butyl piperazine-1-carbodithioate | 1605349-67-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: butyl piperazine-1-carbodithioate
• 英文别名: Butyl piperazine-1-carbodithioate
• CAS: 1605349-67-4
• 化学式: C₉H₁₈N₂S₂
• 分子量: 218.387
• InChiKey: XVBJDDZESFBCMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  72.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  butyl piperazine-1-carbodithioate 在 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 13.0h， 生成 1-butyl 4-(2-(pyrrolidin-1-yl)ethyl)piperazine-1,4-bis(carbodithioate)
  参考文献：
  名称：

  新型精子固定剂的设计和合成过程中独特的二硫代氨基甲酸酯化学物质† ‡

  摘要：

  在设计和合成1,4-（二取代）哌嗪二碳二硫代酸酯为双刃杀精剂的过程中，在酸性和碱性条件下，通过不寻常地除去苄基取代的二硫代氨基甲酸酯衍生物中的CS 2来获得1-取代的哌嗪碳二硫代酸酯。已经提出了一种可行的CS 2去除机理。所有合成的化合物均具有杀精，抗滴虫和抗真菌活性。21种化合物不可逆地固定了100％的精子（MEC，0.06-31.6 mM），而7种化合物表现出多种活性。苄基4-（2-（哌啶-1-基）乙基）哌嗪-1-（碳二硫代酸酯）（18）和1-苄基4-（2-（哌啶基-1-基）乙基）哌嗪-1,4-双（碳二硫代）（24）表现出明显的杀精子活性（MEC，0.07和0.06 mM），抗真菌剂（MIC，0.069–0.14和> 0.11 mM）和抗毛滴虫活性（MIC，1.38和0.14 mM）。这些化合物可能的作用方式似乎是通过巯基结合，这通过精子硫醇的荧光标记证实。

  DOI：

  10.1039/c4ob00005f
• 作为产物：
  描述：

  tert-butyl 4-(butylthiocarbonothioyl)piperazine-1-carboxylate 在 三氟乙酸 、 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以87%的产率得到butyl piperazine-1-carbodithioate
  参考文献：
  名称：

  新型精子固定剂的设计和合成过程中独特的二硫代氨基甲酸酯化学物质† ‡

  摘要：

  在设计和合成1,4-（二取代）哌嗪二碳二硫代酸酯为双刃杀精剂的过程中，在酸性和碱性条件下，通过不寻常地除去苄基取代的二硫代氨基甲酸酯衍生物中的CS 2来获得1-取代的哌嗪碳二硫代酸酯。已经提出了一种可行的CS 2去除机理。所有合成的化合物均具有杀精，抗滴虫和抗真菌活性。21种化合物不可逆地固定了100％的精子（MEC，0.06-31.6 mM），而7种化合物表现出多种活性。苄基4-（2-（哌啶-1-基）乙基）哌嗪-1-（碳二硫代酸酯）（18）和1-苄基4-（2-（哌啶基-1-基）乙基）哌嗪-1,4-双（碳二硫代）（24）表现出明显的杀精子活性（MEC，0.07和0.06 mM），抗真菌剂（MIC，0.069–0.14和> 0.11 mM）和抗毛滴虫活性（MIC，1.38和0.14 mM）。这些化合物可能的作用方式似乎是通过巯基结合，这通过精子硫醇的荧光标记证实。

  DOI：

  10.1039/c4ob00005f

文献信息

• Role of disulfide linkage in action of bis(dialkylaminethiocarbonyl)disulfides as potent double-Edged microbicidal spermicide: Design, synthesis and biology
  作者：Nand Lal、Santosh Jangir、Veenu Bala、Dhanaraju Mandalapu、Amit Sarswat、Lalit Kumar、Ashish Jain、Lokesh Kumar、Bhavana Kushwaha、Atindra K. Pandey、Shagun Krishna、Tara Rawat、Praveen K. Shukla、Jagdamba P. Maikhuri、Mohammad I. Siddiqi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2016.03.012

