MK-0359   

GtoPdb Ligand ID: 9852

Synonyms: L-454,560 [1] | L-454560 | MK0359
Compound class: Synthetic organic
Comment: MK-0359 is a potent and selective, oral PDE4 inhibitor that has a competitive and reversible mode of interaction. MK-0359 is identified as L-454,560 [1] by citation in [2]. MK-0359 inhibits both the apo- (Mg2+ free) and holoenzyme ((Mg2+-bound) states of PDE4 [1].
2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 6
Hydrogen bond donors 0
Rotatable bonds 7
Topological polar surface area 136.85
Molecular weight 587.15
XLogP 6.09
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
Canonical SMILES Cc1noc(n1)C(=Cc1cccc(c1)c1cc(cc2c1nccc2)C(S(=O)(=O)C)(C)C)c1ccc(cc1)S(=O)(=O)C
Isomeric SMILES Cc1noc(n1)/C(=C/c1cccc(c1)c1cc(cc2c1nccc2)C(S(=O)(=O)C)(C)C)/c1ccc(cc1)S(=O)(=O)C
InChI InChI=1S/C31H29N3O5S2/c1-20-33-30(39-34-20)28(22-11-13-26(14-12-22)40(4,35)36)17-21-8-6-9-23(16-21)27-19-25(31(2,3)41(5,37)38)18-24-10-7-15-32-29(24)27/h6-19H,1-5H3/b28-17+
InChI Key YYGZHVJDHMMABU-OGLMXYFKSA-N
References
1. Huang Z, Dias R, Jones T, Liu S, Styhler A, Claveau D, Otu F, Ng K, Laliberte F, Zhang L et al.. (2007)
L-454,560, a potent and selective PDE4 inhibitor with in vivo efficacy in animal models of asthma and cognition.
Biochem. Pharmacol., 73 (12): 1971-81. [PMID:17428447]
2. Lu S, Liu N, Dass SB, Reiss TF, Knorr BA. (2009)
Randomized, placebo-controlled study of a selective PDE4 inhibitor in the treatment of asthma.
Respir Med, 103 (3): 342-7. [PMID:19135348]
3. Robichaud A, Stamatiou PB, Jin SL, Lachance N, MacDonald D, Laliberté F, Liu S, Huang Z, Conti M, Chan CC. (2002)
Deletion of phosphodiesterase 4D in mice shortens alpha(2)-adrenoceptor-mediated anesthesia, a behavioral correlate of emesis.
J. Clin. Invest., 110 (7): 1045-52. [PMID:12370283]