CAS 103177-37-3|Pranlukast

Introduction：Basic information about CAS 103177-37-3|Pranlukast, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Table of Contents

1. Names
2. Pranlukast BiologicalActivity
3. Chemical & Physical Properties
4. Toxicological Information
CHEMICAL IDENTIFICATION
HEALTH HAZARD DATA
ACUTE TOXICITY DATA
5. Safety Information
6. Synonyms

Common Name	Pranlukast
CAS Number	103177-37-3	Molecular Weight	481.503
Density	1.4±0.1 g/cm3	Boiling Point	/
Molecular Formula	C₂₇H₂₃N₅O₄	Melting Point	236-238ºC
MSDS	/	Flash Point	/

Names

Name	Pranlukast
Synonym	More Synonyms

Pranlukast BiologicalActivity

Description	Pranlukast is a highly potent, selective and competitive antagonist of peptide leukotrienes. Pranlukast inhibits [3H]LTE4, [3H]LTD4, and [3H]LTC4 bindings to lung membranes with Kis of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively.
Related Catalog	Signaling Pathways >>GPCR/G Protein >>Leukotriene ReceptorResearch Areas >>Inflammation/Immunology
Target	LTE4:0.63 nM (Ki) LTD4:0.99 nM (Ki) LTC4:5640 nM (Ki)
In Vitro	In the radioligand binding assay, Pranlukast (ONO-1078) inhibits [3H]LTE4, [3H]LTD4, and [3H]LTC4 bindings to lung membranes with Kis of 0.63±0.11, 0.99±0.19, and 5640±680 nM, respectively. The antagonism of Pranlukast against [3H]LTD4 binding is competitive. In functional experiments, Pranlukast shows competitive antagonism against the LTC4- and LTD4-induced contractions of guinea pig trachea and lung parenchymal strips with a pA2 range of 7.70 to 10.71. In the presence of an inhibitor of the bioconversion of LTC4 to LTD4, Pranlukast also antagonizes the LTC4-induced contraction of guinea pig trachea (pA2=7.78). Pranlukast significantly reverses the LTD4-induced prolonged contraction without effect on the KCl- and BaCl2-induced contractions of guinea pig trachea[1]. Oxygen-glucose deprivation (OGD)-induced nuclear translocation of CysLT1 receptors is inhibited by pretreatment with the CysLT1 receptor antagonist Pranlukast (10 μM). Pranlukast protects endothelial cells against ischemia-like injury. The effects of the CysLT1 receptor antagonist Pranlukast and the 5-lipoxygenase inhibitor Zileuton on translocation are also assessed. The results show that Pranlukast, but not Zileuton, inhibits the translocation of the CysLT1 receptor 6 h after OGD[2].
In Vivo	Carrageenan (CAR, 5 mg per mouse) is injected i.p. 24 h before LPS (50 p,g per mouse) is injected i.v. Various doses of Pranlukast (ONO-1078; 40, 20, and 10 mmol/kg), AA-861 (20, 10, and 5 mmol/kg), Indomethacin (40 mmollkg), and the controls are injected s.c. into mice 30 min before they are challenged with 50 p,g of LPS. The maximum soluble doses are 0.6 mmol/mL in 10% DMSO for AA-861 and 1.2 mmol/mL in 10% ethanol for Pranlukast. These solutions are used as the maximum doses for the treatments. The mortality of mice is significantly decreased in AA-861- Pranlukast-treated mice relative to that in the control mice. Pretreatment with CAR (5 mg i.p.) renders the mice more sensitive to the effect of LPS. Although the survival rate of mice treated with each solvent is 20% at 72 h after LPS (50 p,g per mouse) administration, s.c. treatment with AA-861 (20 mmol/kg) or Pranlukast (40 mmol/kg) significantly increases the survival rate after the LPS administration (AA-861, P<0.001; Pranlukast, P<0.01)[3].
Cell Assay	EA.hy926 cells are cultured in Dulbecco's modified Eagle's medium (DMEM), supplemented with 10% heat-inactivated fetal calf serum, Penicillin (100 U/mL) and Streptomycin (100 mg/mL). Experiments are conducted 24 h after cells are seeded. OGD is performed. Briefly, the original medium is removed; the cells are washed twice with glucose-free Earle's balanced salt solution (EBSS) and placed in fresh glucose-free EBSS. Cultures are then placed in an incubator containing 5% CO2 and 95% N2 at 37°C for 2 to 8 h. Control cultures are maintained in glucose-containing EBSS under normal conditions. 10 μM Pranlukast, 10 μM Zileuton, a 5-LOX inhibitor or 10 μM Pyrrolidine dithiocarbamate (PDTC), is added to the culture 30 min before OGD exposure and maintained during OGD[2].
Animal Admin	Mice[3] Male ddY mice are used. All mice used are 7 to 8 weeks of age. Endotoxin shock is induced in mice. In brief, CAR (5 mg in 0.5 mL of physiological saline) is injected intraperitoneally (i.p.) as a priming agent 24 h before LPS challenge. LPS (50 p,g in 0.5 mL of physiological saline) is injected intravenously into the tail vein as an inducing agent. The indicated doses of AA-861, Pranlukast (40, 20, and 10 mmol/kg), saline, DMSO, or ethanol are administrated subcutaneously (s.c.) in a volume of 1 mL into the backs of mice 30 min before the LPS provocation. Both drugs are injected s.c., because CAR i.p. pretreatment caused peritonitis. To examine the role of endogenous TNF in CAR pretreated mice, 2×105 U of rabbit anti-TNF-a antibody or normal serum of rabbit in 0.2 mL is injected intravenously (i.v.) before the LPS challenge[3].
References	[1]. Obata T, et al. In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues. Jpn J Pharmacol. 1992 Nov;60(3):227-37. [2]. Fang SH, et al. Nuclear translocation of cysteinyl leukotriene receptor 1 is involved in oxygen-glucose deprivation-induced damage to endothelial cells. Acta Pharmacol Sin. 2012 Dec;33(12):1511-7. [3]. Ogata M, et al. Protective effects of a leukotriene inhibitor and a leukotriene antagonist on endotoxin-induced mortality in carrageenan-pretreated mice. Infect Immun. 1992 Jun;60(6):2432-7.