  日期：2016.6

  generally treated by Metronidazole and Fluconazole respectively. Poor vaginal efficacy, drug-resistance and non-spermicidal nature limit their use as topical microbicidal contraceptives. Bis(dialkylaminethiocarbonyl)disulfides (4–38) were designed as dually active, non-surfactant molecules capable of eliminating Trichomonas vaginalis and Candida strains as well as irreversibly immobilizing 100% human sperm

  滴虫病和念珠菌病是最常见的致病性生殖道感染，通常分别用甲硝唑和氟康唑治疗。阴道功效差，耐药性和非杀精性限制了它们作为局部杀微生物避孕药的使用。双（二烷基胺硫代羰基）二硫化物（4 – 38）被设计为具有双重活性的非表面活性剂分子，能够消除阴道毛滴虫和念珠菌菌株，并且能够以不可细胞毒性的剂量立即不可逆地固定100％人类精子，对人类宫颈上皮细胞和体外阴道菌群。化合物12，16，17它们的活性是非氧化酚9，OTC阴道杀精子剂的50倍，并且化合物12和17在兔模型中显示出显着的体内活性。最有前途的化合物17由于具有更高的活性和安全性以及显着的体内滴虫杀菌活性，已显示出有望进一步发展为双刃阴道杀微生物剂。二硫化物基团的作用是由于化学修饰过程中杀精子活性的丧失而确立的（39 – 56）。这些二硫化物可能靶向存在于人精子和滴虫的细胞膜上的巯基，如游离巯基的荧光标记所示。
• [EN] CARBODITHIOATES WITH SPERMICIDAL ACTIVITY AND PROCESS FOR PREPARATION THEREOF<br/>[FR] CARBODITHIOATES AYANT UNE ACTIVITÉ SPERMICIDE ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2014122670A1

  公开（公告）日：2014-08-14

  The present invention relates to the synthesis and biological evaluation of compound of formula I as spermicidal agents, and its pharmaceutically acceptable acid salt thereof. The invention provides bis(4- substituted-1-piperazinylthiocarbonyl) disulfide (when n = 0) and alkane-1,n-diylbis(4-substituted piperazine-1-carbodithioate) (when n = 0, 1, 2 or 3) as shown in figure 1 of the accompanying drawing. These compounds are found to be useful for spermicidal activity.

  本发明涉及将式I化合物合成为杀精子剂，并其在药学上可接受的酸盐。该发明提供了双(4-取代-1-哌嗪基硫代羰基)二硫化物(当n = 0)和烷基-1,n-二基(4-取代哌嗪-1-羰基二硫代酸酯)(当n = 0, 1, 2或3)如附图1所示。这些化合物被发现对杀精子活性有用。
• Dithiocarbamate–thiourea hybrids useful as vaginal microbicides also show reverse transcriptase inhibition: Design, synthesis, docking and pharmacokinetic studies
  作者：Veenu Bala、Santosh Jangir、Dhanaraju Mandalapu、Sonal Gupta、Yashpal S. Chhonker、Nand Lal、Bhavana Kushwaha、Hardik Chandasana、Shagun Krishna、Kavita Rawat、Jagdamba P. Maikhuri、Rabi S. Bhatta、Mohammad I. Siddiqi、Rajkamal Tripathi、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.bmcl.2014.12.062

  日期：2015.2

  Prophylactic prevention is considered as the most promising strategy to tackle STI/HIV. Twenty-five dithiocarbamate-thiourea hybrids (14-38) were synthesized as woman controlled topical vaginal microbicides to counter Trichomonas vaginalis and sperm along with RT inhibition potential. The four promising compounds (18, 26, 28 and 33) were tested for safety through cytotoxic assay against human cervical cell line (HeLa) and compatibility with vaginal flora, Lactobacillus. Docking study of most promising vaginal microbicide (33) revealed that it docked in a position and orientation similar to known reverse transcriptase inhibitor Nevirapine. The preliminary in vivo pharmacokinetics of compound 33 was performed in NZ-rabbits to evaluate systemic toxicity in comparison to Nonoxynol-9. (C) 2014 Elsevier Ltd. All rights reserved.
• Substituted carbamothioic amine-1-carbothioic thioanhydrides as novel trichomonicidal fungicides: Design, synthesis, and biology
  作者：Dhanaraju Mandalapu、Bhavana Kushwaha、Sonal Gupta、Shagun Krishna、Nidhi Srivastava、Mahendra Shukla、Pratiksha Singh、Bhavana S. Chauhan、Ravi Goyani、Jagdamba P. Maikhuri、Koneni V. Sashidhara、Brijesh Kumar、Renu Tripathi、Praveen K. Shukla、Mohammad I. Siddiqi、Jawahar Lal、Gopal Gupta、Vishnu L. Sharma

