DR ANTHONY MELVIN CRASTO,WorldDrugTracker, helping millions, A 90 % paralysed man in action for you, I am suffering from transverse mylitis and bound to a wheel chair, With death on the horizon, nothing will not stop me except God................DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 25Yrs Exp. in the feld of Organic Chemistry,Working for GLENMARK GENERICS at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution

Wednesday 13 January 2016

Ponalrestat



CAS # 72702-95-5, Ponalrestat, Statil, Statyl, 3-[(4-Bromo-2-fluorophenyl)methyl]-3,4-dihydro-4-oxo-1-phthalazineacetic acid
Ponalrestat
Phase III
An aldose reductase inhibitor potentially for the treatment of diabetes.
ICI-128436; MK-538; ICI-plc
CAS No.72702-95-5
Statil; Statyl;
3-[(4-Bromo-2-fluorophenyl)methyl]-3,4-dihydro-4-oxo-1-phthalazineacetic acid

Statil™ (3-(4-bromo-2-fluorobenzyl)-4-oxo-3H-phthalazin-1-ylacetic acid)

Molecular FormulaC17H12BrFN2O3
Molecular Weight391.19
IC50:Aldose reductase: IC50 = 7 nM (bovine); Aldose reductase: IC50 = 16 nM (rat); Aldose reductase: IC50 = 21 nM (pig); Aldose Reductase: IC50 = 21 nM (human); Rattus norvegicus:

400 MHz 1H-NMR spectrum of the dosing solution containing Statil™; HOD, residual ...
str1
Medicinal Chemistry, 2009, Vol. 5, No. 5,
str1
Synthesis of ethyl 2-(3-oxo-1,3-dihydro-1-isobenzofurany liden)acetate (2) A solution of phthalic anhydride (1.0 equiv.) and ethyl 2- (1,1,1-triphenyl-5 -phosphanylidene)acetate (1.1 equiv.) in 300 ml of dichloromethane (DCM) was refluxed for 3 hr. DCM was removed by vacuum at 40-50 o C. 2×150 ml of hexane was added to the resulting sticky solid, stirred for 10 min and the un-reacted 2-(1,1,1-triphenyl-5 -phosphanylidene)acetate was removed by filtration. The organic solvent was removed under vacuum and the resulting crude semisolid was taken to next step without further purification. Yield: 84%. 1 H-NMR CDCl3; (ppm): 1.1 (t, 3H), 4.2 (q, 2H), 6.0 (s, 1H), 7.6 (t, 1H), 7.7 (t, 1H), 7.8 (d, 1H), 8.9 (d, 1H). S
Synthesis of ethyl 2-(4-oxo-3,4-dihydro-1-phthalazinyl) acetate (3) A mixture of 2 (1.0 equiv.), hydrazine hydrate (0.8 equiv) and PTSA (1.0 equiv.) was ground by pestle and mortar at room temperature for 8 min. On completion, as indicated by TLC, the reaction mixture was treated with water. The resultant product was filtered, washed with water and recrystallized from DMF to give 3 in high yields (86%).1 H-NMR CDCl3; (ppm): 1.1 (t, 3H), 3.9 ( s, 2H), 4.1 (q, 2H), 7.6
Synthesis of 2-[3-(4-bromo-2-fluorobenzyl)-4-oxo-3,4- dihydro-1-phthalazinyl]acetic acid (4)
A mixture of 3 (1.0 equiv.), NaOH (5.0 equiv.), and THF was stirred for 30 min at 40-50 o C. 4-bromo-1-bromomethyl-2-fluoro benzene (1.1 equiv.) was added to the reaction mixture and stirred for 2 hr at 50-60 o C. Water was added to the reaction mixture and stirred at room temperature for 1 hr. pH was adjusted to 2-3 using cold acetic acid. THF was removed and the aqueous phase was extracted with ethyl acetate (2×50 ml), washed with brine, dried over sodium sulphate and evaporated. The solid was crystallized with methanol to give 4 with 54 % yield.
1H-NMR (DMSOd6); (ppm): 3.98 (s, 2H), 5.3 (s, 2H), 7.17 (t, 1H), 7.35 ( dd, 1H, J1= 8.0, J2= 1.6), 7.55 (dd, 1H, J1= 8.0, J2= 1.6), 7.87 (t, 1H), 7.9 (t, 1H), 7.95 (t, 1H0, 8.29 (d, 1H).
str1

///////////Ponalrestat, ICI-128436, MK-538, ICI-plc,
C1=CC=C2C(=C1)C(=NN(C2=O)CC3=C(C=C(C=C3)Br)F)CC(=O)O



take a tour

Department of Pharmaceutics
Cairo, Giza, Egypt
Map of Cairo University Department of Pharmaceutics Cairo, Giza, Egypt


Cairo, Giza, Egypt




//////Cairo, Giza, Egypt,

No comments:

Post a Comment