Synthesis and evaluation of carbamate prodrugs of SQ109 as antituberculosis agents

A new series of carbamate prodrugs of SQ109 is disclosed. 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...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2009-05, Vol.19 (10), p.2808-2810
Hauptverfasser: Meng, Qingyi, Luo, Huibing, Liu, Yibin, Li, Wei, Zhang, Wen, Yao, Qizheng
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container_end_page 2810
container_issue 10
container_start_page 2808
container_title Bioorganic & medicinal chemistry letters
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creator Meng, Qingyi
Luo, Huibing
Liu, Yibin
Li, Wei
Zhang, Wen
Yao, Qizheng
description A new series of carbamate prodrugs of SQ109 is disclosed. 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. 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.
doi_str_mv 10.1016/j.bmcl.2009.03.091
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subjects Adamantane - administration & dosage
Adamantane - analogs & derivatives
Adamantane - chemical synthesis
Adamantane - chemistry
Administration, Oral
Animals
Anti-tuberculosis
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antitubercular Agents - administration & dosage
Antitubercular Agents - chemical synthesis
Antitubercular Agents - chemistry
Bioavailability
Biological and medical sciences
Carbamates - administration & dosage
Carbamates - chemical synthesis
Carbamates - chemistry
Ethylenediamines - administration & dosage
Ethylenediamines - chemical synthesis
Ethylenediamines - chemistry
General pharmacology
Medical sciences
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Prodrug
Prodrugs - administration & dosage
Prodrugs - chemical synthesis
Prodrugs - chemistry
Rats
SQ109
Tissue Distribution
title Synthesis and evaluation of carbamate prodrugs of SQ109 as antituberculosis agents
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