- Radiosensitizers of hypoxic mammalian cells. 1-(hydroxyaminoalkyl)-substituted nitroimidazoles
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A series of novel 1-(hydroxyaminoalkyl)-substituted nitroimidazoles has been synthesized as potential radiosensitizers for hypoxic mammalian cells. These compounds were synthesized via N-(hydroxyalkyl)phthalimide nitroimidazole intermediates which, on reaction with hydrazine hydrate, yielded the corresponding amines. The intermediates were prepared by reacting the epoxide derived from nitroimidazole with phthalimide and/or the epoxide derived from phthalimide with the nitroimidazole. The method was used successfully for the preparation of 2-, 4- and 5-nitroimidazole derivatives. In a modification of this procedure, 1-(2-aminoethyl)-2-nitroimidazole has been prepared by a new route which avoids the use of aziridine. These agents were tested for cytotoxicity and radiosensitizing ability in vitro using Chinese hamster V79 cells. All of the 2-nitroimidazoles tested showed toxicity similar to that previously reported for misonidazole and Ro 03-8799 (1-(2-hydroxy-3-piperidinopropyl)-2-nitroimidazole), two compounds currently undergoing clinical evaluation. In addition, all the novel primary amines were shown to function as hypoxic cell radiosensitizers. The 2-nitroimidazole derivatives were the most efficient compounds to be examined and showed at least as much activity as misonidazole.
- Ahmed,Stratford,Jenkins
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p. 1763 - 1768
(2007/10/02)
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- Filaricidal 2-nitroimidazole compounds
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2-Nitroimidazoles having filaricidal activity of the formula STR1 wherein A is one of the groups STR2 --C(R3)=C(R1)(R2),--CHBr--CH2 Br or --CH2 --CCl=CH2 ; n is 1, 2, 3 or 4; R1 and R2 are hydrogen or C1-3 -alkyl and R3 is hydrogen, C1-3 -alkyl, chlorine or bromine, and processes for their preparation are described. The compounds of formula I and compounds of formula STR3 wherein R4 is --CH2 --CH2 OH, --CH2 --CHOH--CH2 OCH3, --CH2 --CHOH--CH2 OH or STR4 are useful in the treatment of filariasis is also described.
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