tamatinib   

GtoPdb Ligand ID: 5706

Synonyms: R 406 | R-406 | R406 free base
Compound class: Synthetic organic
Comment: Tamatinib (R406) is a potent ATP-competitive (Type I) Syk inhibitor. It is the active form of the prodrug fostamatinib.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 7
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 128.75
Molecular weight 470.17
XLogP 2.72
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES COc1cc(Nc2ncc(c(n2)Nc2ccc3c(n2)NC(=O)C(O3)(C)C)F)cc(c1OC)OC
Isomeric SMILES COc1cc(Nc2ncc(c(n2)Nc2ccc3c(n2)NC(=O)C(O3)(C)C)F)cc(c1OC)OC
InChI InChI=1S/C22H23FN6O5/c1-22(2)20(30)28-19-13(34-22)6-7-16(27-19)26-18-12(23)10-24-21(29-18)25-11-8-14(31-3)17(33-5)15(9-11)32-4/h6-10H,1-5H3,(H3,24,25,26,27,28,29,30)
InChI Key NHHQJBCNYHBUSI-UHFFFAOYSA-N
References
1. Braselmann S, Taylor V, Zhao H, Wang S, Sylvain C, Baluom M, Qu K, Herlaar E, Lau A, Young C et al.. (2006)
R406, an orally available spleen tyrosine kinase inhibitor blocks fc receptor signaling and reduces immune complex-mediated inflammation.
J. Pharmacol. Exp. Ther., 319 (3): 998-1008. [PMID:16946104]
2. Clemens GR, Schroeder RE, Magness SH, Weaver EV, Lech JW, Taylor VC, Masuda ES, Baluom M, Grossbard EB. (2009)
Developmental toxicity associated with receptor tyrosine kinase Ret inhibition in reproductive toxicity testing.
Birth Defects Res. Part A Clin. Mol. Teratol., 85 (2): 130-6. [PMID:19107952]
3. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011)
Comprehensive analysis of kinase inhibitor selectivity.
Nat. Biotechnol., 29 (11): 1046-51. [PMID:22037378]
4. Lucas MC, Goldstein DM, Hermann JC, Kuglstatter A, Liu W, Luk KC, Padilla F, Slade M, Villaseñor AG, Wanner J et al.. (2012)
Rational design of highly selective spleen tyrosine kinase inhibitors.
J. Med. Chem., 55 (23): 10414-23. [PMID:23151054]
5. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010)
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
Chem. Biol., 17 (11): 1241-9. [PMID:21095574]
6. Xie HZ, Li LL, Ren JX, Zou J, Yang L, Wei YQ, Yang SY. (2009)
Pharmacophore modeling study based on known spleen tyrosine kinase inhibitors together with virtual screening for identifying novel inhibitors.
Bioorg. Med. Chem. Lett., 19 (7): 1944-9. [PMID:19254842]