For research use only. Not for therapeutic Use.
BAY 85-8501 (Cat.No:I004062) is a new, highly potent and selective neutrophil elastase inhibitor (IC50 for HNE = 0.065 nM, LipE = 7.2). BAY 85-8501 has shown in vivo efficacy in various preclinical animal models. BAY 85-8501 is currently being tested in clinical studies for the treatment of pulmonary diseases.
| Catalog Number | I004062 |
| CAS Number | 1161921-82-9 |
| Synonyms | BAY 85-8501; BAY85-8501; BAY-85-8501; BAY 858501; BAY858501; BAY-858501.;(S)-4-(4-cyano-2-(methylsulfonyl)phenyl)-3,6-dimethyl-2-oxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidine-5-carbonitrile |
| Molecular Formula | C22H17F3N4O3S |
| Purity | ≥95% |
| Target | Elastase |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term or -20 °C for long term |
| IUPAC Name | (4S)-4-(4-cyano-2-methylsulfonylphenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4H-pyrimidine-5-carbonitrile |
| InChI | InChI=1S/C22H17F3N4O3S/c1-13-18(12-27)20(17-8-7-14(11-26)9-19(17)33(3,31)32)28(2)21(30)29(13)16-6-4-5-15(10-16)22(23,24)25/h4-10,20H,1-3H3/t20-/m1/s1 |
| InChIKey | YAJWYFPMASPAMM-HXUWFJFHSA-N |
| SMILES | CC1=C(C(N(C(=O)N1C2=CC=CC(=C2)C(F)(F)F)C)C3=C(C=C(C=C3)C#N)S(=O)(=O)C)C#N |
| Reference | 1:ChemMedChem. 2015 Jul;10(7):1163-73. doi: 10.1002/cmdc.201500131. Epub 2015 Jun 17. Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY 85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases.von Nussbaum F,Li VM,Allerheiligen S,Anlauf S,Bärfacker L,Bechem M,Delbeck M,Fitzgerald MF,Gerisch M,Gielen-Haertwig H,Haning H,Karthaus D,Lang D,Lustig K,Meibom D,Mittendorf J,Rosentreter U,Schäfer M,Schäfer S,Schamberger J,Telan LA,Tersteegen A, PMID: 26083237 PMCID: PMC4515084 DOI: 10.1002/cmdc.201500131 </br><span>Abstract:</span> Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH). HNE inhibitors should reestablish the protease-anti-protease balance. By means of medicinal chemistry a novel dihydropyrimidinone lead-structure class was identified. Further chemical optimization yielded orally active compounds with favorable pharmacokinetics such as the chemical probe BAY-678. While maintaining outstanding target selectivity, picomolar potency was achieved by locking the bioactive conformation of these inhibitors with a strategically positioned methyl sulfone substituent. An induced-fit binding mode allowed tight interactions with the S2 and S1 pockets of HNE. BAY 85-8501 ((4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) was shown to be efficacious in a rodent animal model related to ALI. BAY 85-8501 is currently being tested in clinical studies for the treatment of pulmonary diseases.© 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