Chemical & Physical Properties

Density	1.4±0.1 g/cm3
Melting Point	236-238ºC
Molecular Formula	C₂₇H₂₃N₅O₄
Molecular Weight	481.503
Exact Mass	481.175018
PSA	123.00000
LogP	3.88
Index of Refraction	1.681
InChIKey	NBQKINXMPLXUET-UHFFFAOYSA-N
SMILES	O=C(Nc1cccc2c(=O)cc(-c3nn[nH]n3)oc12)c1ccc(OCCCCc2ccccc2)cc1
Storage condition	Store at +4°C

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: CV5647500

CHEMICAL NAME :: Benzamide, N-(4-oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl)-4 -(4-phenylbutoxy)-, hemihydrate

CAS REGISTRY NUMBER :: 103177-37-3

LAST UPDATED :: 199312

DATA ITEMS CITED :: 10

MOLECULAR FORMULA :: C27-H23-N5-O4.1/2H2-O

MOLECULAR WEIGHT :: 490.52

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,197,1992

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >2 gm/kg

TOXIC EFFECTS :: 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: 44,197,1992

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >30 mg/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,197,1992

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,197,1992

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Subcutaneous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >2 gm/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,197,1992

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Intravenous

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: >30 mg/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,197,1992

TYPE OF TEST :: LD - Lethal dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: >3 gm/kg

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

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,197,1992 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 90 gm/kg/13W-C

TOXIC EFFECTS :: Blood - pigmented or nucleated red blood cells Blood - other changes Blood - changes in erythrocyte (RBC) count

REFERENCE :: OYYAA2 Oyo Yakuri. Pharmacometrics. (Oyo Yakuri Kenkyukai, CPO Box 180, Sendai 980-91, Japan) V.1- 1967- Volume(issue)/page/year: 44,245,1992

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Mammal - dog

DOSE/DURATION :: 360 gm/kg/52W-C

TOXIC EFFECTS :: Kidney, Ureter, Bladder - changes in bladder weight Nutritional and Gross Metabolic - changes in potassium 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: 44,263,1992 ** REPRODUCTIVE DATA **

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

DOSE :: 25 gm/kg

SEX/DURATION :: female 17-21 day(s) after conception lactating female 20 day(s) post-birth

TOXIC EFFECTS :: Reproductive - Maternal Effects - other effects Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: IYKEDH Iyakuhin Kenkyu. Study of Medical Supplies. (Nippon Koteisho Kyokai, 12-15, 2-chome, Shibuya, Shibuya-ku, Tokyo 150, Japan) V.1- 1970- Volume(issue)/page/year: 23,846,1992

Safety Information

Hazard Codes	F,C
Risk Phrases	R11
Safety Phrases	S16-S26-S36/37/39-S45

Synonyms

ONO RS-411

EINECS 201-616-4

N-[4-Oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl]-4-(4-phenylbutoxy)benzamide

8-[4-(4-Phenylbutoxy)benzamido]-2-(tetrazol-5-yl)-4H-1-benzopyran-4-one

Benzamide, N-(4-oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl)-4-(4-phenylbutoxy)-

N-(4-Oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl)-p-(4-phenylbutoxy)benzamide

N-(4-Oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl)-4-(4-phenylbutoxy)benzamide

N-[4-Oxo-2-(1H-tetrazol-5-yl)-4H-chromen-8-yl]-4-(4-phenylbutoxy)benzamide

Pranlukast

Benzamide, N-[4-oxo-2-(1H-tetrazol-5-yl)-4H-1-benzopyran-8-yl]-4-(4-phenylbutoxy)-

MFCD00864631

4-Oxo-8-(4-(4-phenylbutoxy)benzoylamino)-2-(tetrazol-5-yl)-4H-1-benzopyran

8-[p-(4-Phenylbutoxy)benzoyl]amino-2-(5-tetrazolyl)-4-oxo-4H-1-benzopyran

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