Synthesis and structure-activity relationships of some 6 beta-acrylamido penicillins.
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.
Anderson
R K
RK
Department of Synthetic Chemistry, SmithKline Beecham Pharmaceuticals, Tonbridge, Kent, U.K.
Chapman
P C
PC
Cosham
S C
SC
Davies
J S
JS
Grinter
T J
TJ
Harris
M A
MA
Merrikin
D J
DJ
Mitchell
C A
CA
Ponsford
R J
RJ
Smith
C F
CF
D000818:Animals; D001419:Bacteria / Q000187:drug effects; D051379:Mice; D010406:Penicillins / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D012453:Saimiri; D013329:Structure-Activity Relationship
D010406:Penicillins