AZD1446

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Synonyms
Status
Molecule Category Free-form
UNII ANR9OP1V17

Structure

InChI Key GTUIQNHJSXQMKW-UHFFFAOYSA-N
Smiles O=C(c1ccc(Cl)o1)N1CC2CNCC2C1
InChI
InChI=1S/C11H13ClN2O2/c12-10-2-1-9(16-10)11(15)14-5-7-3-13-4-8(7)6-14/h1-2,7-8,13H,3-6H2

Physicochemical Descriptors

Property Name Value
Molecular Formula C11H13ClN2O2
Molecular Weight 240.69
AlogP 1.22
Hydrogen Bond Acceptor 3.0
Hydrogen Bond Donor 1.0
Number of Rotational Bond 1.0
Polar Surface Area 45.48
Molecular species BASE
Aromatic Rings 1.0
Heavy Atoms 16.0

Bioactivity

Mechanism of Action Action Reference
Neuronal acetylcholine receptor; alpha4/beta2 agonist AGONIST PubMed
Protein: Neuronal acetylcholine receptor; alpha4/beta2
Description: Neuronal acetylcholine receptor subunit beta-2
Organism : Homo sapiens
P17787 ENSG00000160716
Protein: Neuronal acetylcholine receptor; alpha4/beta2
Description: Neuronal acetylcholine receptor subunit alpha-4
Organism : Homo sapiens
P43681 ENSG00000101204
Targets EC50(nM) IC50(nM) Kd(nM) Ki(nM) Inhibition(%)
Ion channel Ligand-gated ion channel 5HT3 receptor
- - - 700 87
Ion channel Ligand-gated ion channel Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor alpha subunit
4900-4900 - - 30-30 -
Ion channel Ligand-gated ion channel Nicotinic acetylcholine receptor Nicotinic acetylcholine receptor beta subunit
4900-4900 - - 30-30 -
Assay Description Organism Bioactivity Reference
Inhibition of human ERG at 10 uM Homo sapiens 5.0 %
Inhibition of human 5HT3 receptor Homo sapiens 700.0 nM
Inhibition of human 5HT3 receptor at 10 uM Homo sapiens 87.0 %
Inhibition of mouse 5HT3 receptor at 10 uM Mus musculus 97.0 %
Displacement of [3H]epibatidine from alpha4beta2 nAChR in Sprague-Dawley rat cortex after 2 hrs by liquid scintillation counting Rattus norvegicus 34.0 nM
Displacement of [3H]nicotine from alpha4beta2 nAChR in human SH-EP1 cells after 2 hrs by liquid scintillation assay Homo sapiens 30.0 nM
Displacement of [3H]Nicotine from alpha4beta2 nACHR in human SHEP1 cell membranes after 2 hrs by liquid scintillation counting analysis Homo sapiens 30.0 nM
Radioligand Binding: The binding of [3H]MLA was measured using a modification of the methods of Davies et al., Neuropharmacol. 38: 679 (1999). [3H]MLA (Specific Activity=25-35 Ci/mmol) was obtained from Tocris. The binding of [3H]MLA was determined using a 2 h incubation at 21 C. Incubations were conducted in 48-well micro-titre plates and contained about 200 μg of protein per well in a final incubation volume of 300 uL. The incubation buffer was PBS and the final concentration of [3H]MLA was 5 nM. The binding reaction was terminated by filtration of the protein containing bound ligand onto glass fiber filters (GF/B, Brandel) using a Brandel Tissue Harvester at room temperature. Filters were soaked in de-ionized water containing 0.33% polyethyleneimine to reduce non-specific binding. Each filter was washed with PBS (3x1 mL) at room temperature. Non-specific binding was determined by inclusion of 50 uM non-radioactive MLA in selected wells. Rattus norvegicus 33.0 nM
Radioligand Binding: The binding of [3H]MLA was measured using a modification of the methods of Davies et al., Neuropharmacol. 38: 679 (1999). [3H]MLA (Specific Activity=25-35 Ci/mmol) was obtained from Tocris. The binding of [3H]MLA was determined using a 2 h incubation at 21 C. Incubations were conducted in 48-well micro-titre plates and contained about 200 μg of protein per well in a final incubation volume of 300 uL. The incubation buffer was PBS and the final concentration of [3H]MLA was 5 nM. The binding reaction was terminated by filtration of the protein containing bound ligand onto glass fiber filters (GF/B, Brandel) using a Brandel Tissue Harvester at room temperature. Filters were soaked in de-ionized water containing 0.33% polyethyleneimine to reduce non-specific binding. Each filter was washed with PBS (3x1 mL) at room temperature. Non-specific binding was determined by inclusion of 50 uM non-radioactive MLA in selected wells. Homo sapiens 28.0 nM
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of Caco-2 cells at 10 uM after 48 hours by high content imaging Homo sapiens 5.17 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate Severe acute respiratory syndrome coronavirus 2 14.6 %
Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.04 % Antiviral activity determined as inhibition of SARS-CoV-2 induced cytotoxicity of VERO-6 cells at 10 uM after 48 hours exposure to 0.01 MOI SARS CoV-2 virus by high content imaging Chlorocebus sabaeus 0.04 %

Cross References

Resources Reference
ChEMBL CHEMBL2179529
FDA SRS ANR9OP1V17
SureChEMBL SCHEMBL584395
CONTENTS