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R(-)-去甲胺

R(-)-去甲胺用途

地诺帕明((R)-(-)-地诺帕明)是一种口服活性、选择性β1-肾上腺素能激动剂。地诺帕明延长病毒性心肌炎所致充血性心力衰竭小鼠模型的存活时间：抑制心脏肿瘤坏死因子-α的产生。心血管效应[1]。

R(-)-去甲胺名称

[ CAS 号 ]:
71771-90-9

[ 中文名 ]:
地诺帕明

[ 英文名 ]:
Denopamine

[中文别名 ]:

待罗把胺

[英文别名 ]:

kalgut
TA 064
MFCD00867122
Carguto
(-)-Denopamine
(R)-(-)-denopamine

R(-)-去甲胺生物活性

[ 描述 ]:

[ 相关类别 ]:

研究领域 >> 心血管疾病

信号通路 >> G 蛋白偶联受体/G 蛋白 >> 肾上腺素能受体

[体外研究]

地诺帕明(0.1-100μM)以浓度依赖性方式抑制LPS诱导的TNF-α产生[1]。细胞活力测定[1]细胞系：小鼠脾细胞浓度：0,0.1,1,10,100μM培养时间：5小时结果：在0.1,1,10和100μmol/L浓度下,TNF-α水平分别降低96.9±6.7%,62.7±6.5%,53.2±8.8%和40.3±1.5%。

[体内研究]

地诺帕明(14μmol/kg/天；口服；14天)显著提高动物存活率,减轻心肌损伤,抑制体内TNF-α的产生[1]。地诺帕明给药后1h的血浆浓度为13.1±1.9 nmol/L,2h为4.3±0.9 nmol/L,3h为1.8±0.5 nmol/L,5h为<0.6 nmol/L。小鼠单次14μmol/kg剂量的地诺帕胺在1小时时产生峰值水平[1]。动物模型：4周龄近交雄性DBA/2小鼠[1]剂量：14μmol/kg/天给药：口服；14天结果：治疗显著提高了动物的存活率(25只治疗小鼠中的14只(56%),而25只对照小鼠中的5只(20%)。在第14天,治疗组57.1%(28只小鼠中的16只)的存活率显著高于对照组33.3%(30只小鼠中的10只)的存活率。与对照组(45.5%；22只小鼠中的10只,p<0.05)相比,治疗组(69.6%；23只小鼠中的16只)从第6天到第14天的存活率也显著提高。

[参考文献]

[1]. R Nishio, et al. Denopamine, a beta1-adrenergic agonist, prolongs survival in a murine model of congestive heart failure induced by viral myocarditis: suppression of tumor necrosis factor-alpha production in the heart. J Am Coll Cardiol. 1998 Sep;32(3):808-15.

R(-)-去甲胺物理化学性质

[ 密度 ]:
1.177g/cm3

[ 沸点 ]:
518.8ºC at 760 mmHg

[ 分子式 ]:
C₁₈H₂₃NO₄

[ 分子量 ]:
317.38

[ 闪点 ]:
267.6ºC

[ 精确质量 ]:
317.16300

[ PSA ]:
70.95000

[ LogP ]:
2.66600

[ 外观性状 ]:
固体

[ 折射率 ]:
1.581

[ 储存条件 ]:
2-8°C，密封，干燥

R(-)-去甲胺毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DA4795470

CHEMICAL NAME :: Benzenemethanol, alpha-(((2-(3,4-dimethoxyphenyl)ethyl)amino)methyl)-4 -hydroxy-, (R)-

CAS REGISTRY NUMBER :: 71771-90-9

LAST UPDATED :: 199406

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C18-H23-N-O4

MOLECULAR WEIGHT :: 317.42

WISWESSER LINE NOTATION :: QR DYQ1M2R CO1 DO1

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 :: 9369 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 32,751,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 1785 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - ptosis Behavioral - somnolence (general depressed activity) Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 32,751,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Sense Organs and Special Senses (Eye) - ptosis Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 32,751,1986

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 5672 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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1651 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

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: NIIRDN Drugs in Japan (Ethical Drugs). (Yakugyo Jiho Co., Ltd., Tokyo, Japan) Volume(issue)/page/year: -,700,1990 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 6600 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Specific Developmental Abnormalities - musculoskeletal system

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 32,769,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 660 mg/kg

SEX/DURATION :: female 7-17 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 32,769,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 252 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 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: 32,769,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 810 mg/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: 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: 32,769,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 13 gm/kg

SEX/DURATION :: female 6-18 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 32,769,1986

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1300 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: 32,769,1986

R(-)-去甲胺安全信息

[ 符号 ]:

GHS08

[ 信号词 ]:
Warning

[ 危害声明 ]:
H361

[ 警示性声明 ]:
P281

[ 个人防护装备 ]:
Eyeshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges

[ 危害码 (欧洲) ]:
Xn: Harmful;

[ 风险声明 (欧洲) ]:
R62

[ 安全声明 (欧洲) ]:
S22;S45;S36/S37/S39

[ 危险品运输编码 ]:
NONH for all modes of transport

[ RTECS号 ]:
DA4795470

R(-)-去甲胺上下游产品

R(-)-去甲胺上游产品

R(-)-去甲胺下游产品

R(-)-去甲胺制备

用不对称还原来制备。关键中间体(I)(2.7g)加到手性试剂L-脯氨酸硼烷络合物(II)的悬浮液(190mg和575mg L-脯氨酸溶于10ml四氢呋喃，室温搅拌2h中，在室温下搅拌10d。加入水分解过量的试剂，减压浓缩后用乙酸乙酯提取。提取液用10%盐酸、饱和碳酸氢钠和饱和盐水洗，无水硫酸钠干燥。减压浓缩，剩余物通过一短硅胶柱，用乙醚洗脱。蒸发去乙醚后，得2.73g黏稠液体。该黏稠液体(680mg)溶于甲醇(20m1)，在10%钯-炭(250mg)、室温和常压下催化氢化2h。反应液过滤后，通入干燥的氯化氢气体。减压浓缩，剩余物用甲醇-乙醚重结晶，得355mg地诺帕明，收率80%，熔点130～140℃，[α]_D²³-24.6°～-23.6°(C=1，甲醇)。

R(-)-去甲胺文献

Binding pockets of the beta(1)- and beta(2)-adrenergic receptors for subtype-selective agonists.

Mol. Pharmacol. 56 , 875-885, (1999)

We examined the subtype-selective binding site of the beta-adrenergic receptors (betaARs). The beta(1)/beta(2)-chimeric receptors showed the importance of the second and seventh transmembrane domains ...

Regioselective glucuronidation of denopamine: marked species differences and identification of human udp-glucuronosyltransferase isoform.

Drug Metab. Dispos. 33(3) , 403-12, (2005)

Denopamine is one of the oral beta(1)-adrenoceptor-selective partial agonists. Denopamine glucuronide is the most abundant metabolite in human, rat, and dog urine when administered orally. Species dif...

Vascular responses to beta-adrenoceptor subtype-selective agonists with and without endothelium in rat common carotid arteries.

J. Auton. Pharmacol. 21(1) , 7-13, (2001)

1. Using the cannula inserting method, vasodilator responses to beta-adrenoceptor agonists (isoprenaline, denopamine and procaterol) were investigated in isolated and perfused rat common carotid arter...

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