22345-47-7

• 常用中文名：托非索泮
• 常用英文名：Tofisopam
• CAS号：22345-47-7
• 分子式：C₁₈H₃₉N₅O₁₃S
• 分子量：565.593
• 发布时间：2018-06-20 13:57:28
• 更新时间：2024-01-03 18:57:37
• 托福西泮是一种2,3-苯二氮卓化合物,是一种口服活性抗焦虑剂[1]。

名称

• 中文名: 托非索泮
• 英文名: 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine
• 中文别名: 托非所泮; 7,8-二甲氧基-1-(3,4-二甲氧基苯基)-5-乙基-4-甲基-5H-2,3-苯并二氮杂卓; 甲氧异氮卓
• 英文别名: MFCD00823171; 1-(3,4-Dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-5H-2,3-benzodiazepine; 1-(3,4-dimethoxy-phenyl)-4-methyl-5-ethyl-7,8-dimethoxy-5H-2,3-benzodiazepine; (2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminométhyl)-5-hydroxytétrahydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxyméthyl)tétrahydro-2H-pyran; (2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxytetrahydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol sulfate (salt); Tobra Gobens; Tomycin; 5H-2,3-Benzodiazepine, 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methyl-; 5-aethyl-1-(3,4-dimethoxyphenyl)-7,8-dimethoxy-4-methyl-5H-benzodiazepin; (1S,2S,3R,4S,6R)-4,6-Diamino-3-[(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-3-deoxy-α-D-glucopyranoside sulfate (salt); Dicon; Egyt 341; EINECS 244-922-3; (1S,2S,3R,4S,6R)-4,6-Diamino-3-[(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-3-deoxy-α-D-glucopyranoside sulfate (1:1); Dartobcin; Tofisopamum [INN-Latin]; Tobracin; Tofisopam [INN:DCF:JAN]; Emandaxin; Nebcine; UNII:UZC80HAU42; Obracin; Tobraneg; 7,8-dimethoxy-1-(3,4-dimethoxyphenyl)-5-ethyl-4-methyl-5H-2,3-benzodiazepine; -3,5-diol sulfate (salt); -3,5-diolsulfat(salt); (2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminométhyl)-5-hydroxytétrahydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxyméthyl)tétrahydro-2H-pyran-3,5-diol sulfate (salt); Tobrasix; Grandaxin; 1-[3,4-bis(methyloxy)phenyl]-5-ethyl-4-methyl-7,8-bis(methyloxy)-5H-2,3-benzodiazepine; Tofisopam; 1-(3,4-dimethoxyphenyl)-7,8-dimethoxy-5-ethyl-4-methyl-5H-2,3-benzodiazepine; α-D-Glucopyranoside, (1S,2S,3R,4S,6R)-4,6-diamino-3-[(2,6-diamino-2,3,6-trideoxy-α-D-ribo-hexopyranosyl)oxy]-2-hydroxycyclohexyl 3-amino-3-deoxy-, sulfate (1:1) (salt); 7,8-Dimethoxy-1-(3,4-dimethoxyphenyl)-5-ethyl-4-methyl-5H-2,3-benzodiazepine,EGYT 341,Seriel; Trazil; tofizopam; Tobryne; (2S,3R,4S,5S,6R)-4-Amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxytetrahydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)tetrahydro-2H-pyran; Seriel; (2S,3R,4S,5S,6R)-4-Amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxytetrahydro-2H-pyran-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diolsulfat(salt)

物化性质

• 密度: 1.2±0.1 g/cm3
• 沸点: 479.0±45.0 °C at 760 mmHg
• 熔点: 155-159ºC
• 分子式: C₁₈H₃₉N₅O₁₃S
• 分子量: 565.593
• 闪点: 195.2±21.2 °C
• 精确质量: 565.226501
• PSA: 61.64000
• LogP: 2.39
• 外观性状: 白色固体
• 蒸汽压: 0.0±1.2 mmHg at 25°C
• 折射率: 1.558
• 储存条件:

  放入紧密的贮藏器内，储存在阴凉，干燥的地方

• 稳定性:

  常温常压下稳定

  避免接触 强氧化剂
• 分子结构:

  五、分子性质数据：

  1、 摩尔折射率：106.84

  2、 摩尔体积(cm³/mol)：331.2

  3、 等张比容(90.2K)：810.4

  4、 表面张力(dyne/cm)：35.8

  5、 极化率(10-24cm³)：42.35

• 计算化学:

