尼古博星 | 13912-80-6

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 尼古博星
• 中文别名: 烟波克昔；烟酸丁氧基乙酯；盐酸鱼精蛋白
• 英文名称: nicoboxil
• 英文别名: 2-butoxyethyl nicotinate；beta-butoxyethyl nicotinate；Butoxyethyl nicotinate；2-butoxyethyl pyridine-3-carboxylate
• CAS: 13912-80-6
• 化学式: C₁₂H₁₇NO₃
• mdl: MFCD00047451
• 分子量: 223.272
• InChiKey: IZJRISIINLJVBU-UHFFFAOYSA-N

物化性质

• 沸点：
  287.4±15.0 °C(Predicted)
• 密度：
  1.066±0.06 g/cm3(Predicted)
• LogP：
  2.060 (est)
• 保留指数：
  1640

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

ADMET

代谢

预计系统吸收的尼可氧化物会在血液血浆中被水解成烟酸和2-丁氧乙醇。据报道，在体外，血清白蛋白的酯酶样活性和血浆酯酶可以催化这种水解反应。烟酸代谢物也具有血管扩张的能力。在人体内，也报告了2-丁氧乙醇的代谢物，2-丁氧乙酸的尿液排出。尼可氧化物的代谢被认为是快速的。

Any systemically absorbed nicoboxil is expected to be hydrolyzed to nicotinic acid and 2-butoxyethanol in blood plasma. In vitro it is reported that such hydrolysis reactions are catalyzed by esterase-like activity of serum albumin and by plasma esterases. The nicotinic acid metabolite is also capable of vascular dilatation. In humans, the urinary elimination of 2-butoxyethanol's metabolite, 2-butoxyacetic acid was also reported. The metabolism of nicoboxil is considered to be rapid.

来源:DrugBank

毒理性

• 蛋白质结合

尽管自20世纪50年代以来，局部尼可氧化物和辣椒素产品在一些欧洲地区已被用于治疗肌肉骨骼系统的疼痛，但尼可氧化物和辣椒素的效果尚未被详细研究，关于尼可氧化物药效学和药代动力学的详细研究仍然缺乏。因此，关于尼可氧化物蛋白质结合的易于获取的数据随后不可用。

Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing. Readily accessible data regarding the protein binding of nicoboxil is subsequently not available.

来源:DrugBank

吸收、分配和排泄

• 吸收

关于实验动物或目标物种皮肤应用的尼可氧化物吸收的具体研究是不可用的。然而，与尼可氧化物相关的烟酸酯的已发布数据表明，这类化合物的成员原则上能够穿透皮肤[12]。尽管如此，有研究证明了尼可氧化物与非尼拉胺组合外用制剂作为有效且安全的止痛产品，正因为这类外用制剂预计会具有更低的系统性吸收 - 从而减少系统性副作用的风险（例如，胃肠道不适、嗜睡等） - 比口服非甾体抗炎药、阿片类药物、肌肉松弛剂和类固醇等可能更常开出的药物要低。尽管如此，尽管尼可氧化物和非尼拉胺产品自20世纪50年代以来在欧洲部分地区可用于治疗肌肉骨骼系统的疼痛，但尼可氧化物和非尼拉胺的效果尚未经过详细研究，关于尼可氧化物药效学和药代动力学的详细研究仍然缺乏。

Specific investigations on absorption of dermally applied nicoboxil in laboratory animals or target species were not available. Published data for nicotinate esters related to nicoboxil indicated however, that members of this class of compounds are in principle able to penetrate skin [12]. Regardless, there is interest in the studies that demonstrate nicoboxil and nonivamide combination topical applications as effective and safe analgesic products precisely because such topical formulations are expected to have much lower systemic absorption - and thus less exposure to systemic side effects (ie. like gastrointestinal upset, drowsiness, etc.) - than the oral non-steroidal anti-inflammatory drugs, opioids, muscle relaxants, and steroids that may be more commonly prescribed over a rubefacient like nicoboxil. Nevertheless, despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing.

