52365-63-6 Usage
Description
Dipivefrine, also known as Dipivefrin, is a prodrug of Epinephrine (E) that is formed by the esterification of the catechol hydroxyl (OH) groups of Epinephrine with pivalic acid. It is designed to overcome the pharmacokinetic and pharmaceutical shortcomings of Epinephrine as an ophthalmic agent. Dipivefrine possesses dual solubility properties, which allow for greater penetrability into the eye through the corneal epithelial and endothelial layer. It is also more bioavailable and less irritating to the eye than Epinephrine.
Uses
Used in Ophthalmology:
Dipivefrine is used as an adrenergic ophthalmic agent for the treatment of glaucoma and ocular hypertension. Its increased lipophilicity and hydrophilicity enable better penetration into the eye, making it more effective than the hydrophilic Epinephrine hydrochloride. The prodrug is also more resistant to metabolism by catechol-O-methyltransferase (COMT) and less easily oxidized by air, leading to increased in vivo stability and potency.
Originator
Propine,Allergan,W. Germany,1978
Manufacturing Process
First, 0.27 mol of α-chloro-3',4'-dihydroxyacetophenone are dissolved in 200
ml methanol with warming. Next, 100 ml of a 40% aqueous solution of
methylamine is slowly added and the mixture stirred at 50°C to 55°C for 2
hours. The reaction mixture is then stirred an additional 24 hours at room
temperature. The crude product separates as a solid from the reaction medium and is
recovered by filtration, and it is then washed thoroughly with ether and
dissolved in 350 ml 1 N HCl. Then, approximately 250 ml of the aqueous
solvent is removed with a rotary evaporator and the evaporation residue
combined with 125 ml methanol and filtered through decolorizing charcoal.
The product is precipitated as the HCl salt by the addition of 7 parts of
acetone. The resulting crystalline material is removed by filtration dried at
40°C with vacuum, and has a melting point of about 242°C and is used
without further purification. Next, 25.3 g, 0.125 mol, of the above product are dissolved in 250 ml ethyl
acetate and 0.125 mol perchloric acid as a 70% aqueous solution is slowly
added thereto with continuous stirring. Then, an excess of pivaloyl chloride,
280 ml, is added and the mixture slowly warmed to reflux temperature. The
reaction mixture is refluxed for about 5 hours and allowed to cool to room
temperature with continuous stirring. The product is precipitated as the
perchlorate salt by the addition of perchloric acid, HClO4, in 500 ml ether. The
product is isolated and purified by dissolving in 75 ml acetone and
precipitating it with 150 to 200 ml of water.To 20 g of the above compound dissolved in 300 ml 95% ethanol in a Parr
reaction vessel is added 1.5 g Adams catalyst, platinum dioxide, and the
mixture shaken under hydrogen at 50 psi for 1 hour at ambient temperature.
The mixture is then filtered and the ethanol removed on a standard rotary
evaporator. The resulting oil is dissolved in 200 ml ether and slowly added to
1,200 ml ether with continuous stirring. The product separates as crystals
which are removed after 15 to 30 minutes by filtration. The compound melts
at 146°C to 147°C and needs no further purification.
Therapeutic Function
Adrenergic (ophthalmic)
Check Digit Verification of cas no
The CAS Registry Mumber 52365-63-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 5,2,3,6 and 5 respectively; the second part has 2 digits, 6 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 52365-63:
(7*5)+(6*2)+(5*3)+(4*6)+(3*5)+(2*6)+(1*3)=116
116 % 10 = 6
So 52365-63-6 is a valid CAS Registry Number.
InChI:InChI=1/C19H29NO5/c1-18(2,3)16(22)24-14-9-8-12(13(21)11-20-7)10-15(14)25-17(23)19(4,5)6/h8-10,13,20-21H,11H2,1-7H3
