(+)-L-660,711 | 115104-28-4

• 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 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (+)-L-660,711
• 英文别名: Verlukast；3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-[3-(dimethylamino)-3-oxopropyl]sulfanylmethyl]sulfanylpropanoic acid
• CAS: 115104-28-4
• 化学式: C₂₆H₂₇ClN₂O₃S₂
• 分子量: 515.097
• InChiKey: AXUZQJFHDNNPFG-UXBLZVDNSA-N

物化性质

• 熔点：
  65-70°C
• 沸点：
  712.3±60.0 °C(Predicted)
• 密度：
  1.327±0.06 g/cm3(Predicted)
• 溶解度：
  溶于DMSO（高达50mg/ml）。

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 储存条件：
  20°C

制备方法与用途

生物活性

MK571 (L660711) 是一种具有口服活性的选择性半胱氨酰白三烯受体CysLT1拮抗剂。

靶点

Target	Value
CysLT1
MRP1
MRP4
cMOAT

体外研究

L-660,711 (MK-571) 在豚鼠肺中抑制了 [3H] LTD4 的结合，其 Ki 值为 0.22±0.15 nM（n=35），在人类肺部则为 2.1±1.8 nM（n=29）。L660,711 对 [3H] LTC4 的结合活性较低或没有活性，在豚鼠肺中 IC50 值为 23±11 μM (n=16)，在人类肺部中则为 32 μM (n=1)。

体内研究

MK-571 在健康年轻人中的耐受性良好。口服后，药物被迅速吸收，在给药后约 1.1-1.5 小时达到血药浓度峰值。

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  MK-571甲酯	MK-571 Methyl Ester	115104-27-3	C27H29ClN2O3S2	529.124
  3,3'-[[[3-[(1E)-2-(7-氯-2-喹啉基)乙烯基]苯基]亚甲基]二(硫代)]二-丙酸1,1'-二甲酯	dimethyl 5-<3-<2-(7-chloro-2-quinolinyl)-(E)-ethenyl>phenyl>-4,6-dithianonanedioate	120385-96-8	C26H26ClNO4S2	516.082
  ——	3-[[3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-trimethylsilyloxymethyl]sulfanyl-N,N-dimethylpropanamide	120578-06-5	C26H31ClN2O2SSi	499.149
  (E)-3-[2-(7-氯-2-喹啉基)乙烯基]苯甲醛	(E)-3-[2-(7-chloro-2-quinolinyl)ethenyl]benzaldehyde	120578-03-2	C18H12ClNO	293.752

反应信息

• 作为反应物：
  描述：

  2,2,2-三氟-1-(9-蒽基)乙醇 、 (+)-L-660,711 在 吡啶 、 4-二甲氨基吡啶 、 1-环已基-2-吗啉乙基碳二亚胺对甲苯磺酸盐 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  Young, Robert N.; Gauthier, Jacques Yves; Therien, Michel, Heterocycles, 1989, vol. 28, # 2, p. 967 - 978

  摘要：

  DOI：
• 作为产物：
  描述：

  2-溴甲基-7-氯喹啉 在 lithium hydroxide 、 正丁基锂 、 水 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 正己烷 、 乙腈 为溶剂， 反应 5.5h， 生成 (+)-L-660,711
  参考文献：
  名称：

  Young, Robert N.; Gauthier, Jacques Yves; Therien, Michel, Heterocycles, 1989, vol. 28, # 2, p. 967 - 978

  摘要：

  DOI：

文献信息

• METHODS AND COMPOSITIONS FOR TREATING INFLAMMATION
  申请人：UNIVERSITY OF MASSACHUSETTS

  公开号：US20200138756A1

  公开（公告）日：2020-05-07

  Disclosed herein are methods and compositions for treating neutrophil-mediated inflammation by targeting, in any combination, the pro-inflammatory MRP2/HXA3 pathway and/or the anti-inflammatory P-gp/endocannabinoid pathway and/or the anti-inflammatory MRP 1/L-AMEND pathway, comprising administering to the subject a therapeutically effective amount of (a) one or more first compound that inhibits the activity and/or level of one or more of multidrug resistance protein 2 (MRP2) and hepoxilin A3 (HXA3) synthase, and/or (b) one or more second compound that increases the level and/or activity of one or more N-acylethanolamines (NAEs), and/or (c) one or more third compound that increases the level and/or activity of multidrug resistance protein 1 (MRP1), wherein the therapeutic amount of the first, second, and third compounds reduces migration of neutrophils into the target tissue.

  本文披露了一种治疗中性粒细胞介导炎症的方法和组合物，通过以任何组合方式靶向抗炎 MRP2/HXA3 途径和/或抗炎 P-gp/内源性大麻素途径和/或抗炎 MRP 1/L-AMEND 途径，包括向受试者施用治疗有效量的（a）抑制一种或多种多药耐药蛋白2（MRP2）和肝过氧化脂酸A3（HXA3）合酶的活性和/或水平的一种或多种第一化合物，和/或（b）增加一种或多种N-乙酰基乙醇胺（NAEs）的水平和/或活性的一种或多种第二化合物，和/或（c）增加一种或多种多药耐药蛋白1（MRP1）的水平和/或活性的一种或多种第三化合物，其中第一、第二和第三化合物的治疗量减少中性粒细胞向目标组织的迁移。
• [EN] ANTI-ANGIOGENIC COMPOUNDS<br/>[FR] COMPOSÉS ANTIANGIOGÉNIQUES
  申请人：UNIV DUBLIN

  公开号：WO2014012889A1

  公开（公告）日：2014-01-23

  (E)-2-(2-Quinolin-2-yl-propenyl)-phenol, 2-Quinolin-2-yl-ylethynyl-phenol and salts thereof are useful as medicaments, especially for treatment of an angiogenesis-related disease or disorder.

