title: Optimization of 2,4-diaminopyrimidines as GHS-R antagonists: side chain exploration.
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.
authors.affiliation: Metabolic Disease Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6098, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Zhili
authors.initials: Z
authors.lastname: Xin
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Michael D
authors.initials: MD
authors.lastname: Serby
authors.forename: Christi
authors.initials: C
authors.lastname: Kosogof
authors.forename: Lissa T J
authors.initials: LT
authors.lastname: Nelson
authors.forename: Bruce G
authors.initials: BG
authors.lastname: Szczepankiewicz
authors.forename: Wiweka
authors.initials: W
authors.lastname: Kaszubska
authors.forename: Verlyn G
authors.initials: VG
authors.lastname: Schaefer
authors.forename: H Douglas
authors.initials: HD
authors.lastname: Falls
authors.forename: Chun Wel
authors.initials: CW
authors.lastname: Lin
authors.forename: Christine A
authors.initials: CA
authors.lastname: Collins
authors.forename: Hing L
authors.initials: HL
authors.lastname: Sham
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D054440:Receptors, Ghrelin; D013329:Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000187:drug effects
chemical_list: D011743:Pyrimidines; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D013762:Tetrahydrofolate Dehydrogenase