Seladelpar

Seladelpar

cas 851528-79-5

C₂₁H₂₃F₃O₅S, 444.47

fda approved 8/14/2024, To treat primary biliary cholangitis (PBC), Livdelzi

• (+)-MBX-8025
• MBX 8025
• MBX-8025
• MBX8025
• RWJ-800025

• ((4-(((2R)-2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)THIO)-2-METHYLPHENYL)OXY)ACETIC ACID
• (4-(((2R)-2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)SULFANYL)-2-METHYLPHENOXY)ACETIC ACID PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR (PPAR) AGONIST,ANTIHYPERLIPIDAEMIC
• (R)-2-(4-((2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)-THIO)-2-METHYLPHENOXY)ACETIC ACID
• ACETIC ACID, (4-(((2R)-2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)THIO)-2-METHYLPHENOXY)-
• ACETIC ACID, (4-(((2R)-2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)THIO)-2-METHYLPHENOXY)- ((4-(((2R)-2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)THIO)-2-METHYLPHENYL)OXY)ACETIC ACID
• ACETIC ACID, 2-(4-(((2R)-2-ETHOXY-3-(4-(TRIFLUOROMETHYL)PHENOXY)PROPYL)THIO)-2-METHYLPHENOXY)-
• Seladelpar

Seladelpar, sold under the brand name Livdelzi, is a medication used for the treatment of primary biliary cholangitis.^[1] It is used as the lysine dihydrate salt.^[1] It is a PPARδ receptor agonist.^[1][2][3] The compound was licensed from Janssen Pharmaceutica NV.^[4]

Seladelpar was approved for medical use in the United States in August 2024.^[1][5]

Seladelpar is a peroxisome proliferator-activated receptor (PPAR)-delta (δ) agonist. Seladelpar is a single enantiomer of the R-configuration.⁵ On August 14, 2024, seladelpar was granted accelerated approval by the FDA for the treatment of primary biliary cholangitis,⁶ which is a condition associated with aberrant bile acid metabolism. Seladelpar works to block bile acid synthesis.¹

Medical uses

Seladelpar is indicated for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid in adults who have an inadequate response to ursodeoxycholic acid, or as monotherapy in people unable to tolerate ursodeoxycholic acid.^[1]

Clinically, Seladelpar reduces pruritus and IL-31 in patients with primary biliary cholangitis.^[6]

• compound 3r [PMID: 17524639]
• Bioorg Med Chem Lett. 2007 Jul 15;17(14):3855-9. doi: 10.1016/j.bmcl.2007.05.007. Epub 2007 May 10.
• 10.1016/j.bmcl.2007.05.007

Drug Discovery, Johnson and Johnson Pharmaceutical Research and Development, LLC, 8 Clarke Drive, Cranbury, NJ 08512, USA

Scheme 1. Reagents and condition: (a) Cs2CO3, dioxane, 100 C 80%; (b) TBAF (cat), THF, 85%; (c) NaH, RI, THF or DMF for esters of 2–5, 8–9, 10–80%; iPr2NEt, RBr or MOMCl, THF for esters of 6–7, 58–79%; ADDP, Ph3P, phenol, CH2Cl2 for esters of 10–11, 68–73%; (d) LiOH, H2O, THF, 90–95%.

Scheme 2. Reagents: (a) Ba(MnO4)2, CH2Cl2, 89%; (b) DIAD, Ph3P, DMF, THF, 17%; (c) n-Bu3P, 24, Py, 55%; (d) i—NaHMDS, EtOTf, THF for the ethyl ester of 12, 47%; DIAD, Ph3P, para-trifluoromethylphenol for the ethyl ester of 13, 79%; ii—LiOH, H2O, THF, 84–88%.

References

1. ^ Jump up to:^{a b c d e f} “Livdelzi- seladelpar lysine capsule”. DailyMed. 14 August 2024. Retrieved 5 September 2024.
2. ^ Billin AN (October 2008). “PPAR-beta/delta agonists for Type 2 diabetes and dyslipidemia: an adopted orphan still looking for a home”. Expert Opinion on Investigational Drugs. 17 (10): 1465–1471. doi:10.1517/13543784.17.10.1465. PMID 18808307. S2CID 86564263.
3. ^ Bays HE, Schwartz S, Littlejohn T, Kerzner B, Krauss RM, Karpf DB, et al. (September 2011). “MBX-8025, a novel peroxisome proliferator receptor-delta agonist: lipid and other metabolic effects in dyslipidemic overweight patients treated with and without atorvastatin”. The Journal of Clinical Endocrinology and Metabolism. 96 (9): 2889–2897. doi:10.1210/jc.2011-1061. PMID 21752880.
4. ^ “Targeting Mixed Dyslipidemia and Metabolic Syndrome”. Metabolex, Inc. 2005. Archived from the original on 17 October 2006.
5. ^ “Gilead’s Livdelzi (Seladelpar) Granted Accelerated Approval for Primary Biliary Cholangitis by U.S. FDA” (Press release). Gilead. 14 August 2024. Retrieved 15 August 2024 – via Business Wire.
6. ^ Kremer AE, Mayo MJ, Hirschfield GM, Levy C, Bowlus CL, Jones DE, et al. (July 2024). “Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis”. Hepatology. 80 (1): 27–37. doi:10.1097/HEP.0000000000000728. PMC 11191048.

///////////////Livdelzi, Seladelpar, (+)-MBX-8025, MBX 8025, MBX-8025, MBX8025, RWJ-800025, FDA 2024, APPROVALS 2024