58581-89-8

• 常用中文名：盐酸氮卓斯汀
• 常用英文名：Azelastine
• CAS号：58581-89-8
• 分子式：C₂₂H₂₄ClN₃O
• 分子量：381.898
• 相关类别： 原料药 抗变态反应药 抗组胺药
• 发布时间：2018-04-25 08:00:00
• 更新时间：2024-01-08 09:20:08
• Azelastine是第二代H1受体拮抗剂。

名称

• 中文名: 氮卓斯汀
• 英文名: azelastine
• 中文别名: 4-[(4-氯苯基)甲基]-2-(六氢-1-甲基-1H-氮杂卓-4-基)-1(2H)-酞嗪酮; 4-[(4-氯苯基)甲基]-2-(六氢-1-甲基-1H-氮杂卓)二氮杂萘酮; 氮卓司丁; 4-[(4-氯苯基)甲基]-2-(六氢-1-甲基-1H-氮杂卓-4-基)二氮杂萘酮; 盐酸氮卓斯汀
• 英文别名: UNII:ZQI909440X; 4-(4-Chlorobenzyl)-2-(1-methyl-4-azepanyl)-1(2H)-phthalazinone; 1(2H)-Phthalazinone, 4-[(4-chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-; Optilast; 4-(p-Chlorobenzyl)-2-(N-methylperhydroazepin-4-yl)-1(2H)-phthalazinone; Allergodil; 4-[(4-chlorophenyl)methyl]-2-(1-methylazepan-4-yl)phthalazin-1(2H)-one; Azelastine; 4-[(4-Chlorophenyl)methyl]-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone; 4-(4-Chlorobenzyl)-2-(1-methylazepan-4-yl)phthalazin-1(2H)-one; Rhinolast; MFCD00242781; 4-(p-Chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1(2H)-phthalazinone

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 533.9±60.0 °C at 760 mmHg
• 分子式: C₂₂H₂₄ClN₃O
• 分子量: 381.898
• 闪点: 276.7±32.9 °C
• 精确质量: 381.160797
• PSA: 38.13000
• LogP: 3.71
• 外观性状: 白色晶体粉末
• 蒸汽压: 0.0±1.4 mmHg at 25°C
• 折射率: 1.642
• 储存条件:

  贮藏在密闭容器内，在干燥，阴凉处保存

• 稳定性:

  单水合物：从乙醇-水结晶。可鉴定出两种不同的晶型。; 盐酸氮革斯汀(Azelastine Hydrochloride)：C22H24ClN3O?HCl。[79307-93-0]。白色结晶性粉末，无臭，味苦。溶于氯仿、二氯甲烷或冰醋酸，略溶于甲醇，微溶于无水乙醇或水，不溶于丙酮或乙醚。熔点225～229℃。急性毒性LD₅₀雄、雌小鼠，雄、雌大鼠，雄、雌豚鼠(mg/kg)：124，139，310，417，126，130口服；36.5，35.5，26.9，30.3，23.0，24.8静脉注射；597.0，57.2，143.0，115.0，46.2，52.2肌肉注射；63.0，54.2，66.5，59.6。41.0．37.3皮下注射。

• 分子结构:

  1、 摩尔折射率：109.97

  2、 摩尔体积（cm³/mol）：304.5

  3、 等张比容（90.2K）：799.5

  4、 表面张力（dyne/cm）：47.4

  5、 极化率（10^-24cm³）：43.59

• 计算化学:

  1.疏水参数计算参考值（XlogP）:4.4

  2.氢键供体数量:0

  3.氢键受体数量:3

  4.可旋转化学键数量:3

  5.互变异构体数量:无

  6.拓扑分子极性表面积35.9

  7.重原子数量:27

  8.表面电荷:0

  9.复杂度:558

  10.同位素原子数量:0

  11.确定原子立构中心数量:0

  12.不确定原子立构中心数量:1

  13.确定化学键立构中心数量:0

  14.不确定化学键立构中心数量:0

  15.共价键单元数量:1

• 更多:

  1. 性状：油状物

  2. 密度（g/cm³,20℃）：未确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：未确定

  5. 沸点（ºC,0.01mmHg）：未确定

  6. 沸点（ºC,5.2kPa）：未确定

  7. 折射率（°）：未确定

  8. 闪点（℉）：未确定

  9. 比旋光度（º）：未确定

  10. 自燃点或引燃温度（ºC）：未确定

  11. 蒸气压（kPa,25ºC）：未确定

  12. 饱和蒸气压（kPa,60ºC）：未确定

  13. 燃烧热（KJ/mol）：未确定

  14. 临界温度（ºC）：未确定

  15. 临界压力（KPa）：未确定

  16. 油水（辛醇/水）分配系数的对数值：未确定

  17. 爆炸上限（%,V/V）：未确定

  18. 爆炸下限（%,V/V）：未确定

  19. 溶解性（mg/mL）：溶于二氯甲烷

生物活性

• 描述: Azelastine是第二代H1受体拮抗剂。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 组胺受体
  信号通路 >> 免疫及炎症 >> 组胺受体
  研究领域 >> 炎症/免疫
• 参考文献:

  [1]. Kempuraj, D., et al., Azelastine is more potent than olopatadine n inhibiting interleukin-6 and tryptase release from human umbilical cord blood-derived cultured mast cells. Ann Allergy Asthma Immunol, 2002. 88(5): p. 501-6.

