FILOREXANT

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Search structure


Synonyms	Filorexant MK-6096
Status
Molecule Category	UNKNOWN
UNII	E6BTT8VA5Z
EPA CompTox	DTXSID50148764


Active Pharmaceutical Ingredients Bioactive chemicals	Exact Similarity SubStructure	Threshold (%) >= 70

Structure


InChI Key	NPFDWHQSDBWQLH-QZTJIDSGSA-N
Smiles	Cc1ccc(-c2ncccn2)c(C(=O)N2C[C@H](COc3ccc(F)cn3)CC[C@H]2C)c1
InChI	InChI=1S/C24H25FN4O2/c1-16-4-8-20(23-26-10-3-11-27-23)21(12-16)24(30)29-14-18(6-5-17(29)2)15-31-22-9-7-19(25)13-28-22/h3-4,7-13,17-18H,5-6,14-15H2,1-2H3/t17-,18-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C24H25FN4O2
Molecular Weight	420.49
AlogP	4.31
Hydrogen Bond Acceptor	5.0
Hydrogen Bond Donor	0.0
Number of Rotational Bond	5.0
Polar Surface Area	68.21
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	31.0

Bioactivity

Mechanism of Action	Action	Reference
Orexin receptor antagonist	ANTAGONIST	PubMed PubMed

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Membrane receptor Family A G protein-coupled receptor Peptide receptor (family A GPCR) Short peptide receptor (family A GPCR) Orexin receptor	-	11-16	-	0-0	-

Assay Description	Organism	Bioactivity	Reference
Binding affinity to orexin receptor 1 (unknown origin)	Homo sapiens	2.5 nM
Binding affinity to orexin receptor 2 (unknown origin)	Homo sapiens	0.3 nM
Antagonist activity at human OX2R by radioligand displacement assay	Homo sapiens	0.3 nM
Antagonist activity at human OX1R by radioligand displacement assay	Homo sapiens	2.9 nM
Antagonist activity at human OX2R by FLIPR assay	Homo sapiens	17.0 nM
Antagonist activity at human OX1R by FLIPR assay	Homo sapiens	16.0 nM
Antagonist activity at orexin-1 receptor (unknown origin)	Homo sapiens	2.5 nM
Antagonist activity at orexin-2 receptor (unknown origin)	Homo sapiens	0.3 nM
Radioligand Binding Assay: Radioligand binding assay described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430.	Rattus norvegicus	2.9 nM
Radioligand Binding Assay: Radioligand binding assay described in Bergman et. al. Bioorg. Med. Chem. Lett. 2008, 18, 1425-1430.	Rattus norvegicus	0.31 nM
Antagonist activity at human OX1R expressed in CHO cell membranes assessed as inhibition of orexin-A-induced intracellular calcium release after 120 mins	Homo sapiens	11.0 nM
Binding affinity to OX2R (unknown origin)	Homo sapiens	0.3 nM
Binding affinity to OX1R (unknown origin)	Homo sapiens	2.2 nM
Antagonist activity at human OX2R expressed in CHO cell membranes assessed as inhibition of orexin-A-induced intracellular calcium release after 120 mins	Homo sapiens	11.0 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	-4.63 %
Displacement of [3H]4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethoxypyridin-3-yl)-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide from human wild-type OX1 receptor expressed in baculovirus infected Sf21 insect cell membranes measured after 90 mins by liquid scintillation counting method	Homo sapiens	0.631 nM
Displacement of [3H]4-(2,6-Difluoro-4-methoxybenzyl)-2-(5,6-dimethoxypyridin-3-yl)-2H-1,2,4-benzothiadiazin-3(4H)-one 1,1-dioxide from human wild-type OX2 receptor expressed in baculovirus infected Sf21 insect cell membranes measured after 90 mins by liquid scintillation counting method	Homo sapiens	0.1995 nM
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	20.66 %		SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	13.43 %
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	0.07 %		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	-0.16 %		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	-0.16 %		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	0.07 %

Cross References

Resources	Reference
ChEMBL	CHEMBL2107822
DrugBank	DB12158
FDA SRS	E6BTT8VA5Z
Guide to Pharmacology	4460
PDB	NT5
PubChem	25128145
SureChEMBL	SCHEMBL1716633
ZINC	ZINC000043201232

CONTENTS

PREMIER has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 875508. The JU receives support from the EU’s Horizon 2020 research and innovation programme and the European Federation of Pharmaceutical Industries and Associations (EFPIA). The views reflect only the authors’ perspective and the JU is not responsible for any use that may be made of the information this manuscript contains.

Elements of the website have been developed under projects PREMIER and the Biocenter Finland Drug Discovery and Chemical Biology network. CSC-IT is thanked for providing computational resources. Content of the website is provided without guarantee for correctness. Data has been collected and integrated from multiple public sources, for the largest: FDA, HUGO Gene Nomenclature Committee, ChEMBL, IUPHAR/BPS guide to pharmacology, Reactome, UniProt, and Ensembl. Credit is given to Ensembl for collecting species images (provided under public domain licences such as Wikimedia and NHGRI).