Edward G. Brain

Learn More
The widely used anticancer prodrug cyclophosphamide (CPA) is activated in liver by a 4-hydroxylation reaction primarily catalyzed by cytochrome P-4502B and P-4502C enzymes. An alternative metabolic pathway involves CPA N-dechloroethylation to yield chloroacetaldehyde (CA), a P-4503A-catalyzed deactivation/neurotoxication reaction. The in vivo modulation of(More)
The anti-cancer prodrug ifosfamide (IF) is metabolized by liver P450 enzymes by two alternative pathways. IF is activated to 4-hydroxy IF (4-OH-IF), which ultimately yields the alkylating mustard isophosphoramide, whereas IF N-dechlororethylation inactivates the drug and produces the neurotoxic metabolite chloroacetaldehyde (CA). Both reactions are(More)
Erythromycin A oxime 11,12-carbonate (5a) and its oxime ethers 5b approximately 5p have been prepared and their antibacterial activities compared with those of erythromycin A (1) and its 11,12-carbonate 2. The oxime 5a and many of its oxime ether derivatives showed good activity in vitro against Gram-positive and the more permeable Gram-negative organisms,(More)
tert-Butyl 7beta-aminoceph-3-em-4-carboxylates carrying either benzyl or 3-pyridylmethyl substituents at position 3 have been prepared by a multistep modification of the penicillin nucleus. Acylation of either amine, followed by deprotection, gave a range of new cephalosporins. The relationship between structure and antibacterial activity is discussed.(More)
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-[(S)-carboxy(3,4- dihydroxyphenyl)methyl]oxyimino]acetamido]-3-(1-methylaminopyri dinium-4-thiomethyl)ceph-3-em-4-carboxylate sodium salt (BRL 57342, 1f) combines excellent in vitro antibacterial potency against Gram-positive and Gram-negative bacteria, including P. aeruginosa and Acinetobacter spp., with excellent(More)
Erythromycin A oxime 1 1,12-carbonate (5a) and its oxime ethers 5b~5p have been prepared and their antibacterial activities compared with those of erythromycin A (1) and.its 1 1,12-carbonate 2. The oxime 5a and many of its oxime ether derivatives showed good activity in vitro against Gram-positive and the morepermeable Gram-negative organisms, in some cases(More)
The synthesis and antibacterial activity of a series of beta-lactamase stable, broad spectrum 7-[2-(2-amino-thiazol-4-yl)-2-(Z)-(methoxyimino)acetamido]-cephalo sporins, characterised by a C-3-[N-(substituted-amino)pyridinium-4-thiomethyl] group, is described. Gram-positive and Gram-negative bacteria including extended spectrum beta-lactamase-producing(More)
A previously outlined general procedure for preparing various 3-substituted cephalosporins from the penicillin nucleus has been used, with modifications where required, to prepare a series of analogues of cephalexin with various substituents in the 3-methyl group. The 3-substituents most conducive to broad-spectrum antibacterial activity were(More)