α,α-bis(4-chlorophenyl)-5-pyrimidinemethanol | 26766-35-8

• 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: α,α-bis(4-chlorophenyl)-5-pyrimidinemethanol
• 英文别名: bis(4-chlorophenyl)(pyrimidin-5-yl) methanol；α, α-bis(4-chlorophenyl)-5-pyrimidinemethanol；Bis(4-chlorophenyl)(5-pyrimidinyl)methanol；bis(4-chlorophenyl)-pyrimidin-5-ylmethanol
• CAS: 26766-35-8
• 化学式: C₁₇H₁₂Cl₂N₂O
• 分子量: 331.201
• InChiKey: CSRYTZCLFTYZLS-UHFFFAOYSA-N

物化性质

• 熔点：
  159-161 °C
• 沸点：
  494.9±40.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  α,α-bis(4-chlorophenyl)-5-pyrimidinemethanol 在 三乙基硅烷 、 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 5-[1,1-Bis-(4-chloro-phenyl)-2-phenyl-ethyl]-pyrimidine
  参考文献：
  名称：

  Aromatase inhibition by 5-substituted pyrimidines and dihydropyrimidines

  摘要：

  The inhibition of estrogen biosynthesis has been suggested to be an effective treatment of hormone-dependent diseases, particularly breast cancer. Several series of 5-substituted pyrimidine derivatives have been synthesized and tested for their ability to inhibit the enzyme aromatase (estrogen synthetase). Compounds were evaluated in an in vitro assay that measured the inhibition of rat ovarian microsomal aromatase activity. Greatest inhibitory activity was achieved in the cases of diarylpyrimidinemethanols and diarylpyrimidinyl methanes which were substituted in the 4- and 4'-positions with electron-withdrawing substituents, particularly Cl.

  DOI：

  10.1021/jm00391a016
• 作为产物：
  描述：

  5-溴嘧啶 、 4,4'-二氯二苯甲酮 在 正丁基锂 作用下， 生成 α,α-bis(4-chlorophenyl)-5-pyrimidinemethanol
  参考文献：
  名称：

  雌激素合成酶抑制剂。2.比较体外芳香酶对被二芳基甲烷或二芳基甲醇基团取代的氮杂环的抑制活性。

  摘要：

  描述了多种杂环（4,4'-二氯二苯基）甲烷和-甲醇的制备和体外芳香酶抑制活性。通过将一系列咪唑和吡啶衍生的化合物与先前报道的类似嘧啶化合物进行比较，从而选择了两个带有二芳基的部分作为评估杂环的载体。还介绍了活性最高的化合物的结构模型。发现包含两个杂环部分的一系列相关化合物的活性与模型一致。评估的许多化合物（包括吡啶，咪唑，嘧啶，吡唑，三唑，噻唑和异噻唑类的代表）在低纳摩尔浓度下均具有EC50抑制芳香酶的能力。

  DOI：

  10.1021/jm00163a065

文献信息

• Estrogen synthetase inhibitors. 2. Comparison of the in vitro aromatase inhibitory activity for a variety of nitrogen heterocycles substituted with diarylmethane or diarylmethanol groups
  作者：C. David Jones、Mark A. Winter、Kenneth S. Hirsch、Nancy Stamm、Harold M. Taylor、Howard E. Holden、James D. Davenport、Eriks V. Krumkalns、Robert G. Suhr

  DOI：10.1021/jm00163a065

  日期：1990.1

  The preparation and in vitro aromatase inhibitory activity of a wide variety of heterocyclic (4,4'-dichlorodiphenyl)methanes and -methanols are described. The choice of the two diaryl-bearing moieties as a vehicle for the evaluation of the heterocycles was made by the comparison of series of imidazole and pyridine-derived compounds with similar pyrimidine compounds reported previously. A structural

  描述了多种杂环（4,4'-二氯二苯基）甲烷和-甲醇的制备和体外芳香酶抑制活性。通过将一系列咪唑和吡啶衍生的化合物与先前报道的类似嘧啶化合物进行比较，从而选择了两个带有二芳基的部分作为评估杂环的载体。还介绍了活性最高的化合物的结构模型。发现包含两个杂环部分的一系列相关化合物的活性与模型一致。评估的许多化合物（包括吡啶，咪唑，嘧啶，吡唑，三唑，噻唑和异噻唑类的代表）在低纳摩尔浓度下均具有EC50抑制芳香酶的能力。
• Biological Evaluation of 5-Substituted Pyrimidine Derivatives as Inhibitors of Brassinosteroid Biosynthesis
  作者：Jing-Ming WANG、Tadao ASAMI、Shigeo YOSHIDA、Noboru MUROFUSHI

