Dose-Dependent Prevention of Sugar Cataracts in Galactose-fed Dogs by the Aldose Reductase Inhibitor M79175

Effect of Sorbitol Dehydrogenase Inhibition on Sugar Cataract Formation in Galactose-fed and Diabetic Rats

“…This transgenic data is complemented by prevention studies with aldose reductase inhibitors. Administration of aldose reductase inhibitors at the onset of diabetes or galactosemia have been observed to result in dose dependent inhibition of sugar cataract formation in rats, Octodon degus and dogs (Kador and Kinoshita, 1984 ;Datiles and Fukui, 1989 ;Sato et al, 1998). Age-dependent studies also illustrate the importance of lenticular aldose reductase levels on sugar cataract formation.…”

Aldose Reductase Inhibitors as Potential Therapeutic Drugs of Diabetic Complications

“…In galactose-fed dogs, cataract formation was delayed or prevented either by oral administration of the ARI M79175 [83,84], or topical administration of the formulation Kinostat TM [77]. This has been further confirmed by the more recent experiment in a similar dog model.…”

Spectral assignments for the aldose reductase inhibitor 4(S)-2,3-dihydro-6-fluoro-2(R)-methylspiro[chroman-4,4′-imidazoline]-2′,5′-dione and its synthetic intermediates

“…Changing the configuration from (S) to (R) at C-4 resulted in distinct shifts ranging between υ 0.10 and 0.56 for the protons connected at C-2 and C-3 and shifts ranging from υ 0.53 to 2.57 for the carbons at C-2, C-3 and C-4. For example, in 13 C NMR, C-2 is 71.26 for 4, C-2 is 68.69 for 5, C-4 is 58.73 for 4, C-4 is 59.45 for 5; the differences are 2.57 and 0.72 ppm. On the basis of these observations, the optical purities of the synthetic intermediates and final product in the synthesis of 2-methylsorbinil 2 can be assessed by NMR spectroscopy.…”

“…In the g-HMBC spectrum of 5, long-range correlations were also observed between the carbon at υ 174.69 and the two C-3 protons at υ 2.35 and 2.45; the carbon at υ 59.45 and the protons at υ 2.35, 2.45 and 4.29; the carbon at υ 68.69 and the protons at υ 2.45 and 1.48; the carbon at υ 37.38 and the proton at υ 1.48 and the carbon at υ 20.23 and the protons at υ 2.35, 13 C NMR of 5 as indicated above, the carbon at υ 174.69 was identified to be the C-12 carboxylic acid.…”

“…All eight chiral compounds examined showed complex 1 H and 13 C NMR spectra because of the existence of F-H and F-C coupling. However, with the assistance of DEPT, COSY, g-HSQC and g-HMBC spectra, all of the 1 H and 13 C NMR signals for compounds (2-9) were assigned. Using 4(R)-amino-6-fluoro-2(R)-methylchroman-4-carboxylic acid, 5, as an example, the protons at υ 7.02 (dd, J D 2.…”