GDC-0834   Click here for help

GtoPdb Ligand ID: 9263

Synonyms: GDC 0834
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: GDC-0834 was identified as a clinical candidate antiinflammatory Bruton's tyrosine kinase (BTK) inhibitor, through SAR guided improvements to the pharmacokinetic (PK) properties of the potent and selective BTK inhibitor CGI1746 [4]. GDC-0834 retains CGI1746's selectivity but exhibits significantly improved PK in preclinical animal models [1]. Studies suggest the involvement of aldehyde oxidase (AO) in the rapid amide hydrolysis of GDC-0834 to an inactive metabolite [3], which severly impacted on its ability to sustain beneficial clinical effects. Significant species difference in AO-induced inactivation of GDC-0834 are reported and explain why this was not picked up during preclinical studies [2]. Clinical development was terminated, with the manufacturer using insight gained to inform their search for improved inhibitors.
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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 7
Topological polar surface area 127.81
Molecular weight 596.26
XLogP 4.25
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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Canonical SMILES CN1CCN(C(=O)C1c1ccc(cc1)Nc1nc(cn(c1=O)C)c1cccc(c1C)NC(=O)c1cc2c(s1)CCCC2)C
Isomeric SMILES CN1CCN(C(=O)[C@H]1c1ccc(cc1)Nc1nc(cn(c1=O)C)c1cccc(c1C)NC(=O)c1cc2c(s1)CCCC2)C
InChI InChI=1S/C33H36N6O3S/c1-20-24(9-7-10-25(20)36-31(40)28-18-22-8-5-6-11-27(22)43-28)26-19-39(4)33(42)30(35-26)34-23-14-12-21(13-15-23)29-32(41)38(3)17-16-37(29)2/h7,9-10,12-15,18-19,29H,5-6,8,11,16-17H2,1-4H3,(H,34,35)(H,36,40)/t29-/m1/s1
InChI Key CDOOFZZILLRUQH-GDLZYMKVSA-N
Classification Click here for help
Compound class Synthetic organic
IUPAC Name Click here for help
N-[3-[6-[4-[(2R)-1,4-dimethyl-3-oxopiperazin-2-yl]anilino]-4-methyl-5-oxopyrazin-2-yl]-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide
Synonyms Click here for help
GDC 0834
Database Links Click here for help
BindingDB Ligand 50388183
ChEMBL Ligand CHEMBL2057915
GtoPdb PubChem SID 315661338
PubChem CID 25234918
RCSB PDB Ligand 2VL
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SynPHARM 83743 (in complex with Bruton tyrosine kinase)