celiprolol

Names

[ Name ]:
celiprolol

[Synonym ]:
3-(3-Acetyl-4-{2-hydroxy-3-[(2-methyl-2-propanyl)amino]propoxy}phenyl)-1,1-diethylurea
3-{3-Acetyl-4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl}-1,1-diethylurea
CCRIS 3400
Celectol
3-<3-Acetyl-4-(3-tert-butylamino-2-hydroxy-propoxy)-phenyl>-1,1-diethylharnstoff
EINECS 260-497-7
Celiprololum [INN-Latin]
N-[3-acetyl-4-(3'-tert-butylamino-2'-hydroxy)propoxy]-phenyl-N'-diethylurea
Urea, N'-(3-acetyl-4-(3-((1,1-dimethylethyl)amino)-2-hydroxypropoxy)phenyl)-N,N-diethyl-
RHC-5320A
Urea, N'-[3-acetyl-4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]phenyl]-N,N-diethyl-
UL/1677
N-[3-Acetyl-4-(3'-tert-butylamino-2'-hydroxy)propoxy]phenyl-N'-diethylurea
celiprolol
UNII:DRB57K47QC
N'-[3-Acetyl-4-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]phenyl]-N,N-diethylurea
N'-(3-acetyl-4-(3-((1,1-dimethylethyl)-amino)-2-hydroxypropoxy)-phenyl)-N,N-diethylurea
MFCD00864577
[14C]-Celiprolol

Biological Activity

[Description]:

Celiprolol (REV 5320) is a potent, cardioselective and orally active β1-andrenoceptor r antagonist with partial β2 agonist activity, with Ki values of 0.14-8.3 μM. Celiprolol has antihypertensive and antianginal activity, and can be used for the research of cardiovascular disease such as high blood pressure[1][4].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Immunology/Inflammation >> NO Synthase

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

[Target]

Beta-adrenergic receptor:0.14-8.3 μM (Ki)

[In Vitro]

Celiprolol (0-3 mM, 90 min) is uptaken by human small intestinal transporter OATP-A/1A2 in Xenopus Laevis oocytes[5]. Celiprolol (10 μM, 0-50 min) is transported across human intestinal epithelial (Caco-2) cells by mediation of multiple transporters including P-glycoprotein[6].

[In Vivo]

Celiprolol (Oral administration, 100 mg/kg/day for 31 days) improves endothelial function in the arteries of in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, and restores it 4 weeks after endothelial denudation in the arteries of OLETF rats[2]. Celiprolol (Treated in drinking water, 10 mg/kg/day for 5 weeks) suppresses VCAM-1 expression by inhibition of oxidative stress, NF-κB, signal transduction, and increases eNOS via stimulation of the PI3K-Akt pathway, and improves cardiovascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats[3]. Animal Model: Type II male Otsuka Long-Evans Tokushima Fatty (OLETF) diabetic rats[2] Dosage: 100 mg/kg/day for 31 days Administration: Oral administration Result: Improved acetylcholine-induced NO-dependent relaxation in arteries. Improved tone-related basal NO release and acetylcholine-induced NO-dependent relaxation in the arteries and plasma NOx. Animal Model: Deoxycorticosterone acetate (DOCA)-salt hypertensive rats [3] Dosage: 10 mg/kg/d for 5 weeks Administration: Treated in drinking water Result: Activated phosphorylation of eNOS through the PI3K-Akt signaling pathway. Modulated VCAM-1 expression, which is associated with inhibition of NF-κB phosphorylation. Reduced production of ROS by suppressing NAD(P)H oxidase subunit p22phox, p47phox, gp91phox, and nox1 expression.

[References]

[1]. James J Nawarskas, et, al. Celiprolol: A Unique Selective Adrenoceptor Modulator. Cardiol Rev. Sep/Oct 2017; 25(5): 247-253.

[2]. Toshio Hayashi, et al. beta1 antagonist and beta2 agonist, celiprolol, restores the impaired endothelial dependent and independent responses and decreased TNFalpha in rat with type II diabetes. Life Sci. 2007 Jan 16;80(6):592-9.

[3]. Naohiko Kobayashi, et al. Celiprolol activates eNOS through the PI3K-Akt pathway and inhibits VCAM-1 Via NF-kappaB induced by oxidative stress. Hypertension. 2003 Nov;42(5):1004-13.

[4]. R G Van Inwegen, et al. Effects of celiprolol (REV 5320), a new cardioselective beta-adrenoceptor antagonist, on in vitro adenylate cyclase, alpha- and beta-adrenergic receptor binding and lipolysis. Arch Int Pharmacodyn Ther. 1984 Nov;272(1):40-55.

[5]. Yukio Kato, et al. Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci. 2009 Jul;98(7):2529-39.

[6]. J. Karlsson, et al. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein. Br J Pharmacol. 1993 Nov; 110(3): 1009–1016.

Chemical & Physical Properties

[ Density]:
1.1±0.1 g/cm3

[ Boiling Point ]:
586.5±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₀H₃₃N₃O₄

[ Molecular Weight ]:
379.494

[ Flash Point ]:
308.5±30.1 °C

[ Exact Mass ]:
379.247101

[ PSA ]:
90.90000

[ LogP ]:
1.92

[ Vapour Pressure ]:
0.0±1.7 mmHg at 25°C

[ Index of Refraction ]:
1.545

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: YR6555925

CHEMICAL NAME :: Urea, N'-(3-acetyl-4-(3-((1,1-dimethylethyl)amino)-2-hydrox ypropoxy)phenyl)-N,N- diethyl-

CAS REGISTRY NUMBER :: 56980-93-9

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C20-H33-N3-O4

MOLECULAR WEIGHT :: 379.56

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: 407 gm/kg/2Y-C

TOXIC EFFECTS :: Behavioral - food intake (animal) Nutritional and Gross Metabolic - weight loss or decreased weight gain

REFERENCE :: TOXID9 Toxicologist. (Soc. of Toxicology, Inc., 475 Wolf Ledge Parkway, Akron, OH 44311) V.1- 1981- Volume(issue)/page/year: 6,6,1986

celiprolol

Names

Biological Activity

Chemical & Physical Properties

Toxicological Information

CHEMICAL IDENTIFICATION

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

Safety Information

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Related Compounds