BMS-823778   Click here for help

GtoPdb Ligand ID: 10158

Synonyms: compound 2 [Li et al., 2018]
PDB Ligand
Compound class: Synthetic organic
Comment: BMS-823778 is an orally bioavailable clinical lead inhibitor of hydroxysteroid 11-beta dehydrogenase 1 (11β-HSD) [5] which is the enzyme that converts inactive cortisone to biologically active costisol [2]. We show the chemical structure for BMS-823778 free base. Some bioactivity data may have been determined using the hydrochloride salt (PubChem CID 54669979). BMS-823778 was developed for potential treatment of type 2 diabetes and metabolic syndrome.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 50.42
Molecular weight 327.11
XLogP 5.57
No. Lipinski's rules broken 1
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Canonical SMILES Clc1ccc(cc1)C1(CC1)c1nnc2n1cccc2C(O)(C)C
Isomeric SMILES Clc1ccc(cc1)C1(CC1)c1nnc2n1cccc2C(O)(C)C
InChI InChI=1S/C18H18ClN3O/c1-17(2,23)14-4-3-11-22-15(14)20-21-16(22)18(9-10-18)12-5-7-13(19)8-6-12/h3-8,11,23H,9-10H2,1-2H3
1. Cheng Y, Wang L, Iacono L, Zhang D, Chen W, Gong J, Humphreys WG, Gan J. (2018)
Clinical significance of CYP2C19 polymorphisms on the metabolism and pharmacokinetics of 11β-hydroxysteroid dehydrogenase type-1 inhibitor BMS-823778.
Br J Clin Pharmacol, 84 (1): 130-141. [PMID:28850715]
2. Gathercole LL, Lavery GG, Morgan SA, Cooper MS, Sinclair AJ, Tomlinson JW, Stewart PM. (2013)
11β-Hydroxysteroid dehydrogenase 1: translational and therapeutic aspects.
Endocr Rev, 34 (4): 525-55. [PMID:23612224]
3. Gong J, Hansen L, Iacono L. (2018)
Clinical Pharmacokinetics and the Impact of Genetic Polymorphism on a CYP2C19 Substrate, BMS-823778, in Healthy Subjects.
Drug Metab Dispos, 46 (3): 316-325. [PMID:29311135]
4. Gong J, Iacono L, Iyer RA, Humphreys WG, Zheng M. (2018)
Physiologically-based pharmacokinetic modelling of a CYP2C19 substrate, BMS-823778, utilizing pharmacogenetic data.
Br J Clin Pharmacol, 84 (6): 1335-1345. [PMID:29469197]
5. Li J, Kennedy LJ, Walker SJ, Wang H, Li JJ, Hong Z, O'Connor SP, Ye XY, Chen S, Wu S et al.. (2018)
Discovery of Clinical Candidate BMS-823778 as an Inhibitor of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).
ACS Med Chem Lett, 9 (12): 1170-1174. DOI: 10.1021/acsmedchemlett.8b00307 [PMID:30613321]