Negoro, Toshiyuki published the artcileNovel, Highly Potent Aldose Reductase Inhibitors: (R)-(-)-2-(4-Bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine- 4-spiro-3′-pyrrolidine-1,2′,3,5′-tetrone (AS-3201) and Its Congeners, COA of Formula: C7H8BrClFN, the publication is Journal of Medicinal Chemistry (1998), 41(21), 4118-4129, database is CAplus and MEDLINE.
A series of novel tetrahydropyrrolo[1,2-a]pyrazine derivatives were synthesized and evaluated as aldose reductase inhibitors on the basis of their abilities to inhibit porcine lens aldose reductase in vitro and to inhibit sorbitol accumulation in the sciatic nerve of streptozotocin-induced diabetic rats in vivo. Of these compounds, spirosuccinimide-fused tetrahydropyrrolo[1,2-a]pyrazine-1,3-dione derivatives showed significantly potent aldose reductase inhibitory activity. In the in vivo activity of these derivatives, 2-(4-bromo-2-fluorobenzyl)-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazine-4-spiro-3′-pyrrolidine-1,2′,3,5′-tetrone (I) (SX-3030) showed the best oral activity. The enantiomers of I were synthesized, and the biol. activities were evaluated. It was found that aldose reductase inhibitory activity resides in the (-)-I (AS-3201), which was 10 times more potent in inhibition of the aldose reductase (IC50 = 1.5 × 10-8 M) and 500 times more potent in the in vivo activity (ED50 = 0.18 mg/kg/day for 5 days) than the corresponding (+)-I (SX-3202). From these results, AS-3201 was selected as the candidate for clin. development. The absolute configuration of AS-3201 was also established to be (R)-form by single-crystal X-ray anal. In this article we report the preparation and structure-activity relationship of tetrahydropyrrolopyrazine derivatives including a novel aldose reductase inhibitor, AS-3201.
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, COA of Formula: C7H8BrClFN.
Referemce:
https://en.wikipedia.org/wiki/Bromide,
bromide – Wiktionary