(-)-2-(1-hydroxypentyl)benzoic acid | 380905-53-3

• 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: (-)-2-(1-hydroxypentyl)benzoic acid
• 英文别名: (R)-2-(1-hydroxy-n-pentyl)benzoic acid；2-[(1R)-1-hydroxypentyl]benzoic acid
• CAS: 380905-53-3
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: IEZTYUMJKFZPEW-LLVKDONJSA-N

物化性质

• 沸点：
  367.0±25.0 °C(Predicted)
• 密度：
  1.140±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-2-(1-hydroxypentyl)benzoic acid 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 12.17h， 生成 2,5-bis{2-[(R)-(+)-2-(1-acetoxypentyl)]}benzoate-1,4:3,6-dianhydro-D-glucitol
  参考文献：
  名称：

  Novel Hybrids of Optically Active Ring-Opened 3-n-Butylphthalide Derivative and Isosorbide as Potential Anti-Ischemic Stroke Agents

  摘要：

  In search of novel anti-ischemic stroke agents with higher potency than a known drug 3-n-butylphthalide (NBP), a series of hybrids ((S)- and (R)-5a-f) from optically active ring-opened NBP derivative and isosorbide were synthesized for evaluating their anti-ischemic stroke activity. Compound (S)-5e displayed the strongest activity in inhibiting the adenosine diphosphate (ADP) and arachidonic acid (AA)-induced platelet aggregation in vitro, with 10.0- and 8.4-fold more effectiveness than (S)-NBP, respectively. Furthermore, (S)-5e was stable in artificial gastrointestinal fluids and could penetrate the blood-brain barrier (BBB) with an appreciate lipid/water partition coefficient relative to (S)-NBP. More importantly, oral treatment with (S)-5e protected from acute thrombosis and inhibited the ischemia/reperfusion-related brain injury in animals. Our findings suggest that (S)-5e may be promising for further evaluation for the intervention of ischemic stroke.

  DOI：

  10.1021/jm4001693
• 作为产物：
  描述：

  3-丁基-1(3H)-异苯并呋喃酮 在 sodium hydroxide 作用下， 以 甲醇 、 乙醚 、 水 为溶剂， 反应 2.0h， 生成 (-)-2-(1-hydroxypentyl)benzoic acid
  参考文献：
  名称：

  Studies on the enantiomers of ZJM-289: synthesis and biological evaluation of antiplatelet, antithrombotic and neuroprotective activities

  摘要：

  ZJM-289是一种强效的外消旋剂，其在抑制血小板聚集和血栓形成方面优于已知的抗缺血性脑卒药物3-n-丁基苯酞(NBP)。在此，合成了ZJM-289的两种对映体，即(S)-ZJM-289和(R)-ZJM-289，并对其生物活性进行了评估。观察到这两种对映体在抑制体外血小板聚集和体内血栓形成方面几乎与ZJM-289同样有效。此外，与ZJM-289类似，其对映体能够调节血栓素B2(TXB2)和6-酮前列腺素F1α的比例，并增强一氧化氮(NO)、cAMP和cGMP的水平，这表明对映体和ZJM-289的抗血小板和抗血栓活性与花生四烯酸级联反应和cGMP-NO信号通路有关。进一步发现，口服对映体和ZJM-289三天显著减少了脑缺血再灌注后大鼠的脑梗死面积、脑含水量和神经功能缺损。重要的是，这两种对映体同样改善了缺血性脑卒模型中的血流，并通过释放适度的NO来调节内皮功能，这可能至少部分地促使其神经保护作用。总之，本研究表明，两种对映体在抑制血小板聚集和血栓形成以及神经保护方面与ZJM-289同样强效，并且在某些情况下，(S)-ZJM-289显示出比(R)-ZJM-289和ZJM-289更好的效果。这些发现可能为开发类似于ZJM-289的治疗血栓相关缺血性脑卒的药物提供新的见解。

