94535-50-9

• 常用中文名：左色满卡林
• 常用英文名：Levcromakalim
• CAS号：94535-50-9
• 分子式：C₁₆H₁₈N₂O₃
• 分子量：286.32600
• 相关类别： 信号通路 跨膜转运 钾通道
• 发布时间：2018-05-13 08:00:00
• 更新时间：2024-01-04 14:30:38
• LevCromakalim 是 ATP 敏感性的 K+ 通道 (KATP) 激活剂。

名称

• 中文名: 左色满卡林
• 英文名: Levcromakalim,(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrrolidinyl)-2H-1-benzopyran-6-carbonitrile
• 英文别名: levcromakelim; levcromakalim; lemakalim

物化性质

• 密度: 1.31g/cm3
• 沸点: 482.3ºC at 760mmHg
• 分子式: C₁₆H₁₈N₂O₃
• 分子量: 286.32600
• 闪点: 245.5ºC
• 精确质量: 286.13200
• PSA: 73.56000
• LogP: 1.69158
• 储存条件: 2-8℃

生物活性

• 描述: LevCromakalim 是 ATP 敏感性的 K+ 通道 (KATP) 激活剂。
• 相关类别:
  信号通路 >> 跨膜转运 >> 钾通道
  研究领域 >> 心血管疾病
• 靶点:

  K+ channel[1]

• 体外研究: LevCromakalim(Cromakalim)以格列本脲敏感的方式完全抑制自发性收缩。 LevCromakalim(5μM)抑制自发性收缩,其通过格列本脲回收。 LevCromakalim(1,5和10μM)抑制相位收缩至对照的34±21.1％,20.1±20.0％和0％(分别为n = 5; P <0.05)。格列本脲逆转由LevCromakalim(5μM)引起的自发等长收缩对对照的84±1.5％的抑制(n = 5; P <0.05)。 LevCromakalim(20和100μM)也抑制催产素(OXT)(10nM)诱导的阶段性收缩至对照的34±21.4％和14±12.6％(分别为n = 6和4; P <0.05)。格列本脲逆转LevCromakalim(100μM)对自发等长收缩的抑制,达到对照的79±3.5％(n = 4; P <0.05)。克罗马卡林以格列本脲敏感的方式抑制OXT的强直收缩[2]。用特定的通道开放剂LevCromakalim(Cromakalim)检查KATP通道的功能。 LevCromakalim在年轻和年老的肠系膜动脉(MA)中诱导剂量依赖性舒张;放松与年龄没有区别。然而,响应于旧MA中的高盐(HS)饮食,松弛显着降低(P <0.05)。 LevCromakalim(10-4 M)的最大扩张在年轻MA中为97±3％,而在年轻盐动脉中为98±1％,而旧MA中的扩张为99±0.7％,而在此为85±5％。老盐动脉(P <0.05)[3]。
• 激酶实验: 将LevCromakalim（Cromakalim）溶于10％DMSO和Krebs溶液中[3]。通过用乙酰胆碱（ACh; 10nM-10μM）进行浓度 - 响应实验来测试内皮依赖性舒张。通常，将MA暴露于每剂ACh至少6分钟，并确定最大响应。用10μM格列本脲（选择性KATP通道抑制剂）和LevCromakalim（Cromakalim）（10nM至100μM）（KATP通道开放剂）检查KATP通道的功能。在ACh前10分钟向动脉浴中加入格列本脲不会改变我们组中任何MA的被动最大内径。血管直径变化表示为预收缩血管扩张的百分比（％），计算[3]。
• 参考文献:

  [1]. Matsumoto T, et al. Tunicamycin-Induced Alterations in the Vasorelaxant Response in Organ-Cultured Superior Mesenteric Arteries of Rats. Biol Pharm Bull. 2016;39(9):1475-81.

  [2]. Hong SH, et al. Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via activation of SUR2B and Kir 6.2 in mouse. J Vet Med Sci. 2016 Aug 1;78(7):1153-9.

  [3]. Whidden MA, Altered potassium ATP channel signaling in mesenteric arteries of old high salt-fed rats. J Exerc Nutrition Biochem. 2016 Jun;20(2):58-64.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : DJ2177500 CHEMICAL NAME : 2H-1-Benzopyran-6-carbonitrile, 3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(2-oxo-1-pyrroli dinyl)-, (3S-trans)- CAS REGISTRY NUMBER : 94535-50-9 LAST UPDATED : 199612 DATA ITEMS CITED : 8 MOLECULAR FORMULA : C16-H18-N2-O3 MOLECULAR WEIGHT : 286.36 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2500 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >4 mg/kg TOXIC EFFECTS : Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >750 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - respiratory depression Nutritional and Gross Metabolic - body temperature decrease REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >4 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - coma Lungs, Thorax, or Respiration - respiratory stimulation REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 273 mg/kg/13W-C TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - changes in circulation Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 110 mg/kg/52W-C TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - changes in circulation Cardiac - changes in heart weight Related to Chronic Data - changes in ovarian weight REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 18 mg/kg/13W-I TOXIC EFFECTS : Endocrine - changes in adrenal weight Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 37 mg/kg/52W-I TOXIC EFFECTS : Endocrine - changes in adrenal weight REFERENCE : YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 22(Suppl 7),S1425,1994

安全

• 海关编码: 2934999090

合成路线

616-45-5 65018-90-8 ~62% 94535-50-9

文献：Dai, Wen; Li, Jun; Li, Guosong; Yang, Hua; Wang, Lianyue; Gao, Shuang Organic Letters, 2013 , vol. 15, # 16 p. 4138 - 4141

33143-29-2 ~% 94535-50-9

文献：Page, Philip C. Bulman; Buckley, Benjamin R.; Heaney, Harry; Blacker, A. John Organic Letters, 2005 , vol. 7, # 3 p. 375 - 377

94470-67-4 ~% 94535-50-9 94535-51-0

文献：Sun, Ping; Wang, Chunlei; Breitbach, Zachary S.; Zhang, Ying; Armstrong, Daniel W. Analytical Chemistry, 2009 , vol. 81, # 24 p. 10215 - 10226

33143-92-9 ~% 94535-50-9

文献：Dai, Wen; Li, Jun; Li, Guosong; Yang, Hua; Wang, Lianyue; Gao, Shuang Organic Letters, 2013 , vol. 15, # 16 p. 4138 - 4141

767-00-0 ~% 94535-50-9

文献：Dai, Wen; Li, Jun; Li, Guosong; Yang, Hua; Wang, Lianyue; Gao, Shuang Organic Letters, 2013 , vol. 15, # 16 p. 4138 - 4141

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海关

海关编码	2934999090
中文概述	2934999090. 其他杂环化合物. 增值税率:17.0%. 退税率:13.0%. 监管条件:无. 最惠国关税:6.5%. 普通关税:20.0%
申报要素	品名, 成分含量, 用途
Summary	2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%