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Compound Detail

CHEMBL1272307

SB-649868
🧪 Phase II
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🧪 Phase II
Cc1nc(C(=O)N2CCCC[C@H]2CNC(=O)c2cccc3occc23)c(-c2ccc(F)cc2)s1

Basic Information

ChEMBL ID CHEMBL1272307
Name SB-649868
Phase Phase II
Structure Type MOL
InChI Key ZJXIUGNEAIHSBI-IBGZPJMESA-N

Known Names

GSK649868 Sb-649868
4
Targets
11
Activities
1
Assay Types
12
PK Parameters
20
Publications
2
Known Names
2
Indications
2
Mechanisms

Molecular Properties

477.6
MW (Da)
5.43
ALogP
5
HBA
1
HBD
75.4
PSA (Ų)
0.42
QED
1
Ro5 Violations
5
Rot. Bonds

Drug Information

Molecule Type Small molecule
Chirality Single Enantiomer

Extended Properties

Molecular Formula C26H24FN3O3S
MW 477.56
Aromatic Rings 4
Heavy Atoms 34
NP-Likeness -1.30

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Orexin receptor 1 antagonist ANTAGONIST Orexin/Hypocretin receptor type 1
Orexin receptor 2 antagonist ANTAGONIST Orexin receptor type 2

Indications

Sleep Wake Disorders Sleep Initiation and Maintenance Disorders

Activity Summary

Ki 11 meas. best 10.11

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Orexin receptor type 2
CHEMBL1275216
Ki 10.11 10.11 0.1 1
Orexin/Hypocretin receptor type 1
CHEMBL1075232
Ki 9.93 9.93 0.1 1
Orexin/Hypocretin receptor type 1
CHEMBL5113
Ki 9.52 9.41 0.3 4
Orexin receptor type 2
CHEMBL4792
Ki 9.4 9.032 0.4 5

Pharmacokinetic Data

Parameter Value Units Species
CL 24.0 mL.min-1.kg-1 Rattus norvegicus
CL 8.7 mL.min-1.g-1 Rattus norvegicus
CL 15.1 mL.min-1.g-1 Homo sapiens
Cmax 697.29 nM Rattus norvegicus
F 85.0 % Rattus norvegicus
Fu 0.0528 - Rattus norvegicus
Fu 0.0134 - Rattus norvegicus
T1/2 0.6 hr Rattus norvegicus
T1/2 3.4 hr Homo sapiens
T1/2 5.0 hr Homo sapiens
T1/2 39.0 hr Homo sapiens
T1/2 4.0 hr Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Orexin receptor type 2 Ki = 0.07762 nM 10.11 Antagonist activity at recombinant rat OX2R expressed in CHO cells by FLIPR calc... 21831639
Orexin/Hypocretin receptor type 1 Ki = 0.1175 nM 9.93 Antagonist activity at recombinant rat OX1R expressed in CHO cells by FLIPR calc... 21831639
Orexin/Hypocretin receptor type 1 Ki = 0.3 nM 9.52 Binding affinity to orexin receptor 1 (unknown origin) 23891187
Orexin/Hypocretin receptor type 1 Ki = 0.3162 nM 9.5 Antagonist activity against human orexin 1 receptor expressed in CHO cells asses... 20933413
Orexin/Hypocretin receptor type 1 Ki = 0.3162 nM 9.5 Antagonist activity at recombinant human OX1R expressed in CHO cells by FLIPR ca... 21831639
Orexin receptor type 2 Ki = 0.3981 nM 9.4 Antagonist activity against human orexin 2 receptor expressed in CHO cells asses... 20933413
Orexin receptor type 2 Ki = 0.3981 nM 9.4 Antagonist activity at recombinant human OX2R expressed in CHO cells by FLIPR ca... 21831639
Orexin receptor type 2 Ki = 0.4 nM 9.4 Binding affinity to orexin receptor 2 (unknown origin) 23891187
Orexin/Hypocretin receptor type 1 Ki = 0.7586 nM 9.12 Displacement of [3H]almorexant from recombinant human OX1R expressed in CHO cell... 21831639
Orexin receptor type 2 Ki = 1.288 nM 8.89 Displacement of [3H]almorexant from recombinant human OX2R expressed in CHO cell... 21831639
Orexin receptor type 2 Ki = 8.5 nM 8.07 Displacement of [125I]-Orexin A from human OX2R expressed in CHO cells after 30 ... 25267004

Literature References

PubMed DOI Target Context # Activities
21831639 10.1016/j.bmcl.2011.06.086 Rattus norvegicus 28
26317591 10.1021/acs.jmedchem.5b00832 Homo sapiens 15
21045199 10.1124/dmd.110.035386 Homo sapiens 7
21045199 10.1124/dmd.110.035386 Plasma 6
21831639 10.1016/j.bmcl.2011.06.086 Orexin receptor type 2 5
21831639 10.1016/j.bmcl.2011.06.086 Orexin/Hypocretin receptor type 1 5
- 10.6019/CHEMBL4651402 SARS-CoV-2 2
26317591 10.1021/acs.jmedchem.5b00832 Plasma 2
21831639 10.1016/j.bmcl.2011.06.086 Liver microsomes 2
21045199 10.1124/dmd.110.035386 ADMET 2
23891187 10.1016/j.bmcl.2013.06.057 Orexin/Hypocretin receptor type 1 1
21045199 10.1124/dmd.110.035386 Canis familiaris 1
21045199 10.1124/dmd.110.035386 Rattus norvegicus 1
25693785 10.1016/j.bmc.2015.01.044 Homo sapiens 1
25267004 10.1016/j.bmc.2014.08.034 Orexin receptor type 2 1
20933413 10.1016/j.bmcl.2010.09.090 Orexin receptor type 2 1
23891187 10.1016/j.bmcl.2013.06.057 Orexin receptor type 2 1
21831639 10.1016/j.bmcl.2011.06.086 Nucleic Acid 1
21831639 10.1016/j.bmcl.2011.06.086 Plasma 1
21831639 10.1016/j.bmcl.2011.06.086 Brain 1

Data from ChEMBL 36 via Core Engine