DDR1/2 inhibitor 5n   Click here for help

GtoPdb Ligand ID: 10105

PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: The DDR1 and DDR2 receptor tyrosine kinases are new potential targets for anti-inflammatory drug discovery, as they are critical mediators of inflammatory cytokine secretion whose dysregulation is implicated in the progression of various human inflammatory diseases, including fibrosis, arthritis, atherosclerosis and cancer [1-2]. The dual inhibitor compound 5n was designed to investigate the anti-inflammatory potential of coinhibiting these enzymes, and provides a lead scaffold for further optimisation [3].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 65.77
Molecular weight 560.25
XLogP 5.74
No. Lipinski's rules broken 1
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Canonical SMILES CN1CCN(CC1)Cc1cc(NC(=O)c2ccc(c(c2)C#Cc2cnc3n2ccnc3)C(C)C)cc(c1)C(F)(F)F
Isomeric SMILES CN1CCN(CC1)Cc1cc(NC(=O)c2ccc(c(c2)C#Cc2cnc3n2ccnc3)C(C)C)cc(c1)C(F)(F)F
InChI InChI=1S/C31H31F3N6O/c1-21(2)28-7-5-24(16-23(28)4-6-27-18-36-29-19-35-8-9-40(27)29)30(41)37-26-15-22(14-25(17-26)31(32,33)34)20-39-12-10-38(3)11-13-39/h5,7-9,14-19,21H,10-13,20H2,1-3H3,(H,37,41)
1. Borza CM, Pozzi A. (2014)
Discoidin domain receptors in disease.
Matrix Biol, 34: 185-92. [PMID:24361528]
2. Leitinger B. (2014)
Discoidin domain receptor functions in physiological and pathological conditions.
Int Rev Cell Mol Biol, 310: 39-87. [PMID:24725424]
3. Wang Z, Zhang Y, Pinkas DM, Fox AE, Luo J, Huang H, Cui S, Xiang Q, Xu T, Xun Q et al.. (2018)
Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2.
J Med Chem, 61 (17): 7977-7990. [PMID:30075624]