5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环; Tavaborole | 174671-46-6

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 中文名称: 5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环; Tavaborole
• 中文别名: 5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环;Tavaborole；5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环；他伐硼罗；塔瓦伯勒
• 英文名称: tavaborole
• 英文别名: 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole；5-fluorobenzo[c][1,2]oxaborol-1(3H)-ol；AN-2690；5-fluoro-1,3-dihydro-2,1-benzoxaborol-1-ol；kerydin；1,3-dihydro-5-fluoro-1-hydroxy-2,1-benzoxaborole；5-fluoro-2,1-benzoxaborol-1(3H)-ol；5-fluoro-1-hydroxy-3H-2,1-benzoxaborole
• CAS: 174671-46-6
• 化学式: C₇H₆BFO₂
• mdl: MFCD10699483
• 分子量: 151.933
• InChiKey: LFQDNHWZDQTITF-UHFFFAOYSA-N

物化性质

• 熔点：
  120-122℃
• 沸点：
  230.8±50.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）
• 颜色/状态：
  White to off-white powder
• 蒸汽压力：
  3.25X10-3 mm Hg at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

代谢

Tavaborole 经历广泛的代谢。代谢物分析揭示了一微克级的硫酸结合物和苯甲酸代谢物，这与已知的 tavaborole 生物转化相一致。

Tavaborole undergoes extensive metabolism. Metabolite profiling revealed trace levels of a sulfated-conjugate and a benzoic acid metabolite, consistent with the known biotransformation of tavaborole.

来源:DrugBank

代谢

Tavaborole 经历广泛的代谢。在一项临床药理学试验中，六名健康的成年男性志愿者单次局部应用了5%的(14)C- tavaborole 溶液，结果显示 tavaborole 的结合物和代谢物主要在尿液中排出。

Tavaborole undergoes extensive metabolism. ... In a clinical pharmacology trial of six healthy adult male volunteers who received a single topical application of 5% (14)C-tavaborole solution, tavaborole conjugates and metabolites were shown to be excreted primarily in the urine.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

鉴定和使用：Tavaborole是一种白色至灰白色的粉末，是一种含氧硼的抗菌剂。氧硼类化合物是含有硼的分子，具有抗真菌活性。Tavaborole外用溶液，5%用于治疗由红色毛癣菌或须癣毛癣菌引起的脚趾甲真菌病。人类暴露和毒性：在一项随机、单盲、对照研究中评估了Tavaborole引起过敏反应的潜力，该研究包括了234名18-75岁的成年人。没有发现过敏反应的证据。在另一项研究中，将Tavaborole 5%溶液、载体溶液、阳性刺激物对照（月桂基硫酸钠0.5%溶液）和阴性刺激物对照（0.9%氯化钠）同时每天一次应用于45名18-75岁健康成人的背部不同部位，持续21天。应用后30分钟评估部位是否有局部刺激的迹象。第2-22天的数据显示，Tavaborole 5%溶液的平均刺激反应高于阳性刺激物对照的平均刺激反应。基于体外遗传毒性试验（人淋巴细胞染色体畸变分析）的结果，Tavaborole未显示出致突变或断裂潜力。动物研究：通过皮肤和口服给药研究了Tavaborole的致癌性。在皮肤研究中，将5%、10%和15%的Tavaborole溶液每天一次应用于小鼠，持续104周。在最高15%的Tavaborole溶液的局部剂量下，没有发现与药物相关的肿瘤。在口服研究中，将12.5、25和50 mg/kg/天的Tavaborole剂量每天一次给予大鼠，持续104周。在最高50 mg/kg/天的口服剂量下，没有发现与药物相关的肿瘤。在大鼠的口服孕前和产后发育研究中，从器官形成开始（妊娠第6天）到哺乳期结束（哺乳第20天），分别给予15、60和100 mg/kg/天的Tavaborole剂量。在存在最小母体毒性的情况下，在100 mg/kg/天的剂量下未观察到胚胎胎儿毒性或对产后发育的影响。在兔子的皮肤胚胎胎儿发育研究中，在器官形成期（妊娠第6-28天）将1%、5%和10%的Tavaborole溶液局部应用于怀孕的雌性兔子。在5%和10%的Tavaborole溶液下，治疗部位出现了剂量依赖性的皮肤刺激增加。在10%的Tavaborole溶液下，观察到胎儿体重下降。在兔子中，10%的Tavaborole溶液（基于AUC比较，是MRHD的36倍）下没有发现与药物相关的畸形。在兔子中，5%的Tavaborole溶液（基于AUC比较，是MRHD的26倍）下未观察到胚胎胎儿毒性。在雄性和雌性大鼠中，给予口服剂量最高达300 mg/kg/天的Tavaborole（基于AUC比较，是MRHD的107倍），在孕前和孕早期未观察到对生育能力的影响。基于体外遗传毒性试验（ Ames试验）和体内遗传毒性试验（大鼠微核试验）的结果，Tavaborole未显示出致突变或断裂潜力。

