Fenspiride

Names

[ Name ]:
Fenspiride

[Synonym ]:
8-phenethyl-1-oxa-3,8-diaza-spiro[4.5]decan-2-one
1-Oxa-3,8-diazaspiro[4.5]decan-2-one, 8-(2-phenylethyl)-
Fluiden
Fenspiridum [INN-Latin]
Fenspiride [INN]
EINECS 225-751-3
Viarespan
1-Oxa-3,8-diazaspiro[4.5]dec-2-en-2-ol, 8-(2-phenylethyl)-
8-(2-Phenylethyl)-1-oxa-3,8-diazaspiro[4.5]decan-2-one
Fenspiride
Respiride
Fenspirida [INN-Spanish]

Biological Activity

[Description]:

Fenspiride, an orally active non-steroidal antiinflammatory agent, is an antagonist of H1-histamine receptor. Fenspiride inhibites phosphodiesterase 3 (PDE3), phosphodiesterase 4 (PDE4) and phosphodiesterase 5 (PDE5) activities with -log IC50 values of 3.44, 4.16 and approximately 3.8, respectively. Fenspiride can be used for the research of respiratory diseases[1][2][3].

[Related Catalog]:

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Signaling Pathways >> Metabolic Enzyme/Protease >> Phosphodiesterase (PDE)

Research Areas >> Inflammation/Immunology

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

[Target]

-log IC50: 3.44 (PDE3); 4.16 (PDE4); approximately 3.8 (PDE5)[2]

[In Vitro]

Fenspiride (around 100 μM) inhibits histamine-induced contraction of isolated guinea pig trachea[2]. Fenspiride (≤1000 μM) produces less than 25% inhibition of phosphodiesterase 1 and phosphodiesterase 2 activities[2].

[In Vivo]

Fenspiride (60 mg/kg; p.o. for 3 days) reduces the lipopolysaccharide-induced early rise of tumor necrosis factor concentrations in serum and in the bronchoalveolar lavage fluid (BALF) of the model of endotoxemia[3]. Fenspiride (60 mg/kg; p.o. for 3 days) reduces the lipopolysaccharide-induced primed stimulation of alveolar macrophages[3]. Fenspiride (60 mg/kg; p.o. for 3 days) reduces the increased serum concentrations of extracellular type II phospholipase A 2, the intensity of the neutrophilic alveolar invasion and the lethality due to the lipopolysaccharide[3]. Animal Model: Lipopolysaccharide-treated Male Dunkin-Hartley guinea-pigs weighing 400-600 g[3] Dosage: 60 mg/kg Administration: orally for 3 days; pretreated Result: Reduced the lipopolysaccharide-induced early rise of tumor necrosis factor concentrations in serum (4.2 vs. 2.3 ng/ml) and in the BALF (55.7 vs. 19.7 ng/ml). Reduced the lipopolysaccharide-induced primed stimulation of alveolar macrophages, (1551.5 vs 771.5 pg/μg protein, P<0.05 for thromboxane B2 and 12.6 vs. 3.6 pg/μg protein, P<0.05 for leukotriene C4). Reduced the increased serum concentrations of extracellular type II phospholipase A 2 (3.9 vs. 1.2 nmol/ml per min), the intensity of the neutrophilic alveolar invasion and the lethality due to the lipopolysaccharide.

[References]

[1]. Matuszewska A, et al. Long-term administration of fenspiride has no negative impact on bone mineral density and bone turnover in young growing rats. Adv Clin Exp Med. 2019 Jun;28(6):771-776.

[2]. Cortijo J, et al. Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: functional and biochemical study. Eur J Pharmacol. 1998 Jan 2;341(1):79-86.

[3]. De Castro CM, et al. Fenspiride: an anti-inflammatory drug with potential benefits in the treatment of endotoxemia. Eur J Pharmacol. 1995 Dec 29;294(2-3):669-76.

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
408.3±55.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₅H₂₀N₂O₂

[ Molecular Weight ]:
260.332

[ Flash Point ]:
200.7±31.5 °C

[ Exact Mass ]:
260.152466

[ PSA ]:
41.57000

[ LogP ]:
1.91

[ Vapour Pressure ]:
0.0±1.0 mmHg at 25°C

[ Index of Refraction ]:
1.609

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: RO0373000

CHEMICAL NAME :: 1-Oxa-3,8-diazaspiro(4.5)decan-2-one, 8-phenethyl-

CAS REGISTRY NUMBER :: 5053-06-5

LAST UPDATED :: 199712

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C15-H20-N2-O2

MOLECULAR WEIGHT :: 260.37

WISWESSER LINE NOTATION :: T6N CXTJ A2R& C-& DT5MVOX EHJ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

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

ROUTE OF EXPOSURE :: Intraperitoneal

SPECIES OBSERVED :: Rodent - mouse

DOSE/DURATION :: 230 mg/kg

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

REFERENCE :: CHTPBA Chimica Therapeutica. (Paris, France) V.1-8, 1965-73. For publisher information, see EJMCA5. Volume(issue)/page/year: 4,185,1969

Safety Information

[ HS Code ]:
2934999090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2934999090

[ Summary ]:
2934999090. other heterocyclic compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Related Compounds

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