For research use only. Not for therapeutic Use.
MK-0952 is a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment. It is an intrinsically potent inhibitor displaying limited whole blood activity. Phosphodiesterase inhibitors are used as a target for cognition enhancement in aging and Alzheimer/’s disease.
| Catalog Number | I008044 |
| CAS Number | 934995-87-6 (acid) |
| Synonyms | MK0952; MK 0952; MK-0952;(1R,2R)-2-(3/’-(3-(cyclopropylcarbamoyl)-4-oxo-1,8-naphthyridin-1(4H)-yl)-3-fluoro-[1,1/’-biphenyl]-4-yl)cyclopropane-1-carboxylic acid |
| Molecular Formula | C28H22FN3O4 |
| Purity | ≥95% |
| Target | Phosphodiesterase (PDE) |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| IUPAC Name | (1R,2R)-2-[4-[3-[3-(cyclopropylcarbamoyl)-4-oxo-1,8-naphthyridin-1-yl]phenyl]-2-fluorophenyl]cyclopropane-1-carboxylic acid |
| InChI | InChI=1S/C28H22FN3O4/c29-24-12-16(6-9-19(24)21-13-22(21)28(35)36)15-3-1-4-18(11-15)32-14-23(27(34)31-17-7-8-17)25(33)20-5-2-10-30-26(20)32/h1-6,9-12,14,17,21-22H,7-8,13H2,(H,31,34)(H,35,36)/t21-,22+/m0/s1 |
| InChIKey | PSYPBAHXIIVDCJ-FCHUYYIVSA-N |
| SMILES | C1CC1NC(=O)C2=CN(C3=C(C2=O)C=CC=N3)C4=CC=CC(=C4)C5=CC(=C(C=C5)C6CC6C(=O)O)F |
| Reference | 1:Bioorg Med Chem Lett. 2010 Nov 15;20(22):6387-93. doi: 10.1016/j.bmcl.2010.09.087. Epub 2010 Sep 21. Discovery of MK-0952, a selective PDE4 inhibitor for the treatment of long-term memory loss and mild cognitive impairment.Gallant M,Aspiotis R,Day S,Dias R,Dubé D,Dubé L,Friesen RW,Girard M,Guay D,Hamel P,Huang Z,Lacombe P,Laliberté S,Lévesque JF,Liu S,Macdonald D,Mancini J,Nicholson DW,Styhler A,Townson K,Waters K,Young RN,Girard Y, PMID: 20933411 DOI: 10.1016/j.bmcl.2010.09.087 </br><span>Abstract:</span> The structure-activity relationship of a novel series of 8-biarylnaphthyridinones acting as type 4 phosphodiesterase (PDE4) inhibitors for the treatment of long-term memory loss and mild cognitive impairment is described herein. The manuscript describes a new paradigm for the development of PDE4 inhibitor targeting CNS indications. This effort led to the discovery of the clinical candidate MK-0952, an intrinsically potent inhibitor (IC(50)=0.6 nM) displaying limited whole blood activity (IC(50)=555 nM). Supporting in vivo results in two preclinical efficacy tests and one test assessing adverse effects are also reported. The comparative profiles of MK-0952 and two other Merck compounds are described to validate the proposed hypothesis.Copyright © 2010 Elsevier Ltd. All rights reserved. |
