65043-22-3

• 常用中文名：盐酸茚洛秦
• 常用英文名：Indeloxazine hydrochloride
• CAS号：65043-22-3
• 分子式：C₁₄H₁₈ClNO₂
• 分子量：267.75
• 相关类别： 原料药 循环系统用药 抗心律失常药
• 发布时间：2018-03-08 08:00:00
• 更新时间：2024-01-09 14:30:22
• 盐酸茚洛沙嗪是一种5-羟色胺受体和去甲肾上腺素(NE)再摄取抑制剂。盐酸茚洛沙嗪是一种抗抑郁药和大脑激活剂[1]。

名称

• 中文名: 盐酸茚洛秦
• 英文名: 2-(((1H-Inden-7-yl)oxy)methyl)morpholine hydrochloride
• 中文别名: 茚氯嗪; 2-[(1H-茚-7-基氧基)甲基]-吗啉盐酸盐; 2-(3H-茚-4-基氧甲基)吗啉盐酸盐
• 英文别名: 2-(3H-inden-4-yloxymethyl)morpholine,hydrochloride

物化性质

• 沸点: 401.4ºC at 760 mmHg
• 熔点: 169-170°; mp 155-156°
• 分子式: C₁₄H₁₈ClNO₂
• 分子量: 267.75
• 闪点: 160.3ºC
• 精确质量: 267.10300
• PSA: 30.49000
• LogP: 2.75390
• 稳定性:

  多晶形化合物：从甲醇得淡黄色针状(needles)结晶，熔点169～170℃：从丙酮得无色针状(acicular)结晶，熔点155～156℃。(+)-构型：从乙醇得结晶，熔点112~113℃。[α]_D²¹+4.9°(C=5，甲醇)。; (-)-构型：从异丙醇得结晶，熔点142～142.5℃。[α]_D²⁰-4.9°(C=5，甲醇)。

• 分子结构:

  1、 摩尔折射率：66.12

  2、 摩尔体积（cm³/mol）：205.3

  3、 等张比容（90.2K）：531.5

  4、 表面张力（dyne/cm）：44.8

  5、 极化率（10-24cm3）：26.21

• 计算化学:

  1.疏水参数计算参考值（XlogP）:无

  2.氢键供体数量:2

  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30.5

  7.重原子数量:18

  8.表面电荷:0

  9.复杂度:279

  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:2

生物活性

• 描述: 盐酸茚洛沙嗪是一种5-羟色胺受体和去甲肾上腺素(NE)再摄取抑制剂。盐酸茚洛沙嗪是一种抗抑郁药和大脑激活剂[1]。
• 相关类别:
  研究领域 >> 神经疾病
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 5-HT受体
  信号通路 >> 神经信号通路 >> 5-HT受体
• 参考文献:

  [1]. T Yamaguchi, et al. Facilitation of acetylcholine release in rat frontal cortex by indeloxazine hydrochloride: involvement of endogenous serotonin and 5-HT4 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1997 Dec;356(6):712-20.

毒性和生态

毒理学数据: 急性毒性LD50小鼠(mg/kg)：47静脉注射。 CHEMICAL IDENTIFICATION RTECS NUMBER : QE5210000 CHEMICAL NAME : Morpholine, 2-((1H-inden-7-yloxy)methyl)-, hydrochloride CAS REGISTRY NUMBER : 65043-22-3 LAST UPDATED : 199312 DATA ITEMS CITED : 13 MOLECULAR FORMULA : C14-H17-N-O2.Cl-H MOLECULAR WEIGHT : 267.78 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 : 502 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 206 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 77300 ug/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 444 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 50400 ug/kg TOXIC EFFECTS : Details of toxic effects not reported other than lethal dose value 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: 16,1181,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 245 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 47 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - mydriasis (pupillary dilation) Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold REFERENCE : AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 238,81,1979 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >60 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: 19,544,1988 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 7 gm/kg/5W-C TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - urine volume decreased Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 10920 mg/kg/52W-C TOXIC EFFECTS : Behavioral - food intake (animal) Behavioral - fluid intake Nutritional and Gross Metabolic - weight loss or decreased weight gain REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,5687,1985 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 1100 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,429,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 810 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - live birth index (measured after birth) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,6067,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 50 mg/kg SEX/DURATION : female 17-21 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) REFERENCE : KSRNAM Kiso to Rinsho. Clinical Report. (Yubunsha Co., Ltd., 1-5, Kanda Suda-Cho, Chiyoda-ku, KS Bldg., Tokyo 101, Japan) V.1- 1960- Volume(issue)/page/year: 19,6067,1985

