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Compound Detail

CHEMBL4217988

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N#Cc1cc(S(=O)(=O)Nc2ncns2)ccc1Oc1ccc(-c2cccc(C(F)(F)F)c2)cc1-c1ccnc(CNCCC2CCNCC2)c1

Basic Information

ChEMBL ID CHEMBL4217988
Phase Preclinical
Structure Type MOL
InChI Key WSPHMGORSRQULF-UHFFFAOYSA-N
23
Targets
39
Activities
3
Assay Types
29
PK Parameters
20
Publications
0
Known Names

Molecular Properties

719.8
MW (Da)
7.23
ALogP
10
HBA
3
HBD
141.9
PSA (Ų)
0.11
QED
2
Ro5 Violations
12
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C35H32F3N7O3S2
MW 719.82
Aromatic Rings 5
Heavy Atoms 50
NP-Likeness -1.23

Activity Summary

IC50 32 meas. best 11.0
Ki 6 meas. best 7.37
EC50 1 meas. best 5.84

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Sodium channel protein type 7 subunit alpha
CHEMBL3585
IC50 11.0 11.0 0.0 1
Sodium channel protein type 9 subunit alpha
CHEMBL4296
IC50 11.0 10.76 0.0 2
Sodium channel protein type 2 subunit alpha
CHEMBL4187
IC50 8.6 8.56 2.5 2
Sodium channel protein type 8 subunit alpha
CHEMBL2752
IC50 8.3 8.3 5.0 1
Sodium channel protein type 8 subunit alpha
CHEMBL5202
IC50 8.26 8.25 5.5 2
Unchecked
CHEMBL612545
Ki 7.37 6.375 43.0 2
Unchecked
CHEMBL612545
IC50 7.32 6.3 48.0 2
High affinity choline transporter 1
CHEMBL4507
Ki 7.17 7.17 68.0 1
Sodium channel protein type 9 subunit alpha
CHEMBL3312
IC50 7.12 7.12 75.0 2
High affinity choline transporter 1
CHEMBL4507
IC50 6.92 6.92 120.0 1
Sodium channel protein type 1 subunit alpha
CHEMBL1845
IC50 6.51 6.51 309.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
Ki 5.96 5.96 1091.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.94 5.94 1150.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.88 5.88 1320.0 1
Adenosine receptor A1
CHEMBL226
EC50 5.84 5.84 1430.0 1
Sodium channel protein type 4 subunit alpha
CHEMBL2072
IC50 5.84 5.83 1451.0 2
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 5.7 5.39 2000.0 3
Sodium-dependent dopamine transporter
CHEMBL238
Ki 5.67 5.67 2120.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
Ki 5.5 5.5 3160.0 1
Prostaglandin G/H synthase 2
CHEMBL230
IC50 5.44 5.44 3650.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.43 5.43 3750.0 1
Sodium-dependent dopamine transporter
CHEMBL238
IC50 5.4 5.4 4010.0 1
Sodium-dependent noradrenaline transporter
CHEMBL222
IC50 5.37 5.37 4250.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 5.21 5.21 6170.0 1
Sodium channel protein type 3 subunit alpha
CHEMBL5163
IC50 5.19 5.19 6400.0 2
Cytochrome P450 2D6
CHEMBL289
IC50 5.05 5.05 8830.0 1
Sodium channel protein type 10 subunit alpha
CHEMBL5451
IC50 4.58 4.58 26000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 8.0 mL.min-1.g-1 Homo sapiens
CL 14.1 mL.min-1.g-1 Rattus norvegicus
CL 18.1 mL.min-1.g-1 Canis lupus familiaris
CL 36.5 mL.min-1.kg-1 Mus musculus
CL 12989.0 mL.min-1.kg-1 Mus musculus
CL 67.2 mL.min-1.kg-1 Mus musculus
CL 83.1 mL.min-1.kg-1 Rattus norvegicus
CL 30218.0 mL.min-1.kg-1 Rattus norvegicus
CL 178.0 mL.min-1.kg-1 Rattus norvegicus
CL 59.8 mL.min-1.kg-1 Rattus norvegicus
CL 44.0 mL.min-1.kg-1 Rattus norvegicus
CL 0.0322 mL.min-1.kg-1 Rattus norvegicus
CL 17.8 mL.min-1.kg-1 Canis lupus familiaris
CL 4759.0 mL.min-1.kg-1 Canis lupus familiaris
CL 39.8 mL.min-1.kg-1 Canis lupus familiaris
CL 0.0012 mL.min-1.kg-1 Canis lupus familiaris
Fu 0.00497 - Homo sapiens
Fu 0.00275 - Rattus norvegicus
Fu 0.00374 - Canis lupus familiaris
Fu 0.00281 - Mus musculus
Fu - - Mus musculus
Fu 0.002 - Rattus norvegicus
Fu 0.003 - Canis lupus familiaris
Fu 0.001 - Macaca mulatta
Fu 0.00281 - Mus musculus
T1/2 0.66 hr Mus musculus
T1/2 0.21 hr Rattus norvegicus
T1/2 0.057 hr Canis lupus familiaris
T1/2 5.9 hr Canis lupus familiaris

