title: Generation of 3,8-substituted 1,2,4-triazolopyridines as potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1).
abstract: A series of pyridyl amide/sulfonamide inhibitors of 11β-HSD-1 were modified to incorporate a novel 1,2,4-triazolopyridine scaffold. Optimization of substituents at the 3 and 8 position of the TZP core, with a special focus on enhancing metabolic stability, resulted in the identification of compound 38 as a potent and metabolically stable inhibitor of the enzyme.
authors.affiliation: Research and Development, Bristol-Myers Squibb, PO Box 5400, Princeton, NJ 08543, USA.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wang
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Robl
authors.forename: Lawrence G
authors.initials: LG
authors.lastname: Hamann
authors.forename: Ligaya
authors.initials: L
authors.lastname: Simpkins
authors.forename: Rajasree
authors.initials: R
authors.lastname: Golla
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Li
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Seethala
authors.forename: Tatyana
authors.initials: T
authors.lastname: Zvyaga
authors.forename: David A
authors.initials: DA
authors.lastname: Gordon
authors.forename: James J
authors.initials: JJ
authors.lastname: Li
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D014230:Triazoles; C045575:1,2,4-triazole; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1