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Compound Detail

CHEMBL4208555

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O=C(NC[C@@H](Cc1ccccc1)N1CCC(O)(C(F)(F)F)CC1)C1(c2ccc(Cl)cc2)CCCC1

Basic Information

ChEMBL ID CHEMBL4208555
Phase Preclinical
Structure Type MOL
InChI Key PAEBEJVPSADOMC-HSZRJFAPSA-N
10
Targets
15
Activities
2
Assay Types
6
PK Parameters
19
Publications
0
Known Names

Molecular Properties

509.0
MW (Da)
5.27
ALogP
3
HBA
2
HBD
52.6
PSA (Ų)
0.54
QED
2
Ro5 Violations
7
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C27H32ClF3N2O2
MW 509.01
Aromatic Rings 2
Heavy Atoms 35
NP-Likeness -0.81

Activity Summary

IC50 14 meas. best 9.15
Ki 1 meas. best 4.59

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Transient receptor potential cation channel subfamily A member 1
CHEMBL6007
IC50 9.15 8.03 0.7 3
Transient receptor potential cation channel subfamily A member 1
CHEMBL5160
IC50 8.52 8.52 3.0 1
Transient receptor potential cation channel subfamily A member 1
CHEMBL1075310
IC50 8.4 8.4 4.0 1
Unchecked
CHEMBL612545
IC50 7.7 6.6675 20.0 4
Cytochrome P450 2D6
CHEMBL289
IC50 6.35 6.35 450.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.67 5.67 2164.0 1
Cytochrome P450 2C19
CHEMBL3622
IC50 5.5 5.5 3152.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 4.94 4.94 11405.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 4.93 4.93 11781.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
Ki 4.59 4.59 25700.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 42.0 mL.min-1.kg-1 Rattus norvegicus
F 5.0 % Rattus norvegicus
Fu 0.0011 - Homo sapiens
Fu 0.0008 - Canis lupus familiaris
Fu 0.00057 - Rattus norvegicus
T1/2 4.4 hr Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Transient receptor potential cation channel subfamily A member 1 IC50 = 0.7 nM 9.15 Antagonist activity at human TRPA1 by electrophysiology assay -
Transient receptor potential cation channel subfamily A member 1 IC50 = 0.72 nM 9.14 Antagonist activity at full length human TRPA1 at holding potential of 15 mV mea... -
Transient receptor potential cation channel subfamily A member 1 IC50 = 3.0 nM 8.52 Antagonist activity at rat TRPA1 by electrophysiology assay -
Transient receptor potential cation channel subfamily A member 1 IC50 = 4.0 nM 8.4 Antagonist activity at mouse TRPA1 by electrophysiology assay -
Unchecked IC50 = 20.0 nM 7.7 Antagonist activity at opossum TRPA1 hS5 chimera containing (867 to 983 residues... -
Unchecked IC50 = 65.0 nM 7.19 Antagonist activity at pig TRPA1 by electrophysiology assay -
Cytochrome P450 2D6 IC50 = 450.0 nM 6.35 Inhibition of CYP2D6 (unknown origin) -
Unchecked IC50 = 730.0 nM 6.14 Inhibition of sodium channel site 2 (unknown origin) -
Transient receptor potential cation channel subfamily A member 1 IC50 = 1578.0 nM 5.8 Antagonist activity at human TRPA1 oS5 chimera containing (870 to 896 residues) ... -
Cytochrome P450 3A4 IC50 = 2164.0 nM 5.67 Inhibition of CYP3A4 (unknown origin) -
Unchecked IC50 = 2300.0 nM 5.64 Inhibition of GABA-A (unknown origin) -
Cytochrome P450 2C19 IC50 = 3152.0 nM 5.5 Inhibition of CYP2C19 (unknown origin) -
Cytochrome P450 2C9 IC50 = 11405.0 nM 4.94 Inhibition of CYP2C9 (unknown origin) -
Cytochrome P450 2C8 IC50 = 11781.0 nM 4.93 Inhibition of CYP2C8 (unknown origin) -
Voltage-gated inwardly rectifying potassium channel KCNH2 Ki = 25700.0 nM 4.59 Inhibition of dofetilide binding to human ERG -

Literature References

PubMed DOI Target Context # Activities
- 10.1039/C6MD00387G ADMET 12
- 10.1039/C6MD00387G Transient receptor potential cation channel subfamily A member 1 5
- 10.1039/C6MD00387G Unchecked 5
- 10.1039/C6MD00387G Rattus norvegicus 4
- 10.1039/C6MD00387G No relevant target 4
- 10.1039/C6MD00387G Hepatocyte 2
- 10.1039/C6MD00387G Voltage-gated inwardly rectifying potassium channel KCNH2 2
- 10.1039/C6MD00387G Salmonella typhimurium 1
- 10.1039/C6MD00387G Transient receptor potential cation channel subfamily M member 8 1
- 10.1039/C6MD00387G Transient receptor potential cation channel subfamily V member 1 1
- 10.1039/C6MD00387G Potassium voltage-gated channel subfamily A member 5 1
- 10.1039/C6MD00387G Sodium channel protein type 5 subunit alpha 1
- 10.1039/C6MD00387G Potassium voltage-gated channel subfamily KQT member 1 1
- 10.1039/C6MD00387G Cytochrome P450 1A2 1
- 10.1039/C6MD00387G Cytochrome P450 2C19 1
- 10.1039/C6MD00387G Cytochrome P450 2C8 1
- 10.1039/C6MD00387G Cytochrome P450 2C9 1
- 10.1039/C6MD00387G Cytochrome P450 3A4 1
- 10.1039/C6MD00387G Cytochrome P450 2D6 1

Data from ChEMBL 36 via Core Engine