1-(3-氰基苯基)-3-(二甲氨基)丙烯醛 | 179055-13-1

• 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: 1-(3-氰基苯基)-3-(二甲氨基)丙烯醛
• 英文名称: (E)-3-(3-(dimethylamino)acryloyl)benzonitrile
• 英文别名: 1-(3-Cyanophenyl)-3-(dimethylamino)acrolein；3-[(E)-3-(dimethylamino)prop-2-enoyl]benzonitrile
• CAS: 179055-13-1
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: SLKQIWXTDLZLPZ-VOTSOKGWSA-N

物化性质

• 沸点：
  329.7±42.0 °C(Predicted)
• 密度：
  1.11±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：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-氰基苯基)-3-(二甲氨基)丙烯醛 在 氢氧化钾 、 sodium hydroxide 、 间氯过氧苯甲酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.5h， 生成 4-(3-cyanophenyl)-2-cyanopyrimidine
  参考文献：
  名称：

  S-Adenosylmethionine decarboxylase inhibitors: new aryl and heteroaryl analogs of methylglyoxal bis(guanylhydrazone)

  摘要：

  A series of 3-acylbenzamidine (amidino)hydrazones 7a-h, the corresponding (hetero)aromatic congeners 7i-p, and 3,3'-bis-amidino-biaryls 25a-e were synthesized. The hydrazones 7a-p were prepared by conversion of the corresponding acyl nitriles 1a,c-di,n-p to the imido esters 3a,c-d,i and the amidines 5a,c-d,h-i, followed by a reaction with aminoguanidine, or vice versa. Similarly, the biaryl 3,3'-dinitriles 23a-e were converted, via the imino esters 24a-c or the imino thioesters 27d-e, to the diamidines 25a-e. These new products are conformationally constrained analogues of methylglyoxal bis(guanylhydrazone)(MGBG). They are up to 100 times more potent as inhibitors of rat liver S-adenosylmethionine decarboxylase (SAMDC) and generally low potent inhibitors of rat small intestine diamine oxidase (DAO) than MGBG. Some of these SAMDC inhibitors, eg., compounds 7a, 7e, 7i, 25a, and 25d, have shown antiproliferative effects against T24 human bladder carcinoma cells. These products, whose structure-activity relationships are discussed, are of interest as potential anticancer agents and drugs for the treatment of protozoal and Pneumocystis carinii infections.

  DOI：

  10.1021/jm00053a007
• 作为产物：
  描述：

  3-乙酰苯腈 、 N,N-二甲基甲酰胺二甲基缩醛 以 N,N-二甲基甲酰胺 为溶剂， 以79%的产率得到1-(3-氰基苯基)-3-(二甲氨基)丙烯醛
  参考文献：
  名称：

  FR186054的合成，X射线晶体结构和生物学活性-带有吡唑环的酰基CoA：胆固醇O-酰基转移酶（ACAT）的新型有效口服活性抑制剂。

  摘要：

  描述了FR186054（2c）的合成，单晶X射线结构分析和生物学活性，FR186054（2c）是一种新型的，有效的，口服有效的酰基-CoA：胆固醇O-酰基转移酶抑制剂（ACAT），含有吡唑环。不论给药方法如何，该化合物均显示出优异的体外功效，表明与其他ACAT抑制剂相比具有优越的特性。

  DOI：

  10.1016/s0960-894x(97)10191-3

文献信息

• Inhibitors of Acyl-CoA:Cholesterol <i>O</i>-Acyltransferase. 2. Identification and Structure−Activity Relationships of a Novel Series of <i>N</i>-Alkyl-<i>N</i>-(heteroaryl-substituted benzyl)-<i>N‘</i>-arylureas
  作者：Akira Tanaka、Takeshi Terasawa、Hiroyuki Hagihara、Yuri Sakuma、Noriko Ishibe、Masae Sawada、Hisashi Takasugi、Hirokazu Tanaka

  DOI：10.1021/jm9800853

  日期：1998.6.1

  tuted benzyl)-N'-arylurea and related derivatives represented by 2 and 3 have been prepared and evaluated for their ability to inhibit acyl-CoA:cholesterol O-acyltransferase in vitro and to lower plasma cholesterol levels in cholesterol-fed rats in vivo. Among these novel compounds, the type 3 series was superior. A pyrazol-3-yl group on the N-benzyl group of this trisubstituted urea (i.e. 3, Ar1 =

