56980-93-9

Basic information

• Product Name: Celiprolol
• Synonyms: celiptolol;-diethyl-;n’-(3-acetyl-4-(3-((1,1-dimethylethyl)amino)-2-hydroxypropoxy)phenyl)-n,n-di;3-[3-acetyl-4-(2-hydroxy-3-tert-butylamino-propoxy)-phenyl]-1,1-diethyl-urea;CELIPROLOL;Celiprolol Base;CELIPROLOLHYDROCHLORIDE(SUBJECTTOPANTENTFREE);(R,S)-Celiprolol
• CAS NO: 56980-93-9
• Molecular Formula: C₂₀H₃₃N₃O₄
• Molecular Weight: 379.49
• EINECS: 260-497-7
• Mol File: 56980-93-9.mol
• Article Data: 8

Chemical Properties

• Melting Point: 110-112°
• Boiling Point: 586.5 °C at 760 mmHg
• Flash Point: 308.5 °C
• Appearance: /
• Density: 1.114 g/cm³
• Vapor Pressure: 1.34E-14mmHg at 25°C
• Refractive Index: 1.545
• Storage Temp.: -20°C Freezer, Under Inert Atmosphere
• Solubility: Chloroform (slightly), Methanol (Slightly)
• PKA: pKa ～9.7 (Uncertain)
• Water Solubility: 22.9mg/L(22.5 oC)
• CAS DataBase Reference: Celiprolol(CAS DataBase Reference)
• NIST Chemistry Reference: Celiprolol(56980-93-9)
• EPA Substance Registry System: Celiprolol(56980-93-9)

Safety Data

• Hazardous Substances Data: 56980-93-9(Hazardous Substances Data)

Usage

Originator

Selectol,Chemie Linz,Austria,1983

Uses

Celiprolol is an intermediate in the synthesis of Celiprolol Hydrochloride (C254500). Celiprolol is a cardioselective β1-adrenergic blocker. Antihypertensive, antianginal.

Manufacturing Process

3-Acetyl-4-hydroxyaniline, in solution in pyridine, is reacted with dimethylcarbamoyl chloride at room temperature to give N-(3-acetyl-4- hydroxy)phenyl-N'-dimethylurea, which after evaporating the pyridine, taking up the residue in chloroform and evaporating the latter, is obtained in a crystalline form. Melting point: 160°-162°C. After reaction of the product in alkaline aqueous solution, with epichlorohydrin, N-[3-acetyl-4-(2',3'-epoxy)- propoxy]-phenyl-N'-dimethylurea (melting point: 98°-102°C) is obtained, and this, in turn, is reacted with excess tert-butylamine in aqueous solution at room temperature to give N-[3-acetyl-4-(3'-tert-butylamino-2'-hydroxy)- propoxy)-phenyl-N'-dimethylurea of melting point: 120°-122°C.

Therapeutic Function

Beta-adrenergic blocker

InChI:InChI=1/C20H33N3O4/c1-7-23(8-2)19(26)22-15-9-10-18(17(11-15)14(3)24)27-13-16(25)12-21-20(4,5)6/h9-11,16,21,25H,7-8,12-13H2,1-6H3,(H,22,26)

Upstream product

• 75-64-9 tert-butylamine 
• 85045-98-3 3-<3-Acetyl-4-(3-brom-2-hydroxy-propoxy)-phenyl>-1,1-diethylharnstoff 
• 329722-32-9 1-{2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-nitrophenyl}ethan-1-one 
• 329722-31-8 1-[5-nitro-2-(oxiran-2-ylmethoxy)phenyl]ethan-1-one 
• 1450-76-6 1-(2-hydroxy-5-nitrophenyl)ethanone 
• 56980-94-0 1-{5-amino-2-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl}ethan-1-one 
• 88-10-8 N,N-diethylcarbamyl chloride 
• 100-02-7 4-nitro-phenol 
• 13871-68-6 p-aminophenyl acetate 
• 830-03-5 4-nitrophenol acetate 
• 100-00-5 4-chlorobenzonitrile 
• 56980-98-4 N'-(3-acetyl-4-(2,3-epoxypropoxy)phenyl)-N,N-diethylurea 
• 1357457-94-3 4-(3,3-diethylureido)phenyl acetate 
• 79881-89-3 3-(3-Acetyl-4-hydroxy-phenyl)-1,1-diethylharnstoff 

Downstream Products

• 57470-78-7 (+/-)-celiprolol hydrochloride 

Relevant articles and documents

An improved synthesis of a b-blocker celiprolol hydrochloride

Celiprolol hydrochloride, a β-blocker drug, has been synthesised from 4-chloronitrobenzene. The route involved hydrolysis of the chloride and acetylation of the phenol, reduction of the nitro group, and acylation of theamine. This was followed by Fries rearrangement of the acetyl group, Williamson etherification with epichlorohydrin, followed by opening of the epoxide ring and salt formation. The overall yield of celipropol was 39.1% on the basis of 4-chloronitrobenzene. The Fries rearrangement was substantially improved. The process is suitable for industrial application because of its convenient and environmentally friendly reaction conditions.

ANTIHYPERTENSIVE THERAPY

A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.

Method for treating resistant hypertension

A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.