  DOI：10.1271/bbb.65.817

  日期：2001.1

  A series of 5-substituted pyrimidine derivatives was synthesized, and their ability to inhibit brassinosteroid biosynthesis was tested. The biological activity of these compounds was evaluated by the cress stem elongation method. Among the synthesized compounds, α-(4-chlorophenyl)-α-phenyl-5-pyrimidinemethanol (DPPM 4) exhibited potent inhibitory activity for retarding cress stem elongation in the light. This inhibition was reversed by the application of 10 nM brassinolide, but not by 1 μM GA3. DPPM 4 also affected Arabidopsis growth in the dark. DPPM 4-treated Arabidopsis had phenotypes like those of brassinosteroid-deficient mutants, with short hypocotyls and open cotyledons, in the dark. These biological changes were restored by the co-application of 10 nM brassinolide, but not by 1 μM GA3, suggesting that the primary site of action of DPPM 4 was the brassinosteroid biosynthetic pathway.

  我们合成了一系列 5-取代的嘧啶衍生物，并测试了它们抑制铜绿素生物合成的能力。这些化合物的生物活性通过茎伸长法进行了评估。在合成的化合物中，α-（4-氯苯基）-α-苯基-5-嘧啶甲醇（DPPM 4）在光照下对延缓芹菜茎的伸长有很强的抑制作用。施用 10 nM 黄铜内酯可逆转这种抑制作用，但 1 μM GA3 则不能。DPPM 4 还影响拟南芥在黑暗中的生长。经 DPPM 4 处理的拟南芥在黑暗中的表型与黄铜类固醇缺乏的突变体相似，下胚轴短小，子叶开裂。同时施用 10 nM 的黄铜素内酯可恢复这些生物变化，而施用 1 μM GA3 则无法恢复，这表明 DPPM 4 的主要作用部位是黄铜素类固醇生物合成途径。
• Indenopyrimidine aromatase inhibitors
  申请人：Eli Lilly and Company

  公开号：US04769378A1

  公开（公告）日：1988-09-06

  Certain 5-phenyl-5H-indeno[1,2-d]pyrimidines, their pharmaceutical formulations, and their use in methods for inhibiting aromatase and treating or preventing estrogen-dependent diseases.

  某些5-苯基-5H-吲哚并[1,2-d]嘧啶，其药物配方及其在抑制芳香化酶和治疗或预防雌激素依赖性疾病的方法中的应用。
• Aromatase inhibiting derivatives of
  申请人：Eli Lilly and Company

  公开号：US04609666A1

  公开（公告）日：1986-09-02

  This invention provides certain azole derivatives, their pharmaceutical formulations, and a method of inhibiting aromatase and treating or preventing estrogen-dependent diseases in mammals.

  这项发明提供了某些唑类衍生物、它们的药物配方以及一种抑制芳香化酶、治疗或预防哺乳动物的雌激素依赖性疾病的方法。
• Indenopyrimidine derivatives
  申请人：ELI LILLY AND COMPANY

  公开号：EP0240263A2

  公开（公告）日：1987-10-07

  5-Phenyl-5H-indeno[1,2-d]pyrimidine and ???? thereof are useful for inhibiting aromatase for treating or preventing estrogen dependent doses. The compounds have the formula wherein Y is hydrogen, methyl, hydroxy, methoxy, ????, fluoro, or -NHCOCH3; R1 is hydrogen, chloro, fluoro, methoxy, or flouromethyl; and each of R2 and R3 is independently hydrogen, ????, fluoro, or trifluoromethyl.

  5-苯基-5H-茚并[1,2-d]嘧啶及其 ???? 可抑制芳香化酶，用于治疗或预防雌激素依赖性剂量。这些化合物的化学式为 其中 Y 是氢、甲基、羟基、甲氧基、????、氟或 -NHCOCH3； R1 是氢、氯、氟、甲氧基或氟甲基；以及 R2 和 R3 各自独立地为氢、????、氟或三氟甲基。