LY3372689

LY3372689 is a drug candidate molecule under investigation to treat Alzheimer's disease. It targets the enzyme O-GlcNAcase.^[1] Its result is to reduce formation of tau protein tangles.

LY3372689

Names
IUPAC name N-[4-fluoro-5-[[2-methyl-4-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]piperidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide
Identifiers
3D model (JSmol)	Interactive image
PubChem CID	135271363
InChI InChI=1S/C16H22FN5O3S/c1-9-6-12(24-8-14-19-11(3)25-21-14)4-5-22(9)7-13-15(17)20-16(26-13)18-10(2)23/h9,12H,4-8H2,1-3H3,(H,18,20,23) Key: FRVXHWNHGWUTQO-UHFFFAOYSA-N
SMILES CC(NC1=NC(F)=C(CN2CC[C@H](OCC3=NOC(C)=N3)C[C@@H]2C)S1)=O
Properties
Chemical formula	C16H22FN5O3S
Molar mass	383.44 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

A molecule containing radioactive fluorine was used with a PET scan to show that LY3372689 binds in the human brain.^[2]

Eli Lilly and Company is recruiting subjects for a clinical trial.^[3] Some hospitals in Australia: St Vincent's Hospital, Sydney Hornsby Ku-Ring-Gai Hospital, The Prince Charles Hospital, The Queen Elizabeth Hospital, Adelaide, Box Hill Hospital, and Delmont Private Hospital are involved.^[4] Results of the trial are expected by June 2024.^[5]

Chemical

The molecule contains three rings: thiazole, piperidine and oxadiazole. Other functional groups included are an ether, acetamide, and a fluoride.^[6]

References

1. "LY3372689". www.alzforum.org.
2. Shcherbinin, Sergey; Kielbasa, William; Dubois, Susan; Lowe, Stephen L; Phipps, Krista M; Tseng, James; Kevin, Donnelly B; Natanegara, Fanni; Warner, Susan; Dreyfus, Nicolas; Lindsay-Scott, Peter; Hawk, Mai Khanh; McDonald, Nicholas; Zhang, Xiaoyu; Gilmore, Julie A; Biglan, Kevin; Mergott, Dustin J; Russell, David; Gunn, Roger N; Constantinescu, Cristian; Nuthall, Hugh Norman; Collins, Emily C (December 2020). "Brain target occupancy of LY3372689, an inhibitor of the O-GlcNAcase (OGA) enzyme: Translation from rat to human: Neuroimaging / evaluating treatments". Alzheimer's & Dementia. 16 (S4). doi:10.1002/alz.040558. S2CID 227501893.
3. "Assessment of Safety, Tolerability, and Efficacy of LY3372689 in Early Symptomatic Alzheimer's Disease". clinicaltrials.gov. 22 March 2022. Retrieved 31 March 2022.
4. "A Study of LY3372689 to Assess the Safety, Tolerability, and Efficacy in Participants With Alzheimer's Disease". Retrieved 31 March 2022.
5. Krietsch Boerner, Leigh (25 March 2022). "Hybrid meeting divulges structures of drug candidates". Chemical & Engineering News. ISSN 0009-2347.
6. Dreyfus, Nicolas Jacques Francois; Lindsay-Scott, Peter James (2 August 2018). "N-[4-Fluoro-5-[[(2S,4S)-2-Methyl-4-[(5-Methyl-1,2,4-Oxadiazol-3-Yl)methoxy]-1-Piperidyl]methyl]thiazol-2-Yl]acetamide as Oga Inhibitor". Retrieved 31 March 2022.