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.
Click here for help
2D Structure
Click here for help
Click here for structure editor
Physico-chemical Properties
Click here for help
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
Click here for help
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)
1. An G, Liu W, Katz DA, Marek G, Awni W, Dutta S. (2013)
Effect of ketoconazole on the pharmacokinetics of the 11β-hydroxysteroid dehydrogenase type 1 inhibitor ABT-384 and its two active metabolites in healthy volunteers: population analysis of data from a drug-drug interaction study.
Drug Metab Dispos, 41 (5): 1035-45. [PMID:23431112]
2. Katz DA, Liu W, Locke C, Jacobson P, Barnes DM, Basu R, An G, Rieser MJ, Daszkowski D, Groves F et al.. (2013)
Peripheral and central nervous system inhibition of 11β-hydroxysteroid dehydrogenase type 1 in man by the novel inhibitor ABT-384.
Transl Psychiatry, 3: e295. [PMID:23982627]
3. Marek GJ, Katz DA, Meier A, Greco 4th N, Zhang W, Liu W, Lenz RA. (2014)
Efficacy and safety evaluation of HSD-1 inhibitor ABT-384 in Alzheimer's disease.
Alzheimers Dement, 10 (5 Suppl): S364-73. [PMID:24418055]
4. Sorensen B, Rohde J, Wang J, Fung S, Monzon K, Chiou W, Pan L, Deng X, Stolarik D, Frevert EU et al.. (2006)
Adamantane 11-beta-HSD-1 inhibitors: Application of an isocyanide multicomponent reaction.
Bioorg Med Chem Lett, 16 (23): 5958-62. [PMID:16996734]