81098-60-4

• 常用中文名：西沙必利
• 常用英文名：Cisapride
• CAS号：81098-60-4
• 分子式：C₂₃H₂₉ClFN₃O₄
• 分子量：465.945
• 相关类别： 原料药 消化系统用药 胃肠动力药
• 发布时间：2018-06-23 18:24:39
• 更新时间：2024-01-02 17:50:51
• Cisapride(R 51619)是5-HT4受体激动剂,还是hERG抑制剂。

名称

• 中文名: 西沙必利
• 英文名: cisapride
• 中文别名: 西沙比利; (+/-)-顺式-4-氨基-5-氯-N-[1-[3-(4-氟苯氧基)丙基]-3-甲氧基-4-哌啶基]-2-甲氧基苯甲酰胺
• 英文别名: Cisapride; MFCD03305346; 4-Amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl}-2-methoxybenzamide; prepulsid; EINECS 279-689-7; Benzamide, 4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxy-4-piperidinyl]-2-methoxy-; Risamol; ACENALIN; 4-amino-5-chloro-N-{1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl}-2-methoxybenzamide; Alimix; 4-Amino-5-chlor-N-{1-[3-(4-fluorphenoxy)propyl]-3-methoxypiperidin-4-yl}-2-methoxybenzolcarboxamid; CIPRIL; propulsid; 4-amino-5-chloro-N-[1-{3-[(4-fluorophenyl)oxy]propyl}-3-(methyloxy)piperidin-4-yl]-2-(methyloxy)benzamide; Risamal

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 605.4±55.0 °C at 760 mmHg
• 熔点: 107 - 111ºC
• 分子式: C₂₃H₂₉ClFN₃O₄
• 分子量: 465.945
• 闪点: 319.9±31.5 °C
• 精确质量: 465.183075
• PSA: 86.05000
• LogP: 3.12
• 外观性状: 白色至略米色粉末
• 蒸汽压: 0.0±1.7 mmHg at 25°C
• 折射率: 1.593
• 储存条件:

  密闭，阴凉，干燥处

• 稳定性:

  按规定使用和贮存的不会分解，避氧化物

• 水溶解性: DMSO: ~30 mg/mL
• 计算化学:

  1、 疏水参数计算参考值（XlogP）：3.4

  2、 氢键供体数量：2

  3、 氢键受体数量：7

  4、 可旋转化学键数量：9

  5、 互变异构体数量：3

  6、 拓扑分子极性表面积（TPSA）：86.1

  7、 重原子数量：32

  8、 表面电荷：0

  9、 复杂度：581

  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：2

  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/mL25 ºC）：不确定

  3. 相对蒸汽密度（g/mL,空气=1）：未确定

  4. 熔点（ºC）：单水合物：从2-丙醇结晶，熔点109.8℃。(+)型：熔点129℃。(-)型：熔点125℃。(±)型：熔点131～133℃

  5. 沸点（ºC,常压）：未确定

  6. 沸点（ºC0.35mmHg）：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,）：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（正辛醇/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：溶于丙酮，微溶于甲醇，几乎不溶于水。

生物活性

• 描述: Cisapride(R 51619)是5-HT4受体激动剂,还是hERG抑制剂。
• 相关类别:
  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
  研究领域 >> 神经疾病
• 参考文献:

  [1]. Toga, T., Y. Kohmura, and R. Kawatsu, The 5-HT(4) agonists cisapride, mosapride, and CJ-033466, a Novel potent compound, exhibit different human ether-a-go-go-related gene (hERG)-blocking activities. J Pharmacol Sci, 2007. 105(2): p. 207-10.

  [2]. Sung, K.W. and S.J. Hahn, Effect of mosapride on Kv4.3 potassium channels expressed in CHO cells. Naunyn Schmiedebergs Arch Pharmacol, 2013. 386(10): p. 905-16.

  [3]. Mine, Y, et al. Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther, 1997. 283(3): p. 1000-8.

  [4]. Motavallian, A, et al., Does Cisapride, as a 5HT(4) Receptor Agonist, Aggravate the Severity of TNBS-Induced Colitis in Rat. Gastroenterol Res Pract, 2012. 2012: p. 362536.

毒性和生态

毒理学数据: 1、急性毒性：女性途径未报道TDLo：400μg/kg/2D-I；女性途径未报道TDLo：200μg/kg； 大鼠经口LD50：4166mg/kg；大鼠腹腔LD50：3435mg/kg；大鼠皮肤接触LD50：>2250mg/kg； 大鼠静脉注射LD50：27400μg/kg；小鼠经口LD50：8715mg/kg；小鼠腹腔LD50：>1mg/kg； 小鼠皮肤接触LD50：>1mg/kg；小鼠静脉注射LD50：32200μg/kg； 2、其他多剂量毒性：大鼠经口TDLo：14600 mg/kg/52W-C；大鼠经口TDLo：3600 mg/kg/90D-I； CHEMICAL IDENTIFICATION RTECS NUMBER : CU9372000 CHEMICAL NAME : Benzamide, 4-amino-5-chloro-N-(1-(3-(4-fluorophenoxy)propyl)-3-m ethoxy-4-piperidinyl) -2- methoxy-, monohydrate, cis- CAS REGISTRY NUMBER : 81098-60-4 LAST UPDATED : 199504 DATA ITEMS CITED : 12 MOLECULAR FORMULA : C23-H29-Cl-F-N3-O4.H2-O MOLECULAR WEIGHT : 484.02 HEALTH HAZARD DATA ACUTE TOXICITY DATA TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - woman DOSE/DURATION : 400 ug/kg/2D-I TOXIC EFFECTS : Kidney, Ureter, Bladder - other changes REFERENCE : MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 160,579,1994 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Unreported SPECIES OBSERVED : Human - woman DOSE/DURATION : 200 ug/kg TOXIC EFFECTS : Kidney, Ureter, Bladder - urine volume increased REFERENCE : MJAUAJ Medical Journal of Australia. (Australasian Medical Pub. Co. Ltd., 71-79 Arundel St., Glebe, N.S.W., Australia) V.1- 1914- Volume(issue)/page/year: 160,579,1994 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 4166 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3435 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >2250 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 27400 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 8715 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 32200 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - changes in motor activity (specific assay) Lungs, Thorax, or Respiration - other changes 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: 19,599,1988 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 14600 mg/kg/52W-C TOXIC EFFECTS : Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - death Related to Chronic Data - changes in uterine weight REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 35,85,1988 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 3600 mg/kg/90D-I TOXIC EFFECTS : Liver - changes in liver weight Blood - pigmented or nucleated red blood cells Related to Chronic Data - changes in ovarian weight 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: 19,599,1988

安全

• 危害码 (欧洲): Xi:Irritant
• 风险声明 (欧洲): R41
• 安全声明 (欧洲): S26-S39
• WGK德国: 2
• RTECS号: CU9372000
• 海关编码: 2942000000

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制备

3-甲氧基-4-氨基哌啶和4-乙酰氨基-2-甲氧基-5-氯苯甲酸脱水酰胺化，生成4-乙酰氨基-2-甲氧-5-氯-N-(3-甲氧基-4-哌啶基)苯甲酰胺，再和对氟苯氯丙醚进行氮上的烷基化反应，酸化水解生成西沙必利。

海关

海关编码	2942000000