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吉非罗齐杂质A

吉非罗齐杂质A用途

Proguanil hydrochloride是一种抗疟前药,被代谢为活性代谢物环鸟苷 (HY-12784)。Proguanil hydrochloride是一种二氢叶酸还原酶 (DHFR) 抑制剂。

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吉非罗齐杂质A名称

[ CAS 号 ]:
637-32-1

[ 中文名 ]:
吉非罗齐杂质A

[ 英文名 ]:
proguanil hydrochloride

[中文别名 ]:

盐酸氯胍

[英文别名 ]:

Paludrin
proguanil hydrochloride
Paludrine
Drinupal hydrochloride
Tirian hydrochloride
Palusil hydrochloride

吉非罗齐杂质A生物活性

[ 描述 ]:

Proguanil hydrochloride是一种抗疟前药,被代谢为活性代谢物环鸟苷 (HY-12784)。Proguanil hydrochloride是一种二氢叶酸还原酶 (DHFR) 抑制剂。

[ 相关类别 ]:

研究领域 >> 感染

信号通路 >> 细胞周期/DNA损伤 >> 叶酸

[体外研究]

丙胍本身体外抗疟活性较弱(IC50=2.4-19μM),其有效性取决于活性代谢物环鸟苷(IC50=0.5-2.5nm)。环鸟苷是一种二氢叶酸还原酶(DHFR)抑制剂。阿托瓦醌与普罗瓜尼的联合作用在体外具有协同作用。这两种药物还具有抗疟原虫配子体和红细胞前(肝)阶段的活性[1]。丙胍作为双胍而不是其代谢物环鸟苷(一种寄生虫二氢叶酸还原酶[DHFR]抑制剂)来增强阿托伐酮效应。丙胍介导的增强作用对阿托瓦醌是特异性的,因为其他线粒体电子传递抑制剂(如粘噻唑和抗霉素)的作用不会因包合丙胍而改变[2]。5-HT3受体反应可被丙胍、代谢物4-氯苯基-1-双胍(CPB)和活性代谢物环鸟苷(CG)可逆抑制,IC50分别为1.81、1.48和4.36μM[3]。

[体内研究]

普罗胍(p.o.；2.9mg/kg体重；每日5天和6周)在wistar系白化大鼠中表现出轻微的退行性变化,而在6周内表现出严重的退行性变化[4]。普罗古尼治疗组大鼠血清睾酮水平显著降低[4]。给实验性感染吉布森B.gibsoni的2只狗在慢性期和3只急性期使用马拉酮(阿托瓦醌和普罗古尼)可减少寄生虫血症,并观察到临床改善[5]。

[参考文献]

[1]. Pudney M, et al. Atovaquone and proguanil hydrochloride: a review of nonclinical studies. J Travel Med. 1999 May;6 Suppl 1:S8-12.

[2]. Srivastava IK, et al. A mechanism for the synergistic antimalarial action of atovaquone and proguanil. Antimicrob Agents Chemother. 1999 Jun;43(6):1334-9.

[3]. Lochner M, et al. The antimalarial drug proguanil is an antagonist at 5-HT3 receptors. J Pharmacol Exp Ther. 2014 Dec;351(3):674-84.

[4]. Stephen AO, et al. Prolonged administration of proguanil induces reproductive toxicity in male rats. J Toxicol Sci. 2011 Oct;36(5):587-99.

[5]. Iguchi A, et al. The in vitro interactions and in vivo efficacy of atovaquone and proguanil against Babesia gibsoni infection in dogs. Vet Parasitol. 2013 Nov 8;197(3-4):527-33.

吉非罗齐杂质A物理化学性质

[ 沸点 ]:
402.7ºC at 760 mmHg

[ 熔点 ]:
249-251ºC

[ 分子式 ]:
C₁₁H₁₇Cl₂N₅

[ 分子量 ]:
290.192

[ 闪点 ]:
197.4ºC

[ 精确质量 ]:
289.086090

[ PSA ]:
83.79000

[ LogP ]:
4.06530

[ 储存条件 ]:
-20°C Freezer

[ 水溶解性 ]:
acetonitrile: water: ~1mg/mL (60/40)

吉非罗齐杂质AMSDS

详细MSDS(安全技术说明书)

