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Compound Detail

CHEMBL4876457

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Cc1c(C2(c3ccc(C(F)(F)F)c(C#N)c3)CC2)c[nH]c1C(=O)NC(C)c1nc[nH]n1

Basic Information

ChEMBL ID CHEMBL4876457
Phase Preclinical
Structure Type MOL
InChI Key QOYSJYDAYLKBNM-UHFFFAOYSA-N
9
Targets
19
Activities
2
Assay Types
17
PK Parameters
19
Publications
0
Known Names

Molecular Properties

428.4
MW (Da)
3.90
ALogP
4
HBA
3
HBD
110.2
PSA (Ų)
0.57
QED
0
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Unknown
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C21H19F3N6O
MW 428.42
Aromatic Rings 3
Heavy Atoms 31
NP-Likeness -0.75

Activity Summary

IC50 10 meas. best 7.19
EC50 9 meas. best 8.66

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Plasmodium berghei
CHEMBL612653
EC50 8.66 8.66 2.2 1
Plasmodium falciparum
CHEMBL364
EC50 8.28 7.6029 5.3 7
Plasmodium vivax
CHEMBL613013
EC50 7.36 7.36 44.0 1
Unchecked
CHEMBL612545
IC50 7.19 6.632 64.0 5
Substance-P receptor
CHEMBL249
IC50 5.7 5.7 2000.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 5.54 5.54 2900.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.38 5.38 4200.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 4.77 4.77 17000.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.69 4.69 20400.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 7840.09 ng.hr.mL-1 Mus musculus
AUC 17993.64 ng.hr.mL-1 Rattus norvegicus
CL 12000.0 mL.min-1.g-1 Homo sapiens
CL 15000.0 mL.min-1.g-1 Rattus norvegicus
CL 16000.0 mL.min-1.g-1 Mus musculus
CL 35000.0 mL.min-1.g-1 Homo sapiens
CL 44000.0 mL.min-1.g-1 Rattus norvegicus
CL 47000.0 mL.min-1.g-1 Mus musculus
CL 3.6 mL.min-1.kg-1 Mus musculus
Cmax 2100.0 nM Mus musculus
Cmax 6200.0 nM Rattus norvegicus
F 70.0 % Mus musculus
F 73.0 % Rattus norvegicus
T1/2 3.2 hr Mus musculus
T1/2 3.8 hr Rattus norvegicus
Tmax 4.0 hr Mus musculus
Tmax 1.0 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Plasmodium berghei EC50 = 2.2 nM 8.66 Antiplasmodial activity against liver stage Plasmodium berghei berghei-ANKA-GFP-... 33876936
Plasmodium falciparum EC50 = 5.3 nM 8.28 Antimalarial activity against drug-resistant Plasmodium falciparum 3D7 infected ... 33876936
Plasmodium falciparum EC50 = 5.8 nM 8.24 Antiplasmodial activity against asexual blood stage chloroquine and pyrimethamin... 33876936
Plasmodium falciparum EC50 = 8.0 nM 8.1 Antiplasmodial activity against Plasmodium falciparum 3D7 Brazilian infected in ... 33876936
Plasmodium falciparum EC50 = 11.0 nM 7.96 Antimalarial activity against drug-resistant Plasmodium falciparum 3D7 infected ... 33876936
Plasmodium falciparum EC50 = 20.0 nM 7.7 Antiplasmodial activity against Plasmodium falciparum Dd2 Brazilian infected in ... 33876936
Plasmodium vivax EC50 = 44.0 nM 7.36 Antiplasmodial activity against Plasmodium vivax Brazilian field isolated from p... 33876936
Plasmodium falciparum EC50 = 60.0 nM 7.22 Antiplasmodial activity against Plasmodium falciparum Brazilian field isolated f... 33876936
Unchecked IC50 = 64.0 nM 7.19 Inhibition of Plasmodium vivax DHODH expressed in Escherichia coli BL21-DE3 usin... 33876936
Unchecked IC50 = 69.0 nM 7.16 Inhibition of Plasmodium falciparum DHODH expressed in Escherichia coli BL21-DE3... 33876936
Unchecked IC50 = 140.0 nM 6.85 Inhibition of Plasmodium falciparum DHODH expressed in Escherichia coli BL21-DE3... 33876936
Unchecked IC50 = 260.0 nM 6.58 Inhibition of Plasmodium vivax DHODH expressed in Escherichia coli BL21-DE3 usin... 33876936
Plasmodium falciparum EC50 = 1900.0 nM 5.72 Antimalarial activity against drug-resistant Plasmodium falciparum 3D7 infected ... 33876936
Substance-P receptor IC50 = 2000.0 nM 5.7 Inhibition of NK1 (unknown origin) 33876936
Cytochrome P450 2C9 IC50 = 2900.0 nM 5.54 Inhibition of CYP2C9 (unknown origin) by UPLC-MS analysis 33876936
Unchecked IC50 = 4200.0 nM 5.38 Inhibition of Plasmodium falciparum DHODH expressed in Escherichia coli BL21-DE3... 33876936
Cytochrome P450 2C19 IC50 = 4200.0 nM 5.38 Inhibition of CYP2C19 (unknown origin) by UPLC-MS analysis 33876936
Cytochrome P450 2D6 IC50 = 17000.0 nM 4.77 Inhibition of CYP2D6 (unknown origin) by UPLC-MS analysis 33876936
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 20400.0 nM 4.69 Inhibition of human ERG by QPatch assay 33876936

Literature References

PubMed DOI Target Context # Activities
33876936 10.1021/acs.jmedchem.1c00173 ADMET 29
33876936 10.1021/acs.jmedchem.1c00173 Plasmodium falciparum 12
33876936 10.1021/acs.jmedchem.1c00173 Unchecked 6
33876936 10.1021/acs.jmedchem.1c00173 Dihydroorotate dehydrogenase (quinone), mitochondrial 5
33876936 10.1021/acs.jmedchem.1c00173 No relevant target 4
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 3A4 2
33876936 10.1021/acs.jmedchem.1c00173 Plasmodium vivax 1
33876936 10.1021/acs.jmedchem.1c00173 Plasmodium berghei 1
33876936 10.1021/acs.jmedchem.1c00173 Albumin 1
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 2D6 1
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 2C19 1
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 2C9 1
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 2C8 1
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 2B6 1
33876936 10.1021/acs.jmedchem.1c00173 Cytochrome P450 1A2 1
33876936 10.1021/acs.jmedchem.1c00173 Substance-P receptor 1
33876936 10.1021/acs.jmedchem.1c00173 Voltage-gated inwardly rectifying potassium channel KCNH2 1
33876936 10.1021/acs.jmedchem.1c00173 HepG2 1
33876936 10.1021/acs.jmedchem.1c00173 L1210 1

Data from ChEMBL 36 via Core Engine