example 1 [WO2020051105A1]   Click here for help

GtoPdb Ligand ID: 11304

Synonyms: nezulcitinib (proposed INN)
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: The chemical structure for this Janus kinase inhibitor was obtained from the WHO's special release of proposed INNs for COVID-related therapeutics that was published in October 2020, with the proposed INN being nezulcitinib. The structure is a match to example 1 as claimed in Theravance's 2020 patent WO2020051105A1. Analysis of Theravance's pipeline webpage and ClinicalTrials.gov suggests that this is likely to be their clinical lead TD-0903, which they identify as a lung-selective JAK inhibitor, since TD-0903 has already begun evaluation in COVID-19 patients. At the point of creating this entry (Nov 2020) there had been no formal name>structure disclosure. We will update this as further details become available.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 104.38
Molecular weight 527.3
XLogP 4.36
No. Lipinski's rules broken 0
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Canonical SMILES CCc1cc(O)ccc1c1ccc2c(c1)[nH]nc2c1nc2c([nH]1)C[C@H](N(C2)C(C)C)C(=O)N1CC(C1)N(C)C
Isomeric SMILES CCc1cc(O)ccc1c1ccc2c(c1)[nH]nc2c1nc2c([nH]1)C[C@H](N(C2)C(C)C)C(=O)N1CC(C1)N(C)C
InChI InChI=1S/C30H37N7O2/c1-6-18-11-21(38)8-10-22(18)19-7-9-23-24(12-19)33-34-28(23)29-31-25-13-27(37(17(2)3)16-26(25)32-29)30(39)36-14-20(15-36)35(4)5/h7-12,17,20,27,38H,6,13-16H2,1-5H3,(H,31,32)(H,33,34)/t27-/m0/s1
Bioactivity Comments
Biochemical data presented in WO2020051105A1 indicate that example 1 is a pan-JAK inhibitor.
Selectivity at enzymes
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Target Sp. Type Action Value Parameter Concentration range (M) Reference
Janus kinase 2 Hs Inhibitor Inhibition 10.5 pKi - 1
pKi 10.5 (Ki 3.1x10-11 M) [1]
Janus kinase 1 Hs Inhibitor Inhibition 10.2 pKi - 1
pKi 10.2 (Ki 6.3x10-11 M) [1]
Janus kinase 3 Hs Inhibitor Inhibition 10.2 pKi - 1
pKi 10.2 (Ki 6.3x10-11 M) [1]
tyrosine kinase 2 Hs Inhibitor Inhibition 8.6 pKi - 1
pKi 8.6 (Ki 2.5x10-9 M) [1]