IDENTIFICATION AND USE: Tavaborole, a white to off-white powder, is an oxaborole antifungal agent. Oxaboroles are boron-containing molecules with antifungal activity. Tavaborole topical solution, 5% is indicated for the treatment of onychomycosis of the toenails due to Trichophyton rubrum or Trichophyton mentagrophytes. HUMAN EXPOSURE AND TOXICITY: The potential of tavaborole to cause sensitization was evaluated in a randomized, single-blind, controlled study that included 234 adults 18-75 years of age. There was no evidence of sensitization. In another study, tavaborole 5% solution, vehicle solution, positive irritant control (lauryl sulfate 0.5% solution), and negative irritant control (0.9% sodium chloride) were applied simultaneously once daily at separate sites on the back of 45 healthy adults 18-75 years of age for 21 days. The sites were evaluated 30 minutes after application for signs of local irritation. Data from days 2-22 indicated that the mean irritation response to tavaborole 5% solution was higher than the mean irritation response to the positive irritant control. Tavaborole revealed no evidence of mutagenic or clastogenic potential based on the results of in vitro genotoxicity test (Human lymphocyte chromosomal aberration assay). ANIMAL STUDIES: The carcinogenicity of tavaborole was studied by both dermal and oral administration. In the dermal study, topical doses of 5%, 10%, and 15% tavaborole solution were administered to mice once daily for 104 weeks. No drug related neoplastic findings were noted at topical doses up to 15% tavaborole solution. In the oral study doses of 12.5, 25, and 50 mg/kg/day tavaborole were administered to rats once daily for 104 weeks. No drug related neoplastic findings were noted at oral doses up to 50 mg/kg/day tavaborole. In an oral pre- and post-natal development study in rats, oral doses of 15, 60, and 100 mg/kg/day tavaborole were administered from the beginning of organogenesis (gestation day 6) through the end of lactation (lactation day 20). In the presence of minimal maternal toxicity, no embryofetal toxicity or effects on postnatal development were noted at 100 mg/kg/day. In a dermal embryofetal development study in rabbits, topical doses of 1%, 5%, and 10% tavaborole solution were administered during the period of organogenesis (gestational days 6-28) to pregnant female rabbits. A dose dependent increase in dermal irritation at the treatment site was noted at 5% and 10% tavaborole solution. A decrease in fetal bodyweight was noted at 10% tavaborole solution. No drug related malformations were noted in rabbits at 10% tavaborole solution (36 times the MRHD based on AUC comparisons). No embryofetal toxicity was noted in rabbits at 5% tavaborole solution (26 times the MRHD based on AUC comparisons). No effects on fertility were observed in male and female rats that were administered oral doses up to 300 mg/kg/day tavaborole (107 times the MRHD based on AUC comparisons) prior to and during early pregnancy. Tavaborole revealed no evidence of mutagenic or clastogenic potential based on the results of in vitro genotoxicity test (Ames assay) and in vivo genotoxicity test (rat micronucleus assay).

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 在妊娠和哺乳期间的影响

◉ 母乳喂养期间使用总结：局部外用 tavaborole 在哺乳期尚未进行研究。由于局部应用于趾甲后血药浓度非常低，因此药物不太可能以可测量的量进入母乳中。 ◉ 对哺乳婴儿的影响：截至修订日期，未找到相关的已发布信息。 ◉ 对泌乳和母乳的影响：截至修订日期，未找到相关的已发布信息。

◉ Summary of Use during Lactation:Topical tavaborole has not been studied during breastfeeding. Because blood levels are very low after topical application to the toenails, it is unlikely that a measurable amount of the drug will enter the breastmilk. ◉ Effects in Breastfed Infants:Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk:Relevant published information was not found as of the revision date.

