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Investigating Amine Derivatives of Ambruticin VS‐5 and VS‐4
Author(s) -
Tian ZongQiang,
Wang Zhan,
Xu Yuan,
Tran Chau Q.,
Myles David C.,
Zhong Ziyang,
Simmons Jessica,
Vetcher Leandro,
Katz Leonard,
Li Yong,
Shaw Simon J.
Publication year - 2008
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.200800008
Subject(s) - potency , amine gas treating , chemistry , amide , bioavailability , reductive amination , alkyl , urea , carbamate , alkylation , stereochemistry , medicinal chemistry , combinatorial chemistry , organic chemistry , pharmacology , biochemistry , in vitro , biology , catalysis
A structure–activity relationship around the amine group of the ambruticin VS series has been developed for antifungal activity. It was shown that the amine can be alkylated through reductive amination without loss of potency. However, if it is converted into either an amide, carbamate, or urea, a significant loss of potency is observed. Of the alkyl amines, small nonpolar groups are optimal for both potency and oral bioavailability. As a result of this study, one compound (KOS‐2079) was taken into an animal efficacy model with success.