Niflumic acid

Names

[ Name ]:
Niflumic acid

[Synonym ]:
EINECS 224-516-2
MFCD00010569
2-(3-Trifluoromethyl-phenylamino)-; nicotinic acid
3-Pyridinecarboxylic acid, 2-[[3-(trifluoromethyl)phenyl]amino]-
Niflumic acid
2-(a,a,a-Trifluoro-m-toluidino)nicotinic Acid
2-{[3-(Trifluoromethyl)phenyl]amino}nicotinic acid
2-[[3-(Trifluoromethyl)phenyl]amino]-3-pyridinecarboxylic Acid
2-(3-TrifluoroMethylanilino)nicotinic Acid
2-((3-(Trifluoromethyl)phenyl)amino)nicotinic acid
2-[3-(trifluoromethyl)anilino]pyridine-3-carboxylic acid
2-[(3-Trifluoromethylphenyl)amino]nicotinic Acid

Biological Activity

[Description]:

Niflumic acid, a Ca2+-activated Cl- channel blocker, is an analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.Target: Othersniflumic acid, an inhibitor of calcium-activated chloride currents. Niflumic acid does not block directly calcium channels or activate potassium channels. Niflumic acid selectively reduces a component of noradrenaline- and 5-HT-induced pressor responses by inhibiting a mechanism which leads to the opening of voltage-gated calcium channels [1]. Niflumic acid molecule is completely buried in the substrate-binding hydrophobic channel. The conformations of the binding site in PLA(2) as well as that of niflumic acid are not altered upon binding [2]. Niflumic acid (NFA) produces biphasic behavior on human CLC-K channels that suggests the presence of two functionally different binding sites: an activating site and a blocking site [3].

[Related Catalog]:

Signaling Pathways >> Membrane Transporter/Ion Channel >> Chloride Channel

Research Areas >> Inflammation/Immunology

[References]

[1]. Criddle, D.N., et al., Inhibitory action of niflumic acid on noradrenaline- and 5-hydroxytryptamine-induced pressor responses in the isolated mesenteric vascular bed of the rat. Br J Pharmacol, 1997. 120(5): p. 813-8.

[2]. Jabeen, T., et al., Non-steroidal anti-inflammatory drugs as potent inhibitors of phospholipase A2: structure of the complex of phospholipase A2 with niflumic acid at 2.5 Angstroms resolution. Acta Crystallogr D Biol Crystallogr, 2005. 61(Pt 12): p. 1579-

[3]. Picollo, A., et al., Mechanism of interaction of niflumic acid with heterologously expressed kidney CLC-K chloride channels. J Membr Biol, 2007. 216(2-3): p. 73-82.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
378.0±42.0 °C at 760 mmHg

[ Melting Point ]:
203-204ºC

[ Molecular Formula ]:
C₁₃H₉F₃N₂O₂

[ Molecular Weight ]:
282.218

[ Flash Point ]:
182.4±27.9 °C

[ Exact Mass ]:
282.061615

[ PSA ]:
62.22000

[ LogP ]:
4.94

[ Vapour Pressure ]:
0.0±0.9 mmHg at 25°C

[ Index of Refraction ]:
1.589

[ Storage condition ]:
Store at RT

[ Water Solubility ]:
Soluble in ethanol (~50 mg/ml), acetone (50 mg/ml, Clear to Slightly Hazy, Yellow), methanol (~50 mg/ml), DMSO (56 mg/ml at 25°C), and acetonitrile (~50 mg/ml).

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: QT2999100

CHEMICAL NAME :: Nicotinic acid, 2-(alpha,alpha,alpha-trifluoro-m-toluidino)-

CAS REGISTRY NUMBER :: 4394-00-7

BEILSTEIN REFERENCE NO. :: 0489360

LAST UPDATED :: 199612

DATA ITEMS CITED :: 6

MOLECULAR FORMULA :: C13-H9-F3-N2-O2

MOLECULAR WEIGHT :: 282.24

WISWESSER LINE NOTATION :: T6NJ BMR CXFFF& CVQ

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 :: 250 mg/kg

TOXIC EFFECTS :: Behavioral - analgesia Biochemical - Metabolism (Intermediary) - effect on inflammation or mediation of inflammation

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 16,780,1973

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 155 mg/kg

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

REFERENCE :: JMCMAR Journal of Medicinal Chemistry. (American Chemical Soc., Distribution Office Dept. 223, POB POB 57136, West End Stn., Washington, DC 20037) V.6- 1963- Volume(issue)/page/year: 19,135,1976

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

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 350 mg/kg

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

REFERENCE :: USXXAM United States Patent Document. (U.S. Patent Office, Box 9, Washington, DC 20231) Volume(issue)/page/year: #4122202

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 196 mg/kg

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

REFERENCE :: NYKZAU Nippon Yakurigaku Zasshi. Japanese Journal of Pharmacology. (Nippon Yakuri Gakkai, c/o Kyoto Daigaku Igakubu Yakurigaku Kyoshitsu, Konoe-cho, Yoshida, Sakyo-ku, Kyoto 606, Japan) V.40- 1944- Volume(issue)/page/year: 68,683,1972

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

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 152 mg/kg

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

REFERENCE :: THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946- Volume(issue)/page/year: 22,157,1967 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 100 mg/kg

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

TOXIC EFFECTS :: Reproductive - Fertility - other measures of fertility

REFERENCE :: FESTAS Fertility and Sterility. (American Fertility Soc., 608 13th Ave. S, Birmingham, AL 35282) V.1- 1950- Volume(issue)/page/year: 38,238,1982

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302 + H312 + H332-H315-H319-H335

[ Precautionary Statements ]:
P261-P280-P301 + P312 + P330-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ Hazard Codes ]:
Xn:Harmful;

[ Risk Phrases ]:
R20/21/22;R36/37/38

[ Safety Phrases ]:
S26-S36/37/39

[ RIDADR ]:
UN 2811 6.1/PG 3

[ WGK Germany ]:
3

[ RTECS ]:
QT2999100

[ Packaging Group ]:
Ⅲ

[ HS Code ]:
2933399090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2933399090

[ Summary ]:
2933399090. other compounds containing an unfused pyridine 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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