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Compound Detail

CHEMBL4557670

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C[C@H]1SC(N)=N[C@](C)(c2cc(NC(=O)c3cnc(OCF)cn3)ccc2F)[C@H]1F
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL4557670
Phase Preclinical
Structure Type MOL
InChI Key JWJQXZNLFNMIHE-AHRODOEDSA-N
6
Targets
17
Activities
3
Assay Types
30
PK Parameters
20
Publications
0
Known Names

Molecular Properties

425.4
MW (Da)
3.18
ALogP
7
HBA
2
HBD
102.5
PSA (Ų)
0.76
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 C18H18F3N5O2S
MW 425.44
Aromatic Rings 2
Heavy Atoms 29
NP-Likeness -1.17

Activity Summary

IC50 13 meas. best 9.42
EC50 2 meas. best 8.74
Ki 2 meas. best 9.92

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Beta-secretase 2
CHEMBL2525
 Ki 9.92 9.92 0.1 1
Beta-secretase 1
CHEMBL4822
 Ki 9.47 9.47 0.3 1
Beta-secretase 1
CHEMBL4822
 IC50 9.42 8.8467 0.4 6
Canis familiaris
CHEMBL373
 EC50 8.74 8.21 1.8 2
Beta-secretase 2
CHEMBL2525
 IC50 8.15 7.78 7.1 2
Cytochrome P450 2D6
CHEMBL289
 IC50 5.48 5.48 3300.0 2
Cytochrome P450 2C9
CHEMBL3397
 IC50 5.46 5.46 3500.0 2
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
 IC50 5.29 5.29 5100.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 596.0 ng.hr.mL-1 Mus musculus
AUC 566.0 ng.hr.mL-1 Rattus norvegicus
AUC 10366.0 ng.hr.mL-1 Canis lupus familiaris
AUC 429.0 ng.hr.mL-1 Macaca fascicularis
AUC 68000.0 ng.hr.mL-1 Rattus norvegicus
AUC 41000.0 ng.hr.mL-1 Canis lupus familiaris
CL 24.8 mL.min-1.kg-1 Rattus norvegicus
CL 41.0 mL.min-1.kg-1 Mus musculus
CL 2.6 mL.min-1.kg-1 Canis lupus familiaris
CL 23.0 mL.min-1.kg-1 Macaca fascicularis
Cmax 90.26 nM Rattus norvegicus
Cmax 458.35 nM Mus musculus
Cmax 347.88 nM Rattus norvegicus
Cmax 1610.1 nM Canis lupus familiaris
Cmax 126.93 nM Macaca fascicularis
F 31.0 % Rattus norvegicus
F 58.0 % Mus musculus
F 38.0 % Rattus norvegicus
F 95.0 % Canis lupus familiaris
F 24.0 % Macaca fascicularis
Fu 0.083 - Homo sapiens
Fu 0.12 - Rattus norvegicus
Fu 0.15 - Mus musculus
Fu 0.078 - Canis lupus familiaris
Fu 0.12 - Macaca mulatta
Fu 0.034 - Mus musculus
T1/2 3.2 hr Mus musculus
T1/2 2.2 hr Rattus norvegicus
T1/2 13.7 hr Canis lupus familiaris
T1/2 4.9 hr Macaca fascicularis

