ABT-384   Click here for help

GtoPdb Ligand ID: 7357

Synonyms: ABT 384 | ABT384
Compound class: Synthetic organic
Comment: A range of medical conditions, including major depressive disorder and Alzheimer's disease, have been associated with excess levels of the stress hormone cortisol. ABT-384 is a potent and selective inhibitor of 11-beta-hydroxysteroid dehydrogenase type 1 (HSD-1) that generates cortisol. It has completed a phase 1 trial [2] but failed a phase II trial for Alzheimer's disease [3]. ChEMBL represents this compound with specified stereochemistry with the entry CHEMBL222670.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 7
Topological polar surface area 91.56
Molecular weight 493.27
XLogP 2.77
No. Lipinski's rules broken 0
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Canonical SMILES O=C(C(N1CCN(CC1)c1ccc(cn1)C(F)(F)F)(C)C)NC1C2CC3CC1CC(C2)(C3)C(=O)N
Isomeric SMILES O=C(C(N1CCN(CC1)c1ccc(cn1)C(F)(F)F)(C)C)NC1C2CC3CC1CC(C2)(C3)C(=O)N
InChI InChI=1S/C25H34F3N5O2/c1-23(2,33-7-5-32(6-8-33)19-4-3-18(14-30-19)25(26,27)28)22(35)31-20-16-9-15-10-17(20)13-24(11-15,12-16)21(29)34/h3-4,14-17,20H,5-13H2,1-2H3,(H2,29,34)(H,31,35)
Bioactivity Comments
Ki of 9 nM for human truncated 11beta-HSD1 assessed as inhibition of radiolabeled cortisone to cortisol conversion. Slightly more potent against the mouse enzyme [4]. Two active metabolites have been identified [1].
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
hydroxysteroid 11-beta dehydrogenase 1 Primary target of this compound Hs Inhibitor Inhibition 8.1 pKi - 4
pKi 8.1 (Ki 9x10-9 M) [4]