Synthesis, SAR, and antitumor properties of diamino-C,N-diarylpyrimidine positional isomers: inhibitors of lysophosphatidic acid acyltransferase-beta

Baoqing Gong; Feng Hong; Cory Kohm; Scott Jenkins; John Tulinsky; Rama Bhatt; Peter De Vries; Jack W Singer; Peter Klein

doi:10.1016/j.bmcl.2004.01.104

Synthesis, SAR, and antitumor properties of diamino-C,N-diarylpyrimidine positional isomers: inhibitors of lysophosphatidic acid acyltransferase-beta

Bioorg Med Chem Lett. 2004 May 3;14(9):2303-8. doi: 10.1016/j.bmcl.2004.01.104.

Authors

Baoqing Gong¹, Feng Hong, Cory Kohm, Scott Jenkins, John Tulinsky, Rama Bhatt, Peter De Vries, Jack W Singer, Peter Klein

Affiliation

¹ Cell Therapeutics, Inc, 201 Elliott Ave W, Suite 400, Seattle, WA 98119, USA.

PMID: 15081029
DOI: 10.1016/j.bmcl.2004.01.104

Abstract

2,4-Diamino-N(4),6-diarylpyrimidines were identified as potent, isoform specific inhibitors of lysophosphatidic acid acyltransferase-beta (LPAAT-beta). Active inhibitors also blocked proliferation of tumor cell lines in vitro. The effect of 2j in an in vivo tumor model was investigated.

MeSH terms

Acyltransferases / antagonists & inhibitors*
Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / pharmacology*
Cell Division / drug effects
Cell Line, Tumor
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology*
Humans
Isomerism
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Enzyme Inhibitors
Pyrimidines
Acyltransferases
2-acylglycerophosphate acyltransferase
pyrimidine