  [2]. Canonica, G.W., et al., Topical azelastine in perennial allergic conjunctivitis. Curr Med Res Opin, 2003. 19(4): p. 321-9.

  [3]. Lieberman, P., M.A. Kaliner, and W.J. Wheeler, Open-label evaluation of azelastine nasal spray in patients with seasonal allergic rhinitis and nonallergic vasomotor rhinitis. Curr Med Res Opin, 2005. 21(4): p. 611-8.

毒性和生态

生态学数据: 对水是稍微危害的，若无政府许可，勿将材料排入周围环境 CHEMICAL IDENTIFICATION RTECS NUMBER : TH9203800 CHEMICAL NAME : 1(2H)-Phthalazinone, 4-((4-chlorophenyl)methyl)-2-(hexahydro-1-methyl-1H-a zepin-4-yl)- CAS REGISTRY NUMBER : 58581-89-8 LAST UPDATED : 199612 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C22-H24-Cl-N3-O MOLECULAR WEIGHT : 381.94 WISWESSER LINE NOTATION : T66 BVNNJ E1R DG& C- DT7NTJ A1 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 310 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 43200 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 59600 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 26900 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 115 mg/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 17,1106,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 124 mg/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 42800 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 54200 ug/kg TOXIC EFFECTS : Peripheral Nerve and Sensation - flaccid paralysis without anesthesia (usually neuromuscular blockage) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - other changes REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 25400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 17,1106,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intramuscular SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 59700 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value REFERENCE : IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 17,1106,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 51300 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - changes in motor activity (specific assay) Gastrointestinal - nausea or vomiting REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 13700 ug/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - changes in motor activity (specific assay) Gastrointestinal - nausea or vomiting REFERENCE : ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 31,1184,1981

安全

• 危害码 (欧洲): N-T,N,T
• 风险声明 (欧洲): R50/53:Very Toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment . R23/25:Toxic by inhalation and if swallowed .
• 安全声明 (欧洲): S61-S60-S45-S28A-S20/21-S28
• 危险品运输编码: 1557
• RTECS号: CY5950000
• 包装等级: III
• 危险类别: 6.1(b)
• 海关编码: 2933990090

合成路线

1878-66-6 ~% 58581-89-8

文献：Archiv der Pharmazie, , vol. 321, # 4 p. 205 - 208

85-44-9 ~% 58581-89-8

文献：Archiv der Pharmazie, , vol. 321, # 4 p. 205 - 208

105279-16-1 ~% 58581-89-8

文献：Archiv der Pharmazie, , vol. 321, # 4 p. 205 - 208

1859-33-2 ~% 58581-89-8

文献：Archiv der Pharmazie, , vol. 321, # 4 p. 205 - 208

53242-76-5 ~% 58581-89-8

文献：Archiv der Pharmazie, , vol. 321, # 4 p. 205 - 208

上下游产品

上游产品  4
1878-66-6 85-44-9 1859-33-2 53242-76-5
下游产品  0

制备

30.6g的对氯苄基苯乙酮-邻-羧酸(I)及16g硫酸肼和9.4g氢氧化钠溶于250ml水的溶液一起加热。洗涤和干燥后，得27g 4-(4-氯苄基)-1-(2H)-酞嗪酮(化合物(Ⅱ))。
将20g的2-(2-氯乙基)-N-甲基四氢吡咯盐酸盐加入4.4g氢氧化钠溶于20ml水的溶液。加热到70℃后，将其滴人加热到70℃的27g的化合物(Ⅱ)的40ml50%氢氧化钠水溶液中。在该温度再加热lh。冷却后，用水稀释，过滤除去不溶物后，溶入二氯甲烷。用稀盐酸进行提取，提取液用氢氧化钾水溶液碱化。析出的油状物再溶入二氯甲烷，干燥，浓缩。粗品的收率在90%以上。转化为盐酸盐后，再重结晶提纯，得盐酸氮革斯汀，熔点225~229℃。

海关

海关编码	2933990090
中文概述	2933990090. 其他仅含氮杂原子的杂环化合物. 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, 乌洛托品请注明外观, 6－己内酰胺请注明外观, 签约日期
Summary	2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%