Dual-function radiosensitizers. Alpha-[[(2-bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol and related compounds: preparation via an aziridine equivalent.
An improved synthesis of the dual-function radiosensitizer alpha-[[(2-bromoethyl)amino]methyl]-2-nitro-1H-imidazole-1-ethanol (2, RB 6145) has been developed. Previously, the synthetic difficulties associated with this compound limited its attractiveness as a clinical candidate, although its radiosensitizing activity in preclinical models warranted its further development. The synthesis described uses a 2-oxazolidinone as an aziridine equivalent and provides 2 in 47% yield.
Suto
M J
MJ
Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, Michigan 48105.
Stier
M A
MA
Werbel
L M
LM
D000085:Acetates; D019342:Acetic Acid; D001388:Aziridines / Q000737:chemistry*; D055598:Chemical Phenomena; D002621:Chemistry; D004951:Esterification; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry; D023303:Oxazolidinones; D011355:Prodrugs / Q000737:chemistry; D011838:Radiation-Sensitizing Agents / Q000138:chemical synthesis*
D000085:Acetates; D001388:Aziridines; D009593:Nitroimidazoles; D010080:Oxazoles; D023303:Oxazolidinones; D011355:Prodrugs; D011838:Radiation-Sensitizing Agents; C067834:RB 6145; C067835:3-(2-hydroxy-3-(2-nitro-1H-imidazol-1-yl)propyl)-2-oxazolidinone; C033132:aziridine; D019342:Acetic Acid