GLPG1205

GLPG1205

Identifiers
IUPAC name 9-(2-cyclopropylethynyl)-2-[[(2S)-1,4-dioxan-2-yl]methoxy]-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one
CAS Number	1445847-37-9
PubChem CID	71616860
IUPHAR/BPS	10171
DrugBank	DB15346
ChemSpider	58906524
UNII	K9WR6LRA5D
ChEMBL	ChEMBL3716365
Chemical and physical data
Formula	C22H22N2O3
Molar mass	362.429 g·mol−1
3D model (JSmol)	Interactive image
SMILES C1CC1C#CC2=CC3=C(C=C2)C4=CC(=NC(=O)N4CC3)OC[C@@H]5COCCO5
InChI InChI=1S/C22H22N2O4/c25-22-23-21(28-14-18-13-26-9-10-27-18)12-20-19-6-5-16(4-3-15-1-2-15)11-17(19)7-8-24(20)22/h5-6,11-12,15,18H,1-2,7-10,13-14H2/t18-/m0/s1 Key:IRBAWVGZNJIROV-SFHVURJKSA-N

GLPG1205 is an experimental drug which acts as a selective antagonist (or perhaps negative allosteric modulator) at the free fatty acid receptor GPR84. ^[1] It has antiinflammatory and anti-fibrotic effects and reached Phase II human clinical trials for treatment of both ulcerative colitis and idiopathic pulmonary fibrosis, although development for both indications was ultimately dropped due to poor efficacy. ^[2] However, it continues to be researched for potential applications in the treatment of other conditions such as asthma and acute immune-mediated liver injury. ^{[3] [4]}

References

1. Labéguère F, Dupont S, Alvey L, Soulas F, Newsome G, Tirera A, et al. (November 2020). "Discovery of 9-Cyclopropylethynyl-2-((S)-1-[1,4]dioxan-2-ylmethoxy)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one (GLPG1205), a Unique GPR84 Negative Allosteric Modulator Undergoing Evaluation in a Phase II Clinical Trial". Journal of Medicinal Chemistry. 63 (22): 13526–13545. doi: 10.1021/acs.jmedchem.0c00272 . PMID   32902984.
2. Strambu IR, Seemayer CA, Fagard LM, Ford PA, Van der Aa TA, de Haas-Amatsaleh AA, et al. (March 2023). "GLPG1205 for idiopathic pulmonary fibrosis: a phase 2 randomised placebo-controlled trial". The European Respiratory Journal. 61 (3). doi:10.1183/13993003.01794-2022. PMC   9978158 . PMID   36328358.
3. Donovan C, Thorpe AE, Gomez HM, Carroll OR, Feng M, Bai X, et al. (May 2024). "The GPR84 Antagonist GLPG1205 Reduces Features of Disease in Experimental Severe Asthma". American Journal of Respiratory Cell and Molecular Biology. 70 (5): 424–427. doi:10.1165/rcmb.2023-0221LE. PMID   38690993.
4. Zheng Y, Wang Y, Xu Y, Shen S, Xu H, Hu C, et al. (May 2025). "Targeting GPR84 to alleviate acute immune-mediated liver injury". Molecular Medicine. 31 (1). Cambridge, Mass.: 187. doi: 10.1186/s10020-025-01248-9 . PMC   12080032 . PMID   40369402.