  (E)-2-(2-喹啉-2-基-丙烯基)-苯酚、2-喹啉-2-基-乙炔基-苯酚及其盐类是有用的药物，特别用于治疗与血管生成相关的疾病或紊乱。
• Manipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defenses
  申请人：——

  公开号：US20030207815A1

  公开（公告）日：2003-11-06

  Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include &agr;-alkyl-S-alkyl-homocysteine sulfoximines wherein the &agr;-alkyl contains 2 to 8 carbon atoms, and the S-alkyl-contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated. Treatments to increase nitrosative stress defenses include, for example, repeated administrations of low doses of manipulators of nitrosative stress so that the subject treated has increased tolerance to nitrosative stress. In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress.

  哺乳动物被治疗感染或与病理增殖哺乳动物细胞生长相关的情况（例如某些癌症，再狭窄，良性前列腺增生）通过给予一种硝化应激调节剂，以选择性地杀死或减少微生物或蠕虫引起的感染或受微生物感染的宿主细胞或病理增殖的哺乳动物细胞的生长。新型药剂包括α-烷基-S-烷基-同型半胱氨酸亚砜，其中α-烷基含2至8个碳原子，S-烷基含1至10个碳原子。在本发明的另一种方法中，需要增加硝化应激防御的哺乳动物被治疗，例如，由于患有短暂性缺血性发作而处于中风风险的人类被治疗。增加硝化应激防御的治疗包括例如反复给予低剂量的硝化应激调节剂，以使受治疗的对象对硝化应激具有增加的耐受性。在另一种发明中，哺乳动物通过系统给药L-丁硫氧嘧啶和增加硝化应激的药物来治疗原虫感染。
• MANIPULATING NITROSATIVE STRESS TO KILL PATHOLOGIC MICROBES, PATHOLOGIC HELMINTHS AND PATHOLOGICALLY PROLIFERATING CELLS OR TO UPREGULATE NITROSATIVE STRESS DEFENSES
  申请人：——

  公开号：US20030096870A1

  公开（公告）日：2003-05-22

  Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example, certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include &agr;-alkyl-S-alkyl-homocysteine sulfoximines wherein the &agr;-alkyl contains 2 to 8 carbon atoms, and the S-alkyl- contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated. Treatments to increase nitrosative stress defenses include, for example, repeated administrations of low doses of manipulators of nitrosative stress so that the subject treated has increased tolerance to nitrosative stress. In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress.

  哺乳动物被用于治疗感染或与病理性增殖的哺乳动物细胞生长有关的疾病（例如某些癌症、再狭窄、良性前列腺肥大），通过给予一种硝化应激的调节剂，以选择性地杀死或减少引起感染的微生物或线虫或被微生物感染的宿主细胞或病理性增殖的哺乳动物细胞的生长。新型药剂包括α-烷基-S-烷基-同型半胱氨酸磺酰亚胺，其中α-烷基含有2至8个碳原子，S-烷基含有1至10个碳原子。在本发明的另一个方案中，需要增强硝化应激防御的哺乳动物被治疗，例如因为曾经有过短暂性缺血性发作而有中风风险的人类被治疗。增强硝化应激防御的治疗包括例如重复给予硝化应激调节剂的低剂量，以使受治疗的对象对硝化应激有增强的耐受性。在另一个发明中，哺乳动物通过系统给药L-丁硫氨酸-S-磺酰亚胺和增加硝化应激的药剂来治疗原虫感染。
• Manipulating nitrosative stress to kill pathologic microbes, pathologic
  申请人：Duke University

  公开号：US06057367A1

  公开（公告）日：2000-05-02

  Mammals are treated for infections or for conditions associated with pathologically proliferating mammalian cell growth (for example, certain cancers, restenosis, benign prostatic hypertrophy) by administration of a manipulator of nitrosative stress to selectively kill or reduce the growth of the microbes or helminths causing the infection or of host cells infected with the microbes or of the pathologically proliferating mammalian cells. Novel agents include .alpha.-alkyl-S-alkyl-homocysteine sulfoximines wherein the .alpha.-alkyl contains 2 to 8 carbon atoms, and the S-alkyl-contains 1 to 10 carbon atoms. In another invention herein, mammals in need of increased nitrosative stress defenses are treated, e.g., humans at risk for a stroke because of having had a transient ischemic attack, are treated. Treatments to increase nitrosative stress defenses include, for example, repeated administrations of low doses of manipulators of nitrosative stress so that the subject treated has increased tolerance to nitrosative stress. In still another invention, mammals are treated for protozoal infections by systemic administration of L-buthionine-S-sulfoximine and agent that increases nitrosative stress.

  哺乳动物可以通过给予一种氮化应激的调节剂来治疗感染或与病理性增殖的哺乳动物细胞生长相关的疾病（例如某些癌症、再狭窄、良性前列腺增生），以选择性地杀死或减少导致感染的微生物或寄生虫或者感染微生物的宿主细胞或病理性增殖的哺乳动物细胞的生长。新型药物包括α-烷基-S-烷基-同型半胱氨酸亚磺酰胺，其中α-烷基含有2至8个碳原子，而S-烷基含有1至10个碳原子。在另一项发明中，需要增强氮化应激防御的哺乳动物得到了治疗，例如，因为曾经发生过短暂性缺血性发作而有中风风险的人类得到了治疗。增加氮化应激防御的治疗方法包括，例如，反复给予低剂量的氮化应激调节剂，以使接受治疗的受试者对氮化应激具有增加的耐受性。在另一项发明中，哺乳动物通过全身给药L-丁硫氨酸-S-亚磺酰胺和增加氮化应激的药物来治疗原虫感染。