Apraclonidine CAS 66711-21-5
Introduction：Basic information about Apraclonidine CAS 66711-21-5, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Apraclonidine Basic information
| Product Name: | Apraclonidine |
| Synonyms: | 4-aminoclonidine;APRACLONIDINE;Apraclonldine;2-((4-Amino-2,6-dichlorophenyl)imino)imidazolidine;Apraclondine Hcl;2,6-Dichloro-N-(4,5-dihydro-1H-imidazol-2-yl)benzene-1,4-diamine;2,6-Dichloro-N-[(4,5-dihydro-1H-imidazol)-2-yl]-1,4-benzenediamine;Aplonidine |
| CAS: | 66711-21-5 |
| MF: | C9H10Cl2N4 |
| MW: | 245.11 |
| EINECS: | |
| Product Categories: | |
| Mol File: | 66711-21-5.mol |
Apraclonidine Chemical Properties
| Melting point | >230° |
| Boiling point | 395.5±52.0 °C(Predicted) |
| density | 1.63±0.1 g/cm3(Predicted) |
| storage temp. | Sealed in dry,2-8°C |
| solubility | 45% (w/v) aq 2-hydroxypropyl-β-cyclodextrin: 1.4 mg/mL Solutions may be stored for several days at 4°C |
| pka | 9.26±0.50(Predicted) |
| form | solid |
| color | white |
| CAS DataBase Reference | 66711-21-5(CAS DataBase Reference) |
Safety Information
| Hazard Codes | T |
| Risk Statements | 23/24/25 |
| Safety Statements | 22-36/37/39-45 |
| RIDADR | UN 2811 6.1/PG 1 |
| WGK Germany | 3 |
| Originator | Alfadrops,Cipla Limited,India |
| Definition | ChEBI: An imidazoline compound having a 4-amino-2,6-dichloroanilino group at the 2-position. |
| Manufacturing Process | The preparation of p-aminoclonidine (apraclonidine) consists of 6 steps. In the first step 2,6-dichloro-4-nitroaniline was converted to 2,6-dicloro-4-nitrophenylisothiocyanate by addition of thiophosgene in toluene according tothe method described in Great Britain Patent No.: 1,131,780 (Beck et al.). The second step involved the conversation of 2,6-dichloro-4-nitrophenylisothiocyanateto 1-(2-aminoethyl)-3-(2,6-dichloro-4-nitrophenyl)-thioureaethylenediamine solvate. The solution of 2,6-dicloro-4-nitrophenylisothiocyanate(432 g, 1.73 mol) in 2 L of toluene was added dropwise to thecooled (0°C) solution ethylenediamine (244 ml, 3.66 mol, 2.1 eq.) in toluene(4 L) under a nitrogen atmosphere. 2-Propanol (1 L) was added and after 5minutes, the solid was collected by filtration, washed with 20% 2-propanol/toluene, and dried to a constant weight of 602 g (94%). Thisproduct is hygroscopic, mp 120°C (dec.). The third step was the conversation of 1-(2-aminoethyl)-3-(2,6-dichloro-4-nitrophenyl)-thiourea ethylenediamine solvate to 2-[(2,6-dicloro-4-nitrophenyl)imino]imidazoline ethylenediamine solvate. (500 g, 1.35 mol) ofabove prepared thiourea solvate was suspended with toluene (4 L) and washeated at reflux for 15 hours. The mixture was cooled to 23°C and 1 Maqueous hydrochloric acid (4 L) was added. After stirring for 10 min thebiphasic mixture was filtered to remove a sticky insoluble material. Theaqueous phase was neutralized to pH=7.0 using 50% NaOH. After stirring for1 hour the yellow solid was collected by filtration, washed with water (4 L)and t-butyl methyl ether (2 L) and dried in air to constant weight of 195 g(52%), m.p. 289-292°C. The fourth step was the conversation of 2-[2,6-dichloro-4-nitrophenyl)imino]imidazoline (150 g, 0.55 mol) in methanol (1,5 L) to 2-[(2,6-dichloro-4-aminophenyl)imino]imidazoline by hydrogen with 30 g Raney nickel catalyst at23°C for 22 hours. After removing the catalyst hydrogen chloride gas wasbubbled into solution until pH of the reaction mixture was 1.0. The solventwas rotary removed in vacuum and the residual solid was slurried with 2-propanol (1 L). The solvent was again removed by rotary evaporation, thecream solid was triturated with 2-propanol (600 ml). After aging for 1 hour,the solid was collected by filtration, washed with 2-propanol and t-butylmethyl ether, and dried for 15 hours at 6°C and t-butyl methyl ether, anddried for 15 hours at 60°C and 20 mm Hg. Yield of dihydrochloride 167 g (96%), mp 260°C (dec.). The dihydrochloride was converted to the monochloride (step 5) by adding 5M aqueous sodium hydroxide dropwise to pH=6.5 at 5°C for 2 hours. Yield ofhydrochloride 87%. The last step was recrystallization of product from water. The recrystallizedmaterial had m.p. 300°C. Calculated for: C9H10Cl2N4HCl: C, 38.39; H, 3.94;N, 19.90; Cl, 37.78. Found: C, 38.36; H, 3.91; N, 19.83; Cl, 37.77. |
| Therapeutic Function | Antiglaucoma |
| General Description | In addition to its therapeutic use as an antihypertensiveagent, clonidine has been found to provide beneficialeffects in several other situations, including glaucoma,spasticity, migraine prophylaxis, opiate withdrawal syndrome,and anesthesia. This has prompted the developmentof analogs of clonidine for specific use in some of the mentionedareas. Two of such examples are apraclonidine andbrimonidine. Apraclonidine does not cross the BBB.However, brimonidine can cross the BBB and hence canproduce hypotension and sedation, although these CNSeffects are slight compared with those of clonidine. CNS effectsof these drugs are correlated well to their log P, pKa,and thus log D value. Both apraclonidine and brimonidineare selective α2-agonists with α1: α2 ratios of 30:1 and1,000:1, respectively. Brimonidine is a much more selectiveα2-agonist than clonidine or apraclonidine and is a firstlineagent for treating glaucoma. Apraclonidines’s primarymechanism of action may be related to a reduction of aqueousformation, whereas brimonidine lowers intraocularpressure by reducing aqueous humor production and increasinguveoscleral outflow. Apraclonidine is used specificallyto control elevations in intraocular pressure that canoccur during laser surgery on the eye. Another example istizanidine (Zanaflex), which finds use in treating spasticityassociated with multiple sclerosis or spinal cord injury. Bystimulating 2-adrenergic receptors, it is believed to decreasethe release of excitatory amino acid NTs from spinalcord interneurons. |
| Veterinary Drugs and Treatments | Apraclonidine is an alpha2 adrenergic agonist used to reduce aqueoushumor secretion. Apraclonidine is a relatively selective, alphaadrenergicagonist and does not have significant membrane stabilizing(local anesthetic) activity. The onset of action is within 3 – 5hours of a single dose. It apparently is less effective than brimonidinein dogs and is very potent, causing vomiting and diarrhea incats and dogs. Apraclonidine will reduce aqueous production butmust be combined with other agents for adequate control. Neitherthe beta-blockers nor alpha-agonists are as effective as the carbonicanhydrase inhibitors in decreasing aqueous production. |
Apraclonidine Preparation Products And Raw materials
| Raw materials | Toluene-->Ethylenediamine-->Thiophosgene-->Aluminium-nickel-->tert-Butyl methyl ether-->Hexane-->Isopropyl alcohol-->Methanol |
| Preparation Products | Apraclonidine hydrochloride |
