Synthesis and anticancer activity of nitrosourea derivatives of phensuximide

Abstract

Nitrosourea derivatives 9--13 which utilize phensuximide (1) as the carrier were synthesized as potential central nervous system antitumor agents. The N-(2-chloroethyl)-N-nitrosourea 13 was active in the mouse ependymoblastoma brain-tumor system, as well as the intraperitoneal L1210 leukemia system.

Crystal structure of 4,5,6,7,8,8-hexachloro-2-(3,4-dimethoxyphenethyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione [+solvent]

“…The variety of biological activities and pharmaceutical uses of compounds containing a succinimide moiety is considerable. They include activities such as antifungal (Hazra et al, 2004), anti-tubercular (Isaka et al, 2006), CNS depressant (Aeberli et al, 1976), antispasmodic (Nunes et al, 1995), cytostatic (Crider et al, 1980), analgesic (Correa et al, 1997), antibacterial (Zentz et al, 2002), anticancer (Hall et al, 1995), anorectic (Rich & Gardner, 1983), hypotensive (Coram & Brezenoff, 1983), nerve conduction blocking (Kaczorowski et al, 2008), bacteriostatic (Piper et al, 1971), anti-convulsant (Kornet et al, 1977) and muscle relaxant (Musso et al, 2003).…”

Highly EnantioselectiveMichael Addition Promoted by a New Diterpene‐Derived Bifunctional Thiourea Catalyst: A Doubly Stereocontrolled Approach to Chiral Succinimide Derivatives

“…Substituted maleimides are important structural scaffolds and other precursors of some biologically interesting substances. The chiral α‐substituted succinimides are prevalent in a variety of natural products and some clinical drug candidates . Since the report of Komura and co‐workers in 1987, on the isolation of andrimid as a new and highly specific antibiotic, a great deal of effort has been dedicated to the discovery and synthesis of chiral succinimides.…”

“…The chiral α-substituted succinimides are prevalent in a variety of natural products and some clinical drug candidates. [1][2][3][4][5] Since the report of Komura and co-workers in 1987, on the isolation of andrimid as a new and highly specific antibiotic, 2 a great deal of effort has been dedicated to the discovery and synthesis of chiral succinimides. Notably, organocatalytic versions using maleimides as substrates for the synthesis of chiral succinimides have been actively pursued recently.…”

Enantioselective Synthesis of Succinimides by Michael Addition of 1,3‐Dicarbonyl Compounds to Maleimides Catalyzed by a Chiral Bis(2‐aminobenzimidazole) Organocatalyst

“…Cyclic imides play a vital role in polymer, biological, medicinal, and synthetic chemistry 1. In particular, succinimides are important building blocks that are often present in natural products and drugs such as phensuximide,2 ethosuximide,3 and andrimid4 (Figure 1).…”