Edelinontrine

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H25N7O2
Molecular Weight	395.4582
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H]1CN(CC2=NC=CC=N2)C[C@H]1C3=NC4=C(C=NN4C5CCOCC5)C(=O)N3

InChI

InChIKey=IWXUVYOOUMLUTQ-CZUORRHYSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/22070409 | https://www.ncbi.nlm.nih.gov/pubmed/25328054
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/22780914

PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 was being developed by Pfizer for the treatment of cognitive disorders. PF-04447943 attenuates a scopolamine-induced deficit in a novel rodent attention task. PF-04447943 enhances synaptic plasticity and cognitive function in rodents. PF-04447943 has completed Phase II clinical trials in subjects with mild to moderate AD in 2013 but this research was discontinued. Pfizer completes a phase I trial in Sickle cell anaemia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Phosphodiesterase 9A 3 Target ID: CHEMBL3535 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22780914	Inhibitor 8297		8.3 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT00930059 http://adisinsight.springer.com/drugs/800028797	Primary		Phase II 1132	Unknown Approved Use Unknown
Sickle cell anemia 12 Sources: http://adisinsight.springer.com/drugs/800028797 https://clinicaltrials.gov/ct2/show/NCT02114203	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
45.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30597771	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04447943 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1170 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30597771	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04447943 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
242 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30597771	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04447943 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
248.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/30597771	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:		PF-04447943 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	HLM 31 P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678313	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678313	no
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363678313	no

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22780914/	no
HLM 31	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/22780914/	unlikely

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34272	https://www.001chemical.com/chem/search?q=DY34272
1PlusChem LLC	1P008TZK	https://www.1pchem.com/search?query=1P008TZK
AChemBlock	L13959	http://www.achemblock.com/catalogsearch/result/?q=L13959
AK Scientific	3967AH	https://aksci.com/item_detail.php?cat=3967AH
Angene	AGN-PC-0WHEX1	http://www.angenechemical.com/productshow/AGN-PC-0WHEX1.html
AstaTech	42271	http://astatechinc.com/CPSResult.php?CRNO=42271
Axon MedChem	2148	https://www.axonmedchem.com/product/2148
Chem Scene	CS-0942	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0942
KeyOrganics	AS-35203	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-35203
MedChem Express	HY-15441	https://www.medchemexpress.com/search.html?q=HY-15441&ft=&fa=&fp=
MolPort	MolPort-039-139-772	https://www.molport.com/shop/molecule-link/MolPort-039-139-772
MolPort	MolPort-046-426-413	https://www.molport.com/shop/molecule-link/MolPort-046-426-413
Molcore	MC34272	http://www.molcore.com/CatMC34272.html
Molnova	M10326	https://www.molnova.com/en/serch-list.html?keywords=M10326
Ryan Scientific	101-94118	https://ryansci.com/products?q=101-94118&list_q=&search_type=exact
eMolecules	271380522	https://orderbb.emolecules.com/search/#?query=271380522
eMolecules	300755989	https://orderbb.emolecules.com/search/#?query=300755989
eMolecules	313088314	https://orderbb.emolecules.com/search/#?query=313088314
eMolecules	44811342	https://orderbb.emolecules.com/search/#?query=44811342
mcule	MCULE-6189008811	https://mcule.com/MCULE-6189008811/

PubMed

Title	Date	PubMed
		252160769

Patents

Sample Use Guides

In Vivo Use Guide

tablets, 25 mg every 12 hours for 12 wks

Route of Administration: Oral

In Vitro Use Guide

PF-04447943 inhibits human recombinant PDE9A expressed in Sf9 cells with IC50 8.3nM

Name

Type

Language

Edelinontrine

Official Name

English

CRD740

Code

English

4H-PYRAZOLO(3,4-D)PYRIMIDIN-4-ONE, 1,5-DIHYDRO-6-((3S,4S)-4-METHYL-1-(2-PYRIMIDINYLMETHYL)-3-PYRROLIDINYL)-1-(TETRAHYDRO-2H-PYRAN-4-YL)-

Systematic Name

English

PF04447943

Code

English

CRD-740

Code

English

6-{(3S,4S)-4-methyl-1-[(pyrimidin-2-yl)methyl]pyrrolidin-3-yl}-1-(oxan-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one

Systematic Name

English

PF-04447943

Code

English

edelinontrine [INN]

Common Name

English

PF-4447943

Code

English

PF4447943

Code

English

Classification Tree Code System Code

FDA ORPHAN DRUG

440514