title: Investigating amine derivatives of ambruticin VS-5 and VS-4.
abstract: 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.
authors.affiliation: Department of Chemistry, Kosan Biosciences, Inc. 3832 Bay Center Place, Hayward, CA 95454, USA.
authors.forename: Zong-Qiang
authors.initials: ZQ
authors.lastname: Tian
authors.forename: Zhan
authors.initials: Z
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Chau Q
authors.initials: CQ
authors.lastname: Tran
authors.forename: David C
authors.initials: DC
authors.lastname: Myles
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Zhong
authors.forename: Jessica
authors.initials: J
authors.lastname: Simmons
authors.forename: Leandro
authors.initials: L
authors.lastname: Vetcher
authors.forename: Leonard
authors.initials: L
authors.lastname: Katz
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Shaw
mesh_terms: D000478:Alkylation; D000586:Amination; D000588:Amines / Q000737:chemistry*; D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D003045:Coccidioides / Q000187:drug effects*; D015195:Drug Design; D051379:Mice; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000935:Antifungal Agents; D011714:Pyrans; C014964:ambruticin