氟托西泮
氟托西泮用途
Flutoprazepam is a benzodiazepine derivative extensively biotransformed by hepatic microsomal oxidation. This drug is unschedule in the USA but classified as a Schedule IV controlled substance in Canada.
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氟托西泮名称
[ CAS 号 ]:
25967-29-7
[ 中文名 ]:
氟托西泮
[ 英文名 ]:
Flutoprazepam
[中文别名 ]:
[英文别名 ]:
- flutoprazepam
- Flutoprazepamum [INN-Latin]
- Restar
- KB-509
- Flutoprazepam [INN:JAN]
- Restas
- ID-1937
氟托西泮物理化学性质
[ 密度 ]:
1.37g/cm3
[ 沸点 ]:
539.3ºC at 760mmHg
[ 分子式 ]:
C19H16ClFN2O
[ 分子量 ]:
342.79500
[ 闪点 ]:
279.9ºC
[ 精确质量 ]:
342.09400
[ PSA ]:
32.67000
[ LogP ]:
3.57370
[ 蒸汽压 ]:
1.07E-11mmHg at 25°C
[ 折射率 ]:
1.661
氟托西泮毒性和生态
CHEMICAL IDENTIFICATION
- RTECS NUMBER :
- DF0650000
- CHEMICAL NAME :
- 2H-1,4-Benzodiazepin-2-one, 7-chloro-1-(cyclopropylmethyl)-5-(o-fluorophenyl)-1,3 -dihydro-
- CAS REGISTRY NUMBER :
- 25967-29-7
- BEILSTEIN REFERENCE NO. :
- 0898682
- LAST UPDATED :
- 199701
- DATA ITEMS CITED :
- 17
- MOLECULAR FORMULA :
- C19-H16-Cl-F-N2-O
- MOLECULAR WEIGHT :
- 342.82
- WISWESSER LINE NOTATION :
- T67 GNV JN IHJ CG KR BF& G1- AL3TJ
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 :
- 10060 mg/kg
- TOXIC EFFECTS :
- Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1055,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 2230 mg/kg
- TOXIC EFFECTS :
- Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1055,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- >5 gm/kg
- TOXIC EFFECTS :
- Behavioral - muscle weakness Behavioral - ataxia
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1005,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 2430 mg/kg
- TOXIC EFFECTS :
- Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1055,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Intraperitoneal
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- 2110 mg/kg
- TOXIC EFFECTS :
- Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1055,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Subcutaneous
- SPECIES OBSERVED :
- Rodent - mouse
- DOSE/DURATION :
- >5 gm/kg
- TOXIC EFFECTS :
- Behavioral - muscle weakness Behavioral - ataxia
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1005,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- >10 gm/kg
- TOXIC EFFECTS :
- Sense Organs and Special Senses (Eye) - ptosis Behavioral - altered sleep time (including change in righting reflex) Gastrointestinal - nausea or vomiting
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1005,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Primate - monkey
- DOSE/DURATION :
- >4 gm/kg
- TOXIC EFFECTS :
- Gastrointestinal - changes in structure or function of salivary glands Gastrointestinal - nausea or vomiting Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1005,1980
- TYPE OF TEST :
- LD50 - Lethal dose, 50 percent kill
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rabbit
- DOSE/DURATION :
- 1 gm/kg
- TOXIC EFFECTS :
- Behavioral - changes in motor activity (specific assay) Behavioral - ataxia Nutritional and Gross Metabolic - body temperature decrease
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1055,1980 ** OTHER MULTIPLE DOSE TOXICITY DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 65520 mg/kg/13W-I
- TOXIC EFFECTS :
- Liver - other changes Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1061,1980
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Rodent - rat
- DOSE/DURATION :
- 136 gm/kg/27W-I
- TOXIC EFFECTS :
- Liver - changes in liver weight Kidney, Ureter, Bladder - changes in bladder weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol)
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1061,1980
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- SPECIES OBSERVED :
- Mammal - dog
- DOSE/DURATION :
- 2275 mg/kg/13W-C
- TOXIC EFFECTS :
- Liver - changes in liver weight Blood - changes in serum composition (e.g. TP, bilirubin, cholesterol) Related to Chronic Data - changes in uterine weight
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 20,1105,1980 ** REPRODUCTIVE DATA **
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 9800 mg/kg
- SEX/DURATION :
- female 14 day(s) pre-mating
- 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: 21,1,1981
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 11 mg/kg
- SEX/DURATION :
- female 7-17 day(s) after conception
- TOXIC EFFECTS :
- 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: 21,13,1981
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 110 mg/kg
- SEX/DURATION :
- female 7-17 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - behavioral
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 21,13,1981
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 2700 mg/kg
- SEX/DURATION :
- female 17-22 day(s) after conception lactating female 21 day(s) post-birth
- TOXIC EFFECTS :
- Reproductive - Effects on Newborn - viability index (e.g., # alive at day 4 per # born alive) Reproductive - Effects on Newborn - physical
- REFERENCE :
- OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 21,27,1981
- TYPE OF TEST :
- TDLo - Lowest published toxic dose
- ROUTE OF EXPOSURE :
- Oral
- DOSE :
- 13 mg/kg
- SEX/DURATION :
- female 6-18 day(s) after conception
- TOXIC EFFECTS :
- Reproductive - Specific Developmental Abnormalities - musculoskeletal system
- 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: 16,658,1982
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氟托西泮制备
化合物(Ⅰ)在氯化氢-乙醇中，于70℃加热，环合得到化合物(1I)。然后氨解为酰胺(Ⅲ)，用氢化铝锂还原为胺(Ⅳ)。最后用三氧化铬，在乙酸-水中，于室温氧化扩环，得到氟托西泮。
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