compound 86 [PMID: 26982234]   

GtoPdb Ligand ID: 9251

Compound class: Synthetic organic
Comment: Compound 86 is reported as a selective inhibitor of sirtuin 2 (SIRT2) [1], a NAD-dependent protein deacetylase with protective effects neurodegenerative disease. Compound 86 is shown to be competitive with NAD+ and the enzyme's peptide substrate, with acceptable blood-brain barrier penetrance (a property essential for any drug being developed for neuroprotective activity).

Drug-like SIRT2 inhibitors are being developed to determine if SIRT2 blockade could be of clinical benefit in Parkinson's disease [2].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 8
Topological polar surface area 106.78
Molecular weight 432.18
XLogP 2.18
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES O=C(c1ccc(cc1)N1CCOCC1)Nc1cccc(c1)COc1cncc(c1)C(=O)N
Isomeric SMILES O=C(c1ccc(cc1)N1CCOCC1)Nc1cccc(c1)COc1cncc(c1)C(=O)N
InChI InChI=1S/C24H24N4O4/c25-23(29)19-13-22(15-26-14-19)32-16-17-2-1-3-20(12-17)27-24(30)18-4-6-21(7-5-18)28-8-10-31-11-9-28/h1-7,12-15H,8-11,16H2,(H2,25,29)(H,27,30)
InChI Key VKLKXFOZNHEBSW-UHFFFAOYSA-N
References
1. Ai T, Wilson DJ, More SS, Xie J, Chen L. (2016)
5-((3-Amidobenzyl)oxy)nicotinamides as Sirtuin 2 Inhibitors.
J. Med. Chem., 59 (7): 2928-41. [PMID:26982234]
2. Donmez G, Outeiro TF. (2013)
SIRT1 and SIRT2: emerging targets in neurodegeneration.
EMBO Mol Med, 5 (3): 344-52. [PMID:23417962]
3. Luk KC, Kehm V, Carroll J, Zhang B, O'Brien P, Trojanowski JQ, Lee VM. (2012)
Pathological α-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice.
Science, 338 (6109): 949-53. [PMID:23161999]
4. Wang MS, Boddapati S, Emadi S, Sierks MR. (2010)
Curcumin reduces alpha-synuclein induced cytotoxicity in Parkinson's disease cell model.
BMC Neurosci, 11: 57. [PMID:20433710]