  制备了一系列N-烷基-N-（杂芳基取代的苄基）-N'-芳基脲和相关的衍生物（用2和3表示），并对其在体外和体外抑制酰基辅酶A：胆固醇O-酰基转移酶的能力进行了评估。降低体内胆固醇喂养大鼠的血浆胆固醇水平。在这些新型化合物中，3型系列更为出色。该三取代脲的N-苄基上的吡唑-3-基（即3，Ar1 =吡唑-3-基）被鉴定为杂芳环，提供了良好的生物活性。通过优化与N-烷基（R）和N-芳基（Ar3）的组合的结果，化合物3aq（FR186054）被确定为一种新型的口服有效ACAT抑制剂，在胆固醇喂养的大鼠中表现出有效的体外ACAT抑制活性（兔子肠道微粒体IC50 = 99 nM）和出色的降胆固醇作用，而与给药方式无关（ED50 = 0.046 mg / kg，通过饮食给药，ED50 = 0. 44 mg /通过在PEG400载体中的管饲法施用1kg）。此外，一项毒理学研究表明，以10 mg / kg
• PROCESS OF SYNTHESIZING SUBSTITUTED PYRIDINE AND PYRIMIDINE COMPOUND
  申请人：SHANGHAI INSTITUTE OF MATERIA MEDICA,CHINESE ACADEMY OF SCIENCES

  公开号：US20180079749A1

  公开（公告）日：2018-03-22

  Provided is a process of synthesizing a substituted pyridine and pyrimidine compound. Particularly, provided is a method for preparing a compound of formula III via a compound of formula II′, wherein the definition of each of groups is as described as the description. Compound with other methods, the method in the present invention has features of high yield and a result product being easier to separate.

  提供了一种合成取代吡啶和嘧啶化合物的过程。特别地，提供了一种通过式II′化合物制备式III化合物的方法，其中各个基团的定义如描述中所述。与其他方法相比，本发明的方法具有高产率和更容易分离的产物的特点。
• Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as janus kinase inhibitors
  申请人：Rodgers D. James

  公开号：US20070135461A1

  公开（公告）日：2007-06-14

  The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

  本发明提供了杂环取代的吡咯并[2,3-b]吡啶和杂环取代的吡咯并[2,3-b]嘧啶，可以调节雅努斯激酶的活性，并且在治疗与雅努斯激酶活性相关的疾病中具有用处，例如免疫相关疾病、皮肤疾病、髓增生性疾病、癌症和其他疾病。
• Engineering Selectivity for Reduced Toxicity of Bacterial Kinase Inhibitors Using Structure-Guided Medicinal Chemistry
  作者：Nathan Wlodarchak、John B. Feltenberger、Zhengqing Ye、Jeffrey Beczkiewicz、Rebecca Procknow、Gang Yan、Troy M. King、Jennifer E. Golden、Rob Striker

  DOI：10.1021/acsmedchemlett.0c00580

  日期：2021.2.11

  Tuberculosis is a major global public health concern, and new drugs are needed to combat both the typical form and the increasingly common drug-resistant form of this disease. The essential tuberculosis kinase PknB is an attractive drug development target because of its central importance in several critical signaling cascades. A major hurdle in kinase inhibitor development is the reduction of toxicity

  结核病是一个主要的全球公共卫生问题，需要新药来对抗这种疾病的典型形式和日益常见的耐药形式。基本结核激酶 PknB 是一个有吸引力的药物开发目标，因为它在几个关键的信号级联中具有核心重要性。激酶抑制剂开发的一个主要障碍是降低宿主细胞中非特异性激酶活性导致的毒性。这里从命中氨基嘧啶1开发了一类新的 PknB 抑制剂(GW779439X)，最初是为人类CDK4设计的，但由于毒性高、特异性低而未能在临床上取得进展。用取代的吡啶或苯基头基取代原始命中的吡唑并哒嗪头基导致 Cdk 活性降低，特异性比人类激酶组提高 3 倍，同时保持 PknB 活性。这也提高了 THP-1 细胞和斑马鱼的微生物活性并降低了毒性。
• [EN] PURINES AND METHODS OF THEIR USE<br/>[FR] PURINES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：YUMANITY THERAPEUTICS INC

  公开号：WO2021247841A1

  公开（公告）日：2021-12-09

  Disclosed are compounds useful in the treatment of neurological disorders. The compounds described herein, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological diseases.

  本文披露了在治疗神经系统疾病中有用的化合物。这些化合物可以单独或与其他药用活性剂结合使用，用于治疗或预防神经系统疾病。