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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H22ClN3O2
Molecular Weight 419.903
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PF-03882845

SMILES

[H][C@]12CCC3=CC(=CC=C3C1=NN([C@H]2C4CCCC4)C5=CC=C(C#N)C(Cl)=C5)C(O)=O

InChI

InChIKey=XNULRSOGWPFPBL-REWPJTCUSA-N
InChI=1S/C24H22ClN3O2/c25-21-12-18(8-5-17(21)13-26)28-23(14-3-1-2-4-14)20-10-6-15-11-16(24(29)30)7-9-19(15)22(20)27-28/h5,7-9,11-12,14,20,23H,1-4,6,10H2,(H,29,30)/t20-,23-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24738581

Pfizer was developing PF-3882845, an orally available nonsteroidal antagonist of the mineralocorticoid receptor, for the treatment of diabetic nephropathies. PF‐03882845 is a highly potent (IC50 = 6.3‐13.4 nM, 10% fetal bovine serum & IC50 = 0.504–1.11 nM, absence of serum) selective orally bioavailable mineralocorticoid receptor antagonist. It is a non‐steroidal pyrazoline, unlike steroidal compounds eplerenone and spironolactone. It does not significantly activate or inhibit human androgen receptor, estrogen receptor alpha, and glucocorticoid receptor. PF‐03882845 has been shown to modestly inhibit the progesterone receptor (PR) yielding a 45‐fold selectivity over PR in a cell‐based functional assay. PF‐03882845 was previously in development for the treatment of diabetic nephropathy — development for this indication was terminated for strategic reasons. An alternative indication of hypertension also was not pursued for strategic reasons.

Originator

Curator's Comment: # Pfizer

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
9.2 nM [IC50]
Conditions

Conditions

Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 29.0929 uM]
PubMed

PubMed

TitleDatePubMed
Discovery of (3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (PF-3882845), an orally efficacious mineralocorticoid receptor (MR) antagonist for hypertension and nephropathy.
2010 Aug 26
Patents

Sample Use Guides

3 - 30 mg tablet once daily
Route of Administration: Oral
PF-3882845 inhibited mineralocorticoid receptor with IC50 9.2 nM in Gal4-based cellular assay
Name Type Language
PF-03882845
Common Name English
PF-3882845
Code English
2H-BENZ(G)INDAZOLE-7-CARBOXYLIC ACID, 2-(3-CHLORO-4-CYANOPHENYL)-3-CYCLOPENTYL-3,3A,4,5-TETRAHYDRO-, (3S,3AR)-
Common Name English
(3S,3AR)-2-(3-CHLORO-4-CYANOPHENYL)-3-CYCLOPENTYL-3,3A,4,5-TETRAHYDRO-2HBENZO(G)INDAZOLE-7-CARBOXYLIC ACID
Common Name English
Code System Code Type Description
ChEMBL
CHEMBL3545175
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
PRIMARY
CAS
1023650-66-9
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
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FDA UNII
34ZKU73FU3
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
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EPA CompTox
DTXSID70144940
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
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SMS_ID
300000041323
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
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DRUG BANK
DB11814
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
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PUBCHEM
46871935
Created by admin on Sat Dec 16 01:37:02 GMT 2023 , Edited by admin on Sat Dec 16 01:37:02 GMT 2023
PRIMARY