68377-92-4

Basic information

• Product Name: AROTINOLOL
• Synonyms: AROTINOLOL;Arottnolol;Arotinolo;2-(3-tert-Butylamino-2-hydroxypropylthio)-4-(5-carbamoyl-2-thienyl)thiazole;2-Thiophenecarboxamide, 5-[2-[[3-[(1,1-dimethylethyl)amino]-2-hydroxypropyl]thio]-4-thiazolyl]-;2-Thiophenecarboxamide, 5-[2-[[3-[(1,1-dimethylethyl)amino]-2-hydroxypropyl]thio]-4-thiazolyl]-, (+-)-;NSC 317940;5-[2-[[3-(tert-butylamino)-2-hydroxy-propyl]thio]thiazol-4-yl]thiophene-2-carboxamide
• CAS NO: 68377-92-4
• Molecular Formula: C15H21N3O2S3
• Molecular Weight: 371.54
• Mol File: 68377-92-4.mol
• Article Data: 6

Chemical Properties

• Melting Point: 148-149°
• Boiling Point: 599.8 °C at 760 mmHg
• Flash Point: 316.6 °C
• Appearance: White solid
• Density: 1.35
• Storage Temp.: 2-8°C(protect from light)
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 13.71±0.20(Predicted)
• CAS DataBase Reference: AROTINOLOL(CAS DataBase Reference)
• NIST Chemistry Reference: AROTINOLOL(68377-92-4)
• EPA Substance Registry System: AROTINOLOL(68377-92-4)

Safety Data

• Hazardous Substances Data: 68377-92-4(Hazardous Substances Data)

Usage

Originator

Arotinolol,ZYF Pharm

Uses

Arotinolol is both and alpha- and beta-adrenoceptor antagonist and is used to treat essential tremors and hypertension.

Manufacturing Process

To a solution of 2-mercapto-4-(5'-carbamoyl-2'-thiophenyl)thiazole, 3.2 g in 20 ml of 0.3 % aqueous sodium hydroxide solution, 1-chloro-3-tbutylaminopropanol, 12.64 g in 20 ml of methanol was added, while the temperature was maintained at 20°C. The reaction solution was stirred at room temperature for 4 h, and then condensed to a half volume in vacuo. The residual solution, added with 100 ml of water, was extracted with chloroform. The chloroform extract was washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo to give 4.8 g of 2-(3'-t-butylamino-2'-hydroxypropylthio)-4-(5'-carbamoyl-2'- thiophenyl)thiazole, as crystals, melting point 234°-235.5°C (dec., recrystallized from methanol/water). In practice it is usually used as hydrochloride.

Therapeutic Function

Beta-adrenergic blocker

InChI:InChI=1/C15H21N3O2S3/c1-15(2,3)17-6-9(19)7-21-14-18-10(8-22-14)11-4-5-12(23-11)13(16)20/h4-5,8-9,17,19H,6-7H2,1-3H3,(H2,16,20)

Upstream product

• 52560-89-1 5-(2-mercapto-1,3-thiazol-4-yl)-2-thiophene carboxamide 
• 101540-26-5 arotinolol hydrochloride 
• 75-64-9 tert-butylamine 

Downstream Products

• 101540-26-5 arotinolol hydrochloride 
• 52560-77-7 C₁₅H₂₁N₃O₂S₃ 
• 52560-77-7 C₁₅H₂₁N₃O₂S₃ 

Relevant articles and documents

Preparation method of arotinolol hydrochloride

The invention relates to the technical field of medicines, particularly provides a preparation method of arotinolol hydrochloride, and relates to the technical field of medicines. The preparation method of the arotinolol hydrochloride, provided by the invention, comprises the following steps: (1) enabling tetrahydrofuran, 2-formamide-5-(2-sulfydryl-1, 3-thiazole-4-yl)-thiophene, water, sodium bicarbonate and epoxy chloropropane to react to generate an intermediate product C181101170-I03; (2) carrying out a reaction on absolute ethyl alcohol, C181101170-I03 and tert-butylamine, so as to obtain an intermediate product C181101170-I02; (3) subjecting methanol, ethyl acetate, C181101170-I02 and concentrated hydrochloric acid to a reaction, and obtaining an arotinolol hydrochloride crude product; and (4) treating the arotinolol hydrochloride crude product with DMSO and acetone to obtain arotinolol hydrochloride. The product arotinolol hydrochloride obtained by the method is high in yield, high in purity and small in impurity, the purity of the product can be well controlled, and the method is suitable for industrial production.

Refinement method of arotinolol hydrochloride

The invention relates to a refinement method of arotinolol hydrochloride and belongs to the field of chemical medicines. The refinement method is characterized in that crude arotinolol hydrochloride is added to a system containing ethyl acetate, methanol and pure water, subjected to an alkali recovery operation under a weak alkaline condition, then pulped and purified, and free alkaline arotinolol with higher purity is obtained; arotinolol forms salt in an alcoholic solution, and refined arotinolol hydrochloride is obtained. The method is simple to operate, the yield is relatively high, and industrial production is facilitated.

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.