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Fluindarol is a phenylindandione derivative and an orally active anticoagulant. Fluindarol acts as a toxicant that induces organ and tissue haemorrhages and liver parenchymal necrosis in rats. Fluindarol exhibits acute and cumulative preclinical toxicity in rats, rabbits, and dogs, with higher toxicity in female rats than male rats. Fluindarol lacks analgesic action, produces only minor blood pressure effects, and does not alter circulation, respiration, CNS, or cardiac activity. Fluindarol is considered too toxic for clinical use based on preclinical data.

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Fluindarol

Fluindarol Chemical Structure

CAS No. : 6723-40-6

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Description

Fluindarol is a phenylindandione derivative and an orally active anticoagulant. Fluindarol acts as a toxicant that induces organ and tissue haemorrhages and liver parenchymal necrosis in rats. Fluindarol exhibits acute and cumulative preclinical toxicity in rats, rabbits, and dogs, with higher toxicity in female rats than male rats. Fluindarol lacks analgesic action, produces only minor blood pressure effects, and does not alter circulation, respiration, CNS, or cardiac activity. Fluindarol is considered too toxic for clinical use based on preclinical data[1].

In Vivo

Fluindarol (100-350 mg/kg; p.o.; single dose) has an acute oral LD50 of 198 mg/kg in albino Wistar TNO rats, with greater mortality observed in female animals[1].
Fluindarol (100-200 mg/kg; i.p.; single dose) has an acute intraperitoneal LD50 of 125 mg/kg in albino Wistar TNO rats, with equal mortality observed in male and female animals[1].
Fluindarol (p.o.; single dose) has an acute oral LD50 of 123 mg/kg in tame rabbits, with non-surviving animals experiencing sudden nocturnal death[1].
Fluindarol (2810 mg/kg; p.o.; single dose) does not cause mortality in mongrel dogs, but induces gastrointestinal distress and inactivity[1].
Fluindarol (p.o.; once daily; 4 consecutive days) has a cumulative oral LD50 of 118 mg/kg in mongrel dogs after 4 consecutive daily doses, inducing drowsiness, anorexia, severe blood loss, and organ congestion[1].
Fluindarol (7-108 mg/kg; p.o.; once daily; 28 days) causes dose-dependent mortality (greater in females), severe anemia, organ hemorrhages, and liver necrosis in albino Wistar TNO rats, with total mortality reaching 47 out of 76 animals across all tested doses[1].
Fluindarol (13.5-54 mg/kg; p.o.; once daily; 28 days) causes dose-dependent mortality, hematological abnormalities, and liver necrosis in albino Wistar TNO rats, with 100% mortality observed at 54 mg/kg within 12 days[1].
Fluindarol (35 mg/kg; p.o.; once daily; 10 days) results in 40% mortality in albino Wistar TNO rats[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Albino Wistar TNO rat (young males and females, weight 90-120 g)[1]
Dosage: 100 mg/kg; 350 mg/kg
Administration: p.o.; single dose
Result: Determined acute oral LD50 as 198 mg/kg (95% confidence limits 161-244).
Determined acute oral LD10 as 100 mg/kg (95% confidence limits 73-160).
Observed greater mortality in female animals, with highest mortality on the 3rd day after administration and no deaths on the final 4 days of observation.
Animal Model: Albino Wistar TNO rat (young males and females, weight 90-120 g)[1]
Dosage: 100 mg/kg; 200 mg/kg
Administration: i.p.; single dose
Result: Determined acute intraperitoneal LD50 as 125 mg/kg (95% confidence limits 117-134).
Determined acute intraperitoneal LD10 as 113 mg/kg (95% confidence limits 103-124).
Observed no difference in mortality between males and females, with death occurring on the 1st and 2nd day after administration.
Animal Model: Mongrel dog (weight 3.5-10.7 kg)[1]
Dosage: 2810 mg/kg
Administration: p.o.; single dose
Result: Observed no mortality occurred.
Observed dogs exhibited vomiting, anorexia, blood-stained mucus in feces, and inactivity.
Animal Model: Albino Wistar TNO rat (males and females, starting weight 112-154 g [females], 140-199 g [males] in Experiment I; 76-101 g [females], 90-121 g [males] in Experiment II)[1]
Dosage: 108 mg/kg; 54 mg/kg; 27 mg/kg; 28 mg/kg; 14 mg/kg; 7 mg/kg
Administration: p.o.; once daily; 28 days
Result: Observed total mortality across all dose groups as 47 out of 76 rats, with females dying sooner and in greater numbers than males.
Observed clinical signs including blindness, white ears, shallow/irregular respiration, and weakness.
Detected severe anemia (erythrocyte counts <1 million/mm3 in some rats), reduced hemoglobin content, increased blood urea nitrogen levels, and burr-shaped erythrocytes in highest-dose groups via blood tests.
Identified extensive hemorrhages in subcutaneous tissue and organs, and liver parenchymal cell damage, necrosis, and inflammatory foci via post-mortem analysis, with severity and incidence increasing with dose.
Animal Model: Albino Wistar TNO rat (males and females)[1]
Dosage: 54 mg/kg; 27 mg/kg; 13.5 mg/kg
Administration: p.o.; once daily; 28 days
Result: Observed all rats receiving 54 mg/kg died within 12 days.
Observed 80% of rats receiving 27 mg/kg died within 28 days.
Observed 50% of rats receiving 13.5 mg/kg died within 28 days.
Observed clinical signs including weight loss 1-2 days before death, blindness, white ears/extremities, nasal/urinary blood loss, and weakness.
Detected anemia, reduced hemoglobin, increased blood urea nitrogen levels (up to 180 mg% in 27 mg/kg group), presence of myeloblasts, erythroblasts, multinucleated polynuclear erythroblasts, and burr-shaped erythrocytes, and rapid rises in SGPT and alkaline phosphatase values preceding death via blood tests.
Identified widespread organ hemorrhages, frequent haemothorax, and dose-related liver necrosis (highest incidence and severity in highest-dose groups) via post-mortem analysis.
Animal Model: Albino Wistar TNO rat (males and females, weight 90-120 g [females], 110-135 g [males])[1]
Dosage: 35 mg/kg
Administration: p.o.; once daily; 10 days
Result: Observed fluindarol caused death in 8 out of 20 rats (40% mortality) over the 10-day period.
Molecular Weight

290.24

Formula

C16H9F3O2
CAS No.
SMILES

O=C1C=2C=CC=CC2C(=O)C1C3=CC=C(C=C3)C(F)(F)F
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Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
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Keywords:

Fluindarol6723-40-6Biochemical Assay Reagentsorgan haemorrhagesdogsmongrel dogscumulative toxicityacute toxicityrabbitsratsliver parenchymal necrosistame rabbitsalbino Wistar TNO ratsInhibitorinhibitorinhibit

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