85815-37-8

• 常用中文名：利马扎封盐酸盐
• 常用英文名：450191S
• CAS号：85815-37-8
• 分子式：C₂₁H₂₁Cl₃N₆O₃
• 分子量：511.78900
• 相关类别： 研究领域 神经疾病
• 发布时间：2018-06-22 15:46:07
• 更新时间：2024-01-13 19:00:40
• 450191S 是一种新型睡眠诱导剂。

名称

• 中文名: 盐酸利马扎封
• 英文名: 5-[[(2-aminoacetyl)amino]methyl]-1-[4-chloro-2-(2-chlorobenzoyl)phenyl]-N,N-dimethyl-1,2,4-triazole-3-carboxamide,hydrochloride
• 英文别名: Rilmazafone HCl; rilmazafone hydrochloride; 1H-1,2,4-Triazole-3-carboxamide,5-(((aminoacetyl)amino)methyl)-1-(4-chloro-2-(2-chlorobenzoyl)phenyl)-N,N-dimethyl-,monohydrochloride,dihydrate; 450191S

物化性质

• 分子式: C₂₁H₂₁Cl₃N₆O₃
• 分子量: 511.78900
• 精确质量: 510.07400
• PSA: 126.70000
• LogP: 4.42440
• 储存条件: -20°C，密闭，干燥

生物活性

• 描述: 450191S 是一种新型睡眠诱导剂。
• 相关类别:
  信号通路 >> 其他 >> 其他
  研究领域 >> 神经疾病
• 体内研究: 当动物用高剂量的450191S(200或600 mg/kg,分别为5或3天)进行预处理以诱导肝脏药物代谢酶时,口服200 mg/kg剂量后代谢物的血药浓度450191S显着降低,取决于诱导的酶活性。用苯巴比妥预处理大鼠也导致血浆代谢物水平降低,这与450191S-预处理中的几乎相同。另一方面,与对照组和450191S或苯巴比妥预处理的大鼠相比,给大鼠施用β-萘黄酮导致更高的代谢物血浆水平和更慢的消除。 450191S被证明可刺激大鼠,小鼠和狗的肝脏药物代谢酶,伴随着戊巴比妥在大鼠中的药理活性的显着降低。仅当其代谢物的血浆浓度非常高时才能检测到450191S对肝酶活性的诱导[1]。
• 动物实验: 小鼠[1] 7-8周龄的Jcl Sprague-Dawley株的成年雄性大鼠用于实验。将动物保持在空调房间（25±1℃，50-60％湿度）中，每天12小时（8：00-20：00）点燃，并随意保持食物中的大鼠食物和水。将450191S以20或60mg / mL溶解于5％（w / v）阿拉伯树胶中，并将所得溶液以1.0mL / 100g体重口服给予大鼠3-5天。典型的诱导剂，苯巴比妥（在生理盐水中）和β-萘黄酮（在芝麻油中）以40mg / kg的剂量腹膜内给药，每天一次，持续3天。在最后一次施用450191S或诱导剂后，将动物禁食24小时，然后以200mg / kg的剂量口服给予大鼠450191S（20mg / mL的5％阿拉伯树胶）的试验溶液。在乙醚麻醉下从腹主动脉获得肝素化血液样品，并立即离心以使用Eppendorf 5414S型离心机获得血浆样品。
• 参考文献:

  [1]. Matsubara T, et al. Effect of change of hepatic drug-metabolizing activity on plasma concentrations of major metabolites of the new sleep inducer 450191-S, a 1H-1,2,4-triazolyl benzophenone derivative. Jpn J Pharmacol. 1987 Aug;44(4):429-36.

毒性和生态

CHEMICAL IDENTIFICATION RTECS NUMBER : XZ4179000 CHEMICAL NAME : 1H-1,2,4-Triazole-3-carboxamide, 5-(((aminoacetyl)amino)methyl)-1-(4-chloro-2-(2- chlorobenzoyl)phenyl)-N,N-dimethyl-, monohydrochloride, dihydrate CAS REGISTRY NUMBER : 85815-37-8 LAST UPDATED : 199506 DATA ITEMS CITED : 16 MOLECULAR FORMULA : C21-H20-Cl2-N6-O3.Cl-H.2H2-O MOLECULAR WEIGHT : 547.87 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 : 680 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea 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: 20,8543,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 91 mg/kg TOXIC EFFECTS : Behavioral - somnolence (general depressed activity) Lungs, Thorax, or Respiration - dyspnea Gastrointestinal - hypermotility, diarrhea 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: 20,8543,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 1600 mg/kg TOXIC EFFECTS : Sense Organs and Special Senses (Eye) - ptosis Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea 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: 20,8543,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 540 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea 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: 20,8543,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Intraperitoneal SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 72 mg/kg TOXIC EFFECTS : Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity) Gastrointestinal - hypermotility, diarrhea 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: 20,8543,1986 TYPE OF TEST : LD50 - Lethal dose, 50 percent kill ROUTE OF EXPOSURE : Subcutaneous SPECIES OBSERVED : Rodent - mouse DOSE/DURATION : 620 mg/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - ataxia Lungs, Thorax, or Respiration - dyspnea 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: 20,8543,1986 TYPE OF TEST : LD - Lethal dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : >1 gm/kg TOXIC EFFECTS : Behavioral - convulsions or effect on seizure threshold Behavioral - excitement Gastrointestinal - nausea or vomiting 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: 20,8543,1986 ** OTHER MULTIPLE DOSE TOXICITY DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 5600 mg/kg/35D-C TOXIC EFFECTS : Liver - other changes Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) 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: 20,8557,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Rodent - rat DOSE/DURATION : 2275 mg/kg/13W-I TOXIC EFFECTS : Liver - other changes Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - phosphatases Biochemical - Metabolism (Intermediary) - lipids including transport 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: 21,1561,1987 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 1500 mg/kg/30D-C TOXIC EFFECTS : Liver - other changes Kidney, Ureter, Bladder - other changes in urine composition Endocrine - other changes 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: 20,8597,1986 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral SPECIES OBSERVED : Mammal - dog DOSE/DURATION : 9125 mg/kg/1Y-I TOXIC EFFECTS : Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) 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: 21,1651,1987 ** REPRODUCTIVE DATA ** TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 4400 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) Reproductive - Specific Developmental Abnormalities - musculoskeletal system Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,765,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 650 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 20 day(s) post-birth TOXIC EFFECTS : Reproductive - Maternal Effects - parturition Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,793,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 2600 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 20 day(s) post-birth TOXIC EFFECTS : Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Maternal Effects - ovaries, fallopian tubes Reproductive - Effects on Newborn - delayed effects REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,793,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 10400 mg/kg SEX/DURATION : female 17-22 day(s) after conception lactating female 20 day(s) post-birth TOXIC EFFECTS : Reproductive - Paternal Effects - prostate, seminal vesicle, Cowper's gland, accessory glands Reproductive - Maternal Effects - uterus, cervix, vagina Reproductive - Effects on Newborn - live birth index (measured after birth) REFERENCE : OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 30,793,1985 TYPE OF TEST : TDLo - Lowest published toxic dose ROUTE OF EXPOSURE : Oral DOSE : 91 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: 30,819,1985