p-Tolylbiguanide hydrochloride

• 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: p-Tolylbiguanide hydrochloride
• 英文别名: N-(p-tolyl)biguanide hydrochloride；1-(p-methyl)biguanide hydrochloride；1-p-tolyl-biguanide; hydrochloride；1-p-Tolyl-biguanid; Hydrochlorid；diaminomethylidene-[N'-(4-methylphenyl)carbamimidoyl]azanium;chloride
• 化学式: C₉H₁₃N₅*ClH
• 分子量: 227.697
• InChiKey: ZNJNFUSJCJOWNJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.25
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  p-Tolylbiguanide hydrochloride 在 sodium methylate 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 6-[(1H-benzo[d]imidazol-2-ylthio)methyl]-N2-p-tolyl-1,3,5-triazine-2,4-diamine
  参考文献：
  名称：

  Synthesis and antiviral activity of benzimidazolyl- and triazolyl-1,3,5-triazines

  摘要：

  A novel series of 1,3,5-triazine analogs was successfully synthesized through conjugation with benzimidazole or 1,2,4-triazole derivatives via a methylenethio linker. The new analogs were in vitro evaluated against HSV-1 in Vero cells; among these analogs, two compounds exhibited good effect in inhibiting HSV-1 replication (for compound 5p: EC50 = 3.5 mu g/ml, SI = 358; for compound 5r: EC50 = 5.0 mu g/ml, SI = 300) in comparison to acyclovir.

  DOI：

  10.1007/s00044-011-9574-8
• 作为产物：
  描述：

  乙烷,三氯氟- 、 二聚氰胺 在 三甲基氯硅烷 作用下， 以 乙腈 为溶剂， 以5%的产率得到p-Tolylbiguanide hydrochloride
  参考文献：
  名称：

  结合双胍支架可增强有机阳离子转运蛋白1和2的药物吸收。

  摘要：

  膜转运蛋白在许多内源性和外源性化合物的转运中起着重要作用。转运蛋白底物要求的知识允许进一步开发利用它们来确保组织渗透的药物。在这项研究中，我们证明了包含双胍类功能可以增强有机阳离子转运蛋白1和2（OCT1和OCT2）的吸收。我们合成了18对结构上不同的化合物，每对均由母体氨基化合物及其双胍类似物组成；然后评估它们在过量表达人OCT1或OCT2的HEK293细胞中的细胞摄取。我们的结果表明，对于大多数化合物，双胍的添加显着改善了OCT1和OCT2介导的转运。双胍类也抑制了两种转运蛋白的原型底物的摄取，+）和二甲双胍。我们发现分子量，分子体积，Log D（pH 7.4）和可及表面积是OCT2底物的重要决定因素，但这些参数都不是OCT1的重要因素。更重要的是，两种细胞系中被测试的双胍类药物对MPP +摄取的抑制作用与二甲双胍的摄取抑制作用呈线性相关。两者合计，我们得出的结论是，在OCT1和OCT

  DOI：

  10.1021/acs.molpharmaceut.7b00285

文献信息

• Synthesis and in vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors
  作者：Hend Kothayer、Sebastian M. Spencer、Kaushlendra Tripathi、Andrew D. Westwell、Komaraiah Palle

  DOI：10.1016/j.bmcl.2016.02.085

  日期：2016.4

  abbreviate our compound names as 'new triazines', have been synthesized, based on the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ9 and 4-amino-N'-phenyl-6-(arylamino)-1,3,5-triazine-2-carbohydrazides. Synthesis of the target compounds was readily accomplished in two steps from either bis-aryl/aryl biguanides via reaction of phenylhydrazine or hydrazinehydrate

