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尼伐地平

尼伐地平用途

Nilvadipine 是一种有效的钙离子通道 (calcium channel) 拮抗剂,IC50 为 0.1 nM。

尼伐地平名称

[ CAS 号 ]:
75530-68-6

[ 中文名 ]:
尼伐地平

[ 英文名 ]:
Nilvadipine

[中文别名 ]:

[英文别名 ]:

Nivadipine
4-dihydropyridine-3-carboxylate
Nilvadipine
Nilvadipine [USAN:INN:JAN]
Nilvadipino [Spanish]
UNII:0214FUT37J
Nivaldipine
Escor
Nivadil
Nilvadipinum [Latin]

尼伐地平生物活性

[ 描述 ]:

Nilvadipine 是一种有效的钙离子通道 (calcium channel) 拮抗剂,IC50 为 0.1 nM。

[ 相关类别 ]:

信号通路 >> 跨膜转运 >> 钙通道

研究领域 >> 心血管疾病

[ 靶点 ]

IC50: 0.1 nM (Calcium channel)[1]

[体外研究]

在体外实验中,抑制大鼠主动脉平滑肌细胞的迁移,使用酵母多糖激活的空气囊渗出物作为改良Boyden室中的化学引诱剂。对于尼伐地平(FR34235),IC50值为0.033nM。还研究了尼伐地平对大鼠主动脉平滑肌细胞增殖和兔血小板聚集的影响。尼伐地平应该用于预防和治疗动脉粥样硬化。抑制平滑肌细胞迁移被认为是其抗动脉粥样硬化活性的机制[2]。利用非酶活性氧生成系统(DHF/FeC13-ADP)通过大鼠心肌膜脂质过氧化作用研究钙拮抗剂尼伐地平的抗氧化作用,IC50为25.1μM。尼伐地平在添加活性氧之前和之后都显示出抗氧化作用,并且降低了二羟基富马酸(DHF)的自氧化速率,是断链和预防性抗氧化剂。尼卡地平仅在暴露于活性氧之前显示出抗氧化作用并降低DHF自氧化速率,主要是预防性抗氧化剂[3]。

[体内研究]

在用聚乙烯袖套包裹颈动脉的兔子中检查钙拮抗剂尼伐地平(FR34235)的抗动脉粥样硬化活性,并与硝苯地平,维拉帕米和地尔硫卓相比较。从袖带放置当天开始,以0.01-10mg/kg的每日剂量肌肉内给予尼伐地平3周。 FR34235剂量依赖性地抑制袖带诱导的内膜增厚[2]。尼伐地平在视网膜变性期间提供显着的保护以防止RCS大鼠视网膜层变薄。电子显微镜显示未处理视网膜中感光器OS的显着不规则[4]。

[动物实验]

大鼠[4]在本研究中，使用在循环光条件下（12小时，12小时关闭）饲养的3至5周大的近交系RCS（rdy - / - ）大鼠。将尼伐地平和硝苯地平溶于乙醇，聚乙二醇400和蒸馏水（2：1：7）的混合物中，浓度为0.1 mg / mL，使用前用生理盐水稀释两次，腹腔注射（1.0 mL / kg））每天早晨每天麻醉大鼠麻醉大鼠，持续2周。在对照大鼠中，类似地给予不含尼伐地平或硝苯地平（溶媒溶液）的相同溶液。尼卡地平和地尔硫卓分别以0.25mg / mL和1mg / mL溶解于PBS中，并且与其他激动剂类似地腹膜内注射（1mL / kg）。作为对照，给予相同体积的乙醇，聚乙二醇400和蒸馏水（2：1：7）或PBS的混合物。在给药前，将所有药物溶液的pH调节至约7.4。给予RCS大鼠的这些药物的浓度通过它们在我们的临床实践中对患有高血压的人类患者口服给药1天的浓度来确定（尼伐地平，0.05-0.3mg / kg;硝苯地平，0.1-0.5mg / kg;尼卡地平， 0.2-1mg / kg;和地尔硫卓，0.3-3mg / kg）。

[参考文献]

[1]. Nomoto A, et al. Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, Nilvadipine. Atherosclerosis. 1988 Aug;72(2-3):213-9.

