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42017-89-0

42017-89-0 structure
42017-89-0 structure
  • Name: Fenofibric acid
  • Chemical Name: fenofibric acid
  • CAS Number: 42017-89-0
  • Molecular Formula: C17H15ClO4
  • Molecular Weight: 318.752
  • Catalog: analytical chemistry Analytical reagent Ion chromatography reagent
  • Create Date: 2018-05-11 08:00:00
  • Modify Date: 2024-01-02 15:58:30
  • Fenofibric acid, an active metabolite of fenofibrate, is a PPAR activitor, with EC50s of 22.4 µM, 1.47 µM, and 1.06 µM for PPARα, PPARγ and PPARδ, respectively; Fenofibric acid also inhibits COX-2 enzyme activity, with an IC50 of 48 nM.

Name fenofibric acid
Synonyms Procetofenic acid
2-(4'-(p-chlorobenzoyl)phenoxy)-2-methylpropionic acid
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methyl-propanoic acid
Fibricor
Propanoic acid, 2-[4-(4-chlorobenzoyl)phenoxy]-2-methyl-
Fenofibric acid
Fenofibrate Related Compound B
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropanoic acid
Fenofibrate impurity B
EINECS 255-626-9
MFCD00792461
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropionic acid
2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropanoic acid
Description Fenofibric acid, an active metabolite of fenofibrate, is a PPAR activitor, with EC50s of 22.4 µM, 1.47 µM, and 1.06 µM for PPARα, PPARγ and PPARδ, respectively; Fenofibric acid also inhibits COX-2 enzyme activity, with an IC50 of 48 nM.
Related Catalog
Target

PPARδ:1.06 μM (EC50)

PPARγ:1.47 μM (EC50)

PPARα:22.4 μM (EC50)

COX-2:48 μM (IC50)

In Vitro Fenofibric acid is a PPAR activitor, with EC50s of 22.4 µM, 1.47 µM, and 1.06 µM for PPARα, PPARγ and PPARδ, respectively[1]. Fenofibric acid (10, 25, 50, 75, and 100 nM) dose-dependently inhibits COX-2 enzyme, with IC50 of 48 nM[2]. Fenofibric acid (500 nM) reduces abundance of AOX1 protein in HepG2 cells[3]. Fenofibric acid (100 µM) decreases JNK1/2, c-Jun, and p38 MAPK phosphorylation, and prevents the accumulation of reactive oxygen species, endoplasmic reticulum (ER) stress and disruption of blood retinal barrier (BRB) in response to the combination of high-glucose (HG) and hypoxia in ARPE-19 cells. Fenofibric acid (100 µM) activates IGF-IR/Akt/ERK1/2-mediated survival signaling pathways in ARPE-19 cells under HG conditions and hypoxia[4].
In Vivo Fenofibric acid (1, 5, 10 mg/kg, p.o.) shows anti-inflammatory activity in Wistar rats with acute inflammation induced by carrageenan[2].
Cell Assay ARPE-19 cells are cultured under normoglycemic (5.5 mM D-glucose) or hyperglycemic (25 mM D-glucose) conditions for 18 days at 37°C under 5% (v/v) CO2 in medium DMEM/F12 supplemented with 10% (v/v) fetal serum (FS) and penicillin/streptomycin. ARPE-19 cells are used and the media is changed every 3-4 days. The conditions tested are: (1) Control cells which are maintained in 5.5 mM D-glucose (normal glucose) for 18 days. (2) Cells cultured in 5.5 mM D-glucose treated with 100 µM Fenofibric acid for 72 h (days 16, 17, and 18; 1 application/day). (3) Cells cultured as in (1) or (2) and submitted to hypoxia (1% oxygen) for the last 6 or 24 h. (4) Cells maintained in 25 mM D-glucose (HG) for 18 days. (5) Cells cultured in 25 mM D-glucose treated with 100 µM Fenofibric acid for 72 h (days 16, 17, and 18; 1 application/day). (6)Cells cultured as in (4) or (5) and submitted to hypoxia (1% oxygen) for the last 6 or 24 h[4].
Animal Admin The anti-inflammatory activity of fenofibrate and its active metabolite fenofibric acid is assessed by injecting 0.1 mL of 1% carrageenan solution prepared in saline (sub-plantar) to the right hind paw of the rats. Rats are divided into 6 groups of six animals each. The first group serves as negative control and receives 1% tween-80 in distilled water, 10 mL/kg body mass. Group 2 and 3 receive a single dose of fenofibrate and standard drug diclofenac at 10 mg/kg body mass, whereas groups 4, 5, and 6 receive 3 doses of Fenofibric acid at 1, 5, and 10 mg/kg body mass, respectively. All the drugs are given orally using gavages 60 min before the injection of 0.1 mL of 1% carrageenan through sub-plantar route. The volume of oedema of test and control groups is measured using plethysmometer at 0, 1, 2, and 3 h after induction of inflammation[2].
References

[1]. Dietz M, et al. Comparative molecular profiling of the PPARα/γ activator aleglitazar: PPAR selectivity, activity and interaction with cofactors. ChemMedChem. 2012 Jun;7(6):1101-11.

