6-氯-N4-(1-甲基乙基)-4,5-嘧啶二胺 | 18202-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-氯-N4-(1-甲基乙基)-4,5-嘧啶二胺
• 英文名称: 6-chloro-N4-isopropylpyrimidine-4,5-diamine
• 英文别名: 6-chloro-4-N-propan-2-ylpyrimidine-4,5-diamine
• CAS: 18202-82-9
• 化学式: C₇H₁₁ClN₄
• 分子量: 186.644
• InChiKey: LWHSQBMRCOGJRA-UHFFFAOYSA-N

物化性质

• 沸点：
  332.4±42.0 °C(Predicted)
• 密度：
  1.305±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 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：

  6-氯-N4-(1-甲基乙基)-4,5-嘧啶二胺 在 乙基磺酸 作用下， 以 乙醇 为溶剂， 反应 86.0h， 生成 (9-isopropyl-9H-purin-6-yl)-dimethyl-amine
  参考文献：
  名称：

  6-(Alkylamino)-9-alkylpurines. A New Class of Potential Antipsychotic Agents

  摘要：

  A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive behavior in rats and apomorphine-induced climbing in mice, but that do not block stereotyped behavior, could have an antipsychotic effect in humans without producing extrapyramidal side effects. The antiaggressive-behavior activity of lead compound 1 (6-(dimethylamino)-9-(3-phenylalaninamidobenzyl)-9H-purine) was improved 48-fold with 6-(cyclopropylamino)-9-(cyclopropylmethyl)-2-(trifluoromethyl)-9H-purine (80) (po ED50 of 2 mg/kg), which was obtained through an iterative sequence of structure-activity relationship studies that encompassed evaluation of the effects of structure variations at the purine 9-, 6-, and 2-positions. Potency was enhanced with a 9-cyclopropyl group, the duration of action was improved with the 6-(cyclopropylamino) substituent, potency was further enhanced with an N-formyl prodrug, and an agent with reduced cardiovascular effect emerged with the 2-trifluoromethyl purine 80. This potential antipsychotic agent was not developed further due to undesirable effects on the stomach.

  DOI：

  10.1021/jm960662s
• 作为产物：
  描述：

  6-氯-N-(1-甲基乙基)-5-硝基-4-嘧啶胺 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 6-氯-N4-(1-甲基乙基)-4,5-嘧啶二胺
  参考文献：
  名称：

  Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic inducers of human leukemic lymphocytes and DAPK-1 inhibitors

  摘要：

  研究DAPK1在凋亡中的作用的嘌呤。

  DOI：

  10.1039/c5ob00230c

文献信息

• An efficient one-pot synthesis of 6-alkoxy-8,9-dialkylpurines via reaction of 5-amino-4-chloro-6-alkylaminopyrimidines with N,N-dimethylalkaneamides and alkoxide ions
  作者：Pier Giovanni Baraldi、Asier Unciti Broceta、Maria Josè Pineda de las Infantas、Juan Josè Dı̀az Mochun、Antonio Espinosa、Romeo Romagnoli

  DOI：10.1016/s0040-4020(02)00867-0

  日期：2002.9

  ines has been accomplished by the cyclization of the corresponding intermediate 5-amino-4-chloro-6-(alkylamino)pyrimidines promoted by alkoxides and various N,N-dimethyl amides, where the latter act as solvent–reagents. By this three-component condensation reaction we are able to introduce an alkyl group in the 8 position of the purine ring with the concomitant nucleophilic replacement of the 6-chloro

  许多新的6-烷氧基-8,9-（二取代）嘌呤的合成是通过将相应的中间体5-氨基-4-氯-6-（烷基氨基）嘧啶经醇盐和各种N促进的环化来完成的，N-二甲基酰胺，后者用作溶剂-试剂。通过这种三组分缩合反应，我们能够在嘌呤环的8位引入烷基，同时用烷氧基部分亲核取代6-氯。
• ¹ H and ¹³ C assignments of 6-, 8-, 9- substituted purines
  作者：Álvaro Lorente-Macías、Manuel Benítez-Quesada、Ignacio J. Molina、Asier Unciti-Broceta、Juan José Díaz-Mochón、María José Pineda de las Infantas Villatoro

