Ibudilast

Bezeichnung:Ibudilast

CAS-Nr50847-11-5

Englisch Name:Ibudilast

CBNumberCB0145945

SummenformelC14H18N2O

Molgewicht230.31

MOL-Datei50847-11-5.mol

Ibudilast physikalisch-chemischer Eigenschaften

Schmelzpunkt	53-54°C
Siedepunkt	175°C/7.5mmHg(lit.)
Dichte	1.09
Brechungsindex	1.5500 (estimate)
storage temp.	Sealed in dry,2-8°C
Löslichkeit	DMSO: 28 mg/mL, soluble
pka	1.22±0.30(Predicted)
Aggregatzustand	solid
Farbe	white
Merck	14,4879
Stabilität	Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 3 months.
InChI	InChI=1S/C14H18N2O/c1-9(2)13-12(14(17)10(3)4)11-7-5-6-8-16(11)15-13/h5-10H,1-4H3
InChIKey	ZJVFLBOZORBYFE-UHFFFAOYSA-N
SMILES	C(C1=C2N(N=C1C(C)C)C=CC=C2)(=O)C(C)C
CAS Datenbank	50847-11-5(CAS DataBase Reference)

Sicherheit

Kennzeichnung gefährlicher	Xn
R-Sätze:	22-36/37/38
S-Sätze:	26-36
WGK Germany	3
RTECS-Nr.	UR0711200
HS Code	2933.99.8290
Speicherklasse	11 - Combustible Solids
Hazard Classifications	Acute Tox. 4 Oral Eye Irrit. 2 Skin Irrit. 2 STOT SE 3
Toxizität	LD50 i.v. in mice: 260 mg/kg (Irikura, 1973)

Gefahreninformationscode (GHS)

Ibudilast Chemische Eigenschaften,Einsatz,Produktion Methoden

R-Sätze Betriebsanweisung:
R22:Gesundheitsschädlich beim Verschlucken.
R36/37/38:Reizt die Augen, die Atmungsorgane und die Haut.
S-Sätze Betriebsanweisung:
S26:Bei Berührung mit den Augen sofort gründlich mit Wasser abspülen und Arzt konsultieren.
S36:DE: Bei der Arbeit geeignete Schutzkleidung tragen.
Beschreibung
Ibudilast is a leukomene antagonist and phosphodiesterase inhibitor useful in the treatment of bronchial asthma. It antagonizes leukotriene D4-induced contractions of guinea pig ileum and tracheal muscles in virro, and inhibits eosinophil accumulation in vivo.
Chemische Eigenschaften
White Solid
Originator
Kyorin (Japan)
Verwenden
a phosphodiesterase inhibitor with anti-inflammatory activity
Verwenden
A leukotriene D4 antagonist. Used as an antiallergic, antiasthmatic, and vasodilator (cerebral)
Verwenden
Inhibitors of phosphodiesterase 4 (PDE4), which catalyzes the hydrolysis of cAMP, have potential applications in a variety of diseases, including asthma. Ibudilast is an inhibitor of PDE4 (IC50 = 54-239 nM) that, at higher doses, also inhibits PDE3 and PDE5 (IC50 = 1,600-3,510 nM). Through this action, it suppresses the elaboration of mediators involved in asthma and inflammation.[Cayman Chemical]
Definition
ChEBI: Ibudilast is a pyrazolopyridine.
Trademarks
Ketas
Biologische Aktivität
Phosphodiesterase inhibitor (IC 50 values are 53, 35, 48, 12 and 10 mM for PDE Ia, II, III, IV and V respectively). Inhibits platelet aggregation and is an orally-active cerebral vasodilator, bronchodilator and antiallergic agent.
Biochem/physiol Actions
Phosphodiesterase IV (PDE4) inhbitor. Inhibits platelet aggregation. Anti-asthma drug.
Synthese