  4-氨基-6-（芳基氨基）-1,3,5-三嗪-2-碳酰肼（3a-e）和N'-苯基-4,6-双（芳基氨基）-1,3,5-三嗪系列为方便读者阅读，我们合成了-2-碳酰肼（6a-e），根据先前报道的Rad6B抑制性二氨基三嗪基甲基苯甲酸酯苯甲酸酯类抗癌剂TZ9和4-氨基合成了我们的化合物名称“新三嗪”。 -N′-苯基-6-（芳基氨基）-1,3,5-三嗪-2-碳酰肼。通过苯肼或肼与关键的4-氨基-6-双（芳基氨基）/（芳基氨基）-1,3,5-三嗪- 2-羧酸盐中间体。评估了这些新的三嗪衍生物抑制Rad6B泛素结合的能力以及针对几种人类癌细胞系的体外抗癌活性：卵巢癌（OV90和A2780），肺部（H1299和A549），乳腺（MCF-7和MDA-MB231） MTS分析检测结肠癌和结肠癌（HT29）细胞。与先前报道的选择性Rad6抑制剂TZ9相比，所有10种新的三嗪均表现出优异的Rad6B抑制活性。
• [EN] HETEROARYL COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEUR UTILISATION
  申请人：MINORYX THERAPEUTICS S L

  公开号：WO2018122775A1

  公开（公告）日：2018-07-05

  The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

  该申请涉及式(I)的化合物及其盐和溶剂合物，其中R1、R2、R3、A1、A2、A3和n如规范中所述，以及它们的制备方法，包含它们的药物组合物，以及用于治疗和/或预防溶酶体贮积病（如高雪氏病）和其他α-突触核蛋白病的用途。
• AN EFFICIENT SYNTHESIS OF 1-ARYL-4,6-DIAMINO-1,2-DIHYDRO- 1,3,5-TRIAZINES
  作者：Neungruthai Saesaengseerung、Tirayut Vilaivan、Yodhathai Thebtaranonth

  DOI：10.1081/scc-120005415

  日期：2002.1.1

  ABSTRACT 1-Aryl-4,6-diamino-1,2-dihydro-1,3,5-triazines bearing diverse substituents at C2 and on the aromatic ring have been synthesized in good yield from an acid-catalyzed reaction between corresponding arylbiguanide and carbonyl compound in the presence of triethyl orthoacetate as a water scavenger.

  摘要 1-Aryl-4,6-diamino-1,2-dihydro-1,3,5-triazines 在 C2 和芳环上具有不同的取代基，通过相应的芳基双胍和芳环之间的酸催化反应合成，收率良好。在作为水清除剂的原乙酸三乙酯存在下羰基化合物。
• Heteroaryl compounds and their use
  申请人：Minoryx Therapeutics S.L.

  公开号：US11174242B2

  公开（公告）日：2021-11-16

  The application is directed to compounds of formula (I): and their salts and solvates, wherein R1, R2, R3, A1, A2, A3, and n are as set forth in the specification, as well as to a method for their preparation, pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of a lysosomal storage disease, such as Gaucher's, and other diseases or disorders that are synucleinopathies.

  本申请涉及式（I）化合物：及其盐类和溶解物，其中 R1、R2、R3、A1、A2、A3 和 n 如说明书所述，还涉及其制备方法、包含这些化合物的药物组合物，以及将其用于治疗和/或预防溶酶体贮积疾病（如戈谢病）和属于突触核蛋白病的其他疾病或紊乱的用途。
• Design, synthesis and in vitro anticancer evaluation of 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides
  作者：Hend Kothayer、Abdalla A. Elshanawani、Mansour E. Abu Kull、Osama I. El-Sabbagh、Malathy P.V. Shekhar、Andrea Brancale、Arwyn T. Jones、Andrew D. Westwell

  DOI：10.1016/j.bmcl.2013.09.087

  日期：2013.12

  Series of substituted 4,6-diamino-1,3,5-triazine-2-carbohydrazides and -carboxamides have been synthesised, based on molecular modelling of candidate structures related to the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ8 and TZ9. Synthesis of the target compounds was readily accomplished in two steps from aryl biguanides via reaction of phenylhydrazine or benzylamines with key 4-amino-6-(arylamino)-1,3,5-triazine-2-carboxylate intermediates. These new triazine derivatives were tested for in vitro anticancer activity against the Rad6B expressing human breast cancer cell lines MDA-MB-231 and MCF-7. Active compounds, such as the triazinyl-carbohydrazides 3a-e, were found to exhibit low micromolar IC50 values particularly in the Rad6B-overexpressing MDA-MB-231 cell line. (C) 2013 Elsevier Ltd. All rights reserved.