来源:Drugs and Lactation Database (LactMed)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预期癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能够吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于昏迷、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W TKO /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液（LR）。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。/毒物A和B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

• 吸收

7.5%。甲下型甲癣由于感染部位在甲床的血供较差，因此难以治疗。为了有效，外用治疗必须渗透甲板并达到感染部位，并且浓度足够以发挥抗真菌作用。研究显示，在连续5天的局部使用Tavaborole后，可以产生抗真菌效果。

7.5%. Subungual onychomycosis is difficult to treat due to the poorly perfused location of the infection in the nailbed. To be effective, a topical treatment must penetrate the nail plate and reach the site of infection at a concentration sufficient to exert anti-fungal activity. Tavaborole was shown to produce anti-fungal effects after 5 days of topical administration.

来源:DrugBank

吸收、分配和排泄

• 消除途径

主要在肾脏。

Primarily renal.

来源:DrugBank

吸收、分配和排泄

在24名患有远端甲下真菌病，涉及至少4个趾甲（包括至少1个大趾甲）的患者中，研究了tavaborole的药代动力学。这些患者接受了一次剂量的tavaborole，并在接下来的2周内，每天将200微升5%的tavaborole溶液涂抹到所有10个趾甲和每个趾甲周围2毫米的皮肤上。在14天的给药后达到了稳态。单次给药后，tavaborole的平均（±标准差）峰浓度（Cmax）为3.54 ± 2.26 ng/mL（n=21，可测量浓度范围0.618-10.2 ng/mL，定量下限LLOQ=0.5 ng/mL），平均AUClast为44.4 ± 25.5 ng·hr/mL（n=21）。经过2周的每日给药后，平均Cmax为5.17 ± 3.47 ng/mL（n=24，范围1.51-12.8 ng/mL），平均AUCt为75.8 ± 44.5 ng·hr/mL。

The pharmacokinetics of tavaborole was investigated in 24 subjects with distal subungual onychomycosis involving at least 4 toenails (including at least 1 great toenail) following a single dose and a 2-week daily topical application of 200 uL of a 5% solution of tavaborole to all ten toenails and 2 mm of skin surrounding each toenail. Steady state was achieved after 14 days of dosing. After a single dose, the mean (+ or - standard deviation) peak concentration (Cmax) of tavaborole was 3.54 + or - 2.26 ng/mL (n=21 with measurable concentrations, range 0.618-10.2 ng/mL, LLOQ=0.5 ng/mL), and the mean AUClast was 44.4 + or - 25.5 ng*hr/mL (n=21). After 2 weeks of daily dosing, the mean Cmax was 5.17 + or - 3.47 ng/mL (n=24, range 1.51-12.8 ng/mL), and the mean AUCt was 75.8 + or - 44.5 ng*hr/mL.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

肾脏排泄是消除的主要途径。在一项临床药理学试验中，六名健康的成年男性志愿者单次局部应用了5%（14）C- tavaborole溶液，结果显示tavaborole的共轭物和代谢物主要在尿液中排出。

Renal excretion is the major route of elimination. In a clinical pharmacology trial of six healthy adult male volunteers who received a single topical application of 5% (14)C-tavaborole solution, tavaborole conjugates and metabolites were shown to be excreted primarily in the urine.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

/MILK/ 目前尚不清楚局部应用Kerydin后，塔瓦博洛尔是否会在人类乳汁中排泄。

/MILK/ It is not known whether tavaborole is excreted in human milk following topical application of Kerydin.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  -20°C，干燥

制备方法与用途

抗真菌药物：他伐硼罗Tavaborole

他伐硼罗 (Tavaborole) 是一种抗真菌剂，能够抵抗毛癣菌属，有效治疗甲真菌病。他伐硼罗（商品名Kerydin®）是Anacor公司首个基于硼的局部用抗真菌药物，于2014年7月7日经FDA批准用于局部治疗趾甲真菌感染。未来也可用于手指甲感染。

作用机理

Tavaborole通过与细胞质亮氨酰氨酰基转移RNA（tRNA）合成酶形成加合物来阻止细胞蛋白质合成，从而发挥其抗真菌活性。它是一种具有氨酰-tRNA 合成酶抑制作用的含硼抗真菌剂，独特地抑制真菌蛋白质合成中的氨酰基转移核糖核酸 (tRNA) 合成酶（AARS），在遗传密码翻译过程中催化正确的氨基酸与其相应的 tRNA 的连接。