  DOI：10.1016/j.ejmech.2017.11.060

  日期：2018.1

  Sexually transmitted diseases like trichomoniasis along with opportunistic fungal infections like candidiasis are major global health burden in female reproductive health. In this context a novel non-nitroimidazole class of substituted carbamothioic amine-1-carbothioic thioanhydride series was designed, synthesized, evaluated for trichomonacidal and fungicidal activities, and was found to be more active than the standard drug Metronidazole (MTZ). Compounds were trichomonicidal in the MIC ranges of 4.77-294.1 mu M and 32.46-735.20 mu M against MTZ-susceptible and-resistant strains, respectively. Further, compounds inhibited the growth of at least two out of ten fungal strains tested at MIC of 7.50 -240.38 mu M. The most active compound (20) of this series was 3.8 and 9.5 fold more active than the MTZ against the two Trichomonas strains tested. Compound 20 also significantly inhibited the sulfhydryl groups present over Trichomonas vaginalis and was found to be more active than the MTZ in vivo. Further, a docking analysis carried out with cysteine proteases supported their thiol inhibiting ability and preliminary pharmacokinetic study has shown good distribution and systemic clearance. (C) 2017 Elsevier Masson SAS. All rights reserved.
• A unique dithiocarbamate chemistry during design &amp; synthesis of novel sperm-immobilizing agents
  作者：Santosh Jangir、Veenu Bala、Nand Lal、Lalit Kumar、Amit Sarswat、Lokesh Kumar、Bhavana Kushwaha、Pratiksha Singh、Praveen Kumar Shukla、Jagdamba Prasad Maikhuri、Gopal Gupta、Vishnu Lal Sharma

  DOI：10.1039/c4ob00005f

  日期：——

  4-(2-(piperidin-1-yl)ethyl) piperazine-1-(carbodithioate) (18) and 1-benzyl 4-(2-(piperidin-1-yl)ethyl)piperazine-1,4-bis(carbodithioate) (24) exhibited appreciable spermicidal (MEC, 0.07 and 0.06 mM), antifungal (MIC, 0.069–0.14 and >0.11 mM) and antitrichomonal (MIC, 1.38 and 0.14 mM) activities. The probable mode of action of these compounds seems to be through sulfhydryl binding which was confirmed by fluorescence

  在设计和合成1,4-（二取代）哌嗪二碳二硫代酸酯为双刃杀精剂的过程中，在酸性和碱性条件下，通过不寻常地除去苄基取代的二硫代氨基甲酸酯衍生物中的CS 2来获得1-取代的哌嗪碳二硫代酸酯。已经提出了一种可行的CS 2去除机理。所有合成的化合物均具有杀精，抗滴虫和抗真菌活性。21种化合物不可逆地固定了100％的精子（MEC，0.06-31.6 mM），而7种化合物表现出多种活性。苄基4-（2-（哌啶-1-基）乙基）哌嗪-1-（碳二硫代酸酯）（18）和1-苄基4-（2-（哌啶基-1-基）乙基）哌嗪-1,4-双（碳二硫代）（24）表现出明显的杀精子活性（MEC，0.07和0.06 mM），抗真菌剂（MIC，0.069–0.14和> 0.11 mM）和抗毛滴虫活性（MIC，1.38和0.14 mM）。这些化合物可能的作用方式似乎是通过巯基结合，这通过精子硫醇的荧光标记证实。