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Synthesis and Structure Determination of µ-Conotoxin PIIIA Isomers with Different Disulfide Connectivities
Published on: October 2, 2018
Synthesis and structure-activity relationships of some 6 beta-acrylamido penicillins
R K Anderson1, P C Chapman, S C Cosham
1Department of Synthetic Chemistry, SmithKline Beecham Pharmaceuticals, Tonbridge, Kent, U.K.
Abstract:
Syntheses are described for penicillins (4b approximately 4i, 5a and 5b) which possess a 6 beta-(2-heteroaryl-3-substituted)-propenamido side-chain of fixed geometry. In vitro results for these compounds against a range of Gram-positive and Gram-negative bacteria showed in most cases good stability against both penicillinase and TEM-1 beta-lactamase; analogues (4b approximately 4i) bearing a 2-(2-aminothiazol-4-yl) unit showed the best intrinsic activity, the cyclohexyl compound (4b) being the most promising. The 1-acetoxyethyl ester (6) of 4b was also prepared; in experimental animal studies the in vivo properties of this compound compared favourably with cefuroxime axetil and are reported together with selected in vivo data for the other compounds.
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