[2]. Prasad GS, et al. Anti-inflammatory activity of anti-hyperlipidemic drug, fenofibrate, and its phase-I metabolite fenofibric acid: in silico, in vitro, and in vivo studies. Inflammopharmacology. 2017 Dec 13.

[3]. Neumeier M, et al. Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro. Biochem Biophys Res Commun. 2006 Nov 24;350(3):731-5. Epub 2006 Sep 27.

[4]. Miranda S, et al. Beneficial effects of fenofibrate in retinal pigment epithelium by the modulation of stress and survival signaling under diabetic conditions. J Cell Physiol. 2012 Jun;227(6):2352-62.

Density 1.3±0.1 g/cm3
Boiling Point 486.5±35.0 °C at 760 mmHg
Melting Point 176--179ºC
Molecular Formula C17H15ClO4
Molecular Weight 318.752
Flash Point 248.0±25.9 °C
Exact Mass 318.065887
PSA 63.60000
LogP 3.86
Vapour Pressure 0.0±1.3 mmHg at 25°C
Index of Refraction 1.585
Storage condition -20°C Freezer

SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name: Fenofibric acid
REACH No.: A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No.: 42017-89-0
Relevant identified uses of the substance or mixture and uses advised against
Identified uses: Laboratory chemicals, Manufacture of substances



SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
Acute aquatic toxicity (Category 1), H400
Chronic aquatic toxicity (Category 1), H410
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xn, N Harmful, Dangerous for the R22, R50/53
environment
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal wordWarning
Hazard statement(s)
H302Harmful if swallowed.
H410Very toxic to aquatic life with long lasting effects.
Precautionary statement(s)
P273Avoid release to the environment.
P501Dispose of contents/ container to an approved waste disposal plant.
Supplemental Hazardnone
Statements
Other hazards - none

SECTION 3: Composition/information on ingredients
Substances
Formula: C17H15ClO4
Molecular Weight: 318,75 g/mol
CAS-No.: 42017-89-0
EC-No.: 255-626-9
Hazardous ingredients according to Regulation (EC) No 1272/2008
ComponentClassificationConcentration
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropionic acid
CAS-No.42017-89-0Acute Tox. 4; Aquatic Acute 1;<= 100 %
EC-No.255-626-9Aquatic Chronic 1; H302,
H410
Hazardous ingredients according to Directive 1999/45/EC
ComponentClassificationConcentration
2-[4-(4-Chlorobenzoyl)phenoxy]-2-methylpropionic acid
CAS-No.42017-89-0Xn, N, R22 - R50/53<= 100 %
EC-No.255-626-9
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
Indication of any immediate medical attention and special treatment needed
no data available

SECTION 5: Firefighting measures
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, Hydrogen chloride gas
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

SECTION 6: Accidental release measures
Personal precautions, protective equipment and emergency procedures
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the
environment must be avoided.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. Keep in suitable, closed
containers for disposal.
Reference to other sections
For disposal see section 13.

SECTION 7: Handling and storage
Precautions for safe handling
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Specific end use(s)
Apart from the uses mentioned in section 1.2 no other specific uses are stipulated

SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 Use equipment for eye protection tested
and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into
the environment must be avoided.

SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) AppearanceForm: powder
Colour: white
b) Odourno data available
c) Odour Thresholdno data available
d) pHno data available
e) Melting point/freezingno data available
point
f) Initial boiling point and no data available
boiling range
g) Flash pointno data available
h) Evapouration rateno data available
i) Flammability (solid, gas) no data available
j) Upper/lowerno data available
flammability or
explosive limits
k) Vapour pressureno data available
l) Vapour densityno data available
m) Relative densityno data available
n) Water solubilityno data available
o) Partition coefficient: n- log Pow: 3,895
octanol/water
p) Auto-ignitionno data available
temperature
q) Decompositionno data available
temperature
r) Viscosityno data available
s) Explosive propertiesno data available
t) Oxidizing propertiesno data available
Other safety information
no data available

SECTION 10: Stability and reactivity
Reactivity
no data available
Chemical stability
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

SECTION 11: Toxicological information
Information on toxicological effects
Acute toxicity
LD50 Oral - rat - 1.242 mg/kg
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
Germ cell mutagenicity
no data available
Carcinogenicity
IARC:No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Additional Information
RTECS: UA2453000
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

SECTION 12: Ecological information
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
Other adverse effects
Very toxic to aquatic life with long lasting effects.