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Sodium channel protein type 9 subunit alpha IC50 = 0.01 nM 11.0 Inhibition of human Nav1.7 expressed in HEK cells by patch clamp electrophysiolo... 29029933
Sodium channel protein type 7 subunit alpha IC50 = 0.01 nM 11.0 Inhibition of human Nav1.7 expressed in HEK293 cells by electrophysiology assay 31012583
Sodium channel protein type 9 subunit alpha IC50 = 0.03 nM 10.52 Inhibition of human Nav1.7 expressed in HEK cells by automated patchXpress elect... 29029933
Sodium channel protein type 2 subunit alpha IC50 = 2.519 nM 8.6 Inhibition of human Nav1.2 expressed in HEK cells by patch clamp electrophysiolo... 29029933
Sodium channel protein type 2 subunit alpha IC50 = 3.0 nM 8.52 Inhibition of human Nav1.2 expressed in HEK293 cells by electrophysiology assay 31012583
Sodium channel protein type 8 subunit alpha IC50 = 5.014 nM 8.3 Inhibition of rat Nav1.6 expressed in HEK cells by patch clamp electrophysiology... 29029933
Sodium channel protein type 8 subunit alpha IC50 = 5.461 nM 8.26 Inhibition of human Nav1.6 expressed in HEK cells by patch clamp electrophysiolo... 29029933
Sodium channel protein type 8 subunit alpha IC50 = 5.8 nM 8.24 Inhibition of human Nav1.6 expressed in HEK293 cells by electrophysiology assay 31012583
Unchecked Ki = 43.0 nM 7.37 Inhibition of sodium channel site2 (unknown origin) by radioligand binding assay... 29029933
Unchecked IC50 = 48.0 nM 7.32 Inhibition of sodium channel site2 (unknown origin) by radioligand binding assay... 29029933
High affinity choline transporter 1 Ki = 68.0 nM 7.17 Displacement of [3H]hemicholinium-3 from recombinant human choline transporter a... 29029933
Sodium channel protein type 9 subunit alpha IC50 = 75.0 nM 7.12 Inhibition of rat Nav1.7 expressed in HEK cells by patch clamp electrophysiology... 29029933
Sodium channel protein type 9 subunit alpha IC50 = 75.0 nM 7.12 Inhibition of rat Nav1.7 expressed in HEK293 cells by electrophysiology assay 31012583
High affinity choline transporter 1 IC50 = 120.0 nM 6.92 Displacement of [3H]hemicholinium-3 from recombinant human choline transporter a... 29029933
Sodium channel protein type 1 subunit alpha IC50 = 309.0 nM 6.51 Inhibition of human Nav1.1 expressed in HEK cells by patch clamp electrophysiolo... 29029933
Sodium channel protein type 1 subunit alpha IC50 = 310.0 nM 6.51 Inhibition of human Nav1.1 expressed in HEK293 cells by electrophysiology assay 31012583
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 1091.0 nM 5.96 Displacement of [3H]Dofetilide from recombinant human ERG after 60 mins by scint... 29029933
Cytochrome P450 3A4 IC50 = 1150.0 nM 5.94 Inhibition of CYP3A4 (unknown origin) 29029933
Cytochrome P450 2C19 IC50 = 1320.0 nM 5.88 Inhibition of CYP2C19 (unknown origin) 29029933
Sodium channel protein type 4 subunit alpha IC50 = 1451.0 nM 5.84 Inhibition of human Nav1.4 expressed in HEK cells by patch clamp electrophysiolo... 29029933

Literature References

PubMed DOI Target Context # Activities
29029933 10.1016/j.bmcl.2017.09.056 Unchecked 89
29029933 10.1016/j.bmcl.2017.09.056 ADMET 30
31012583 10.1021/acs.jmedchem.8b01906 Unchecked 8
29029933 10.1016/j.bmcl.2017.09.056 No relevant target 5
29029933 10.1016/j.bmcl.2017.09.056 Mus musculus 4
29029933 10.1016/j.bmcl.2017.09.056 Hepatocyte 4
29029933 10.1016/j.bmcl.2017.09.056 Sodium channel protein type 9 subunit alpha 4
29029933 10.1016/j.bmcl.2017.09.056 Sodium-dependent noradrenaline transporter 3
29029933 10.1016/j.bmcl.2017.09.056 Histamine H1 receptor 3
29029933 10.1016/j.bmcl.2017.09.056 D(1A) dopamine receptor 3
29029933 10.1016/j.bmcl.2017.09.056 Muscarinic acetylcholine receptor M1 3
29029933 10.1016/j.bmcl.2017.09.056 Alpha-1A adrenergic receptor 3
29029933 10.1016/j.bmcl.2017.09.056 Cannabinoid receptor 1 3
29029933 10.1016/j.bmcl.2017.09.056 High affinity choline transporter 1 3
29029933 10.1016/j.bmcl.2017.09.056 Canis familiaris 3
29029933 10.1016/j.bmcl.2017.09.056 Sodium-dependent dopamine transporter 3
29029933 10.1016/j.bmcl.2017.09.056 Beta-2 adrenergic receptor 3
29029933 10.1016/j.bmcl.2017.09.056 Rattus norvegicus 3
29029933 10.1016/j.bmcl.2017.09.056 Sodium channel protein type 8 subunit alpha 2
29029933 10.1016/j.bmcl.2017.09.056 D(2) dopamine receptor 2

Data from ChEMBL 36 via Core Engine