Download MendeleyIdentification of 3,6-disubstituted dihydropyrones as inhibitors of human lactate dehydrogenase.
Fauber, B.P., Dragovich, P.S., Chen, J., Corson, L.B., Ding, C.Z., Eigenbrot, C., Labadie, S., Malek, S., Peterson, D., Purkey, H.E., Robarge, K., Sideris, S., Ultsch, M., Wei, B., Yen, I., Yue, Q., Zhou, A.(2014) Bioorg Med Chem Lett 24: 5683-5687
- PubMed: 25467161
- DOI: https://doi.org/10.1016/j.bmcl.2014.10.067
- Primary Citation of Related Structures:
4RLS - PubMed Abstract:
A series of 3,6-disubstituted dihydropyrones were identified as inhibitors of human lactate dehydrogenase (LDH)-A. Structure activity relationships were explored and a series of 6,6-spiro analogs led to improvements in LDHA potency (IC50 <350 nM). An X-ray crystal structure of an improved compound bound to human LDHA was obtained and it illustrated additional opportunities to enhance the potency of these compounds, resulting in the identification of 51 (IC50=30 nM).
Organizational Affiliation:
Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