药物代谢

单次给药后，Tavaborole的平均峰值浓度（Cmax）为3.54±2.26 ng/mL，平均AUClast为44.4±25.5 nghr/mL。每日给药两周后，平均Cmax上升至5.17±3.47 ng/mL，平均AUCτ增加到75.8±44.5 nghr/mL。Tavaborole经局部给药五天后显示出抗真菌作用，半衰期为28.5小时，并主要通过肾脏清除代谢产生的硫酸盐结合物和苯甲酸代谢物。

关键临床数据

FDA基于两项共纳入1194例患者的多中心、随机、双盲临床试验确定Tavaborole的有效性和安全性。对比含有活性护肤品成分的局部赋形剂，试验结果表明使用Tavaborole治疗趾甲真菌病在完全治愈方面有明显优势。两个试验中，“完全治愈”的比例分别为6.5% 和9.1%，而对照组的比例为0.5%和1.5%。

次要终点“完全或接近完全治愈”也显示了相似的优势，即真菌感染治愈的同时临床病变小于10%，或者仅有真菌感染的治愈。Tavaborole通常具有良好的耐受性，大多数不良事件为轻度且与治疗无关。超过1% 的参与者发生的与治疗相关的不良事件包括应用部位剥落、红斑和皮炎以及趾甲向内生长。

AN2690对真核亮氨酰-tRNA合成酶的作用

2010年8月，中科院上海生命科学研究院生物化学与细胞生物学研究所王恩多研究组在Biochemical Journal发表的研究论文揭示了抗广谱药物AN2690对真核亮氨酰-tRNA合成酶（LeuRS）的转移后编校功能。

该研究表明，LeuRS具有多种编校途径，其转移后的编校结构域位于插入活性中心的长连接肽链1 (CP1) 结构域。美国科学院院刊（Science, 2007, 316, 1759-1761）报道了AN2690通过影响LeuRS CP1结构域来抑制其氨基酸活化和tRNA氨基酰化。

周小龙博士基于真核来源的贾第虫LeuRS（GlLeuRS）的研究，发现ESI参与氨基酸活化、tRNA氨基酰化和转移后编校反应，并揭示了GlLeuRS与人胞质LeuRS在CP1结构域中的差异。这些研究结果表明，在进化过程中，LeuRS的结构变化与其功能的相应调整有关。

本项工作的意义在于：发现LeuRS的结构变化及其功能的变化将为设计治疗贾第虫病的专一药物提供依据，并指出该药物应针对GlLeuRS CP1结构域进行优化。

反应信息

• 作为反应物：
  描述：

  5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环; Tavaborole 在 硝酸 作用下， 生成 5-fluoro-6-nitrobenzo[c][1,2]oxaborol-1(3H)-ol
  参考文献：
  名称：

  Synthesis and biological evaluations of P4-benzoxaborole-substituted macrocyclic inhibitors of HCV NS3 protease

  摘要：

  We disclose here a series of P4-benzoxaborole-substituted macrocyclic HCV protease inhibitors. These inhibitors are potent against HCV NS3 protease, their anti-HCV replicon potencies are largely impacted by substitutions on benzoxaborole ring system and P2* groups. P2* 2-thiazole-isoquinoline provides best replicon potency. The in vitro SAR studies and in vivo PK evaluations of selected compounds are described herein. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.071
• 作为产物：
  描述：

  5-fluoro-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以80%的产率得到5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环; Tavaborole
  参考文献：
  名称：

  [EN] NOVEL PROCESS FOR THE PREPARATION OF TAVABOROLE, ITS NOVEL POLYMORPHIC FORMS AND THE POLYMORPHS THEREOF
  [FR] NOUVEAU PROCÉDÉ DE PRÉPARATION DE TAVABOROLE, SES NOUVELLES FORMES POLYMORPHES ET POLYMORPHES ASSOCIÉS

  摘要：

  该发明涉及一种新型塔伐博瑞的制备工艺。该发明还涉及塔伐博瑞的新型多形态形式以及制备这些多形态形式的工艺。该发明还涉及一种用于纯化塔伐博瑞以获得高产率和基本纯净形式的工艺。

  公开号：

  WO2017183043A1
• 作为试剂：
  描述：

  丙烯酸甲酯（MA） 、 环己醇 在 奎宁环 、 5-氟-1,3-二氢-1-羟基-2,1-苯并氧杂硼戊环; Tavaborole 、 [Ir(dF(CF₃)ppy)₂(dtbbpy)](PF₆) 作用下， 以 1,2-二氯乙烷 为溶剂， 以71 %的产率得到methyl 3-(1-hydroxycyclohexyl)propanoate
  参考文献：
  名称：

