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Compound Detail

CHEMBL4277264

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Cc1cc(Oc2nccc3occc23)ccc1-c1c(C)ncc2nccn12

Basic Information

ChEMBL ID CHEMBL4277264
Phase Preclinical
Structure Type MOL
InChI Key HWAIAGZSWHOLLK-UHFFFAOYSA-N
31
Targets
46
Activities
3
Assay Types
14
PK Parameters
20
Publications
0
Known Names

Molecular Properties

356.4
MW (Da)
4.95
ALogP
6
HBA
0
HBD
65.5
PSA (Ų)
0.46
QED
0
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
Availability Unknown
Chirality Unknown

Flags

First in Class Prodrug

Extended Properties

Molecular Formula C21H16N4O2
MW 356.39
Aromatic Rings 5
Heavy Atoms 27
NP-Likeness -0.77

Activity Summary

Ki 31 meas. best 8.32
EC50 10 meas. best 9.61
IC50 5 meas. best 5.96

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
D(1A) dopamine receptor
CHEMBL2056
EC50 9.61 7.664 0.2 10
D(1B) dopamine receptor
CHEMBL1850
Ki 8.32 7.87 4.8 2
D(1A) dopamine receptor
CHEMBL2056
Ki 8.05 7.65 8.9 4
Sodium channel protein type 5 subunit alpha
CHEMBL1980
IC50 5.96 5.96 1100.0 1
5-hydroxytryptamine receptor 1A
CHEMBL214
Ki 5.92 5.92 1200.0 1
Cannabinoid receptor 1
CHEMBL218
IC50 5.68 5.68 2100.0 1
Kappa-type opioid receptor
CHEMBL237
Ki 5.51 5.51 3100.0 1
Alpha-2A adrenergic receptor
CHEMBL1867
Ki 5.47 5.47 3400.0 1
Alpha-1A adrenergic receptor
CHEMBL229
Ki 5.47 5.47 3400.0 1
5-hydroxytryptamine receptor 2B
CHEMBL1833
Ki 5.39 5.39 4100.0 1
D(4) dopamine receptor
CHEMBL219
Ki 5.35 5.35 4500.0 1
Histamine H1 receptor
CHEMBL231
IC50 5.34 5.34 4600.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
IC50 5.31 5.31 4900.0 1
5-hydroxytryptamine receptor 2A
CHEMBL224
Ki 5.31 5.31 4900.0 1
Beta-1 adrenergic receptor
CHEMBL213
Ki 5.12 5.12 7600.0 1
5-hydroxytryptamine receptor 7
CHEMBL3155
Ki 5.11 5.11 7800.0 1
Muscarinic acetylcholine receptor M2
CHEMBL211
Ki 5.11 5.11 7700.0 1
Histamine H2 receptor
CHEMBL1941
Ki 5.1 5.1 8000.0 1
5-hydroxytryptamine receptor 3A
CHEMBL1899
Ki 5.1 5.1 7900.0 1
D(3) dopamine receptor
CHEMBL234
Ki 5.1 5.1 7900.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 5.09 5.09 8200.0 1
5-hydroxytryptamine receptor 6
CHEMBL3371
Ki 5.09 5.09 8100.0 1
Mu-type opioid receptor
CHEMBL233
Ki 5.09 5.09 8200.0 1
D(2) dopamine receptor
CHEMBL217
Ki 5.08 5.08 8300.0 1
Sodium-dependent dopamine transporter
CHEMBL238
Ki 5.08 5.08 8300.0 1
Muscarinic acetylcholine receptor M1
CHEMBL216
Ki 5.06 5.06 8800.0 1
Alpha-1B adrenergic receptor
CHEMBL232
Ki 5.04 5.04 9200.0 1
5-hydroxytryptamine receptor 4
CHEMBL1875
Ki 5.04 5.04 9100.0 1
Beta-2 adrenergic receptor
CHEMBL210
Ki 5.03 5.03 9300.0 1
5-hydroxytryptamine receptor 1D
CHEMBL1983
Ki 5.03 5.03 9300.0 1
5-hydroxytryptamine receptor 1B
CHEMBL1898
Ki 5.03 5.03 9300.0 1
5-hydroxytryptamine receptor 1E
CHEMBL2182
Ki 5.01 5.01 9800.0 1
Voltage-gated inwardly rectifying potassium channel KCNH2
CHEMBL240
IC50 4.92 4.92 12000.0 1

Pharmacokinetic Data

Parameter Value Units Species
CL 22.0 mL.min-1.kg-1 Homo sapiens
CL 23.0 mL.min-1.kg-1 Rattus norvegicus
F 85.0 % Rattus norvegicus
Fu 0.04 - Homo sapiens
Fu 0.04 - Rattus norvegicus
Fu 0.04 - Mus musculus
Fu 0.02 - Rattus norvegicus
T1/2 2.3 hr Rattus norvegicus
T1/2 329551200.0 hr -
T1/2 4800480.0 hr -
T1/2 802416.0 hr -
T1/2 36792.0 hr -
T1/2 432.0 hr -
T1/2 0.009722 hr -

