Orally absorbable cephalosporin antibiotics. 1. Structure-activity relationships of benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid.
A structure-activity relationship study of a number of orally absorbed cephalosporins together with their syntheses is described. These new cephalosporins are benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid. Several different synthetic methods for the glycine side chains, their protection, and the final acylations are reported. Several of these analogues were more active than cephalexin both in vitro and in vivo against commonly encountered Gram-positive bacteria. (R)-7-(3-Benzothienylglycylamido)-3-methyl-3-cephem-4-carboxylic acid (1R) has emerged as a potent antibacterial agent and is currently undergoing preclinical evaluation.
Kukolja
S
S
Draheim
S E
SE
Pfeil
J L
JL
Cooper
R D
RD
Graves
B J
BJ
Holmes
R E
RE
Neel
D A
DA
Huffman
G W
GW
Webber
J A
JA
Kinnick
M D
MD
D000284:Administration, Oral; D002506:Cephalexin / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006193:Haemophilus influenzae / Q000187:drug effects; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology*; D013210:Staphylococcus / Q000187:drug effects; D013237:Stereoisomerism; D013291:Streptococcus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology*
D002511:Cephalosporins; D009281:Naphthalenes; D013876:Thiophenes; C048386:LY 164846; D002506:Cephalexin; D005998:Glycine