N4-phenyl modifications of N2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease

Wenwei Huang; Wei Zheng; Daniel J Urban; James Inglese; Ellen Sidransky; Christopher P Austin; Craig J Thomas

doi:10.1016/j.bmcl.2007.08.050

N4-phenyl modifications of N2-(2-hydroxyl)ethyl-6-(pyrrolidin-1-yl)-1,3,5-triazine-2,4-diamines enhance glucocerebrosidase inhibition by small molecules with potential as chemical chaperones for Gaucher disease

Bioorg Med Chem Lett. 2007 Nov 1;17(21):5783-9. doi: 10.1016/j.bmcl.2007.08.050. Epub 2007 Aug 28.

Authors

Wenwei Huang¹, Wei Zheng, Daniel J Urban, James Inglese, Ellen Sidransky, Christopher P Austin, Craig J Thomas

Affiliation

¹ NIH Chemical Genomics Center, National Human Genome Research Institute, NIH, 9800 Medical Center Drive, MSC 3370, Bethesda, MD 20892-3370, USA.

Abstract

A series of 1,3,5-triazine-2,4,6-triamines were prepared and analyzed as inhibitors of glucocerebrosidase. Synthesis, structure activity relationships and the selectivity of chosen analogues against related sugar hydrolases enzymes are described.

Publication types

Research Support, N.I.H., Intramural

MeSH terms

Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology*
Gaucher Disease / enzymology*
Glucosylceramidase / antagonists & inhibitors*
Humans
Triazines / chemistry*
Triazines / pharmacology*

Substances

Enzyme Inhibitors
Triazines
Glucosylceramidase

Grants and funding

Z99 HG999999/Intramural NIH HHS/United States