title: Optimization of 1,2,4-Triazolopyridines as Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).
abstract: Small alkyl groups and spirocyclic-aromatic rings directly attached to the left side and right side of the 1,2,4-triazolopyridines (TZP), respectively, were found to be potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase-type 1 (11β-HSD-1) enzyme. 3-(1-(4-Chlorophenyl)cyclopropyl)-8-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridine (9f) was identified as a potent inhibitor of the 11β-HSD-1 enzyme with reduced Pregnane-X receptor (PXR) transactivation activity. The binding orientation of this TZP series was revealed by X-ray crystallography structure studies.
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Jun
authors: J
authors: Li
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Lawrence J
authors: LJ
authors: Kennedy
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Haixia
authors: H
authors: Wang
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: James J
authors: JJ
authors: Li
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Steven J
authors: SJ
authors: Walker
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Zhenqiu
authors: Z
authors: Hong
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Stephen P
authors: SP
authors: O'Connor
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Akbar
authors: A
authors: Nayeem
authors: Protein Science & Structure, Research & Development, Bristol-Myers Squibb , Princeton, New Jersey 08543, United States.
authors: Daniel M
authors: DM
authors: Camac
authors: Protein Science & Structure, Research & Development, Bristol-Myers Squibb , Princeton, New Jersey 08543, United States.
authors: Paul E
authors: PE
authors: Morin
authors: Protein Science & Structure, Research & Development, Bristol-Myers Squibb , Princeton, New Jersey 08543, United States.
authors: Steven
authors: S
authors: Sheriff
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Mengmeng
authors: M
authors: Wang
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Timothy
authors: T
authors: Harper
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Rajasree
authors: R
authors: Golla
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Ramakrishna
authors: R
authors: Seethala
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Thomas
authors: T
authors: Harrity
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Randolph P
authors: RP
authors: Ponticiello
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Nathan N
authors: NN
authors: Morgan
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Joseph R
authors: JR
authors: Taylor
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Rachel
authors: R
authors: Zebo
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: David A
authors: DA
authors: Gordon
authors: Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
authors: Jeffrey A
authors: JA
authors: Robl
keywords: Enzyme inhibitors; human 11β-hydroxysteroid dehydrogenase-type 1; triazolopyridines