75272-39-8

• 常用中文名：奈莫必利
• 常用英文名：Nemonapride
• CAS号：75272-39-8
• 分子式：C₂₁H₂₆ClN₃O₂
• 分子量：387.90300
• 发布时间：2018-05-03 08:00:00
• 更新时间：2024-01-03 06:05:18
• 尼莫那普利是一种高效的多巴胺D2受体拮抗剂,Ki为0.06 nM。尼莫那普利还激活5-HT1A受体,IC50为34 nM。尼莫那普利是一种抗精神病药物,很容易通过血脑屏障,在动物身上表现出强大的抗精神病作用[1][2][3]。

名称

• 中文名: 奈莫必利
• 英文名: (2R,3R)-nemonapride
• 中文别名: 顺-5-氯-2-甲氧基-4-(甲基氨基)-N-[2-甲基-2-(苯基甲基)-3-吡咯烷基]苯甲酰胺
• 英文别名: cis-(+-)-rrolidinyl); nobenzamide; Emilace; [3H]nemonapride; NEMONAPRIDE; N-((2S,3S)-1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-(methylamino)benzamide; inobenzamide; (+-)-cis-n-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylami; emonapride

物化性质

• 熔点: 152-153ºC
• 分子式: C₂₁H₂₆ClN₃O₂
• 分子量: 387.90300
• 精确质量: 387.17100
• PSA: 53.60000
• LogP: 4.18490
• 分子结构:

  1、 摩尔折射率：108.90

  2、 摩尔体积（cm³/mol）：314.2

  3、 等张比容（90.2K）：846.4

  4、 表面张力（dyne/cm）：52.6

  5、 极化率（10-24cm3）：43.17

• 更多:

  1.性状：白色结晶或结晶性粉末，无臭。

  2.溶解度：易溶于氯仿或冰醋酸，较难溶于甲醇或乙醇，难溶于乙醚，几不溶于水。

  3.熔点：152-153℃;150℃。

生物活性

• 描述: 尼莫那普利是一种高效的多巴胺D2受体拮抗剂,Ki为0.06 nM。尼莫那普利还激活5-HT1A受体,IC50为34 nM。尼莫那普利是一种抗精神病药物,很容易通过血脑屏障,在动物身上表现出强大的抗精神病作用[1][2][3]。
• 相关类别:
  信号通路 >> G 蛋白偶联受体/G 蛋白 >> 多巴胺受体
  信号通路 >> 神经信号通路 >> 多巴胺受体
  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
• 靶点:

  5-HT1A Receptor:34 nM (IC50)

  D2 Receptor:0.06 nM (Ki)

• 参考文献:

  [1]. Terai M, et al. Selective binding of YM-09151-2, a new potent neuroleptic, to D2-dopaminergic receptors. Jpn J Pharmacol. 1983 Aug;33(4):749-55.

  [2]. Seeman P, Van Tol HH. Dopamine receptor pharmacology. Trends Pharmacol Sci. 1994 Jul;15(7):264-70.

  [3]. Assié MB, et al. 5-HT1A receptor agonist properties of the antipsychotic, nemonapride: comparison with bromerguride and clozapine. Eur J Pharmacol. 1997 Sep 10;334(2-3):141-7.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : CV2450815 CHEMICAL NAME : Benzamide, 5-chloro-2-methoxy-4-(methylamino)-N-(2-methyl-1-(phe nylmethyl)-3-pyrrolid inyl)-, cis-(+-)- CAS REGISTRY NUMBER : 75272-39-8 LAST UPDATED : 199501 DATA ITEMS CITED : 17 MOLECULAR FORMULA : C21-H26-Cl-N3-O2 MOLECULAR WEIGHT : 387.95 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 : >367 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease 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: 23,4831,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : >320 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease 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: 23,4831,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 17 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease 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: 23,4831,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 604 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Behavioral - ataxia 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: 23,4831,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : >320 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease 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: 23,4831,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intravenous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 24500 ug/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - convulsions or effect on seizure threshold Nutritional and Gross Metabolic - body temperature decrease 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: 23,4831,1989 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >200 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: 22,769,1991 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Primate - monkey DOSE/DURATION : >300 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: 22,769,1991 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 9100 mg/kg/13W-C TOXIC EFFECTS : Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Metabolism (Intermediary) - Plasma proteins not involving coagulation Related to Chronic Data - death 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: 23,4831,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5460 mg/kg/26W-C TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes Nutritional and Gross Metabolic - changes in sodium 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: 23,4831,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 364 mg/kg/52W-C TOXIC EFFECTS : Blood - other changes Nutritional and Gross Metabolic - changes in potassium Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases 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: 23,4831,1989 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 6300 mg/kg SEX/DURATION : male 63 day(s) pre-mating TOXIC EFFECTS : Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 38,109,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 10800 ug/kg SEX/DURATION : female 2 week(s) pre-mating - 22 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Newborn - stillbirth Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 38,113,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 10800 ug/kg SEX/DURATION : female 2 week(s) pre-mating - 22 day(s) after conception TOXIC EFFECTS : Reproductive - Maternal Effects - menstrual cycle changes or disorders REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 38,113,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2 mg/kg SEX/DURATION : female 21-22 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Newborn - stillbirth REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 39,191,1990 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 130 mg/kg SEX/DURATION : female 6-18 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: 38,121,1989 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 390 mg/kg SEX/DURATION : female 6-18 day(s) after conception TOXIC EFFECTS : Reproductive - Effects on Embryo or Fetus - fetal death REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 38,121,1989

制备

化合物(I)先和盐酸羟胺反应后，再还原得到化合物(Ⅲ)。
2.15g化合物(Ⅳ)和1.12g三乙胺混合，在-10--40℃加入1.2g氯甲酸乙酯，搅拌3h。然后加入2.1g化合物(Ⅲ)，反应得到3.1g奈莫必利。