4-(5-嘧啶基氨基)苯甲腈 | 157911-57-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(5-嘧啶基氨基)苯甲腈
• 英文名称: 4-(pyrimidin-5-ylamino)benzonitrile
• 英文别名: 5-[(4-cyanophenyl)amino]pyrimidine；4-(5-Pyrimidinylamino)benzonitrile
• CAS: 157911-57-4
• 化学式: C₁₁H₈N₄
• 分子量: 196.211
• InChiKey: PZGBIRFTZMNBSP-UHFFFAOYSA-N

物化性质

• 沸点：
  411.6±25.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  4-(5-嘧啶基氨基)苯甲腈 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 4.0h， 生成 4-(pyrimidin-5-yl(4-(tributylstannyl)benzyl)amino)benzonitrile
  参考文献：
  名称：

  4-(((4-Iodophenyl)methyl)-4H-1,2,4-triazol-4-ylamino)-benzonitrile: A Potential Imaging Agent for Aromatase

  摘要：

  Aromatase (CYP19) is a rate-limiting enzyme that catalyzes the biosynthesis of estrogens. Imaging agents based on aromatase inhibitors (AIs) have been developed for a PET/SPECT study. A series of compounds was synthesized based on YM511, which has previously been used for breast cancer treatment. Two examples of these derivatives, 4-(((4-iodophenyl)methyl)-4H-1,2,4-triazol-4-yl-amino)-benzonitrile (5) and 44(1H-imidazol-1-yl)(4-iodobenzyl)amino)-benzonitrile (11), displayed potent binding affinities to human aromatase (IC50 = 0.17 and 0.04 nM, respectively). Biodistribution and autoradiographic studies revealed that [I-125]5 and [I-125]11 were highly accumulated in the stomach (16.21 and 10.88% dose/g, respectively) and ovaries (8.56 and 3.32% dose/g, respectively) of female rats. Log P of [I-125]5 was 2.49, meaning good brain penetration. Autoradiograms of brain sections showed a high uptake in the bed nucleus of the stria terminalis and amygdala. These results suggest that [I-125]5 and [I-125]11 are potent probes for aromatase imaging in both the brain and peripheral organs.

  DOI：

  10.1021/acs.jmedchem.6b00849
• 作为产物：
  描述：

  5-溴嘧啶 、 对氨基苯腈 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以87%的产率得到4-(5-嘧啶基氨基)苯甲腈
  参考文献：
  名称：

  微波辅助2,5-二取代的嘧啶衍生物的合成通过Buchwald-Hartwig偶联反应

  摘要：

  在Buchwald-Hartwig胺化的微波辐射下，合成了各种2，5-二取代的嘧啶衍生物。这种简洁的方法以高到高的产量提供了有趣的支架，并且具有大的官能团相容性。这些新颖的化学实体可以用作药物设计的基础。

  DOI：

  10.1016/j.tetlet.2019.151406

文献信息

• Substituted tertiary amino compound or salt thereof
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05538976A1

  公开（公告）日：1996-07-23

  A substituted tertiary amino compound represented by general formula (I) or a pharmaceutically acceptable salt thereof. They have an aromatase inhibiting activity and are useful as a prophylactic and/or therapeutic agent for breast cancer, mastopathy, endometriosis, prostatic-hypertrophy, and so forth.

  由一般式（I）表示的替代三级胺化合物或其药用可接受的盐。它们具有抑制芳香化酶的活性，并可用作乳腺癌、乳腺病、子宫内膜异位症、前列腺肥大等疾病的预防和/或治疗药物。
• Studies on Aromatase Inhibitors IV. Synthesis and Biological Evaluation of N,N-Disubstituted-5-aminopyrimidine Derivatives.
  作者：Minoru OKADA、Toru YODEN、Eiji KAWAMINAMI、Yosiaki SHIMADA、Masafumi KUDOU、Yasuo ISOMURA

  DOI：10.1248/cpb.45.1293

  日期：——

  In order to study the potency of the 5-aminopyrimidine skeleton as an aromatase inhibitor, we synthesized various N, N-disubstituted-5-aminopyrimidine derivatives and evaluated their aromatase-inhibitory activity (in vitro) and their inhibitory activity on pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis (in vivo). Compounds with the fluoro-substituted benzyl group showed potent aromatase inhibition. Among them, 5-[(4-cyanophenyl)(3, 5-difluorobenzyl)amino]pyrimidine (5w, YM553) was a highly potent compound with an IC50 value of 0.038nM for aromatase from human placenta. Its inhibitory effect was approximately four times greater than that of YM511. In addition, YM553 was a weak inhibitor of other enzymes involved in steroid hormone synthesis. These results indicate that YM553, as well as YM511 (a 4-amino-4H-1, 2, 4-triazole derivative), is a promising agent for the treatment of estrogen-dependent diseases.