吉非罗齐杂质A毒性和生态

CHEMICAL IDENTIFICATION

RTECS NUMBER :: DU1750000

CHEMICAL NAME :: Biguanide, 1-(p-chlorophenyl)-5-isopropyl-, monohydrochloride

CAS REGISTRY NUMBER :: 637-32-1

LAST UPDATED :: 199606

DATA ITEMS CITED :: 16

MOLECULAR FORMULA :: C11-H16-Cl-N5.Cl-H

MOLECULAR WEIGHT :: 290.23

WISWESSER LINE NOTATION :: GR DMYUM&MYUM&MY1&1 &GH

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 :: 58 mg/kg

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

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 91,157,1947

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 33 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 91,157,1947

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 27 mg/kg

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

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 91,157,1947

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 35 mg/kg

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

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,474,1960

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 23 mg/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 91,157,1947

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 150 mg/kg

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

REFERENCE :: BJPCAL British Journal of Pharmacology and Chemotherapy. (London, UK) V.1-33, 1946-68. For publisher information, see BJPCBM. Volume(issue)/page/year: 2,181,1947

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 44850 ug/kg

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

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 91,157,1947

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 15 mg/kg

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

REFERENCE :: TXAPA9 Toxicology and Applied Pharmacology. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1959- Volume(issue)/page/year: 2,474,1960

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - guinea pig

DOSE/DURATION :: 39510 ug/kg

TOXIC EFFECTS :: Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 91,157,1947

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Bird - chicken

DOSE/DURATION :: 400 mg/kg

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

REFERENCE :: BJPCAL British Journal of Pharmacology and Chemotherapy. (London, UK) V.1-33, 1946-68. For publisher information, see BJPCBM. Volume(issue)/page/year: 2,181,1947 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 350 mg/kg/7D-I

TOXIC EFFECTS :: Related to Chronic Data - death

REFERENCE :: BJPCAL British Journal of Pharmacology and Chemotherapy. (London, UK) V.1-33, 1946-68. For publisher information, see BJPCBM. Volume(issue)/page/year: 2,181,1947

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 3088 mg/kg/9W-C

TOXIC EFFECTS :: Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 90,233,1947

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 515 mg/kg/10D-C

TOXIC EFFECTS :: Behavioral - food intake (animal) Related to Chronic Data - death

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 90,233,1947

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 709 mg/kg/31D-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of salivary glands Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 90,233,1947

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Primate - monkey

DOSE/DURATION :: 1006 mg/kg/22D-I

TOXIC EFFECTS :: Gastrointestinal - changes in structure or function of salivary glands Nutritional and Gross Metabolic - weight loss or decreased weight gain Related to Chronic Data - death

REFERENCE :: JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 90,233,1947 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 168 mg/kg

SEX/DURATION :: female 7 day(s) pre-mating female 1-7 day(s) after conception

TOXIC EFFECTS :: Reproductive - Fertility - female fertility index (e.g. # females pregnant per # sperm positive females; # females pregnant per # females mated)

REFERENCE :: ANTCAO Antibiotics and Chemotherapy (Washington, DC). (Washington, DC) V.1-12, 1951-62. For publisher information, see CLMEA3. Volume(issue)/page/year: 12,671,1962

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吉非罗齐杂质A安全信息

[ 符号 ]:

GHS06

[ 信号词 ]:
Danger

[ 危害声明 ]:
H301

[ 警示性声明 ]:
Missing Phrase - N15.00950417

[ 危害码 (欧洲) ]:
T

[ 风险声明 (欧洲) ]:
25

[ 安全声明 (欧洲) ]:
45

[ 危险品运输编码 ]:
UN 3249

[ RTECS号 ]:
DU1750000

[ 包装等级 ]:
III

[ 危险类别 ]:
6.1(b)

吉非罗齐杂质A文献

CYP2C19*17 increases clopidogrel-mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel.

Clin. Exp. Pharmacol. Physiol. 41(11) , 870-8, (2014)

The aim of the present study was to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus,...

The antimalarial drug proguanil is an antagonist at 5-HT3 receptors.

J. Pharmacol. Exp. Ther. 351(3) , 674-84, (2014)

Proguanil is an antimalarial prodrug that is metabolized to 4-chlorophenyl-1-biguanide (CPB) and the active metabolite cycloguanil (CG). These compounds are structurally related to meta-chlorophenyl b...

Paper test cards for presumptive testing of very low quality antimalarial medications.

Am. J. Trop. Med. Hyg. 92 , 17-23, (2015)

Carrying out chemical analysis of antimalarials to detect low-quality medications before they reach a patient is a costly venture. Here, we show that a library of chemical color tests embedded on a pa...

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