compound 15a [PMID: 32069401]   Click here for help

GtoPdb Ligand ID: 10702

Compound class: Synthetic organic
Comment: Compound 15a is a dual phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibitor that was designed for potential anti-tumour activity [1]. Dysregulation of the PI3K-Akt-mTOR signalling pathway is often observed in cancers, and simultaneous inhibition of PI3K and mTOR is predicted to offer improved antitumour activity compared to drugs that target single components of the pathway. A number of dual PI3K/mTOR inhibitors are in clinical development (for example gedatolisib, bimiralisib, apitolisib, samotolisib and omipalisib). All of these inhibitors are associated with adverse effects. Compound 15a was designed to address issues around selectivity and toxicity. Unfortunately 15a produced hepatic toxicity in vivo, so further optimisation would be essential to identify a more suitable derivative.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 9
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 139.37
Molecular weight 610.19
XLogP 4.48
No. Lipinski's rules broken 0
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Canonical SMILES COc1ncc(cc1NS(=O)(=O)c1ccc(cc1F)F)c1ccc2n(c1)c(cn2)c1nnc(o1)CCN1CCN(CC1)C
Isomeric SMILES COc1ncc(cc1NS(=O)(=O)c1ccc(cc1F)F)c1ccc2n(c1)c(cn2)c1nnc(o1)CCN1CCN(CC1)C
InChI InChI=1S/C28H28F2N8O4S/c1-36-9-11-37(12-10-36)8-7-26-33-34-28(42-26)23-16-31-25-6-3-18(17-38(23)25)19-13-22(27(41-2)32-15-19)35-43(39,40)24-5-4-20(29)14-21(24)30/h3-6,13-17,35H,7-12H2,1-2H3