  Direct α-C–H Alkylation of Structurally Diverse Alcohols via Combined Tavaborole and Photoredox Catalysis

  摘要：

  DOI：

  10.1021/acs.orglett.2c03117

文献信息

• 苯并氧杂硼-1-醇类化合物及其制备方法和应用
  申请人：南京农业大学

  公开号：CN111233908A

  公开（公告）日：2020-06-05

  本发明属于杀菌剂领域，具体涉及苯并氧杂硼‑1‑醇类化合物及其制备方法和用途。苯并氧杂硼‑1‑醇类化合物具有很好的杀菌活性，可以有效地控制番茄早疫病、小麦赤霉病、水稻纹枯病、草莓灰霉病、苹果斑点病、黄瓜炭疽病等农作物病害，在低浓度下即可获得优异的抑菌效果，且表现出良好的选择性。该类化合物作为亮氨酰‑tRNA合成酶抑制剂，利用病菌和真核生物的氨酰‑tRNA合成酶的进化差异，在杀灭病菌的同时，对非靶标生物具有很高安全性，在农业上可用作杀菌剂。
• Scalable, Metal- and Additive-Free, Photoinduced Borylation of Haloarenes and Quaternary Arylammonium Salts
  作者：Adelphe M. Mfuh、John D. Doyle、Bhuwan Chhetri、Hadi D. Arman、Oleg V. Larionov

  DOI：10.1021/jacs.6b01376

  日期：2016.3.9

  We report herein a simple, metal- and additive-free, photoinduced borylation of haloarenes, including electron-rich fluoroarenes, as well as arylammonium salts directly to boronic acids. This borylation method has a broad scope and functional group tolerance. We show that it can be further extended to boronic esters and carried out on gram scale as well as under flow conditions.

  我们在此报告了一种简单的、无金属和无添加剂的、光诱导的卤代芳烃硼化反应，包括富电子氟芳烃，以及芳基铵盐直接转化为硼酸。这种硼酸化方法具有广泛的范围和官能团耐受性。我们表明它可以进一步扩展到硼酸酯并在克级以及在流动条件下进行。
• [EN] PROCESS FOR PREPARATION OF TAVABOROLE<br/>[FR] PROCÉDÉ DE PRÉPARATION DE TAVABOROLE
  申请人：GLENMARK PHARMACEUTICALS LTD

  公开号：WO2017125835A1

  公开（公告）日：2017-07-27

  The present invention relates to process for preparation of tavaborole with high purity. The present invention relates to method of assessing the purity of tavaborole.

  本发明涉及一种制备高纯度塔伐硼酮的方法。本发明涉及一种评估塔伐硼酮纯度的方法。
• [EN] HETEROAROMATIC MACROCYCLIC ETHER CHEMOTHERAPEUTIC AGENTS<br/>[FR] AGENTS CHIMIOTHÉRAPEUTIQUES À BASE D'ÉTHER MACROCYCLIQUE HÉTÉROAROMATIQUE
  申请人：NUVALENT INC

  公开号：WO2021226269A1

  公开（公告）日：2021-11-11

  Disclosed are heterocyclic heteroaromatic macrocyclic ether compounds, pharmaceutically acceptable salts of the compounds and pharmaceutical compositions thereof. Also disclosed are methods of treating or preventing cancer using the heterocyclic heteroaromatic macrocyclic ether compounds, pharmaceutically acceptable salts of the compounds, and pharmaceutical compositions thereof.

  揭示了杂环杂芳大环醚化合物，这些化合物的药用盐以及它们的药物组合物。还揭示了使用这些杂环杂芳大环醚化合物、这些化合物的药用盐以及它们的药物组合物来治疗或预防癌症的方法。
• Hydrolytically-Resistant Boron-Containing Therapeutics And Methods Of Use
  申请人：Lee Ving

  公开号：US20070265226A1

  公开（公告）日：2007-11-15

  Compositions and methods of use of boron derivatives, including benzoxaboroles, benzazaboroles and benzthiaboroles, as therapeutic agents for treatment of diseases caused by fungi, yeast, bacteria or viruses are disclosed, as well as methods for synthesis of said agents and compositions thereof.

  揭示了硼衍生物的组合物和使用方法，包括苯硼酚酯、苯氮硼酚酯和苯硫硼酚酯，作为治疗由真菌、酵母、细菌或病毒引起的疾病的治疗剂，以及合成所述药剂和组合物的方法。