  DOI：

  10.1039/c2ob26511g

文献信息

• 2-(1-酰氧正戊基)苯甲酸与碱性氨基酸或氨基胍形成的盐、其制备方法及用途
  申请人：中国药科大学

  公开号：CN109678715A

  公开（公告）日：2019-04-26

  本发明公开了一种2‑(1‑酰氧正戊基)苯甲酸与碱性氨基酸或氨基胍形成的盐、其制备方法、含有这些盐的药物制剂，及其在制备预防或治疗心脑缺血性疾病、抗血栓、改善心脑循环障碍药物中的应用。本发明的化合物不仅具有优良的水溶性、水溶液稳定性及药代动力学性质，还具有强效的抗血小板聚集、抗血栓、抗脑缺血以及保护神经的活性，效果优于(S)‑丁苯酞和(R/S)‑2‑(1‑羟基正戊基)苯甲酸钾盐(PHPB)，并且本发明化合物对小鼠静脉注射给药的急性毒性显著小于丁苯酞和PHPB，对CHO‑hERG细胞hERG钾通道的抑制率低于(S)‑丁苯酞，微生物回复突变试验(Ames试验)的结果为阴性。
• 2-(1-ACYLOXYPENTYL) BENZOIC ACID SALT FORMED BY BASIC AMINO ACID OR AMINOGUANIDINE, PREPARATION METHOD THEREFOR AND USES THEREOF
  申请人：China Pharmaceutical University

  公开号：EP3838887A1

  公开（公告）日：2021-06-23

  The present disclosure discloses salts formed by 2-(1-acyloxy-n-pentyl)benzoic acid and basic amino acid or aminoguanidine, a preparation method thereof, pharmaceutical preparations containing these salts, and application thereof in preparation of drugs for preventing or treating ischemic cardiovascular and cerebrovascular diseases, resisting thrombosis and improving cardio-cerebral circulation disorders. The compound of the present disclosure has excellent water solubility, aqueous solution stability and pharmacokinetic properties, also has significant anti-platelet aggregation, anti-thrombosis, anti-cerebral ischemia and neuroprotective activity. The compound of the present disclosure has significantly better effects than those of (S)-butylphthalide and potassium (R/S)-2-(1-hydroxy-n-pentyl) benzoate (PHPB), has significantly lower acute toxicity to mice by intravenous injection than that of butylphthalide and PHPB, has a lower inhibition rate of the hERG potassium channel in CHO-hERG cells than that of (S)-butylphthalide, and has a negative result in Bacterial Reverse Mutation Test (Ames test).

  本发明公开了2-(1-乙酰氧基-n-戊基)苯甲酸与碱性氨基酸或氨基胍形成的盐、其制备方法、含有这些盐的药物制剂，以及其在制备预防或治疗缺血性心脑血管疾病、抗血栓形成和改善心脑循环障碍药物中的应用。本公开的化合物具有优异的水溶性、水溶液稳定性和药代动力学特性，还具有显著的抗血小板聚集、抗血栓形成、抗脑缺血和神经保护活性。与(S)-丁基苯酞和(R/S)-2-(1-羟基-n-戊基)苯甲酸钾（PHPB）相比，本公开的化合物具有明显更好的效果，静脉注射对小鼠的急性毒性明显低于丁基苯酞和 PHPB、在 CHO-hERG 细胞中对 hERG 钾通道的抑制率低于(S)-丁基苯酞，并且在细菌反向突变试验（Ames 试验）中呈阴性结果。
• Synthesis, resolution, and antiplatelet activity of 3-substituted 1(3H)-isobenzofuranone
  作者：Hua Yang、Gao-Yun Hu、Jun Chen、Yi Wang、Zhong-Hua Wang

  DOI：10.1016/j.bmcl.2007.06.082

  日期：2007.9

  A series of 3-substituted-1(3H)-isobenzofuranone 6a-g and 7a-g were synthesized from phthalic anhydride. The compound 6a-g was resolved. The antiplatelet activities of these compounds were evaluated using in vitro experiment of platelet aggregation. The levels of antiplatelet activity were displayed as following sequence: l-isomer > dl-isomer > d-isomer, respectively. The alkylphthalide is more active than the corresponding alkenephthalide. All these compounds were less active than n-butylphthalide (NBP, 6c) and Aspirin (Asp). (c) 2007 Elsevier Ltd. All rights reserved.
• SALTS FORMED BY 2-(1-ACYLOXY-N-PENTYL) BENZOIC ACID AND BASIC AMINO ACID OR AMINOGUANIDINE, AND PREPARATION METHOD AND APPLICATION THEREOF
  申请人：CHINA PHARMACEUTICAL UNIVERSITY

