Investigating amine derivatives of ambruticin VS-5 and VS-4.

Zong-Qiang Tian, Zhan Wang, Yuan Xu, Chau Q Tran, David C Myles, Ziyang Zhong, Jessica Simmons, Leandro Vetcher, Leonard Katz, Yong Li, Simon J Shaw

Department of Chemistry, Kosan Biosciences, Inc. 3832 Bay Center Place, Hayward, CA 95454, USA.

ChemMedChem 2008 Jun

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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.

Citation

Zong-Qiang Tian, Zhan Wang, Yuan Xu, Chau Q Tran, David C Myles, Ziyang Zhong, Jessica Simmons, Leandro Vetcher, Leonard Katz, Yong Li, Simon J Shaw. Investigating amine derivatives of ambruticin VS-5 and VS-4. ChemMedChem. 2008 Jun;3(6):963-9