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Compound Detail

CHEMBL111201

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O=S(=O)(Nc1ccc(CCNC[C@H](O)c2cccnc2)cc1)c1ccc(-c2nc(-c3ccc(C(F)(F)F)cc3)cs2)cc1

Basic Information

ChEMBL ID CHEMBL111201
Phase Preclinical
Structure Type MOL
InChI Key MSOUIIHPMJCUNI-LJAQVGFWSA-N
12
Targets
25
Activities
2
Assay Types
30
PK Parameters
20
Publications
0
Known Names

Molecular Properties

624.7
MW (Da)
6.56
ALogP
7
HBA
3
HBD
104.2
PSA (Ų)
0.14
QED
2
Ro5 Violations
11
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C31H27F3N4O3S2
MW 624.71
Aromatic Rings 5
Heavy Atoms 43
NP-Likeness -1.57

Activity Summary

IC50 13 meas. best 7.34
EC50 12 meas. best 9.37

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Beta-3 adrenergic receptor
CHEMBL3124732
EC50 9.37 8.57 0.4 2
Beta-3 adrenergic receptor
CHEMBL246
EC50 8.7 8.4533 2.0 6
Beta-3 adrenergic receptor
CHEMBL4400
EC50 7.6 7.6 25.0 1
Beta-3 adrenergic receptor
CHEMBL246
IC50 7.34 7.34 46.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 6.66 6.66 220.0 1
Beta-2 adrenergic receptor
CHEMBL210
IC50 6.17 5.8167 670.0 3
Beta-1 adrenergic receptor
CHEMBL213
IC50 6.0 5.76 1000.0 3
Voltage-dependent L-type calcium channel subunit alpha-1C
CHEMBL1940
IC50 5.77 5.77 1700.0 1
Beta-2 adrenergic receptor
CHEMBL210
EC50 5.62 5.62 2400.0 1
Beta-3 adrenergic receptor
CHEMBL4031
EC50 5.47 5.47 3400.0 1
Beta-1 adrenergic receptor
CHEMBL213
EC50 5.32 5.32 4800.0 1
Sodium-dependent serotonin transporter
CHEMBL228
IC50 5.3 5.3 5000.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.03 5.03 9300.0 1
Cytochrome P450 2D6
CHEMBL289
IC50 4.96 4.96 11000.0 1
Cytochrome P450 2C9
CHEMBL3397
IC50 4.62 4.62 24000.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1933.33 ng.hr.mL-1 Canis lupus familiaris
AUC 2266.67 ng.hr.mL-1 Canis lupus familiaris
AUC 0.07 microM.hr/mg/kg Rattus norvegicus
AUC 0.64 microM.hr/mg/kg Canis lupus familiaris
AUC 0.04 microM.hr/mg/kg Macaca mulatta
CL 26.8 mL.min-1.kg-1 Canis lupus familiaris
CL 62.0 mL.min-1.kg-1 Rattus norvegicus
CL 20.0 mL.min-1.kg-1 Canis lupus familiaris
CL 19.0 mL.min-1.kg-1 Macaca mulatta
CL 62.0 mL.min-1.kg-1 Rattus norvegicus
CL 20.0 mL.min-1.kg-1 Canis lupus familiaris
CL 19.0 mL.min-1.kg-1 Macaca mulatta
CL 62.0 mL.min-1.kg-1 Rattus norvegicus
CL 20.0 mL.min-1.kg-1 Canis lupus familiaris
CL 19.0 mL.min-1.kg-1 Macaca mulatta
CL 3100.0 mL.min-1.kg-1 Rattus norvegicus
CL 1000.0 mL.min-1.kg-1 Canis lupus familiaris
CL 950.0 mL.min-1.kg-1 Macaca mulatta
F 38.0 % Canis lupus familiaris
F 17.0 % Rattus norvegicus
F 17.0 % Rattus norvegicus
F 27.0 % Canis lupus familiaris
F 4.0 % Macaca mulatta
F 17.0 % Rattus norvegicus
F 27.0 % Canis lupus familiaris
F 4.0 % Macaca mulatta
F 27.0 % Canis lupus familiaris
F 17.0 % Rattus norvegicus
F 4.0 % Macaca mulatta
F 17.0 % Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Beta-3 adrenergic receptor EC50 = 0.43 nM 9.37 Agonist activity at rhesus monkey beta3 adrenergic receptor expressed in CHO cel... 26709102
Beta-3 adrenergic receptor EC50 = 2.0 nM 8.7 Agonist activity at human beta3 adrenergic receptor expressed in CHO cells asses... 26709102
Beta-3 adrenergic receptor EC50 = 3.0 nM 8.52 Agonist activity (EC50) was assessed by measuring cAMP levels in CHO cells expre... 15149682
Beta-3 adrenergic receptor EC50 = 3.0 nM 8.52 Agonist activity at human adrenergic beta-3 receptor expressed in CHO cells asse... 17632003
Beta-3 adrenergic receptor EC50 = 3.6 nM 8.44 In vitro functional efficacy as increased cAMP in chinese hamster ovary (CHO) ce... 11052788
Beta-3 adrenergic receptor EC50 = 3.6 nM 8.44 Agonistic activity at human beta3 adrenergic receptor expressed in CHO cells ass... 20181479
Beta-3 adrenergic receptor EC50 = 7.9 nM 8.1 Agonist activity at human adrenergic beta3 receptor expressed in CHO cells asses... 26709102
Beta-3 adrenergic receptor EC50 = 17.0 nM 7.77 Agonist activity at rhesus monkey beta3 adrenergic receptor expressed in CHO cel... 26709102
Beta-3 adrenergic receptor EC50 = 25.0 nM 7.6 Agonist activity at dog beta3 adrenergic receptor expressed in CHO cells assesse... 26709102
Beta-3 adrenergic receptor IC50 = 46.0 nM 7.34 Binding affinity was evaluated on chinese hamster ovary (CHO) cells expressing t... 11052788
Voltage-gated inwardly rectifying potassium channel KCNH2 IC50 = 220.0 nM 6.66 Binding affinity to human ERG channel 26709102
Beta-2 adrenergic receptor IC50 = 670.0 nM 6.17 Displacement of [125]I-cyanopindolol from human recombinant beta2 adrenergic rec... 26709102
Beta-1 adrenergic receptor IC50 = 1000.0 nM 6.0 Displacement of [125]I-cyanopindolol from recombinant human beta1 adrenergic rec... 26709102
Voltage-dependent L-type calcium channel subunit alpha-1C IC50 = 1700.0 nM 5.77 Displacement of [3H]-diltiazem from human Cav1.2 channel 26709102
Beta-1 adrenergic receptor IC50 = 2300.0 nM 5.64 Binding affinity was evaluated on chinese hamster ovary (CHO) cells expressing t... 11052788
Beta-2 adrenergic receptor IC50 = 2300.0 nM 5.64 Binding affinity was evaluated on chinese hamster ovary (CHO) cells expressing t... 11052788
Beta-2 adrenergic receptor IC50 = 2300.0 nM 5.64 Displacement of [125I]cyanopindolol from human beta 2 adrenergic receptor expres... 20181479
Beta-1 adrenergic receptor IC50 = 2300.0 nM 5.64 Displacement of [125I]cyanopindolol from human beta 1 adrenergic receptor expres... 20181479
Beta-2 adrenergic receptor EC50 = 2400.0 nM 5.62 In vitro functional efficacy in stimulating increase in cAMP in chinese hamster ... 11052788
Beta-3 adrenergic receptor EC50 = 3400.0 nM 5.47 Agonist activity at rat beta3 adrenergic receptor expressed in CHO cells assesse... 26709102

