Galapagos MAPKAPK5 inhibitor D   Click here for help

GtoPdb Ligand ID: 9848

Synonyms: compound 183 [WO2007138072A2]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: This compound was developed by Galapagos as a MAPKAPK5 inhibitor, in the search for a novel anti-inflammatory mechanism that would be applicable to the treatment of rheumatoid arthritis (RA). The discovery pathway is detailed in the pdf entitled 'Discovery of inhibitors of MAPKAPK5, a novel target for rheumatoid arthritis', which is available online here. The chemical structure is claimed in Galapagos patent WO2007138072A2, as compound 183 [2]. This compound (compound D) is likely to be a relation of the Galapagos clinical candidate GLPG0259, which failed in Phase 2 clinical trial in patients with methotrexate-refractory RA [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 8
Hydrogen bond donors 2
Rotatable bonds 6
Topological polar surface area 117.82
Molecular weight 460.23
XLogP 2.22
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES NC(=O)c1occ(c1)c1cnc(c2n1ncn2)Nc1ccc(cc1)N1CCN(CC1)C(C)(C)C
Isomeric SMILES NC(=O)c1occ(c1)c1cnc(c2n1ncn2)Nc1ccc(cc1)N1CCN(CC1)C(C)(C)C
InChI InChI=1S/C24H28N8O2/c1-24(2,3)31-10-8-30(9-11-31)18-6-4-17(5-7-18)29-22-23-27-15-28-32(23)19(13-26-22)16-12-20(21(25)33)34-14-16/h4-7,12-15H,8-11H2,1-3H3,(H2,25,33)(H,26,29)
InChI Key DLGZLIXYVSQGOX-UHFFFAOYSA-N
References
1. Andrews M. 
Discovery of inhibitors of MAPKAPK5, a novel target for rheumatoid arthritis.
Accessed on 15/03/2018. Modified on 15/03/2018. www.rsc.org, https://www.google.co.uk/url?sa=t&rct=j&q=&esrc=s&source=web&cd=7&cad=rja&uact=8&ved=0ahUKEwiEjPvHy-7ZAhUGKewKHf2vBYAQFghJMAY&url=http%3A%2F%2Fwww.rsc.org%2Fimages%2FMartinAndrews_tcm18-195242.pdf&usg=AOvVaw38oSSfFTUgOzaYq791YK8Q
2. Andrews MJI, Edwards P, Chambers MS, Schmidt W, Clase JA, Bar G, Hirst KL, Macleod A. (2007)
Triazolopyrazine compounds useful for the treatment of degenerative & inflammatory diseases.
Patent number: WO2007138072A2. Assignee: Galapagos N.V.. Priority date: 31/05/2006. Publication date: 06/12/2007.
3. Westhovens R, Keyser FD, Rekalov D, Nasonov EL, Beetens J, Van der Aa A, Wigerinck P, Namour F, Vanhoutte F, Durez P. (2013)
Oral administration of GLPG0259, an inhibitor of MAPKAPK5, a new target for the treatment of rheumatoid arthritis: a phase II, randomised, double-blind, placebo-controlled, multicentre trial.
Ann. Rheum. Dis., 72 (5): 741-4. [PMID:23161899]