38363-40-5

Usage

Originator

Betapressin, Hoechst , W. Germany ,1980

Uses

Anti-adrenergic (β-receptor).

Manufacturing Process

21.8 g (0.1 mol) of 1,2-epoxy-3-(2'-cyclopentylphenoxy)propane, boiling at 113°C to 115°C/0.2 mm Hg (prepared from 2-cyclopentylphenol and epichlorhydrin in the presence of alkali) were dissolved in 250 ml of ethanol; to this solution, there were added dropwise, while stirring.8.9 g (0.15 mol) of t-butylamine. The reaction mixture was stirred for 2 hours at 60°C and then the solvent and the excess t-butylamine were removed by distillation. The residue which had been purified via the aqueous hydrochloride, crystallized, after removal of the ether by evaporation, upon rubbing or inoculation and yielded, after recrystallization from n-heptane, the 1-t-butylamino-2-hydroxy3-(2'-cyclopentylphenoxy)propane which was found to melt at 69°C to 70°C.

Brand name

Levatol(Schwarz Pharma).

Therapeutic Function

Beta-adrenergic blocker

Safety Profile

Poison by ingestion and intravenous routes. Mutation data reported. When heated to decomposition it emits toxic fumes of NOx.

InChI:InChI=1/C18H29NO2/c1-18(2,3)19-12-15(20)13-21-17-11-7-6-10-16(17)14-8-4-5-9-14/h6-7,10-11,14-15,19-20H,4-5,8-9,12-13H2,1-3H3

Upstream product

• 118629-68-8 (R)-1,2-epoxy-3-(2'-cyclopentylphenoxy)propane 
• 75-64-9 tert-butylamine 
• 154531-76-7 (S)-1,2-epoxy-3-(2'-cyclopentylphenoxy)propane 
• 254430-81-4 (R)-4-(2-Cyclopentyl-phenoxymethyl)-[1,3,2]dioxathiolane 2,2-dioxide 
• 96-41-3 Cyclopentanol 
• 142037-07-8 (R)-1-Chloro-3-(2-cyclopentyl-phenoxy)-propan-2-ol 
• 68430-38-6 (5S)-3-tert-butyl-5-(p-tosyloxymethyl)oxazolidin-2-one 
• 56526-14-8 (S)-(+)-5-(hydroxymethyl)-3-tert-butyloxazolidin-2-one 
• 254430-79-0 (S)-3-(2-Cyclopentyl-phenoxy)-propane-1,2-diol 
• 122030-10-8 Allyl 2-cyclopentylphenyl ether 
• 1518-84-9 2-cyclopentylphenol 
• 90970-95-9 (S)-5-(2-cyclopentylphenoxymethyl)-3-tert-butyl-2-oxazolidinone 
• 38363-22-3 1-Chloro-3-(2-cyclopentyl-phenoxy)-propan-2-ol 
• 108-95-2 phenol 

Relevant academic research and scientific papers

THERAPY FOR COMPLICATIONS OF DIABETES

A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.

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.

Regioselective alkylation of phenol with cyclopentanol over montmorillonite K10: An efficient synthesis of l-(2-cyclopentylphenoxy)-3-[(l,l-dimethylethyl)amino]propan-2-ol {(S')-penbutolol}

Regioselective alkylation of phenol with cyclopentanol is achieved over Montmorillonite K10 clay, producing 2-cycIopentylphenol, the key intermediate. The synthesis of optically active (S)-penbutoIol 1, an important antihypertensive drug, is realized in 5 steps from 2-cyclopentylphenol by employing Sharpless asymmetric dihydroxylation. The Royal Society of Chemistry 1999.

Enzyme Assisted Preparation of Enantiomerically Pure β-Adrenergic Blockers III. Optically Active Chlorohydrin Derivatives and Their Conversion

Optical active chlorohydrin derivatives 2a-m and 3a-m of both enantiomeric series were prepared via both enzymatic hydrolyses and acyltransfer reactions catalysed by a highly selective lipase from Pseudomonas sp..The resulting building blocks were further transformed into the corresponding β-blockers of high enantiomeric purity.

Arenesulfonate Derivatives of Homochiral Glycidol: Versatile Chiral Building Blocks for Organic Synthesis

The preparation of a series of crystalline arenesulfonate derivatives of enantiomerically enriched glycidol is described.The enhancement of optical purity by recrystallization was particularly successful for two of these derivatives, glycidyl tosylate and glycidyl 3-nitrobenzenesulfonate, which were obtained in 97 percent ee and 99 percent ee, respectively.Very high regioselectivity was observed in the reactions of these compounds with a variety of nucleophiles, including aryl oxides, Et2AlCN, organometallic reagents, and BH3-NaBH4.The application of this methodology to the synthesis of homochiral β-adrenergic blocking agents and homochiral terminal epoxides is discussed.