PF-04447943

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Search structure


Synonyms	Pf-04447943
Status
Molecule Category	UNKNOWN
UNII	7N969W8Y4O


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

Structure


InChI Key	IWXUVYOOUMLUTQ-CZUORRHYSA-N
Smiles	C[C@@H]1CN(Cc2ncccn2)C[C@H]1c1nc2c(cnn2C2CCOCC2)c(=O)[nH]1
InChI	InChI=1S/C20H25N7O2/c1-13-10-26(12-17-21-5-2-6-22-17)11-16(13)18-24-19-15(20(28)25-18)9-23-27(19)14-3-7-29-8-4-14/h2,5-6,9,13-14,16H,3-4,7-8,10-12H2,1H3,(H,24,25,28)/t13-,16-/m1/s1

Physicochemical Descriptors

Property Name	Value
Molecular Formula	C20H25N7O2
Molecular Weight	395.47
AlogP	1.5
Hydrogen Bond Acceptor	8.0
Hydrogen Bond Donor	1.0
Number of Rotational Bond	4.0
Polar Surface Area	101.82
Molecular species	NEUTRAL
Aromatic Rings	3.0
Heavy Atoms	29.0

Bioactivity

Mechanism of Action	Action	Reference
Phosphodiesterase 9A inhibitor	INHIBITOR	PubMed PubMed PubMed


Protein: Phosphodiesterase 9A Description: High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A Organism : Homo sapiens O76083 ENSG00000160191

Targets	EC50(nM)	IC50(nM)	Kd(nM)	Ki(nM)	Inhibition(%)
Enzyme Phosphodiesterase Phosphodiesterase 1 Phosphodiesterase 1C	-	1394	-	-	-
Enzyme Phosphodiesterase Phosphodiesterase 9 Phosphodiesterase 9A	-	8-49	-	-	-

Assay Description	Organism	Bioactivity	Reference
Inhibition of human recombinant PDE9A expressed in Sf9 cells using [3H]cGMP as substrate after 30 mins by scintillation proximity assay	Homo sapiens	8.3 nM
Inhibition of PDE9 (unknown origin) using [3H]-cGMP as substrate after 1 hr by scintillation counting method	Homo sapiens	49.0 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	0.76 %
SARS-CoV-2 3CL-Pro protease inhibition percentage at 20µM by FRET kind of response from peptide substrate	Severe acute respiratory syndrome coronavirus 2	4.142 %
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	-0.13 %		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	-0.13 %

Cross References

Resources	Reference
ChEMBL	CHEMBL2179105
DrugBank	DB11953
FDA SRS	7N969W8Y4O
PDB	7RG
PubChem	135564558
SureChEMBL	SCHEMBL1716847
ZINC	ZINC000068199983

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).