compound 7 [PMID: 31955578]   

GtoPdb Ligand ID: 10649

Compound class: Synthetic organic
Comment: Compound 7 was designed by scientists at Novartis, as a potent and selective brain-penetrant inhibitor of mechanistic target of rapamycin (mTOR) [1]. It is an ATP-competitive inhibitor. It is already established that inhibition of mTOR in the CNS providees clinical efficacy in certain seizure disorders (such as tuberous sclerosis complex; TSC [2]) that are associated with overactivated mTOR signalling [3-4]. The allosteric mTOR inhibitor everolimus is already approved as adjunctive treatment for patients with TSC-associated partial-onset seizures. Compound 7 was optimised to provide a molecule with improved brain permeability compared to everolimus.
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 8
Hydrogen bond donors 1
Rotatable bonds 3
Topological polar surface area 120.53
Molecular weight 401.16
XLogP 2.22
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES C[C@@H]1COCCN1c1nc(nc2c1nc(s2)c1n[nH]cc1)N1CCOC[C@@H]1C
Isomeric SMILES C[C@@H]1COCCN1c1nc(nc2c1nc(s2)c1n[nH]cc1)N1CCOC[C@@H]1C
InChI InChI=1S/C18H23N7O2S/c1-11-9-26-7-5-24(11)15-14-17(28-16(20-14)13-3-4-19-23-13)22-18(21-15)25-6-8-27-10-12(25)2/h3-4,11-12H,5-10H2,1-2H3,(H,19,23)/t11-,12+/m1/s1
InChI Key ZJXHODMMACVLQQ-NEPJUHHUSA-N
Classification
Compound class Synthetic organic
IUPAC Name
(S)-3-Methyl-4-(7-((R)-3-methylmorpholino)-2-(1H-pyrazol-3-yl)thiazolo[5,4-d]pyrimidin-5-yl)morpholine
Comments
Compound 7 was designed by scientists at Novartis, as a potent and selective brain-penetrant inhibitor of mechanistic target of rapamycin (mTOR) [1]. It is an ATP-competitive inhibitor. It is already established that inhibition of mTOR in the CNS providees clinical efficacy in certain seizure disorders (such as tuberous sclerosis complex; TSC [2]) that are associated with overactivated mTOR signalling [3-4]. The allosteric mTOR inhibitor everolimus is already approved as adjunctive treatment for patients with TSC-associated partial-onset seizures. Compound 7 was optimised to provide a molecule with improved brain permeability compared to everolimus.
Database Links
GtoPdb PubChem SID 404859096
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