S-(2-naphthylmethyl)-2-pyridylthioimidate hydrobromide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: S-(2-naphthylmethyl)-2-pyridylthioimidate hydrobromide
• 英文别名: naphthalen-2-ylmethyl pyridine-2-carbimidothioate hydrobromide；2-Pyridinecarboximidothioic acid, 2-naphthalenylmethyl ester, monohydrobromide；naphthalen-2-ylmethyl pyridine-2-carboximidothioate;hydrobromide
• 化学式: BrH*C₁₇H₁₄N₂S
• 分子量: 359.289
• InChiKey: PCTUVVCZQDBPOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.32
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  联苯胺 、 S-(2-naphthylmethyl)-2-pyridylthioimidate hydrobromide 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 乙腈 为溶剂， 以97%的产率得到N,N'-([1,1'-biphenyl]-4,4'-diyl)dipicolinimidamide dihydrochloride
  参考文献：
  名称：

  Synthesis, DNA binding and antileishmanial activity of low molecular weight bis-arylimidamides

  摘要：

  The effects of reducing the molecular weight of the antileishmanial compound DB766 on DNA binding affinity, antileishmanial activity and cytotoxicity are reported. The bis-arylimidamides were prepared by the coupling of aryl S-(2-naphthylmethyl)thioimidates with the corresponding amines. Specifically, we have prepared new series of bis-arylimidamides which include 3a, 3b, 6, 9a, 9b, 9c, 13, and 18. Three compounds 9a, 9c, and 18 bind to DNA with similar or moderately lower affinity to that of DB766, the rest of these compounds either show quite weak binding or no binding at all to DNA. Compounds 9a, 9c, and 13 were the most active against Leishmania amazonensis showing IC50 values of less than 1 mu M, so they were screened against intracellular Leishmania donovani showing outstanding activity with IC50 values of 25-79 nM. Despite exhibiting little in vitro cytotoxicity these three compounds were quite toxic to mice. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.058
• 作为产物：
  描述：

  2-氰基吡啶 在 盐酸 、 硫代乙酰胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.83h， 生成 S-(2-naphthylmethyl)-2-pyridylthioimidate hydrobromide
  参考文献：
  名称：

  Diguanidino and “Reversed” Diamidino 2,5-Diarylfurans as Antimicrobial Agents

  摘要：

  Dicationic 2,5-bis(4-guanidinophenyl)furans 5a-5f, 2,5-bis [4-(arylimino)aminophenyl] furans 6a -6b and 6e-6k, and 2,5-bis [4-(alkylimino)aminophenyl] furans 6c -6d have been synthesized starting from 2,5-bis [tri-n-butylstannyl] furan. Thermal melting studies with poly dA . dT and the duplex oligomer d(CGCGAATTCGCG)2 demonstrated high DNA binding affinities for a number of the compounds. The binding affinities are highly dependent on structure and are significantly affected by substituents both on the phenyl rings of the 2,5-diphenylfuran nucleus and on the cationic centers. Of the 17 novel dicationic compounds synthesized, six (6a, 6b, 5b, 6f, 6fi, 6i) exhibited MICs of 2 mug/mL or less versus Mycobacterium tuberculosis. Of the compounds screened against Candida albicans, three gave MICs of 2 mug/mL or less (5b, 6h, Si), and two (5b, 6i) were fungicidal, unlike a standard antifungal drug fluconazole, which was fungistatic. In addition, one of the tested compounds (6i) exhibited a MIC of <1 mug/mL against Aspergillus fumigatus, while also being a fungicidal against this organism. Finally, when evaluated against an expanded fungal panel, compound 6h showed good activity against Cryptococcus neoformans and Rhizopus arrhizus.

  DOI：

  10.1021/jm000413a

文献信息

• <i>In Vitro</i> , <i>In Silico</i> , and <i>In Vivo</i> Analyses of Novel Aromatic Amidines against Trypanosoma cruzi
  作者：Camila C. Santos、Jéssica R. Lionel、Raiza B. Peres、Marcos M. Batista、Patrícia B. da Silva、Gabriel M. de Oliveira、Cristiane F. da Silva、Denise G. J. Batista、Sandra Maria O. Souza、Carolina H. Andrade、Bruno J. Neves、Rodolpho C. Braga、Donald A. Patrick、Svetlana M. Bakunova、Richard R. Tidwell、Maria de Nazaré C. Soeiro

  DOI：10.1128/aac.02205-17

  日期：2018.2

  assayed as anti-Trypanosoma cruzi agents by in vitro, in silico, and in vivo approaches. None were considered to be pan-assay interference compounds. They had a favorable pharmacokinetic landscape and were active against trypomastigotes and intracellular forms, and in combination with benznidazole, they gave no interaction. The most selective agent (28SMB032) tested in vivo led to a 40% reduction in

  通过体外，计算机和体内方法测定了五种双芳基酰胺类药物作为克氏锥虫的抗药性。没有一个被认为是泛测定干扰化合物。它们具有良好的药代动力学特性，并且对锥虫和细胞内形式具有活性，并且与苯硝唑联用时，它们没有相互作用。在体内测试的最具选择性的药物（28SMB032）导致寄生虫病减少40％（腹膜内注射0.1 mg / kg体重/ 5天），但没有死亡保护。在计算机靶标捕鱼中，建议以DNA为主要靶标，但超微结构数据不匹配。
• [EN] ANTI-FUNGAL TREATMENT<br/>[FR] TRAITEMENT ANTIFONGIQUE
  申请人：OHIO STATE INNOVATION FOUNDATION

  公开号：WO2018045106A1

  公开（公告）日：2018-03-08

  Provided are compounds, methods, and pharmaceutical compositions useful for treatment of fungal infections, e.g., aspergillosis, candidiasis, cryptococcosis, histoplasmosis, and the like. For example, the pharmaceutical composition may include a pharmaceutically acceptable carrier or excipient, and a compound represented by Ar— C(=NR1)NR2— A---X— Y— Het2 and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted aryl or nitrogen- containing heteroaryl. R1 and R2 may independently be H, optionally substituted C1-C6 aikyi, or optionally substituted C3-C6 cyeloalkyi. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cyeloalkyi, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C10 alkyi or optionally substituted C2-C10 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.

