compound 3 [PMID: 27347366]   

GtoPdb Ligand ID: 9337

Synonyms: Compound 6412 from US9096541
Compound class: Synthetic organic
Comment: Inhibitor 3 showed potent BACE2 inhibitory activity, ~174,000-fold selectivity over BACE1 and ~15,000-fold selectivity over Cathepsin D [1]. Note the PDB structure 5DQC is a co-crystalisation with comound 2 as PubChem CID 89836206 Inhibitor 3 is described in a patent as example 6412 [2]. Activity data is included for ~30 analogues.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 9
Hydrogen bond donors 5
Rotatable bonds 20
Topological polar surface area 131
Molecular weight 630.38
XLogP 5.09
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
Canonical SMILES CCCC(C(C(=O)NCC(C)C)NCC(C(NC(=O)c1cccc(c1)C(=O)N(C(c1ccccc1)C)C)Cc1ccccc1)O)O
Isomeric SMILES CCC[C@@H]([C@@H](C(=O)NCC(C)C)NC[C@H]([C@@H](NC(=O)c1cccc(c1)C(=O)N([C@@H](c1ccccc1)C)C)Cc1ccccc1)O)O
InChI InChI=1S/C37H50N4O5/c1-6-14-32(42)34(36(45)39-23-25(2)3)38-24-33(43)31(21-27-15-9-7-10-16-27)40-35(44)29-19-13-20-30(22-29)37(46)41(5)26(4)28-17-11-8-12-18-28/h7-13,15-20,22,25-26,31-34,38,42-43H,6,14,21,23-24H2,1-5H3,(H,39,45)(H,40,44)/t26-,31+,32+,33-,34+/m1/s1
InChI Key PHXSVGGLTIKXSW-GUZVZUIYSA-N
References
1. Ghosh AK, Reddy BS, Yen YC, Cardenas E, Rao KV, Downs D, Huang X, Tang J, Mesecar AD. (2016)
Design of Potent and Highly Selective Inhibitors for Human β-Secretase 2 (Memapsin 1), a Target for Type 2 Diabetes.
Chem Sci, 7: 3117-3122. [PMID:27347366]
2. Tang, J et al.. (2015)
Inhibition of memapsin 1 cleavage in the treatment of diabetes.
Patent number: US9096541. Assignee: Oklahoma Medical Research Foundation. Priority date: 03/11/2013. Publication date: 08/04/2015.