Brimonidine CAS 59803-98-4
Introduction：Basic information about Brimonidine CAS 59803-98-4, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Brimonidine Basic information
| Product Name: | Brimonidine |
| Synonyms: | 5-bromo-n-(4,5-dihydro-1h-imidazol-2-yl)-6-quinoxalinamin;Polyubiquitin-C;UBC;UK 14;6-Quinoxalinamine,5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-;UK 14,34;CS-1362;UK 14304, Brimonidine |
| CAS: | 59803-98-4 |
| MF: | C11H10BrN5 |
| MW: | 292.13 |
| EINECS: | 000-000-0 |
| Product Categories: | Adrenoceptor;Other APIs;Brimonidine;Ophthalmic;Hetrerocycles;Intermediates & Fine Chemicals;Pharmaceuticals |
| Mol File: | 59803-98-4.mol |
Brimonidine Chemical Properties
| Melting point | 207.5 °C |
| Boiling point | 432.6±55.0 °C(Predicted) |
| density | 1.82±0.1 g/cm3(Predicted) |
| storage temp. | Keep in dark place,Sealed in dry,2-8°C |
| solubility | 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: <0.8 mg/mL |
| pka | 7.69±0.10(Predicted) |
| form | powder to crystal |
| color | Light yellow to Amber to Dark green |
| biological source | mouse |
| Water Solubility | 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: <0.8mg/mL DMSO: >6.5mg/mL ethanol: <8mg/mL (warm) H2O: insoluble |
| Merck | 14,1375 |
| InChI | InChI=1S/C11H10BrN5/c12-9-7(17-11-15-5-6-16-11)1-2-8-10(9)14-4-3-13-8/h1-4H,5-6H2,(H2,15,16,17) |
| InChIKey | XYLJNLCSTIOKRM-UHFFFAOYSA-N |
| SMILES | N1C2C(=C(Br)C(NC3NCCN=3)=CC=2)N=CC=1 |
| CAS DataBase Reference | 59803-98-4(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 25-36/37/38 |
| Safety Statements | 26-36-45 |
| RIDADR | UN 2811 6.1/PG 3 |
| WGK Germany | - |
| RTECS | VD1200000 |
| HazardClass | 6.1 |
| PackingGroup | Ⅲ |
| HS Code | 29332900 |
| Storage Class | 6.1C - Combustible acute toxic Cat.3 toxic compounds or compounds which causing chronic effects |
| Hazard Classifications | Acute Tox. 3 Oral |
| Description | Launched in the US for open-angle glaucoma and ocular hypertension,brimonidine is a relatively selective and potent α2a,-adrenergic agonist with low affinityfor the imidazoline l1 receptor. Topical application reduces intraocular pressure. Thisbypasses any central hypotensive effects at the l1 receptor (which can also give riseto a decrease in blood pressure and heart rate) if given systemically, since topicalapplication results in low plasma levels concomitant with rapid systemic elimination.Brimonidine can be prepared in a four-step sequence from 4-nitrophenylenediamine. |
| Chemical Properties | Yellow Solid |
| Originator | Allergan (USA) |
| Uses | α2-Adrenoceptor agonist. Antiglaucoma. |
| Uses | a2-Adrenoceptor agonist. Antiglaucoma |
| Uses | coronary vasodilator calcium ion influx inhibitor |
| Definition | ChEBI: Brimonidine is a quinoxaline derivative, a secondary amine and a member of imidazoles. It has a role as an adrenergic agonist, an antihypertensive agent and an alpha-adrenergic agonist. |
| Manufacturing Process | 6-Aminoquinoxaline (2.08 g, 14.4 mmol) was dissolved in 11.5 ml glacialacetic acid. The solution was cooled in water while a solution of bromine (0.74ml, 2.3 g, 14.4 mmol) in 1.5 ml glacial acetic acid was added slowly over 15min. After stirring for an additional 30 min. the orange red solid formed wasfiltered off and washed thoroughly with dry ether. The solid was dried in vacuoovernight to yield 4.44 g crude product (a yield of 100%). The compound, 6-amino-5-bromoquinoxaline hydrobromide, had no definite melting point. A phase change (from fine powder to red crystals) was noticed at about 220°C.Decomposition was observed at about 245°C. It was used directly for the nextstep. The crude 6-amino-5-bromoquinoxaline from above was dissolved in waterand saturated sodium bisulfite solution was added until the resulting solutiontested negative with starch-iodide paper. The solution was then basified with 2N sodium hydroxide and extracted thoroughly with ethyl acetate. The organicextract was dried over magnesium sulfate and concentrated under reducedpressure to give the free base. The crude product was recrystallized fromboiling benzene to give yellow crystals, m.p. 155°-156°C. Using variousanalytical procedures, the yellow crystals were determined to be 6-amino-5-bromoquinoxaline. The yield was 82%. The