Bifonazole

Names

[ Name ]:
Bifonazole

[Synonym ]:
Bifonazole
1-[PHENYL-(4-PHENYLPHENYL)-METHYL]IMIDAZOLE
rac-bifonazole
(±)-Bifonazole
(biphenyl-4-yl)phenyl-imidazol-1-ylmethane
1-[4-Biphenylyl(phenyl)methyl]-1H-imidazole
Canespor
1H-Imidazole, 1-([1,1'-biphenyl]-4-ylphenylmethyl)-
Bifonazol [INN-Spanish]
Azolmen
Trifonazole
EINECS 262-336-6
BAY H 4502
1-[biphenyl-4-yl(phenyl)methyl]imidazole
Amycor
1-[biphenyl-4-yl(phenyl)methyl]-1H-imidazole
1-[Biphenyl-4-yl(phenyl)methyl]-1H-imidazol
Bifazol
1-(biphenyl-4-yl-phenyl-methyl)-1H-imidazole
(±)-1-(p,a-Diphenylbenzyl)imidazole
1-([1,1'-Biphenyl]-4-ylphenylmethyl)-1H-imidazole
Bifonazol
Mycospor
Bifonazolum
MFCD00865567

Biological Activity

[Description]:

Bifonazole is an imidazole antifungal drug.Target: AntifungalBifonazole, a new broad-spectrum antimycotic, interferes with sterol biosynthesis. In dermatophytes bifonazole additionally inhibits directly HMG-CoA-reductase. bifonazole possesses a sequential mode of action, namely inhibition of cytochrome P450-dependent C14-demethylation of sterols and direct inhibition of HMG-CoA-reductase. In vitro bifonazole shows a strongly pH-dependent efficacy. The uptake kinetics of bifonazole have been measured with different pathogens [1]. Bifonazole additionally leads to a generally decreased rate of sterol biosynthesis as compared to clotrimazole, due to a direct inhibition of microsomal HMG-CoA-reductase. The additional fungicidal effects of bifonazole are considered to originate from a sequential action by inhibition of HMG-CoA-reductase and of cytochrome P450 [2]. bifonazole were affected by choice of medium with Kimmig's agar generally giving the lowest MIC's. Bifonazole MICs were shown to vary with pH (maximal activity at pH 6 . 5) with selected yeasts when tested on Kimmig's agar [3].

[Related Catalog]:

Signaling Pathways >> Anti-infection >> Fungal

Research Areas >> Infection

[References]

[1]. Berg, D. and M. Plempel, Bifonazole, a biochemist's view. Dermatologica, 1984. 169 Suppl 1: p. 3-9.

[2]. Berg, D., et al., Bifonazole and clotrimazole. Their mode of action and the possible reason for the fungicidal behaviour of bifonazole. Arzneimittelforschung, 1984. 34(2): p. 139-46.

[3]. Shadomy, S., D.M. Dixon, and R. May, A comparison of bifonazole (BAY H 4502) with clotrimazole in vitro. Sabouraudia, 1982. 20(4): p. 313-23.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
491.7±24.0 °C at 760 mmHg

[ Melting Point ]:
142℃

[ Molecular Formula ]:
C₂₂H₁₈N₂

[ Molecular Weight ]:
310.392

[ Flash Point ]:
251.2±22.9 °C

[ Exact Mass ]:
310.147003

[ PSA ]:
17.82000

[ LogP ]:
4.84

[ Vapour Pressure ]:
0.0±1.2 mmHg at 25°C

[ Index of Refraction ]:
1.616

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: NI3517000

CHEMICAL NAME :: Imidazole, 1-(alpha-(4-biphenylyl)benzyl)-

CAS REGISTRY NUMBER :: 60628-96-8

BEILSTEIN REFERENCE NO. :: 0618427

LAST UPDATED :: 199612

DATA ITEMS CITED :: 12

MOLECULAR FORMULA :: C22-H18-N2

MOLECULAR WEIGHT :: 310.42

WISWESSER LINE NOTATION :: T5N CNJ AYR&R DR

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 :: 1463 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - ataxia Skin and Appendages - hair

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 28,23,1984

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >10 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 28,23,1984

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 63 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 28,23,1984

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 2629 mg/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,739,1983

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

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >15 gm/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Skin and Appendages - dermatitis, other (after systemic exposure)

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 28,23,1984

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 57 mg/kg

TOXIC EFFECTS :: Behavioral - somnolence (general depressed activity) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - respiratory depression

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 28,23,1984

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >500 mg/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,739,1983

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rabbit

DOSE/DURATION :: 4 gm/kg

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,739,1983 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 10500 mg/kg/5W-C

TOXIC EFFECTS :: Liver - other changes Blood - normocytic anemia Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - transaminases

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 28,23,1984 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1160 mg/kg

SEX/DURATION :: female 16-22 day(s) after conception lactating female 22 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Effects on Newborn - growth statistics (e.g.%, reduced weight gain)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,739,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 1200 mg/kg

SEX/DURATION :: male 1 day(s) pre-mating

TOXIC EFFECTS :: Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,739,1983

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 390 mg/kg

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

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

REFERENCE :: ARZNAD Arzneimittel-Forschung. Drug Research. (Editio Cantor Verlag, Postfach 1255, W-7960 Aulendorf, Fed. Rep. Ger.) V.1- 1951- Volume(issue)/page/year: 33,739,1983

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Precautionary Statements ]:
P301 + P312 + P330

[ Hazard Codes ]:
Xn

[ Risk Phrases ]:
22

[ RIDADR ]:
NONH for all modes of transport

[ WGK Germany ]:
1

[ RTECS ]:
NI3517000

[ HS Code ]:
2933290090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933290090

[ Summary ]:
2933290090. other compounds containing an unfused imidazole ring (whether or not hydrogenated) in the structure. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

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