  为了研究5-氨基嘧啶骨架作为芳香化酶抑制剂的效能，我们合成了多种N,N-二取代-5-氨基嘧啶衍生物，并评估了它们的芳香化酶抑制活性（体外）以及对孕马血清促性腺激素（PMSG）诱导雌激素合成的抑制活性（体内）。具有氟取代苄基的化合物显示出强效的芳香化酶抑制作用。其中，5-[(4-氰基苯基)(3,5-二氟苄基)氨基]嘧啶（5w，YM553）是一种高效的化合物，针对人胎盘芳香化酶的IC50值为0.038nM。其抑制效果约为YM511的四倍。此外，YM553对其他参与类固醇激素合成的酶仅表现出较弱的抑制作用。这些结果表明，YM553以及YM511（4-氨基-4H-1,2,4-三唑衍生物）是治疗依赖雌激素疾病的有希望的药物。
• Studies on Aromatase Inhibitors. III. Synthesis and Biological Evaluation of ((4-Bromobenzyl)(4-cyanophenyl)amino)azoles and Their Azine Analogs.
  作者：Minoru OKADA、Toru YODEN、Eiji KAWAMINAMI、Yoshiaki SHIMADA、Masafumi KUDOH、Yasuo ISOMURA

  DOI：10.1248/cpb.45.482

  日期：——

  A series of [(4-bromobenzyl)(4-cyanophenyl)amino]azoles and their azine analogs, which have the side chain of the selective aromatase inhibitor YM511, were synthesized and evaluated for aromatase-inhibitory activity (in vivo) and for pregnant mare serum gonadotropin (PMSG)-induced estrogen synthesis inhibitory activity (in vitro). Among these aza-heterocycles, the pyrimidin-5-yl derivative (6a) was the most potent aromatase inhibitor and its in vitro inhibitory activity was comparable to that of YM511. Compound 6a also showed weak inhibitory activity on aldosterone synthesis. These data indicated that the pyrimidin-5-yl moiety is useful as a new azole fragment in place of the 4H-1, 2, 4-triazol-4-yl moiety of the aromatase inhibitor YM511.

  一系列具有选择性芳香化酶抑制剂YM511侧链的[(4-溴苄)(4-氰基苯)氨基]噁唑及其肼类似物被合成并评估了其芳香化酶抑制活性（体内）和对孕马血清促性腺激素（PMSG）诱导的雌激素合成抑制活性（体外）。在这些杂氮类化合物中，吡啶-5-基衍生物（6a）是最强的芳香化酶抑制剂，其体外抑制活性与YM511相当。化合物6a对醛固酮合成也表现出弱抑制活性。这些数据显示，吡啶-5-基结构可作为芳香化酶抑制剂YM511中4H-1,2,4-三唑-4-基结构的新噁唑片段的替代物。
• NOVEL SUBSTITUTED TERTIARY AMINO COMPOUND OR SALT THEREOF
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0640595A1

  公开（公告）日：1995-03-01

  A substituted tertiary amino compound represented by general formula (I) or a pharmaceutically acceptable salt thererof. They have an aromatase inhibiting activity and are useful as a prophylactic and/or therapeutic agent for breast cancer, mastopathy, endometriosis, prostatic hypertrophy, and so forth.

  由通式（I）代表的取代叔氨基化合物或其药学上可接受的盐。它们具有芳香化酶抑制活性，可作为乳腺癌、乳腺增生症、子宫内膜异位症、前列腺肥大等疾病的预防和/或治疗药物。
• Novel ¹⁸F-Labeled PET Tracers Specific to Aromatase: Design, Synthesis, and Biological Evaluation
  作者：Wei Zheng、Xuebo Cheng、Hualong Chen、Zeng Jiang、Yuli Sun、Ziyue Yu、Tingyu Yang、Lu Zhang、Yajing Liu、Xunming Ji、Zehui Wu

  DOI：10.1021/acs.molpharmaceut.2c00176

  日期：2022.7.4