来源:DrugBank

吸收、分配和排泄

• 排除途径

酯类分解后，预期尼古丁酸代谢物会作为维生素B复合体的一部分进入内源代谢池。认为2-丁氧乙醇代谢物主要在尿液中排出，在一定程度上，还会通过呼出的空气排出。在人类中，也报告了2-丁氧乙醇的代谢物，2-丁氧乙酸的尿液排出。

Following ester cleavage, the nicotinic acid metabolite is expected to enter the endogenous metabolic pool as a part of the vitamin B complex. The 2-butoxyethanol metabolite is believed to be mainly excreted primarily in the urine and to a certain extent, in exhaled air. In humans, the urinary elimination of 2-butoxyethanol's metabolite, 2-butoxyacetic acid was also reported.

来源:DrugBank

吸收、分配和排泄

• 分布容积

尽管自20世纪50年代以来，局部尼可氧化物和辣椒素产品在一些欧洲地区已被用于治疗肌肉骨骼系统的疼痛，但尼可氧化物和辣椒素的效果尚未被详细研究，关于尼可氧化物药效学和药代动力学的详细研究仍然缺乏。因此，关于尼可氧化物分布体积的易获取数据随后也并未提供。

Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing. Readily accessible data regarding the volume of distribution of nicoboxil is subsequently not available.

来源:DrugBank

吸收、分配和排泄

• 清除

尼可氧化物的消除被认为是快速的。尽管自20世纪50年代以来，在欧洲部分地区就已经可以使用局部尼可氧化物和非尼拉胺产品来治疗肌肉骨骼系统的疼痛，但尼可氧化物和非尼拉胺的效果尚未经过详细研究，关于尼可氧化物的药效学和药代动力学的详细研究仍然缺乏。因此，关于尼可氧化物清除的易于获取的数据随后不可用。

The elimination of nicoboxil is considered to be rapid. Despite the fact that topical nicoboxil and nonivamide products been available to use in some parts of Europe since the 1950s to treat discomfort of the muscuoskeletal system, the effects of nicoboxil and nonivamide have not been investigated in detail and a lack of detailed studies on nicoboxil pharmacodynamics and pharmacokinetics remains ongoing. Readily accessible data regarding the clearance of nicoboxil is subsequently not available.

来源:DrugBank

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  尼古博星 在 2,4,6-三甲基吡啶 、 三氟甲磺酸酐 、 二苄胺 、 N-碘代丁二酰亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以59 %的产率得到
  参考文献：
  名称：

  通过锌亚胺中间体卤化吡啶的3位

  摘要：

  吡啶卤化反应对于获得药物和农用化学品开发所需的大量衍生物至关重要。然而，尽管经过一个多世纪的合成努力，选择性官能化多种吡啶前体 3 位碳氢键的卤化过程在很大程度上仍然难以捉摸。我们报道了吡啶基开环、卤化和闭环的反应序列，其中无环锌亚胺中间体在温和条件下经历高度区域选择性卤化反应。实验和计算机理研究表明，卤素亲电子试剂的性质可以改变选择性决定步骤。使用这种方法，我们生产了多种 3-卤代吡啶，并演示了复杂药物和农用化学品的后期卤化。

  DOI：

  10.1126/science.add8980
• 作为产物：
  描述：

  烟酸 、 乙二醇单丁醚 在 硫酸 、 苯 作用下， 生成 尼古博星
  参考文献：
  名称：

  Munoz Mena; Jimenez Nunez, Ciencia, 1954, vol. 14, p. 156,158

  摘要：

  DOI：

文献信息

• ANTI-AGING AGENT CONTAINING ARCTIGENIN DERIVATIVE
  申请人：ROHTO Pharmaceutical Co., Ltd.

  公开号：US20150093345A1

  公开（公告）日：2015-04-02

  An arctigenin derivative used for anti-aging treatment, including protection of the skin from the sun and recovery of skin elasticity. A variety of fatty acid ester derivatives, alcohol ether derivatives and alkylated derivatives are used as the arctigenin derivatives. Agents for controlling ET-1 production, elastase inhibitors, and anti-inflammatory agents are prepared. Such arctigenin derivatives are particularly useful as an external agent for the skin, such as an anti-inflammatory external agent, a sunscreen external agent, or an external agent for recovering elasticity.

