4-(3-thioxo-3H-1,2-dithiol-4-yl)benzoic acid | 127588-56-1

• 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: 4-(3-thioxo-3H-1,2-dithiol-4-yl)benzoic acid
• 英文别名: 4-(3-sulfanylidenedithiol-4-yl)benzoic acid
• CAS: 127588-56-1
• 化学式: C₁₀H₆O₂S₃
• 分子量: 254.354
• InChiKey: CUCCUHOPMKIJNH-UHFFFAOYSA-N

物化性质

• 熔点：
  220-225 °C
• 沸点：
  478.7±55.0 °C(Predicted)
• 密度：
  1.61±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(3-thioxo-3H-1,2-dithiol-4-yl)benzoic acid 在 盐酸 、 potassium fluoride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 生成 [2-[(2S,4S)-4-[(2R,4S,5S,6S)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-3,4-dihydro-1H-tetracen-2-yl]-2-oxoethyl] 4-(3-sulfanylidenedithiol-4-yl)benzoate;hydrochloride
  参考文献：
  名称：

  H₂S-Donating Doxorubicins May Overcome Cardiotoxicity and Multidrug Resistance

  摘要：

  Doxorubicin (DOXO) is one of the most effective antineoplastic agents in clinical practice. Its use is limited by acute and chronic side effects, in particular by its cardiotoxicity and by the rapid development of resistance to it. As part of a program aimed at developing new DOXO derivatives endowed with reduced cardiotoxicity, and active against DOXO-resistant tumor cells, a series of H2S-releasing DOXOs (H2S-DOXOs) were obtained by combining DOXO with appropriate H2S donor substructures. The resulting compounds were studied on H9c2 cardiomyocytes and in DOXO-sensitive U-2OS osteosarcoma cells, as well as in related cell variants with increasing degrees of DOXO-resistance. Differently from DOXO, most of the products were not toxic at 5 mu M concentration on H9c2 cells. A few of them triggered high activity on the cancer cells. H2S-DOXOs 10 and 11 emerged as the most interesting members of the series. The capacity of 10 to impair Pgp transporter is also discussed.

  DOI：

  10.1021/acs.jmedchem.6b00184
• 作为产物：
  描述：

  4-异丙基苯甲酸 在 氯化亚砜 、 硫酸 、 sulfur 作用下， 以 溶剂黄146 为溶剂， 反应 10.0h， 生成 4-(3-thioxo-3H-1,2-dithiol-4-yl)benzoic acid
  参考文献：
  名称：

  在关节炎大鼠模型中开发具有增强抗痛觉过敏作用的硫化氢释放碳酸酐酶 IX 和 XII 选择性抑制剂

  摘要：

  本文提出了一种基于硫化氢 (H 2 S)的抗炎作用和抑制碳酸酐酶 (CAs) IX 和 XII 的有效治疗方法来治疗关节炎。H 2 S 是一种人体气体递质，可在低浓度下调节炎症反应。抑制 CA IX 和 XII 可以恢复酸性发炎滑液中的正常 pH 值，从而减轻关节炎症状。我们在此报告了 H 2 S 供体─CA 抑制剂 (CAI) 杂化衍生物的设计。后者在体外作为人类 CA I、II、IV、IX 和 XII 的抑制剂进行了测试，与 CAI 合成前体相比，显示出显着增加的抑制效力/异构体选择性。最好的化合物表现出持续释放 H 的能力2 S 并在关节炎大鼠模型中产生有效的疼痛缓解作用。与单一H 2 S供体、CAI片段或其共同给药相比，化合物26在给药后45分钟完全恢复疼痛状态，具有增强的体内抗痛觉过敏作用。

  DOI：

  10.1021/acs.jmedchem.2c00982

文献信息

• Cardiovascular agents
  申请人：CTG Pharma S.r.l.

  公开号：EP1980559A1

  公开（公告）日：2008-10-15

  The present invention relates to novel compounds that are derivatives of angiotensin receptor blocker (ARB) that comprise in their formula a polysulfurated group and that are useful for treating cardio-vascular diseases, such as hypertension, ischemic heart disease, atherosclerosis, metabolic syndrome, etc. also in combination with other cardiovascular agents.

  这项发明涉及一种新型化合物，它们是血管紧张素受体拮抗剂（ARB）的衍生物，在其分子式中包含一个多硫化基团，可用于治疗心血管疾病，如高血压、缺血性心脏病、动脉粥样硬化、代谢综合征等，还可与其他心血管药物联合使用。
• [EN] NEW AGENTS FOR THE TREATMENT OF THE LOW URINARY TRACT DYSFUNCTIONS<br/>[FR] NOUVEAUX AGENTS POUR LE TRAITEMENT DE DYSFONCTIONNEMENTS DU TRACTUS URINAIRE INFÉRIEUR.
  申请人：CTG PHARMA S R L

  公开号：WO2009037556A1

  公开（公告）日：2009-03-26

  The present invention relates to novel compounds that are derivatives of 5 -phosphodiesterase inhibitors that comprise in their formula a polysulfurated group and that are useful for treating dysfunctions of low urinary tract such as incontinence, benign prostatic hyperplasia and erectile dysfunction.