  1.疏水参数计算参考值（XlogP）:3.2

  2.氢键供体数量:0

  3.氢键受体数量:6

  4.可旋转化学键数量:6

  5.互变异构体数量:无

  6.拓扑分子极性表面积61.6

  7.重原子数量:28

  8.表面电荷:0

  9.复杂度:579

  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：白色固体

  2.密度（g/mL,25/4℃）：未确定

  3.相对蒸汽密度（g/mL,空气=1）：未确定

  4.熔点（ºC）：155-159

  5.沸点（ºC,常压）：未确定

  6.沸点（ºC,5.2kPa）：未确定

  7.折射率：未确定

  8.闪点（ºC）：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：溶于DMSO

生物活性

• 描述: 托福西泮是一种2,3-苯二氮卓化合物,是一种口服活性抗焦虑剂[1]。
• 相关类别:
  信号通路 >> 其他 >> 其他
  研究领域 >> 神经疾病
• 体外研究: 以50 mg/kg的剂量给药七天,可改善受损的认知能力,增强海马中减弱的突触传递,增加颗粒下区的增殖,并改善健忘症大鼠星形胶质细胞的减少[1]。
• 参考文献:

  [1]. Umut İrfan Üçel, et al. Antiamnesic effects of tofisopam against scopolamine-induced cognitive impairments in rats. Pharmacol Biochem Behav. 2020 Mar;190:172858.

毒性和生态

毒理学数据: 生态学数据: CHEMICAL IDENTIFICATION RTECS NUMBER : DE9540000 CHEMICAL NAME : 5H-2,3-Benzodiazepine, 1-(3,4-dimethoxyphenyl)-5-ethyl-7,8-dimethoxy-4-methy l- CAS REGISTRY NUMBER : 22345-47-7 LAST UPDATED : 199506 DATA ITEMS CITED : 13 MOLECULAR FORMULA : C22-H26-N2-O4 MOLECULAR WEIGHT : 382.50 WISWESSER LINE NOTATION : T67 HNN KHJ CO1 DO1 GR CO1 DO1& J1 K2 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 : 825 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1270 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 103 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 3800 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 1950 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >10 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold 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: 12,547,1981 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 415 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Lungs, Thorax, or Respiration - respiratory stimulation 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: 12,547,1981 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9 gm/kg/30D-I TOXIC EFFECTS : Liver - changes in liver weight Endocrine - changes in thymus weight Blood - changes in leukocyte (WBC) count 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: 12,547,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 36400 mg/kg/26W-I TOXIC EFFECTS : Lungs, Thorax, or Respiration - changes in lung weight Liver - changes in liver weight Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases 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: 12,547,1981 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 110 mg/kg SEX/DURATION : female 7-17 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - sex ratio 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: 12,565,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 270 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 21 day(s) post-birth TOXIC EFFECTS : Reproductive - Effects on Newborn - behavioral 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: 12,565,1981 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 12 gm/kg SEX/DURATION : male 30 day(s) pre-mating TOXIC EFFECTS : Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands 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: 12,547,1981

安全

• 符号: GHS07, GHS09
• 信号词: Warning
• 危害声明: H302-H400
• 警示性声明: P273
• 个人防护装备: dust mask type N95 (US);Eyeshields;Gloves
• 危害码 (欧洲): Xn: Harmful;N: Dangerous for the environment;
• 风险声明 (欧洲): R22;R50
• 安全声明 (欧洲): 60-61
• 危险品运输编码: UN 3077
• WGK德国: 2
• RTECS号: DE9540000
• 包装等级: III
• 危险类别: 6.1(b)

合成路线

15462-91-6 ~60% 22345-47-7

文献：Gatta; Piazza; Del Giudice; Massotti Farmaco, Edizione Scientifica, 1985 , vol. 40, # 12 p. 942 - 955

82059-51-6 ~95% 22345-47-7

文献：Vela Pharmaceuticals, Inc. Patent: US2006/264421 A1, 2006 ; Location in patent: Page/Page column 3 ;

55300-10-2 ~% 22345-47-7

文献：US2006/264421 A1, ; Page/Page column 2 ;

2029-86-9 ~% 22345-47-7

文献：Farmaco, Edizione Scientifica, , vol. 40, # 12 p. 942 - 955

120-14-9 ~% 22345-47-7

文献：Farmaco, Edizione Scientifica, , vol. 40, # 12 p. 942 - 955

102728-10-9 ~% 22345-47-7

文献：Farmaco, Edizione Scientifica, , vol. 40, # 12 p. 942 - 955

776-99-8 ~% 22345-47-7

文献：Heterocycles, , vol. 88, # 1 p. 287 - 295

546104-93-2 ~% 22345-47-7

文献：Heterocycles, , vol. 88, # 1 p. 287 - 295

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