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Discovery of Isoxazole Amides as Potent and Selective SMYD3 Inhibitors.

Authors :
Su DS
Qu J
Schulz M
Blackledge CW
Yu H
Zeng J
Burgess J
Reif A
Stern M
Nagarajan R
Pappalardi MB
Wong K
Graves AP
Bonnette W
Wang L
Elkins P
Knapp-Reed B
Carson JD
McHugh C
Mohammad H
Kruger R
Luengo J
Heerding DA
Creasy CL
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2019 Dec 27; Vol. 11 (2), pp. 133-140. Date of Electronic Publication: 2019 Dec 27 (Print Publication: 2020).
Publication Year :
2019

Abstract

We report herein the discovery of isoxazole amides as potent and selective SET and MYND Domain-Containing Protein 3 (SMYD3) inhibitors. Elucidation of the structure-activity relationship of the high-throughput screening (HTS) lead compound 1 provided potent and selective SMYD3 inhibitors. The SAR optimization, cocrystal structures of small molecules with SMYD3, and mode of inhibition (MOI) characterization of compounds are described. The synthesis and biological and pharmacokinetic profiles of compounds are also presented.<br />Competing Interests: The authors declare no competing financial interest.<br /> (Copyright © 2019 American Chemical Society.)

Details

Language :
English
ISSN :
1948-5875
Volume :
11
Issue :
2
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
32071679
Full Text :
https://doi.org/10.1021/acsmedchemlett.9b00493