Literature References

PubMed DOI Target Context # Activities
26709102 10.1021/acs.jmedchem.5b01372 Beta-3 adrenergic receptor 13
11052788 10.1021/jm000286i Canis familiaris 6
26709102 10.1021/acs.jmedchem.5b01372 Canis familiaris 6
26709102 10.1021/acs.jmedchem.5b01372 Rhesus monkey 6
26709102 10.1021/acs.jmedchem.5b01372 Rattus norvegicus 6
21353541 10.1016/j.bmcl.2010.12.087 Rhesus monkey 5
21353541 10.1016/j.bmcl.2010.12.087 Canis familiaris 5
21353541 10.1016/j.bmcl.2010.12.087 Rattus norvegicus 5
24437735 10.1021/jm4017224 Plasma 3
26709102 10.1021/acs.jmedchem.5b01372 NON-PROTEIN TARGET 3
24437735 10.1021/jm4017224 Rhesus monkey 3
24437735 10.1021/jm4017224 Canis familiaris 3
24437735 10.1021/jm4017224 Rattus norvegicus 3
26709102 10.1021/acs.jmedchem.5b01372 Homo sapiens 3
11052788 10.1021/jm000286i Beta-2 adrenergic receptor 3
11052788 10.1021/jm000286i Beta-1 adrenergic receptor 3
11052788 10.1021/jm000286i Beta-3 adrenergic receptor 3
17632003 10.1016/j.bmcl.2007.06.072 Beta-3 adrenergic receptor 2
15149682 10.1016/s0960-894x(04)00462-7 Beta-3 adrenergic receptor 2
26709102 10.1021/acs.jmedchem.5b01372 No relevant target 2

Data from ChEMBL 36 via Core Engine