7583-90-6

97-72-3

50847-11-5

59942-84-6

(b) Synthesis of 1-(2-isopropylpyrazolo[1,5-α]pyridin-3-yl)-2-methylpropan-1-one. The dried 1-amino-2-methylpyridinium iodide salt (113 g) from step (a) was suspended in isobutyric anhydride (515 g) in a round-bottomed flask fitted with a mechanical stirrer, followed by the addition of potassium carbonate (85 g) under stirring. The reaction mixture was heated to reflux for 8 h. After cooling to room temperature, water (10 mL) was added and potassium carbonate (10 g) was added in batches. After the initial vigorous reaction subsided, water (500 mL) and ethyl acetate (500 mL) were added, followed by the addition of potassium carbonate (280 g) in batches while continuous mechanical stirring was used to control foaming. The mixture was stirred at room temperature for 1 h. 50% sodium hydroxide solution (50 mL) was added and extracted with ethyl acetate (4 x 250 mL). The organic phases were combined and the solvents were evaporated to give a viscous oil, which was separated by high-vacuum distillation to give 25.2 g (32.9% yield) of 2-isopropylpyrazolo[1,5-α]pyridine (boiling point 45-75 °C/0.25-0.5 mmHg) and 60.4 g (51.3% yield) of 1-(2-isopropylpyrazolo[1,5-α]pyridin-3-yl)-2-methyl propan-1-one (boiling point 125-135°C/0.1 mmHg; melting point 53-55°C) (T. Irikura et al., U.S. Patent 3,850,941, November 26, 1974)
in vitro
ibudilast could potently inhibit purified human pde4a, 4b, 4c and 4d with ic50 values at 54, 65, 239 and 166 nm, respectively. ibudilast was also able to effectively block lps-induced tumor necrosis factor and n-formyl-metleu-phe-induced leukotriene b4 biosynthesis in human whole blood [1].
in vivo
rats received a daily oral administration of 10, 30 or 60 mg/kg ibudilast. results showed that in the vehicle-treated animals, white matter lesions and microglial activation occurred in the optic tract, internal capsule and corpus callosum. a low dose of ibudilast failed to suppress the white matter lesions and microglial activation, whereas a dose of either 30 or 60 mg/kg ibudilast ameliorated these lesions [2].
IC 50
54-239 nm
Lager
Store at RT
Einzelnachweise
[1] Y. KISHI. Ibudilast: a non-selective PDE inhibitor with multiple actions on blood cells and the vascular wall.[J]. Cardiovascular drug reviews, 2006, 5 1: 215-225. DOI:10.1111/j.1527-3466.2001.tb00066.x
[2] TAKANOBU YAMAZAKI Shigeki M Tsuyoshi Anraku. Ibudilast, a mixed PDE3/4 inhibitor, causes a selective and nitric oxide/cGMP-independent relaxation of the intracranial vertebrobasilar artery[J]. European journal of pharmacology, 2011, 650 2: Pages 605-611. DOI:10.1016/j.ejphar.2010.10.033
[3] JORGE L. CUEVA VARGAS Adriana D P Nicolas Belforte. The glial cell modulator ibudilast attenuates neuroinflammation and enhances retinal ganglion cell viability in glaucoma through protein kinase A signaling[J]. Neurobiology of Disease, 2016, 93: Pages 156-171. DOI:10.1016/j.nbd.2016.05.002
[4] TETSUYA MIZUNO . Neuroprotective role of phosphodiesterase inhibitor ibudilast on neuronal cell death induced by activated microglia[J]. Neuropharmacology, 2004, 46 3: Pages 404-411. DOI:10.1016/j.neuropharm.2003.09.009
[5] ANNEMARIE LEDEBOER. Ibudilast (AV-411). A new class therapeutic candidate for neuropathic pain and opioid withdrawal syndromes.[J]. Expert opinion on investigational drugs, 2007, 16 7: 935-950. DOI:10.1517/13543784.16.7.935

Ibudilast Upstream-Materialien And Downstream Produkte

Ibudilast Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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