crude hydrobromide product previously noted (4.27 g, 14.0 mmol) wasdissolved in 60 ml of water and thiophosgene (1.28 ml, 16.8 mmol) wasadded in small portions with vigorous stirring. After 2 hours, the red color ofthe solution was discharged. The solid formed was filtered off and washedthoroughly with water. After drying in vacuo at 25°C 3.38 g (a yield of 90%)of brick red crystals was obtained, m.p. 157°-158°C. A portion of this materialwas further purified by column chromatography to give white crystals, m.p.157°-158°C. Using various analytical procedures, these crystals weredetermined to be 5-bromo-6-isothiocyanatoquinoxaline. A solution of the isothiocyanate (3.25 g, 12.2 mmol) in 145 ml benzene wasadded to a solution of ethylenediamine (5.43 g, 90.0 mmol) in 18 ml benzeneat 25°C over 2 hours. After stirring for a further 30 min., the supernatant waspoured off. The oil which remained was washed by swirling with dry etherthree times and used directly for the next step. A portion of this product wasfurther purified by column chromatography (SiO2, CHCl3) for characterization.A white solid was decomposed at 175°C. This white solid was determined tobe 5-bromo-6-(N-2-(aminoethyl)thioureido)quinoxaline. The crude product from above was dissolved in 100 ml dry methanol and thebrown solution was refluxed for 19 hours until hydrogen sulfide gas was nolonger evolved. The mixture was cooled to room temperature andconcentrated to about 50 ml. The yellow solid was filtered off and dried invacuo; weight 2.52 g (a yield of 70%), m.p. 242°-244°C. As the crudeproduct was insoluble in most common organic solvents, initial purificationwas achieved by an acid-base extraction procedure. 23 g of the crude productwas dissolved in 100 ml 0.5 N hydrochloric acid. The turbid yellow solutionwas filtered to give a clear orange yellow solution which was extracted twicewith ethyl acetate (2x10 ml). The aqueous phase was cooled to 0°C andbasified with 6 N sodium hydroxide, keeping the temperature of the solutionbelow 15°C at all times. The yellow solid which precipitated was filtered offand washed thoroughly with water until the washings were neutral to pHpaper. The solid was dried overnight in vacuo to give 1.97 g yellow solid, m.p.249°-250°C. The recovery was about 88%. Further purification was achieved by recrystallization as described below. Thepartially purified product from above was dissolved in N,N-dimethylformamide(about 17 ml/g) at 100°C with vigorous stirring. The solution was filtered hotand set aside to cool overnight. The bright yellow crystals were collected byfiltration, m.p. 252°-253°C. Recovery was from 65-77%. Using various analytical procedures the bright yellow solid was determined to be 5-bromo-6-(2-imidazolin-2-ylamino)quinoxaline. |
| Brand name | Alphagan (Allergan). |
| Therapeutic Function | Antiglaucoma |
| Hazard | A poison by ingestion. |
| Biological Activity | Full α 2 adrenergic agonist. Centrally active following systemic administration in vivo . Also available as part of the α 2 -Adrenoceptor Tocriset™ and Mixed Adrenergic Tocriset™ . |
| Biochem/physiol Actions | UK 14,304 is an α2-adrenoceptor agonist. UK 14,304 inhibits hormone-sensitive lipase (HSL) activity and suppresses lipogenesis in adipose tissue. |
| Veterinary Drugs and Treatments | Brimonidine is an alpha-adrenergic receptor agonist. It has a peakocular hypotensive effect occurring at two hours post-dosing.Fluorophotometric studies in animals and humans suggest thatbrimonidine tartrate has a dual mechanism of action by reducingaqueous humor production and by and increasing uveoscleral outflow.After ocular administration of either a 0.1% or 0.2% solution,plasma concentrations peaked within 0.5 to 2.5 hours and declinedwith a systemic half-life of approximately 2 hours. In humans, systemicmetabolism of brimonidine is extensive. It is metabolizedprimarily by the liver. Urinary excretion is the major route of eliminationof the drug and its metabolites. Approximately 87% of anorally-administered radioactive dose was eliminated within 120hours, with 74% found in the urine. |
| storage | Store at RT |
Brimonidine Preparation Products And Raw materials
| Raw materials | Thiophosgene-->Sodium bisulfite-->6-Aminoquinoxaline-->Ethylenediamine |