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Beta-secretase 2 Ki = 0.12 nM 9.92 Displacement of [3H] JNJ-962 from BACE2 (unknown origin) expressed in HEK293 cel... 34553947
Beta-secretase 1 Ki = 0.34 nM 9.47 Displacement of [3H] JNJ-962 from BACE1 (unknown origin) expressed in HEK293 cel... 34553947
Beta-secretase 1 IC50 = 0.38 nM 9.42 Inhibition of BACE1 in human SH-SY5Y cells expressing human wild type amyloid pr... 31549838
Beta-secretase 1 IC50 = 0.38 nM 9.42 Inhibition of BACE1 in human SKNBE2 cells expressing wildtype APP assessed as re... 34553947
Beta-secretase 1 IC50 = 1.0 nM 9.0 Inhibition of BACE1 in human SKNBE2 cells expressing wildtype APP assessed as re... 34553947
Canis familiaris EC50 = 1.8 nM 8.74 In vivo inhibition of BACE1 in po dosed Beagle dog assessed as unbound plasma le... 31549838
Beta-secretase 1 IC50 = 2.3 nM 8.64 Inhibition of BACE1 (unknown origin) using APP harboring Swedish Lys/Met mutant-... 34553947
Beta-secretase 1 IC50 = 5.0 nM 8.3 Inhibition of recombinant human BACE1 incubated for 3 hrs using APP derived pept... 31549838
Beta-secretase 1 IC50 = 5.0 nM 8.3 Inhibition of BACE1 (unknown origin) by biochemical homogeneous time-resolved fl... 34553947
Beta-secretase 2 IC50 = 7.1 nM 8.15 Inhibition of BACE2 (unknown origin) by HTRF assay 31549838
Canis familiaris EC50 = 21.0 nM 7.68 In vivo inhibition of BACE1 in po dosed Beagle dog assessed as plasma level caus... 31549838
Beta-secretase 2 IC50 = 39.0 nM 7.41 Inhibition of BACE2 (unknown origin) using APP harboring Swedish Lys/Met mutant-... 34553947
Cytochrome P450 2D6 IC50 = 3300.0 nM 5.48 Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substra... 31549838
Cytochrome P450 2D6 IC50 = 3300.0 nM 5.48 Inhibition of CYP2D6 in human liver microsomes using dextromethorphan as substra... 31549838
Cytochrome P450 2C9 IC50 = 3500.0 nM 5.46 Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate in... 31549838
Cytochrome P450 2C9 IC50 = 3500.0 nM 5.46 Inhibition of CYP2C9 in human liver microsomes using tolbutamide as substrate in... 31549838
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 5100.0 nM 5.29 Inhibition of human ERG at -80 mV holding potential by automated Qpatch clamp as... 31549838

Literature References

PubMed DOI Target Context # Activities
31549838 10.1021/acs.jmedchem.9b01140 ADMET 76
34553947 10.1021/acs.jmedchem.1c00359 Beta-secretase 1 6
31549838 10.1021/acs.jmedchem.9b01140 Canis familiaris 6
34553947 10.1021/acs.jmedchem.1c00359 ADMET 3
34553947 10.1021/acs.jmedchem.1c00359 Unchecked 3
31549838 10.1021/acs.jmedchem.9b01140 Mus musculus 3
31549838 10.1021/acs.jmedchem.9b01140 No relevant target 3
31549838 10.1021/acs.jmedchem.9b01140 Beta-secretase 1 2
34553947 10.1021/acs.jmedchem.1c00359 Beta-secretase 2 2
31549838 10.1021/acs.jmedchem.9b01140 Voltage-gated inwardly rectifying potassium channel KCNH2 2
31549838 10.1021/acs.jmedchem.9b01140 Cytochrome P450 2D6 2
31549838 10.1021/acs.jmedchem.9b01140 Cytochrome P450 2C9 2
31549838 10.1021/acs.jmedchem.9b01140 Cytochrome P450 3A4 2
31549838 10.1021/acs.jmedchem.9b01140 Cytochrome P450 2C19 2
31549838 10.1021/acs.jmedchem.9b01140 Cytochrome P450 1A2 2
31549838 10.1021/acs.jmedchem.9b01140 ATP-dependent translocase ABCB1 1
31549838 10.1021/acs.jmedchem.9b01140 Beta-secretase 2 1
31549838 10.1021/acs.jmedchem.9b01140 Cathepsin D 1
34553947 10.1021/acs.jmedchem.1c00359 Voltage-gated inwardly rectifying potassium channel KCNH2 1
34553947 10.1021/acs.jmedchem.1c00359 ATP-dependent translocase ABCB1 1

Data from ChEMBL 36 via Core Engine