Synthesis and evaluation of carbamate prodrugs of SQ109 as antituberculosis agents.
The low bioavailability of SQ109 in rats, resulting from first-pass effect in the liver, may be remedied by prodrug strategy. Based on esterase-sensitive carbamate prodrug strategy, a novel series of prodrugs of SQ109 has been reported. Bioavailability of SQ109 after administration of prodrug 7a was 91.4% compared with 21.4% after oral administration of SQ109. After oral administration of compound 7a, the parent drug SQ109 exhibited preferential tissue distribution into lung and spleen, the target organs of tubercular infection and replication.
Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, China.
Qingyi
Q
Meng
Huibing
H
Luo
Yibin
Y
Liu
Wei
W
Li
Wen
W
Zhang
Qizheng
Q
Yao
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D002219:Carbamates / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D005029:Ethylenediamines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry*; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry; D051381:Rats; D014018:Tissue Distribution
D000995:Antitubercular Agents; D002219:Carbamates; D005029:Ethylenediamines; C506841:N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine; D011355:Prodrugs; D000218:Adamantane