  一种用于抗衰老治疗的牛蒡素衍生物，包括保护皮肤免受阳光伤害和恢复皮肤弹性。使用各种脂肪酸酯衍生物、醇醚衍生物和烷基衍生物作为牛蒡素衍生物。制备用于控制ET-1产生的药剂、弹性蛋白酶抑制剂和抗炎药剂。这种牛蒡素衍生物特别适用于皮肤外用剂，如抗炎外用剂、防晒外用剂或恢复弹性的外用剂。
• Selective Halogenation of Pyridines Using Designed Phosphine Reagents
  作者：Jeffrey N. Levy、Juan V. Alegre-Requena、Renrong Liu、Robert S. Paton、Andrew McNally

  DOI：10.1021/jacs.0c04674

  日期：2020.6.24

  metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational

  卤代吡啶是合成药物、农用化学品和金属配合物配体的关键组成部分，但缺乏选择性卤化吡啶 CH 前体的策略。我们设计了一组杂环膦，它们以鏻盐的形式安装在吡啶的 4 位，然后被卤化物亲核试剂取代。可以卤化多种未活化的吡啶，该方法适用于复杂药物的后期卤化。计算研究表明 C-卤素键的形成是通过 SNAr 途径发生的，而膦的消除是速率决定步骤。CP 键裂解过程中的空间相互作用解释了 2-和 3-取代吡啶之间反应性的差异。
• ALKYL-SUBSTITUTED TETRAHYDROPYRANS AS FLAVORING SUBSTANCES
  申请人：Oertling Heiko

  公开号：US20100226864A1

  公开（公告）日：2010-09-09

  The present invention relates to alkyl-substituted tetrahydropyrans, mixtures containing these alkyl-substituted tetrahydropyrans, their respective use and corresponding flavored products.

  本发明涉及烷基取代的四氢吡喃，含有这些烷基取代的四氢吡喃的混合物，它们的相应用途以及相应的风味产品。
• Cosmetic composition
  申请人：UNILEVER PLC

  公开号：EP0489581A2

  公开（公告）日：1992-06-10

  Compositions containing an ester of nicotinic acid and a cosmetically acceptable surfactant are provided. These compositions, when applied topically to the human body produce a response such as a sensory or therapeutic response, for example a tingling or warming sensation or an increase in blood flow, which persists after the composition is rinsed from the body. The compositions are particularly suitable for application to the hair and/or scalp where they may encourage hair growth. Compositions for application to the hair and/or scalp preferably additionally comprise hair benefit agents such as hair growth promoters.

  提供含有烟酸酯和化妆品可接受的表面活性剂的组合物。这些组合物在局部涂抹到人体时会产生一种感官或治疗反应，例如刺痛或温热感觉，或者增加血液流动，这种反应在组合物被冲洗后仍然持续。这些组合物特别适用于涂抹到头发和/或头皮，可以促进头发生长。用于涂抹到头发和/或头皮的组合物最好还包括头发益处剂，如促进头发生长的剂。
• COSMETIC
  申请人：SHIN-ETSU CHEMICAL CO., LTD.

  公开号：US20200246246A1

  公开（公告）日：2020-08-06

  A cosmetic including at least one cyclic silicone represented by formula (1), and having a boiling point of 205 to 255° C. and a viscosity of less than 5 mm 2 /s (25° C.). This cosmetic has a light touch, a good spread, and excellent water repellency, forms a uniform cosmetic film, can achieve a feeling of use without a strong oily feeling, and has stability over time and cosmetic persistence when a variety of oil such as a silicone, hydrocarbon oil, and ester, an organic ultraviolet absorber, or an oily component being solid at 25° C. is mixed. (Wherein R 1 is a monovalent hydrocarbon group having 2 or 3 carbon atoms, R 2 , R 3 , R 4 , R 5 , and R 6 are each independently a monovalent hydrocarbon group having 1 to 3 carbon atoms, “a” is a positive number satisfying 0

  一种化妆品，包括至少一种由式（1）代表的环状硅氧烷，并且沸点为205至255°C，粘度低于5 mm2/s（25°C）。该化妆品具有轻盈触感，良好延展性和出色的防水性，形成均匀的化妆膜，可以达到使用感受而不产生强烈的油腻感，当混合多种油，如硅油、烃类油、酯类、有机紫外线吸收剂或在25°C下为固体的油性成分时，具有随时间稳定性和化妆持久性。（其中R1是具有2或3个碳原子的一价碳氢基团，R2、R3、R4、R5和R6各自独立地是具有1至3个碳原子的一价碳氢基团，“a”是满足0