65043-22-3

65043-22-3结构式

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]。

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

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.

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

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

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

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

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%

65043-22-3	68906-88-7
81789-85-7	33237-74-0
478182-28-4	98079-52-8
21498-08-8	34552-83-5
134-63-4	26786-32-3