  本发明涉及一种新型化合物，它们是5-磷酸二酯酶抑制剂的衍生物，在其化学式中包含一个多硫化基团，可用于治疗低尿路功能障碍，如尿失禁、良性前列腺增生和勃起功能障碍。
• Synthesis of new dithiolethione and methanethiosulfonate systems endowed with pharmaceutical interest
  作者：Elena Gabriele、Federica Porta、Giorgio Facchetti、Corinna Galli、Arianna Gelain、Fiorella Meneghetti、Isabella Rimoldi、Sergio Romeo、Stefania Villa、Chiara Ricci、Nicola Ferri、Akira Asai、Daniela Barlocco、Anna Sparatore

  DOI：10.3998/ark.5550190.p009.805

  日期：——

  Here we report synthetic methodology affording in the most efficient way the rapid preparation of new dithiolethiones (DTTs) and methanethiosulfonates (MTSs). These were evaluated as STAT3 inhibitors since these electrophilic systems could react with thiol groups of STAT3-SH2 domain. The results showed that MTSs strongly interacted with the SH2 domain, whereas the corresponding DTTs possessed lower

  在这里，我们报告了以最有效的方式快速制备新的二硫硫酮 (DTT) 和甲硫代磺酸盐 (MTS) 的合成方法。这些被评估为 STAT3 抑制剂，因为这些亲电子系统可以与 STAT3-SH2 结构域的硫醇基团反应。结果表明，MTSs 与 SH2 结构域强烈相互作用，而相应的 DTTs 具有较低的亲和力，与连接的杂环支架的性质无关。
• New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-κB transcription factors
  作者：Elena Gabriele、Dario Brambilla、Chiara Ricci、Luca Regazzoni、Kyoko Taguchi、Nicola Ferri、Akira Asai、Anna Sparatore

  DOI：10.1080/14756366.2017.1350658

  日期：2017.1.1

  able to inhibit the NF-κB transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-κB inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents.

  合成了一组新的硫化药物混合物，主要源自咖啡酸、阿魏酸和迷迭香碱，并评估了它们抑制 STAT3 和 NF-κB 转录因子的能力。结果表明，大多数新的杂合化合物能够强烈且选择性地与 STAT3 结合，而母体药物在测试浓度下缺乏这种能力。其中一些还能够抑制HCT-116细胞系中的NF-κB转录活性，并在体外抑制HCT-116细胞增殖，IC50在微摩尔范围内，因此表明具有潜在的抗癌活性。总而言之，我们的研究描述了具有 STAT3/NF-κB 双重抑制活性的新衍生物的鉴定，这可能代表用于开发多靶点抗癌药物的热门化合物。
• Design, Synthesis and Biological Evaluations of Novel Conjugates of Danshensu, Tetramethylpyrazine and Hydrogen Sulfide Donors as Cardioprotective Agents
  作者：Chang-Jiang Xu、Hui-Xing Deng、Hai-Yun Chen、Qing-Bin Cui、Lu-Chen Shan、Pei Yu、Ye-Wei Sun、Yu-Qiang Wang

  DOI：10.14233/ajchem.2016.20101

  日期：——

  A series of molecular hybrids of Danshensu-tetramethylpyrazine-hydrogen sulfide donors have been synthesized and evaluated in vitro as potent antimyocardial ischemia agents. The pharmacological data demonstrated that compound DTA-2 exhibited the most potent protective activities against tert-butyl hydroperoxide (t-BHP) induced injury in H9c2 cells. Further study showed that DTA-2 exhibited better ROS-scavenging activity and mitochondria protective effect than its parental drug DTM, ACS48 and mixtures of these two. These results indicated that DTA-2 may work through a unique mechanism and may serve as a drug candidate for anti-myocardial ischemia therapy that require further study.

  一系列丹参酚-四甲基吡嗪-硫化氢供体的分子杂化物被合成并在体外评估为有效的抗心肌缺血药物。药理数据表明，化合物DTA-2对叔丁基过氧化氢（t-BHP）诱导的H9c2细胞损伤展现出最强的保护活性。进一步研究表明，DTA-2的清除活性氧（ROS）能力和线粒体保护效果优于其母药DTM、ACS48及这两者的混合物。这些结果表明，DTA-2可能通过独特机制发挥作用，并可能作为抗心肌缺血治疗的药物候选者，需进一步研究。