Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C28H30FN5O2 |
| Molecular Weight | 487.5685 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1CCN(CC1)C2=CC=C(C=N2)C(C)(C)NC(=O)C3=CC4=C(C=C3F)C(=O)C5=C(N4)C=CC=C5
InChI
InChIKey=XEVJUIZOZCFECP-UHFFFAOYSA-N
InChI=1S/C28H30FN5O2/c1-4-33-11-13-34(14-12-33)25-10-9-18(17-30-25)28(2,3)32-27(36)20-16-24-21(15-22(20)29)26(35)19-7-5-6-8-23(19)31-24/h5-10,15-17H,4,11-14H2,1-3H3,(H,31,35)(H,32,36)
BMS-566419 is a potent inosine monophosphate dehydrogenase (IMPDH) inhibitor (IC50 = 17 nM). BMS-566419 inhibits proliferation of human T-lymphoblasts and PBMCs in vitro. BMS-566419 reduces paw swelling in a rat adjuvant arthritis model. BMS-566419 is orally available. In experimental rat model BMS-566419 by oral administration showed a significant and dose-dependent suppressive effect on UUO-induced renal fibrosis in histopathological experiments. BMS-566419 treatment also decreased collagen content, as indicated by hydroxyproline concentration, and the expression of collagen type 1 mRNA. BMS-566419 also decreased the expression of mRNA for both MCP-1 and TGF-β1. The antifibrotic effects of treatment with BMS-566419 at 60 mg/kg seemed comparable to those with MMF at 40 mg/kg. These results suggest that BMS-566419 and other chemically synthesized IMPDH inhibitors have beneficial pharmacological effects similar to those of MMF, and are potential pharmaceutical candidates in the treatment of fibrotic renal disease, including CAN.
Originator
Sources: http://adisinsight.springer.com/drugs/800024155 | https://www.ncbi.nlm.nih.gov/pubmed/17585753
Curator's Comment: # Bristol-Myers Squibb
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Effect of the inosine 5'-monophosphate dehydrogenase inhibitor BMS-566419 on renal fibrosis in unilateral ureteral obstruction in rats. | 2010-11 |
|
| Effect of the inosine 5'-monophosphate dehydrogenase inhibitor BMS-566419 on rat cardiac allograft rejection. | 2010-01 |
|
| Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419). | 2007-07-26 |
Patents
Sample Use Guides
Rat adjuvant arthritis model: BMS-566419 was administered at doses of 50 and 25 mg/kg PO/QD in the first experiment, along with MMF at
15 mg/kg, and doses of 10 and 5 mg/kg PO/QD in
a second experiment daily for 21 days starting at day 0. Significant inhibition of paw swelling was seen at doses of 10, 25, and 50 mg/kg PO/QD.
Route of Administration:
Oral
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ACTIVE MOIETY