  提供了用于治疗真菌感染的化合物、方法和药物组合物，例如曲霉病、念珠菌感染、隐球菌病、组织胞浆菌病等。例如，药物组合物可以包括药用可接受载体或赋形剂，以及由Ar—C(=NR1)NR2—A---X—Y—Het2表示的化合物及其药用可接受的盐。Ar可以是可选择取代的芳基或含氮的杂环芳基。R1和R2可以独立地是H、可选择取代的C1-C6烷基或可选择取代的C3-C6环烷基。A可以是键或包含1、2或3个环的可选择取代的连接基。可选择取代的连接基中的每个环可以独立地是以下之一：芳基、环烷基、杂环烷基和杂芳基。X可以是O、S、酰胺或键。Y可以是可选择取代的C1-C10烷基或可选择取代的C2-C10烯基。Het2可以是可选择取代的含五个成员的含氮杂芳环，其中包括1、2或3个环杂原子。
• [EN] ANTI-PARASITIC COMPOUNDS<br/>[FR] COMPOSÉS ANTIPARASITAIRES
  申请人：OHIO STATE INNOVATION FOUNDATION

  公开号：WO2018045104A1

  公开（公告）日：2018-03-08

  Provided are compounds, methods, and pharmaceutical compositions useful for treatment of parasites, e.g., Leishmania. For example, the compound may he represented by Ar—C(=NR1)NR2—A—X—Y—Het2, and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted, aryl or nitrogen-containing heteroaryl. R1 and R2 may independently represent H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cycloalkyl, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C14 alkyl or optionally substituted C2-C14 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.

  提供了一些化合物、方法和药物组合物，用于治疗寄生虫，例如利什曼虫。例如，该化合物可以表示为Ar—C(=NR1)NR2—A—X—Y—Het2，及其药学上可接受的盐。Ar可以是可选择取代的芳基或含氮的杂芳基。R1和R2可以独立表示H、可选择取代的C1-C6烷基或可选择取代的C3-C6环烷基。A可以是一个键或一个可选择取代的连接基，包括1、2或3个环。可选择取代的连接基中的每个环可以独立地是以下之一：芳基、环烷基、杂环烷基和杂芳基。X可以是O、S、酰胺或一个键。Y可以是可选择取代的C1-C14烷基或可选择取代的C2-C14烯基。Het2可以是一个可选择取代的含有5个成员的含氮杂芳环，包括1、2或3个环杂原子。
• [EN] NOVEL AMIDINE COMPOUNDS FOR TREATING MICROBIAL INFECTIONS<br/>[FR] NOUVEAUX COMPOSES D'AMIDINE DANS LE TRAITEMENT D'INFECTIONS MICROBIENNES
  申请人：UNIV NORTH CAROLINA

  公开号：WO2005033065A1

  公开（公告）日：2005-04-14

  Novel amidine and diamidine compounds are useful in the treatment of microbial infections, including mycobacterial, fungal and protozoal infections. Pharmaceutical formulations comprising these compounds can be used in methods of treating microbial infections.

  新型胍和二胍化合物在治疗微生物感染方面具有重要作用，包括结核菌、真菌和原虫感染。含有这些化合物的药物配方可用于治疗微生物感染的方法。
• Synthesis, DNA Affinity, and Antiprotozoal Activity of Fused Ring Dicationic Compounds and Their Prodrugs
  作者：Reem K. Arafa、Reto Brun、Tanja Wenzler、Farial A. Tanious、W. David Wilson、Chad E. Stephens、David W. Boykin

  DOI：10.1021/jm058190h

  日期：2005.8.1

  treated animals in the STIB900 animal model for African trypanosomiasis. The N-methyl analogue showed high activity as well. In addition, with the goal of enhancing the oral bioavailability, two novel classes of potential guanidine prodrugs were prepared. The N-alkoxyguanidine derivatives were not effective as prodrugs. In contrast, a number of the carbamates showed promising activity. The value of the

  由它们相应的双胺合成了稠环系统的二阳离子胍，N-烷基胍和反向am衍生物。DNA结合研究表明，二胍和N-烷基二胍芴以较小的方式结合在小沟中，其方式与先前报道的二甲基咔唑衍生物相似。双胍和N-烷基双胍显示出有希望的针对布鲁氏锥虫和恶性疟原虫的体外活性。有用的N-异丙基胍基-9H-芴获得了有希望的体内生物学结果，为非洲锥虫病的STIB900动物模型提供了4/4种治疗动物的治愈方法。N-甲基类似物也显示出高活性。另外，以提高口服生物利用度为目标，制备了两种新型的潜在胍类前药。N-烷氧基胍衍生物不能有效地用作前药。相反，许多氨基甲酸酯显示出有希望的活性。结果清楚地表明了氨基甲酸酯前药的价值，该药物在STIB900小鼠模型中口服给药时可治愈4/4。