rilapladib   Click here for help

GtoPdb Ligand ID: 7376

Synonyms: SB 659032
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Lipoprotein-associated phospholipase A2 (Lp-PLA2, PLA2-G7) inhibitors such as rilapladib and darapladib have been evaluated in clinical trials: darapladib for coronary heart disease, and rilapladib for Alzheimer's disease. Compounds of different chemotypes are being explored as tools to further optimise the pharmacological modulation of PLA2-G7 as a target for clinical intervention- see also (S)-23 [PMID: 27933945] (tool compound).
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 5
Hydrogen bond donors 0
Rotatable bonds 14
Topological polar surface area 80.08
Molecular weight 735.26
XLogP 10.02
No. Lipinski's rules broken 2
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Canonical SMILES COCCN1CCC(CC1)N(C(=O)Cn1c(SCc2cccc(c2F)F)cc(=O)c2c1cccc2)Cc1ccc(cc1)c1ccc(cc1)C(F)(F)F
Isomeric SMILES COCCN1CCC(CC1)N(C(=O)Cn1c(SCc2cccc(c2F)F)cc(=O)c2c1cccc2)Cc1ccc(cc1)c1ccc(cc1)C(F)(F)F
InChI InChI=1S/C40H38F5N3O3S/c1-51-22-21-46-19-17-32(18-20-46)47(24-27-9-11-28(12-10-27)29-13-15-31(16-14-29)40(43,44)45)37(50)25-48-35-8-3-2-6-33(35)36(49)23-38(48)52-26-30-5-4-7-34(41)39(30)42/h2-16,23,32H,17-22,24-26H2,1H3
1. Davidson JE, Lockhart A, Amos L, Stirnadel-Farrant HA, Mooser V, Sollberger M, Regeniter A, Monsch AU, Irizarry MC. (2012)
Plasma lipoprotein-associated phospholipase A2 activity in Alzheimer's disease, amnestic mild cognitive impairment, and cognitively healthy elderly subjects: a cross-sectional study.
Alzheimers Res Ther, 4 (6): 51. [PMID:23217243]
2. Fitzpatrick AL, Irizarry MC, Cushman M, Jenny NS, Chi GC, Koro C. (2014)
Lipoprotein-associated phospholipase A2 and risk of dementia in the Cardiovascular Health Study.
Atherosclerosis, 235 (2): 384-91. [PMID:24929287]
3. Staurenghi G, Ye L, Magee MH, Danis RP, Wurzelmann J, Adamson P, McLaughlin MM, Darapladib DME Study Group. (2015)
Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, in diabetic macular edema: a 3-month placebo-controlled study.
Ophthalmology, 122 (5): 990-6. [PMID:25749297]
4. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le Trong H, Cousens LS, Zimmerman GA et al.. (1995)
Anti-inflammatory properties of a platelet-activating factor acetylhydrolase.
Nature, 374 (6522): 549-53. [PMID:7700381]
5. Wilensky RL, Macphee CH. (2009)
Lipoprotein-associated phospholipase A(2) and atherosclerosis.
Curr Opin Lipidol, 20 (5): 415-20. [PMID:19667981]