189357-33-3Relevant articles and documents
Design, synthesis, and biological evaluation of anti-HIV double-drugsconjugates of HIV protease inhibitors with a reverse transcriptase inhibitor through spontaneously cleavable linkers
Matsumoto, Hikaru,Kimura, Tooru,Hamawaki, Tomonori,Kumagai, Akira,Goto, Toshiyuki,Sano, Kouichi,Hayashi, Yoshio,Kiso, Yoshiaki
, p. 1589 - 1600 (2007/10/03)
Based o the prodrug concept as well as the combination of two different classes of anti-HIV agents, we designed and synthesized a series of anti-HIV double-drugs consisitng of HIV protease inhibitors conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoins the two different classes of inhibitors has been investigted. Double-drugs using a succinyl amino acid linker were shown to release the parent drugs via spontaneous imide formation at a faster rate compared ring. Among the double-drugs, KNI-1039 (3B) with a glutaryl-glycine linker exhibited extremely potent anti-HIV activity compared with that of the individual components. Double-drug 3b was relatively stable in culture medium, whereas it regenerated active species in cell homogenate. These results suggested that the synergistic enhancement of anti-HIV activities of 3b may be due to their ability to penetrate into the target cell and subsequent regeneration of two diferent classes of anti-HIV agents in the cytoplasm. Copyright
'Double-drugs' - A new class of prodrug form of an HIV protease inhibitor conjugated with a reverse transcriptase inhibitor by a spontaneously cleavable linker
Matsumoto, Hikaru,Hamawaki, Tomonori,Ota, Hisashi,Kimura, Tooru,Goto, Toshiyuki,Sano, Kouichi,Hayashi, Yoshio,Kiso, Yoshiaki
, p. 1227 - 1231 (2007/10/03)
We designed and synthesized a new series of prodrug-type anti-HIV agents consisting of a peptidomimetic HIV protease inhibitor conjugated with a nucleoside reverse transcriptase inhibitor in an effort to enhance the antiviral activity. For the conjugation, a series of linkers that conjoin the two different classes of inhibitors have been investigated. Conjugates using a succinyl amino acid linker were shown to release the parent components via the spontaneous imide formation at a faster rate compared to conjugates using a glutaryl amino acid linker, as expected from the energetically favorable cyclization to the five-membered ring. Herein, we report a new 'double-drug' 4b (KNI-1039) with a glutarylglycine linker, which exhibited extremely potent anti-HIV activity compared with that of the individual components. (C) 2000 Elsevier Science Ltd. All rights reserved.
