| Identification | Back Directory | [Name]
PF-3882845 | [CAS]
1023650-66-9 | [Synonyms]
PF-3882845
PF-03882845
PF3882845,PF 3882845
PF-03882845 >=98% (HPLC)
(3S,3aR)-2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydrobenzo[g]indazole-7-carboxylic acid
(3S,3aR)-2-(3-Chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid
2H-Benz[g]indazole-7-carboxylic acid, 2-(3-chloro-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-, (3S,3aR)- | [Molecular Formula]
C24H22ClN3O2 | [MDL Number]
MFCD28124394 | [MOL File]
1023650-66-9.mol | [Molecular Weight]
419.9 |
| Chemical Properties | Back Directory | [storage temp. ]
room temp | [solubility ]
DMSO: soluble10mg/mL, clear | [form ]
powder | [color ]
white to beige | [InChIKey]
XNULRSOGWPFPBL-REWPJTCUSA-N | [SMILES]
OC(C1=CC2=C(C=C1)C3=NN(C4=CC=C(C#N)C(Cl)=C4)[C@@H](C5CCCC5)[C@@]3([H])CC2)=O |
| Hazard Information | Back Directory | [Uses]
PF-3882845 is a remarkably high affinity selective and orally efficacious mineralocorticoid receptor (MR binding IC50=2.7 nM) antagonist for hypertension and nephropathy. PF-3882845 also binds to progesterone receptor (PR) with the binding IC50 of 310 nM[1]. | [Biological Activity]
PF-03882845 is a potent non-steroidal mineralocorticoid antagonist with and IC50 of 0.755 nM, compared to eplerenone with an IC50 of 109 nM. PF-03882845 was tested in a r at model for renal protection against aldosterone-mediated renal disease, and found to be more potent than eplerenone in suppressing the urinary albumin to creatinine ratio (UACR), a measure of renal fibrosis. The therapeutic index, calculated as the ratio of the EC50 for increasing serum K+ to the EC50 for UACR lowering, was 83.8 for PF-03882845 and 1.47 for eplerenone. | [in vivo]
PF-3882845 reduces blood pressure, decreases urinary albumin, and protects kidney in Dahl SS rat[1].
PF-3882845 exhibits moderate oral bioavailability (F 86%) following oral administration (2 mg/kg) in male Sprague-Dawley rats[1].
PF-3882845 exhibits terminal elimination half-lives (T1/2 1.7 h) due to high plasma clearance (CL 9.8 mL/min/kg) combined with large volumes of distribution (Vdss 1.4 mL/kg respectively) following intravenous administration (2 mg/kg) in male Sprague-Dawley rats[1].
| Animal Model: | Male Dahl salt sensitive (SS) rats[1] | | Dosage: | 10, 40, and 100 mg/kg | | Administration: | Orally via gavage; twice a day; for 21 days | | Result: | Significant blood pressure reduction was observed with 10 mg/kg. Most noticeably, rats dosed at 40 and 100 mg/kg had negligible increase in blood pressure over 21 days in the presence of high salt. |
| [References]
[1] Meyers MJ, et al. 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. J Med Chem. 2010 Aug 26;53(16):5979-6002. DOI:10.1021/jm100505n |
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Energy Chemical
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