chemische Berichte, 1938, vol. 71, p. 2269,2271

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲基间苯二酚 在 硫酸 作用下， 反应 17.0h， 生成 4,6-dimethyl-7-acetoxycoumarin
  参考文献：
  名称：

  Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring

  摘要：

  In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'-dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-beta-D-glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by beta-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK-A(y) mice. Additionally, long-term treatment with 5 dose-dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.

  DOI：

  10.1021/jm990175n

文献信息

• Method of preparing photochemotherapic alkylangelicin compounds
  申请人：——

  公开号：US05179217A1

  公开（公告）日：1993-01-12

  The alkylangelicins according to the invention are obtained starting from an umbelliferone, in which the 6-position is already substituted by an alkyl group; in such a way the 7-allyloxy or 7-acyloxy umbelliferone intermediates can form by transposition of the allyl or acyl group only the 8-allyl and 8-acyl derivatives, and therefore the presence, even in traces, of psoralens is absolutely excluded in the subsequent synthetic steps. The 6-alkylangelicins thus obtained are particularly usable for the photochemotherapy of psoriasys and of other skin diseases characterized by cellular hyperproliferation, as well as for the photochemotherapy of vitiligo and of alopecia aerata.

  本发明中的烷基天使光素是从已经被烷基取代的香豆素开始制备的；这样，仅通过烯丙基或酰基基团的转位，就可以形成7-烯丙氧基或7-酰氧基香豆素中间体，进而形成8-烯丙基和8-酰基衍生物，因此，在随后的合成步骤中，即使是微量的光敏色素的存在也是绝对排除的。因此，这些6-烷基天使光素特别适用于银屑病和其他细胞增殖过度的皮肤疾病的光化学治疗，以及白癜风和斑秃的光化学治疗。
• Photochemotherapic method of treating psoriasis by using methylangelicin
  申请人：Consiglio Nazionale delle Ricerche

  公开号：US05001147A1

  公开（公告）日：1991-03-19

  The alkylangelicins according to the invention are obtained starting from an umbelliferone, in which the 6-position is already substituted by an alkyl group; in such a way the 7-allyloxy or 7-acyloxy umbelliferone intermediates can form by transposition of the allyl or acyl group only the 8-allyl and 8-acyl derivatives, and therefore the presence, even in traces, of psoralens is absolutely excluded in the subsequent synthetic steps. The 6-alkylangelicins thus obtained are particularly usable for the photochemotherapy of psoriasys and of other skin diseases characterized by cellular hyperproliferation, as well as for the photochemotherapy of vitiligo and of alopecia aerata.

  本发明中的烷基天使光素是从已经被烷基取代的香豆素开始制备的；这样，通过转位烯丙基或酰基基团，只能形成8-烯丙基和8-酰基衍生物，因此在随后的合成步骤中绝对排除了苯并三环素的存在，即使是微量。因此，所得的6-烷基天使光素特别适用于银屑病和其他细胞增殖性皮肤疾病的光化学治疗，以及白癜风和斑秃的光化学治疗。
• 6-Methylangelicins: a new series of potential photochemotherapeutic agents for the treatment of psoriasis
  作者：A. Guiotto、P. Rodighiero、P. Manzini、G. Pastorini、F. Bordin、F. Baccichetti、F. Carlassare、D. Vedaldi、F. Dall'Acqua

  DOI：10.1021/jm00374a005

  日期：1984.8

  synthetic pathway starting from umbelliferones carrying a methyl group in the 6-position. The new 6-methylangelicins show a high affinity toward DNA, forming in the dark a molecular complex; the complexed angelicins under UV-A irradiation photobind effectively to the macromolecule, forming only monoadducts. The new compounds show an evident antiproliferative activity by inhibiting DNA synthesis on Ehrlich

  通过从在6-位带有甲基的伞形酮开始的合成途径，已经避免了甲基补骨脂素作为合成的甲基Angelicins中不希望的引发剂的可能存在。新的6-甲基Angelicins对DNA具有高亲和力，在黑暗中形成分子复合物。UV-A辐照下的络合当归有效结合到大分子上，仅形成单加合物。新化合物通过抑制Ehrlich细胞上的DNA合成而表现出明显的抗增殖活性。但是，在各种化合物之间可以看到很大的差异。所有的化合物都缺乏皮肤红斑生成活性。根据致突变活性评估，一些新的6-甲基Angelicins证明不如用于比较的8-甲氧基补骨脂素（8-MOP）有效。基于抗增殖活性，缺乏皮肤光毒性和低致突变性，选择了两种化合物进行临床评估。经局部应用和UV-A照射对7名银屑病患者进行测试的化合物被证明比在相同条件下使用的8-MOP更有效。
• Soman, Shubhangi S.; Trivedi, K. N., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1992, vol. 31, # 8, p. 532 - 534
  作者：Soman, Shubhangi S.、Trivedi, K. N.

  DOI：——

  日期：——