The synthesis and structure-activity relationships of 7-[(Z)-2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetamido]-3-[( Z)-1- propenyl]-3-cephem-4-carboxylic acid (BMY-28232), its 3-alkenyl analogs (6 and 7) and O-substituted derivatives of the oxyimino moiety (10) are described, as well as the oral pharmacokinetics and in vivo activities of the 1-acetoxyethyl ester of BMY-28232 (BMY-28271) and its analogous esters (11). The 3-alkenyl groups were introduced by the Wittig reaction of the ylide (2) prepared from the 3-chloromethyl cephem (1) to afford the Z (main) and E (minor) isomers regarding the 3-side chain. The O-substituted derivatives (10) were prepared by 7-N-acylation of the 7-amino cephem (4a) with the corresponding O-substituted side chain acids (8). The prodrug esters (11) were prepared by esterification of BMY-28232 with an appropriate halide. BMY-28232 was the most active among the 3-alkenyl analogs tested against Gram-negative organisms and much more active than the O-substituted derivatives against Gram-positive bacteria. BMY-28271 showed good oral bioavailability (66%) and good in vivo efficacy in mice against infections of Staphylococcus aureus Smith (PD50, 0.68 mg/kg) and Escherichia coli Juhl (0.54 mg/kg).