  公开号：US20220024848A1

  公开（公告）日：2022-01-27

  The present disclosure discloses salts formed by 2-(1-acyloxy-n-pentyl)benzoic acid and basic amino acid or aminoguanidine, a preparation method thereof, pharmaceutical preparations containing these salts, and application thereof in preparation of drugs for preventing or treating ischemic cardiovascular and cerebrovascular diseases, resisting thrombosis and improving cardio-cerebral circulation disorders. The compound of the present disclosure has excellent water solubility, aqueous solution stability and pharmacokinetic properties, also has significant anti-platelet aggregation, anti-thrombosis, anti-cerebral ischemia and neuroprotective activity. The compound of the present disclosure has significantly better effects than those of (S)-butylphthalide and potassium (R/S)-2-(1-hydroxy-n-pentyl) benzoate (PHPB), has significantly lower acute toxicity to mice by intravenous injection than that of butylphthalide and PHPB, has a lower inhibition rate of the hERG potassium channel in CHO-hERG cells than that of (S)-butylphthalide, and has a negative result in Bacterial Reverse Mutation Test (Ames test).
• Studies on the enantiomers of ZJM-289: synthesis and biological evaluation of antiplatelet, antithrombotic and neuroprotective activities
  作者：Xiaoli Wang、Qian Zhao、Xuliang Wang、Tingting Li、Yisheng Lai、Sixun Peng、Hui Ji、Jinyi Xu、Yihua Zhang

  DOI：10.1039/c2ob26511g

  日期：——

  ZJM-289 is a potent racemic agent which inhibits both platelet aggregation and thrombosis superior to a known anti-ischemic stroke drug 3-n-butylphthalide (NBP). Herein, the enantiomers of ZJM-289, (S)-ZJM-289 and (R)-ZJM-289, were synthesized and evaluated for their biological activities. It was observed that the two enantiomers appeared to be almost as effective as ZJM-289 in inhibiting platelet aggregation in vitro and thrombus formation in vivo. Moreover, like ZJM-289, its enantiomers could regulate the ratio of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α, and enhanced levels of nitric oxide (NO), cAMP and cGMP, suggesting that the anti-platelet and antithrombotic activities of the enantiomers and ZJM-289 are associated with both the arachidonic acid cascade and cGMP–NO signal pathway. Furthermore, it was found that oral administration of the enantiomers and ZJM-289 for three days significantly reduced the infarct size, brain water content and neurological deficit in rats after cerebral ischemia reperfusion. Importantly, the two enantiomers equally improved blood flow in the ischemic stroke model and modulated endothelial function through releasing moderate levels of NO, which might, at least partially, contribute to their neuroprotection. Collectively, the present study demonstrates that the two enantiomers are as potent as ZJM-289 in inhibition of platelet aggregation and thrombosis and in neuroprotection, and (S)-ZJM-289 shows somewhat better effects than (R)-ZJM-289 and ZJM-289 in a few cases. These findings may provide new insights into the development of therapeutic agents like ZJM-289 for the intervention of thrombosis-related ischemic stroke.

  ZJM-289是一种强效的外消旋剂，其在抑制血小板聚集和血栓形成方面优于已知的抗缺血性脑卒药物3-n-丁基苯酞(NBP)。在此，合成了ZJM-289的两种对映体，即(S)-ZJM-289和(R)-ZJM-289，并对其生物活性进行了评估。观察到这两种对映体在抑制体外血小板聚集和体内血栓形成方面几乎与ZJM-289同样有效。此外，与ZJM-289类似，其对映体能够调节血栓素B2(TXB2)和6-酮前列腺素F1α的比例，并增强一氧化氮(NO)、cAMP和cGMP的水平，这表明对映体和ZJM-289的抗血小板和抗血栓活性与花生四烯酸级联反应和cGMP-NO信号通路有关。进一步发现，口服对映体和ZJM-289三天显著减少了脑缺血再灌注后大鼠的脑梗死面积、脑含水量和神经功能缺损。重要的是，这两种对映体同样改善了缺血性脑卒模型中的血流，并通过释放适度的NO来调节内皮功能，这可能至少部分地促使其神经保护作用。总之，本研究表明，两种对映体在抑制血小板聚集和血栓形成以及神经保护方面与ZJM-289同样强效，并且在某些情况下，(S)-ZJM-289显示出比(R)-ZJM-289和ZJM-289更好的效果。这些发现可能为开发类似于ZJM-289的治疗血栓相关缺血性脑卒的药物提供新的见解。