Synthesis and structure-activity relationships of 7-[3-(1-aminoalkyl)pyrrolidinyl]- and 7-[3-1-aminocycloalkyl)pyrrolidinyl]-quinolone antibacterials.
A series of 7-[3-(1-aminoalkyl and 1-aminocycloalkyl)-1-pyrrolidinyl] quinolones have been prepared and their biological properties evaluated. Among them, 1-(S)-aminoalkyl derivatives exhibited potent antibacterial activities against gram-positive and gram-negative organisms. They had moderate lipophilicity and high aqueous solubility compared to their aminomethyl counterparts; e.g., the 3-(1-aminoethyl)-1-pyrrolidinyl compound (83) showed superior pharmacokinetic properties to its aminomethyl counterpart (6).
Kimura
Y
Y
Exploratory Laboratories I, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Atarashi
S
S
Takahashi
M
M
Hayakawa
I
I
D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000890:Anti-Infective Agents; D011759:Pyrrolidines; D015363:Quinolones