[2]. Nomoto A, et al. Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery. Atherosclerosis. 1987 Apr;64(2-3):255-61.

[3]. Sugawara H, et al. Antioxidant effects of calcium antagonists on rat myocardial membrane lipid peroxidation. Hypertens Res. 1996 Dec;19(4):223-8.

[4]. Yamazaki H, et al. Preservation of retinal morphology and functions in royal college surgeons rat by Nilvadipine, a Ca(2+) antagonist. Invest Ophthalmol Vis Sci. 2002 Apr;43(4):919-26.

[相关活性小分子]

尼伐地平物理化学性质

[ 密度 ]:
1.3±0.1 g/cm3

[ 沸点 ]:
526.7±50.0 °C at 760 mmHg

[ 熔点 ]:
148-150ºC

[ 分子式 ]:
C₁₉H₁₉N₃O₆

[ 分子量 ]:
385.371

[ 闪点 ]:
272.3±30.1 °C

[ 精确质量 ]:
385.127380

[ PSA ]:
134.24000

[ LogP ]:
1.72

[ 外观性状 ]:
黄色棱柱

[ 蒸汽压 ]:
0.0±1.4 mmHg at 25°C

[ 折射率 ]:
1.584

[ 储存条件 ]:
-20°C Freezer

[ 水溶解性 ]:
DMSO: soluble15mg/mL, clear

尼伐地平MSDS

详细MSDS(安全技术说明书)

尼伐地平毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: US7968300

CHEMICAL NAME :: 3,5-Pyridinedicarboxylic acid, 2-cyano-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-, 3-methyl- 5-(1-methylethyl) ester

CAS REGISTRY NUMBER :: 75530-68-6

LAST UPDATED :: 199612

DATA ITEMS CITED :: 14

MOLECULAR FORMULA :: C19-H19-N3-O6

MOLECULAR WEIGHT :: 385.41

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 :: 1560 mg/kg

TOXIC EFFECTS :: Sense Organs and Special Senses (Eye) - lacrimation Behavioral - somnolence (general depressed activity)

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: 21,1723,1987

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >1 gm/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: 23,682,1992

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 9650 ug/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: 23,682,1992

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 1300 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold

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: 21,1723,1987

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >320 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: 23,682,1992

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 9150 ug/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: 23,682,1992

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 510 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex)

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: 21,1723,1987

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 3850 ug/kg

TOXIC EFFECTS :: 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: 21,1723,1987 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 22631 mg/kg/53W-C

TOXIC EFFECTS :: Cardiac - other changes Liver - 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: 21,1723,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 1324 mg/kg/13W-C

TOXIC EFFECTS :: Musculoskeletal - changes in teeth and supporting structures

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: 21,1723,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 2698 mg/kg/53W-C

TOXIC EFFECTS :: Musculoskeletal - changes in teeth and supporting structures

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: 21,1723,1987 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 8352 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 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) Reproductive - Fertility - litter size (e.g. # fetuses per litter; measured before birth)

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: 21,1765,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 2784 mg/kg

SEX/DURATION :: male 9 week(s) pre-mating female 2 week(s) pre-mating - 7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

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: 21,1765,1987

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 259 mg/kg

SEX/DURATION :: female 17-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - parturition

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: 21,1765,1987

尼伐地平安全信息

[ 符号 ]:

GHS07

[ 信号词 ]:
Warning

[ 危害声明 ]:
H302

[ 危害码 (欧洲) ]:
Xn

[ 风险声明 (欧洲) ]:
22

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

[ RTECS号 ]:
US7968300

尼伐地平上下游产品

尼伐地平上游产品

尼伐地平下游产品

尼伐地平制备

3-硝基苯甲醛和哌啶、4，4-二甲氧基乙酰乙酸甲酯及乙酸，在苯中回流5h。然后再和2-氨基-2-丁烯酸异丙酯，在78℃下加热40min，再在120℃加热5.5h，最后在125℃加热1h。得到的二氢吡啶化合物用6mol/L盐酸水解，和盐酸羟胺成肟，再在乙酸酐作用下脱水，得尼伐地平。