安全

• 危险品运输编码: UN 3249
• 包装等级: III
• 危险类别: 6.1(b)
• 海关编码: 2934999090

合成路线

60929-60-4 ~% 65043-22-3

文献：US4109088 A1, ;

64966-73-0 ~76% 65043-22-3

文献：Kojima; Niigata; Fujikura; et al. Chemical and Pharmaceutical Bulletin, 1985 , vol. 33, # 9 p. 3766 - 3774

926-39-6 30190-85-3 ~73% 65043-22-3

文献：Kojima; Niigata; Fujikura; et al. Chemical and Pharmaceutical Bulletin, 1985 , vol. 33, # 9 p. 3766 - 3774

40987-24-4 ~% 65043-22-3

文献：Chemical and Pharmaceutical Bulletin, , vol. 33, # 9 p. 3766 - 3774

60929-58-0 ~% 65043-22-3

文献：Chemical and Pharmaceutical Bulletin, , vol. 33, # 9 p. 3766 - 3774

103003-01-6 ~% 65043-22-3

文献：Chemical and Pharmaceutical Bulletin, , vol. 33, # 9 p. 3766 - 3774

131965-77-0 ~% 65043-22-3

文献：Chemical and Pharmaceutical Bulletin, , vol. 33, # 9 p. 3766 - 3774

60929-57-9 ~% 65043-22-3

文献：Chemical and Pharmaceutical Bulletin, , vol. 33, # 9 p. 3766 - 3774

上下游产品

上游产品  8
60929-60-4 64966-73-0 926-39-6 30190-85-3
40987-24-4 60929-58-0 103003-01-6 60929-57-9
下游产品  0

制备

方法1：以7-茚酚为原料，按常法可和氯代环氧丙烷在碱催化下反应，得到环氧化物I。29ml 70％氢氧化钠水溶液和2-氨基乙基硫酸氢酯(35g，0.25mo1)混合，在50～55℃和搅拌下，滴加化合物(I)(9.4g，0.05mol)在50ml甲醇中的溶液。继续搅拌1h后，加入50ml 70%氢氧化钠水溶液，在50～55℃再搅拌16h。用300ml水稀释后，用甲苯(2×100ml)提取。提取液水洗(2×100ml)，无水硫酸镁干燥。蒸去溶剂后，剩余的油状物减压蒸馏，得6.7g粘稠油状的化合物(Ⅱ)，收率58%，沸点146～156℃/67Pa。该油状的化合物(Ⅱ)溶于丙酮，加入5%氯化氢在异丙醇中的溶液，得到的固体再用丙酮重结晶，可得纯的化合物(Ⅱ)的盐酸盐，熔点143～155℃。
化合物(Ⅱ)实际上由两个化合物组成，即盐酸茚洛秦(III)和其互变异构体(Ⅳ)，它们是由烯键的移位所造成的，其平衡组成为(Ⅲ)：(1V)：2：1。该平衡由碱催化。但盐酸茚洛秦在一些溶剂，如甲醇或丙酮中的溶解比其互变异构体(Ⅳ)要小。而在悬浮状态时，它们的平衡比例将改变。如在小量甲醇中，在催化量的碱存在下，它们的比例为(IlI)：(Ⅳ)=9.7：0.3。因而可以利用该性质，从化合物(Ⅱ)得到高收率的盐酸茚洛秦。下面是一则实例：将化合物(II)的盐酸盐(10.0g，0.037mo1)溶于30ml丙酮，加入催化量的化合物(1I)(0.9g，0.0038mo1)作为碱，在室温下剧烈搅拌24h。过滤收集析出的沉淀，用丙酮彻底洗涤。如此得到的盐酸茚洛秦(9.8g)还含有3%的化合物(IV)，再用35ml甲醇重结晶，可以得到7.3g很纯的盐酸茚洛秦，收率为73%，熔点169～170℃。从滤液中回收的化合物(Ⅱ)仍为两个互变异构体的平衡组成。可继续进行分离。
方法2：从这一方法可以直接得到单一的盐酸茚洛秦。但反应相对较繁。2-苄氧基苯乙醇和N-溴代琥珀酰亚胺反应，羟基被溴代，再和氰化钾作用进行氰取代，氢化脱去氧上的苄基，生成2-(2-氰基乙基)苯酚，水解氰基为羧基，在酸性中分子内酯化为内酯、重排生成茚衍生物，和2-溴甲基-4-三苯甲基吗啉作用成醚，氢化羰基为羟基，最后水解脱水消除，得到盐酸茚洛秦。

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%