  DOI：10.1002/mrc.4743

  日期：2018.9

  Purines are heterocyclic aromatic organic compounds consisting of two 5‐ and 6‐membered fused rings containing nitrogen. They are present in numerous compounds, including natural products, with potent biological activity. Purine analogs are used for the treatment of acute leukemias. Thiopurine derivatives are effective antiviral (acyclovir and ganciclovir) or antitumor agents such as vidarabine, among

  嘌呤是杂环芳香族有机化合物，由两个含氮的 5 元和 6 元稠环组成。它们存在于许多具有强大生物活性的化合物中，包括天然产物。嘌呤类似物用于治疗急性白血病。硫嘌呤衍生物是有效的抗病毒剂（阿昔洛韦和更昔洛韦）或抗肿瘤剂，例如阿糖腺苷，以及其他临床用途。多年来，嘌呤核已成为一个重要的药效团。它能够干扰酶和核酸的合成和功能。它也经常用于开发蛋白激酶抑制剂。我们的研究小组开发了生产嘌呤文库的新途径。其中一种途径是一锅法合成以获得 6-、8-、来自 4-烷基氨基-5-氨基-6-氯嘧啶、醇和 N,N-二甲基酰胺的 9-取代嘌呤。我们还提出了一种获得三取代嘌呤的新方法。我们能够制备多取代嘌呤库。发现该文库中的一些化合物是死亡相关蛋白激酶-1 的特异性抑制剂。该文库的主要化合物是肿瘤淋巴细胞凋亡的有效诱导剂，也降低锥虫的活力。我们在此报告了这些新嘌呤衍生物子集的 H 和 C 的明确分配。在化合物 3k 和 3n
• [EN] HETEROCYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2010080503A1

  公开（公告）日：2010-07-15

  In one aspect, the present invention provides for a compound of Formula I; in which the variable X1a, X1b, X1c, X1d, Q, A, R1, B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-xL proteins.

  在一个方面，本发明提供了一种具有式I的化合物；其中变量X1a、X1b、X1c、X1d、Q、A、R1、B、L、E和下标m和n的含义如本文所述。在另一个方面，本发明提供了包括式I化合物的药物组合物，以及使用式I化合物治疗由Bcl-2抗凋亡蛋白（例如抗凋亡Bcl-xL蛋白）的表达或过度表达所特征的疾病和状况（例如癌症、血小板增多症等）的方法。
• A1 adenosine receptor antagonists
  申请人：Cristalli Gloria

  公开号：US20050245546A1

  公开（公告）日：2005-11-03

  Disclosed are A 1 adenosine receptor antagonists, useful for treating various disease states, in particular disease states for which diuretic treatment is appropriate.

  揭示了A1腺苷受体拮抗剂，用于治疗各种疾病状态，特别是适用于利尿治疗的疾病状态。
• HETEROCYCLIC COMPOUNDS AND METHODS OF USE
  申请人：Baell Jonathan Bayldon

  公开号：US20100210622A1

  公开（公告）日：2010-08-19

  In one aspect, the present invention provides for a compound of Formula I in which the variable X 1a , X 1b , X 1c , X 1d , Q, A, R 1 , B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-x L proteins.

  在一个方面，本发明提供了一种式子为I的化合物，其中变量X1a，X1b，X1c，X1d，Q，A，R1，B，L，E和下标m和n的含义如此处所述。在另一个方面，本发明提供了包含式子I化合物的制药组合物，以及使用式子I化合物治疗由Bcl-2抗凋亡蛋白（例如抗凋亡Bcl-xL蛋白）的表达或过表达所特征的疾病和病状（例如癌症，血小板增多症等）的方法。