Ponalrestat

Ponalrestat

Phase III

An aldose reductase inhibitor potentially for the treatment of diabetes.

Imperial Chemical Industries Limited  innovator

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 Formula	C17H12BrFN2O3
Molecular Weight	391.19

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:

Medicinal Chemistry, 2009, Vol. 5, No. 5,

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).

///////////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

Cairo University

Department of Pharmaceutics

Cairo, Giza, Egypt

Cairo, Giza, Egypt

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

ethyl (2Z)-2-(3-oxo-2-benzofuran-1-ylidene)acetate

ethyl (2Z)-2-(3-oxo-2-benzofuran-1-ylidene)acetate
218.2054 g/mol, C12H10O4

Ethyl (Z)-3-phthalidylideneacetate;

[3-Oxoisobenzofuran-1(3H)-ylidene]acetic acid ethyl ester;

 [(Z)-3-Oxoisobenzofuran-1(3H)-ylidene]acetic acid ethyl ester;

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




Medicinal Chemistry, 2009, Vol. 5, No. 5,



Method for producing alkyl 3-phthalidylideneacetate [US5508446]

//////////
O=C(OCC)/C=C1\OC(=O)c2ccccc12


DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO .....FOR BLOG HOME CLICK HERE

Join me on Linkedin

Join me on Facebook FACEBOOK

Join me on twitter     

Join me on google plus Googleplus

 amcrasto@gmail.com

take a tour



















































///////