SECTION 13: Disposal considerations
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
Contaminated packaging
Dispose of as unused product.

SECTION 14: Transport information
UN number
ADR/RID: 3077IMDG: 3077IATA: 3077
UN proper shipping name
ADR/RID: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (2-[4-(4-
Chlorobenzoyl)phenoxy]-2-methylpropionic acid)
IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (2-[4-(4-
Chlorobenzoyl)phenoxy]-2-methylpropionic acid)
IATA:Environmentally hazardous substance, solid, n.o.s. (2-[4-(4-Chlorobenzoyl)phenoxy]-2-
methylpropionic acid)
Transport hazard class(es)
ADR/RID: 9IMDG: 9IATA: 9
Packaging group
ADR/RID: IIIIMDG: IIIIATA: III
Environmental hazards
ADR/RID: yesIMDG Marine pollutant: yesIATA: yes
Special precautions for user
Further information
EHS-Mark required (ADR 2.2.9.1.10, IMDG code 2.10.3) for single packagings and combination
packagings containing inner packagings with Dangerous Goods > 5L for liquids or > 5kg for solids.



SECTION 15 - REGULATORY INFORMATION
N/A


SECTION 16 - ADDITIONAL INFORMATION
N/A

CHEMICAL IDENTIFICATION

RTECS NUMBER :
UA2453000
CHEMICAL NAME :
Propanoic acid, 2-(4-(4-chlorobenzoyl)phenoxy)-2-methyl-
CAS REGISTRY NUMBER :
42017-89-0
LAST UPDATED :
199612
DATA ITEMS CITED :
4
MOLECULAR FORMULA :
C17-H15-Cl-O4
MOLECULAR WEIGHT :
318.77

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 :
1242 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
DRFUD4 Drugs of the Future. (J.R. Prous, S.A., Apartado de Correos 540, 08080 Barcelona, Spain) V.1- 1975/76- Volume(issue)/page/year: 7,229,1982
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intravenous
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
313 mg/kg
TOXIC EFFECTS :
Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - pleural thickening
REFERENCE :
YACHDS Yakuri to Chiryo. Pharmacology and Therapeutics. (Raifu Saiensu Shuppan K.K., 2-5-13, Yaesu, Chuo-ku, Tokyo 104, Japan) V.1- 1972- Volume(issue)/page/year: 23(Suppl 4),S873,1995
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
1200 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: 26,885,1976
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
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: 26,885,1976
Symbol GHS07 GHS09
GHS07, GHS09
Signal Word Warning
Hazard Statements H302-H410
Precautionary Statements P273-P501
Hazard Codes Xn,N
Risk Phrases R36/37/38
Safety Phrases 26-36/37/39
RIDADR UN 3077 9 / PGIII
RTECS UA2453000
HS Code 2918990090

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Literature: AMPLA PHARMACEUTICALS INC. Patent: WO2009/73138 A2, 2009 ; Location in patent: Page/Page column 81-82 ; WO 2009/073138 A2

~72%

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Literature: SIGNATURE PHARMACEUTICALS, LLC Patent: WO2005/46575 A2, 2005 ; Location in patent: Page/Page column 176-177 ;

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Literature: Davis, Roman D.; Fitzgerald, Russ N.; Guo, Jiasheng Synthesis, 2004 , # 12 p. 1959 - 1962

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Literature: Mattsson, Sara; Dahlstroem, Mikael; Karlsson, Staffan Tetrahedron Letters, 2007 , vol. 48, # 14 p. 2497 - 2499

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Literature: Labor. Fournier Patent: FR2300552DE2605382 , 19761976 ; Chem.Abstr., 1976 , vol. 85, # 192382

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Literature: Labor. Fournier Patent: FR2300552DE2605382 , 19761976 ; Chem.Abstr., 1976 , vol. 85, # 192382
HS Code 2918990090
Summary 2918990090. other carboxylic acids with additional oxygen function and their anhydrides, halides, peroxides and peroxyacids; their halogenated, sulphonated, nitrated or nitrosated derivatives. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%