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
D(1A) dopamine receptor EC50 = 0.2455 nM 9.61 Agonist activity at recombinant human D1 receptor expressed in HEK29T cells asse... 30875219
D(1A) dopamine receptor EC50 = 0.25 nM 9.6 Agonist activity at recombinant human D1 receptor expressed in HEK29T cells asse... 30875219
D(1B) dopamine receptor Ki = 4.8 nM 8.32 Agonist activity at dopamine D5 receptor (unknown origin) 30431269
D(1A) dopamine receptor Ki = 8.9 nM 8.05 Displacement of [3H]-SCH23390 from human dopamine D1 receptor expressed in LTK c... 30431269
D(1A) dopamine receptor EC50 = 11.0 nM 7.96 Agonist activity at wild type human D1R expressed in HEK293 cells assessed as ef... 31098001
D(1A) dopamine receptor Ki = 11.9 nM 7.92 Displacement of [3H]-SCH23390 from human dopamine D1 receptor expressed in LTK c... 30431269
D(1A) dopamine receptor EC50 = 17.0 nM 7.77 Agonist activity at dopamine D1 receptor (unknown origin) assessed as increase i... 29939744
D(1A) dopamine receptor Ki = 21.6 nM 7.67 Displacement of [3H]-SCH23390 from human dopamine D1 receptor expressed in LTK c... 30431269
D(1A) dopamine receptor EC50 = 33.0 nM 7.48 Agonist activity at human dopamine D1 receptor expressed in HEK293T cells assess... 30431269
D(1B) dopamine receptor Ki = 38.0 nM 7.42 Displacement of [3H]-SCH23390 from recombinant human D5 receptor transiently exp... 30875219
D(1A) dopamine receptor EC50 = 106.0 nM 6.97 Agonist activity at human dopamine D1 receptor expressed in HEK293T cells assess... 30431269
D(1A) dopamine receptor EC50 = 110.0 nM 6.96 Agonist activity at recombinant C-terminal RLuc8-fused human D1 receptor express... 30875219
D(1A) dopamine receptor Ki = 110.0 nM 6.96 Displacement of [3H]-SCH23390 from recombinant human D1 receptor transiently exp... 30875219
D(1A) dopamine receptor EC50 = 114.82 nM 6.94 Agonist activity at recombinant C-terminal RLuc8-fused human D1 receptor express... 30875219
D(1A) dopamine receptor EC50 = 141.0 nM 6.85 Agonist activity at human dopamine D1 receptor expressed in HEK293T cells assess... 30431269
D(1A) dopamine receptor EC50 = 320.0 nM 6.5 Agonist activity at wild type human D1R expressed in HEK293 cells assessed as ef... 31098001
Sodium channel protein type 5 subunit alpha IC50 = 1100.0 nM 5.96 Inhibition of Nav1.5 (unknown origin) 30431269
5-hydroxytryptamine receptor 1A Ki = 1200.0 nM 5.92 Displacement of [3H]-Way100635 from recombinant human 5HT1A receptor stably expr... 30875219
Cannabinoid receptor 1 IC50 = 2100.0 nM 5.68 Antagonist activity at CB1 receptor (unknown origin) 30431269
Kappa-type opioid receptor Ki = 3100.0 nM 5.51 Displacement of [3H]-U69593 from KOR (unknown origin) measured after 90 mins by ... 30875219

Literature References

PubMed DOI Target Context # Activities
30431269 10.1021/acs.jmedchem.8b01622 D(1A) dopamine receptor 12
30431269 10.1021/acs.jmedchem.8b01622 ADMET 10
30875219 10.1021/acs.jmedchem.9b00351 D(1A) dopamine receptor 8
30431269 10.1021/acs.jmedchem.8b01622 No relevant target 8
31098001 10.1021/acsmedchemlett.9b00050 D(1A) dopamine receptor 4
30431269 10.1021/acs.jmedchem.8b01622 Rattus norvegicus 3
30431269 10.1021/acs.jmedchem.8b01622 Mus musculus 2
29939744 10.1021/acs.jmedchem.8b00435 D(1A) dopamine receptor 2
30431269 10.1021/acs.jmedchem.8b01622 D(2) dopamine receptor 1
30431269 10.1021/acs.jmedchem.8b01622 D(1B) dopamine receptor 1
30431269 10.1021/acs.jmedchem.8b01622 Sodium channel protein type 5 subunit alpha 1
30431269 10.1021/acs.jmedchem.8b01622 Voltage-gated inwardly rectifying potassium channel KCNH2 1
30431269 10.1021/acs.jmedchem.8b01622 Histamine H1 receptor 1
30431269 10.1021/acs.jmedchem.8b01622 Cannabinoid receptor 1 1
30875219 10.1021/acs.jmedchem.9b00351 D(2) dopamine receptor 1
30875219 10.1021/acs.jmedchem.9b00351 D(3) dopamine receptor 1
30875219 10.1021/acs.jmedchem.9b00351 D(4) dopamine receptor 1
30875219 10.1021/acs.jmedchem.9b00351 D(1B) dopamine receptor 1
30875219 10.1021/acs.jmedchem.9b00351 5-hydroxytryptamine receptor 1A 1
30875219 10.1021/acs.jmedchem.9b00351 5-hydroxytryptamine receptor 1B 1

Data from ChEMBL 36 via Core Engine