72952-60-4Relevant academic research and scientific papers
Quinazolineacetic Acids and Related Analogues as Aldose Reductase Inhibitors
Malamas, Michael S.,Millen, Jane
, p. 1492 - 1503 (2007/10/02)
A variety of 2,4-dioxoquinazolineacetic acids (10, 11) were synthesized as hybrids of the known aldose reductase inhibitors alrestatine (8), ICI-105,552 (9), and ICI-128,436 (2) and evaluated for their ability to inhibit partially purified bovine lens aldose reductase (in vitro) and their effectiveness to decrease galactitol accumulation in the 4-day galactosemic rat model (in vivo).In support to SAR studies, related analogues pyrimidinediones (12), dihydroquinazolones (13), and indazolidinones (14, 15) were synthesized and tested in the in vitro and in vivo assays.All prepared compounds (10-15) have shown a high level of in vitro activity (IC50 ca. 10-6 to 4 10-8 M).However, only the 2,4-quinazolinedione analogues 10 and 11, with similar N-aralkyl substitution found in 2 and 9, have exhibited good oral potency.The remaining compounds were either inactive or had only a marginal in vivo activity.The structure-activity data support the presence of a secondary hydrophobic pocket in the vicinity of the primary lipophilic region of the enzyme.
New Synthesis of Diazepam
Gates, Marshall
, p. 1675 - 1681 (2007/10/02)
An efficient preparation of 7-chloro-1-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione from 5-chloro-N-methylisatoic anhydride and glycine has been devised, and from it, by the action of phenylmagnesium chloride on its N-acetyl-derivative followed by treatment with hydroxylamine and cleavage of the resulting desacetyl oxime with sodium bisulfite, diazepam has been synthesized.The overall yield is about 50percent from 5-chloroisatoic anhydride.
