Malamas, Michael S. published the artcileNovel Spirosuccinimide Aldose Reductase Inhibitors Derived from Isoquinoline-1,3-diones: 2-[(4-Bromo-2-fluorophenyl)methyl]-6-fluorospiro[isoquinoline-4(11H),3′-pyrrolidine]-1,2′,3,5′(2H)-tetrone and Congeners. 1, Computed Properties of 147181-08-6, the publication is Journal of Medicinal Chemistry (1994), 37(13), 2043-58, database is CAplus and MEDLINE.
Spiro[isoquinolinepyrrolidine]tetrones I [R1 = H, Cl, F, Br, OMe, CF3, Me, NO2; R2 = (un)substituted benzyl, benzothiazolylmethyl, alkyl] were prepared and evaluated in vitro for their ability to inhibit glyceraldehyde reduction, using a partially purified bovine lens aldose reductase preparation, and in vivo for their ability to inhibit galactitol accumulation in the lens and sciatic nerve of galactose-fed rats. Substitution at the N-2 position of I with diverse structural substituents (i.e., aralkyl, benzothiazolylmethyl, methyl) produced several excellent series of aldose reductase inhibitors. Optimization of these new series of spirosuccinimides through structure-activity relationship (SAR) studies, including analogy from other drug series (ponalrestat, zopolrestat), led to the design of the clin. candidate I [R1 = 6-F, R2 = 2,4-F(Br)C6H3, II]. II exhibited exceptional oral potency in two animal models of diabetic complications, the 14-day galactose-fed and streptozocin-induced diabetic rats, with ED50 values for the sciatic nerve of 0.1 and 0.09 mg/kg/day, resp. Both enantiomeric forms of II exhibited similar inhibitory activity in both in vitro and in vivo assays possibly due to their rapid interconversion. In an ex vivo experiment, the pharmacodynamic effect of II in the plasma of rats and dogs, after a single dose, appeared to be comparable to that of tolrestat.
Journal of Medicinal Chemistry published new progress about 147181-08-6. 147181-08-6 belongs to bromides-buliding-blocks, auxiliary class Fluoride,Bromide,Salt,Amine,Benzene, name is (4-Bromo-2-fluorophenyl)methanamine hydrochloride, and the molecular formula is C7H8BrClFN, Computed Properties of 147181-08-6.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary