3,6-bis(dimethylamino)-9-(methylthio)acridine | 95167-67-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3,6-bis(dimethylamino)-9-(methylthio)acridine
• 英文别名: 3,6-Bis(dimethylamino)-9-methylthioacridine；3-N,3-N,6-N,6-N-tetramethyl-9-methylsulfanylacridine-3,6-diamine
• CAS: 95167-67-2
• 化学式: C₁₈H₂₁N₃S
• 分子量: 311.451
• InChiKey: BQCRYNPOFNYULD-UHFFFAOYSA-N

物化性质

• 沸点：
  525.6±40.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  44.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,6-bis(dimethylamino)-9-(methylthio)acridine 在 茴香硫醚 、 间甲酚 、 三乙胺 作用下， 以 二氯甲烷 、 2,2,2-三氟乙醇 为溶剂， 反应 21.0h， 生成
  参考文献：
  名称：

  Fluorescence enhancement of bis-acridine orange peptide, BAO, upon binding to double stranded DNA

  摘要：

  双吖啶橙肽在四（赖氨酸）链的两个末端赖氨酸的ε-氨基部分带有两个吖啶橙，在加入双链DNA后，荧光强度提高了约200倍。

  DOI：

  10.1039/b417391k
• 作为产物：
  描述：

  吖啶橙 在 sodium 、 sulfur 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 3,6-bis(dimethylamino)-9-(methylthio)acridine
  参考文献：
  名称：

  具有强力碳酸酐酶IX抑制作用的a啶橙磺酰胺衍生物的合成。

  摘要：

  cr啶橙（AO）是一种荧光阳离子染料，用于处理人的肌肉骨骼肉瘤，由于其强大的杀伤作用和在低氧肿瘤典型的酸性环境中的蓄积，可用于制备伯磺酰胺衍生物。药物设计的基本原理是缺氧，酸性肿瘤过表达碳酸酐酶（CA，EC 4.2.1.1）亚型，例如CA IX，其参与pH调节，增殖，细胞迁移和侵袭，该酶是被伯磺酰胺强烈抑制。AO-磺酰胺衍生物确实是一种有效的低纳摩尔CA IX抑制剂，而其对胞质亚型CA I和II的抑制作用在微摩尔范围内。第二个跨膜，与肿瘤相关的同种型CA XII，

  DOI：

  10.1080/14756366.2017.1302441

文献信息

• Synthesis and in vitro Evaluation of 9-Anilino-3,6-diaminoacridines Active Against a Multidrug-Resistant Strain of the Malaria Parasite Plasmodium falciparum
  作者：Swarna A. Gamage、Nisana Tepsiri、Prapon Wilairat、Stanley J. Wojcik、David P. Figgitt、Raymond K. Ralph、William A. Denny

  DOI：10.1021/jm00036a014

  日期：1994.5

  A new synthesis of 3,6-diamino-9-anilinoacridines, via reduction of the corresponding diazides, gives much higher yields than traditional methods. Within the subset of 3,6-diamino-9-anilinoacridines, there was considerable tolerance to substitution at the 1'-anilino position. In a sharp divergence with structure-activity relationships for high mammalian cell toxicity and anticancer effects, derivatives

  已经制备了一系列9-苯胺基oa啶酮，并评估了它们对红细胞悬液中疟原虫恶性疟原虫的多药耐药K1株的活性。与其他取代方式相比，啶环上的3,6-二氨基取代导致较低的哺乳动物细胞细胞毒性和较高的抗寄生虫活性，从而提供具有最高体外治疗指数的化合物。通过还原相应的叠氮化物，新合成3,6-二氨基-9-苯胺基cr啶的产率比传统方法高得多。在3，6-二氨基-9-苯胺基cr啶的子集中，对1'-苯胺基位置的取代具有相当大的耐受性。在具有高哺乳动物细胞毒性和抗癌作用的构效关系方面，带有吸电子1'取代基的衍生物（例如SO2-NHR和CONHR）显示出最有效的抗疟活性（IC50值为10-20 nM）。代表性的化合物显示出是人类拓扑异构酶II的DNA链传递活性和相应寄生虫DNA脱链活性的有效抑制剂。1'-SO2NH2衍生物7n在20 microM时完全抑制了Jurkat拓扑异构酶II的链通过，并且在1 microM或以
• Studies directed towards nonyl acridine orange analogues having the potential to act as FRET donors with the PDT drug Pc 4
  作者：Ping Zhang、Yang Yang、Yun Liu、Myriam E. Rodriguez、Malcolm E. Kenney

  DOI：10.1039/c5ra28126a

  日期：——

  A group of nonyl acridine orange analogues (NAO) was prepared which were designed to have the potential of possessing visible bands allowing them to act in cells as fluorescence resonance energy transfer (FRET) donors with the photodynamic therapy drug Pc 4. The existence of Pc 4-FRET with the analogues of NAO in MCF-7c3 cells was probed. The results suggest that NAO analogues giving strong FRET with

  制备了一组壬基a啶橙类似物（NAO），其被设计为具有可见带的潜力，使它们可以在光动力疗法药物Pc 4中作为荧光共振能量转移（FRET）供体在细胞中发挥作用。探测了在MCF-7c3细胞中带有NAO类似物的4-FRET。结果表明，可以找到在细胞中具有Pc 4的FAO的NAO类似物。
• Structure−Activity Relationships for the Antileishmanial and Antitrypanosomal Activities of 1‘-Substituted 9-Anilinoacridines
  作者：Swarna A. Gamage、David P. Figgitt、Stanley J. Wojcik、Raymond K. Ralph、Adriana Ransijn、Jacques Mauel、Vanessa Yardley、Diane Snowdon、Simon L. Croft、William A. Denny

  DOI：10.1021/jm970232h

  日期：1997.8.1

  Members of the class of 9-anilinoacridine topoisomerase II inhibitors bearing lipophilic electron-donating 1'-anilino substituents are active against both the promastigote and amastigote forms of the parasite Leishmania major. A series of analogues of the known 1'-NHhexyl lead compound were prepared and evaluated against L. major in macrophage culture to further develop structure-activity relationships (SAR). Toxicity toward mammalian cells was measured in a human leukemia cell line, and the ratio of the two IC50 values (IC50(J)/IC50(L)) was used as a measure of the in vitro therapeutic index (IVTI). A 3,6-diNMe(2) substitution pattern on the acridine greatly increased toxicity to L. major without altering mammalian toxicity, increasing IVTIs over that of the lead compound. The 2-OMe, 6-Cl acridine substitution pattern used in the antimalarial drug mepacrine also resulted in potent antileishmanial activity and high IVTIs. Earlier suggestions of the utility of 2'-OR groups in lowering mammalian cytotoxicity were not borne out in this wider study. A series of very lipophilic 1'-NRR (symmetric dialkylamino)-substituted analogues showed relatively high antileishmanial potency, but no clear trend was apparent across the series, and none were superior to the 1'-NH(CH2)(5)Me subclass. Subsets of the most active 1'-N(R)(CH2)(5)Me- and 1'-N(alkyl)(2)-substituted compounds against L. major were also evaluated against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, but no consistent SAR could be discerned in these physiologically diverse test systems. The present study has confirmed earlier conclusions that lipophilic electron-donating groups at the 1'-position of 9-anilinoacridines provide high activity against L. major, but the SAR patterns observed do not carry over to the other parasites studied.
• 9-Substituted 3,6-Bis(dimethylamino)acridines
  作者：Edward F. Elslager

  DOI：10.1021/jo01059a050

  日期：1962.12