Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain exploration

Bo Liu; Mei Liu; Zhili Xin; Hongyu Zhao; Michael D Serby; Christi Kosogof; Lissa T J Nelson; Bruce G Szczepankiewicz; Wiweka Kaszubska; Verlyn G Schaefer; H Douglas Falls; Chun Wel Lin; Christine A Collins; Hing L Sham; Gang Liu

doi:10.1016/j.bmcl.2006.01.012

Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain exploration

Bioorg Med Chem Lett. 2006 Apr 1;16(7):1864-8. doi: 10.1016/j.bmcl.2006.01.012. Epub 2006 Jan 25.

Authors

Bo Liu¹, Mei Liu, Zhili Xin, Hongyu Zhao, Michael D Serby, Christi Kosogof, Lissa T J Nelson, Bruce G Szczepankiewicz, Wiweka Kaszubska, Verlyn G Schaefer, H Douglas Falls, Chun Wel Lin, Christine A Collins, Hing L Sham, Gang Liu

Affiliation

¹ Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA.

PMID: 16442284
DOI: 10.1016/j.bmcl.2006.01.012

Abstract

The synthesis and structure-activity relationships of the 4- and 6-substituents of 2,4-diaminopyrimidine-based growth hormone secretagogue receptor (GHS-R) antagonists are described. Diaminopyrimidines with 6-norbornenyl (4n) and 6-tetrahydrofuranyl (4p) substitutents were found to exhibit potent GHS-R antagonism and good selectivity (approximately 1000-fold) against dihydrofolate reductase.

MeSH terms

Pyrimidines / chemistry
Pyrimidines / pharmacology*
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, Ghrelin
Structure-Activity Relationship
Tetrahydrofolate Dehydrogenase / drug effects

Substances

Pyrimidines
Receptors, G-Protein-Coupled
Receptors, Ghrelin
Tetrahydrofolate Dehydrogenase