For research use only. Not for therapeutic Use.
Ralinepag (CAT: I008972), also referred to as APD-811, is a promising investigational drug designed by Arena Pharmaceuticals. Acting as an orally administered agonist of the prostacyclin (IP) receptor, Ralinepag holds therapeutic potential for addressing vasospastic conditions like Pulmonary Arterial Hypertension. By mimicking the actions of prostacyclin, a key product of cyclooxygenase in macrovascular endothelium, Ralinepag interacts with the IP receptor to induce potent vasodilation and inhibit platelet aggregation. This innovative compound offers a novel approach to managing vasospastic diseases and represents a significant step in advancing treatment options for patients with these conditions.
| Catalog Number | I008972 |
| CAS Number | 1187856-49-0 |
| Synonyms | APD-811; APD 811; APD811; Ralinepag;2-(((1r,4r)-4-((((4-chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetic acid |
| Molecular Formula | C23H26ClNO5 |
| Purity | ≥95% |
| Target | Prostaglandin Receptor |
| Solubility | Soluble in DMSO, not in water |
| Storage | 0 - 4 °C for short term, or -20 °C for long term |
| IUPAC Name | 2-[[4-[[(4-chlorophenyl)-phenylcarbamoyl]oxymethyl]cyclohexyl]methoxy]acetic acid |
| InChI | InChI=1S/C23H26ClNO5/c24-19-10-12-21(13-11-19)25(20-4-2-1-3-5-20)23(28)30-15-18-8-6-17(7-9-18)14-29-16-22(26)27/h1-5,10-13,17-18H,6-9,14-16H2,(H,26,27) |
| InChIKey | NPDKXVKJRHPDQT-UHFFFAOYSA-N |
| SMILES | C1CC(CCC1COCC(=O)O)COC(=O)N(C2=CC=CC=C2)C3=CC=C(C=C3)Cl |
| Reference | 1:J Med Chem. 2017 Feb 9;60(3):913-927. doi: 10.1021/acs.jmedchem.6b00871. Epub 2017 Jan 19. Discovery of 2-(((1r,4r)-4-(((4-Chlorophenyl)(phenyl)carbamoyl)oxy)methyl)cyclohexyl)methoxy)acetate (Ralinepag): An Orally Active Prostacyclin Receptor Agonist for the Treatment of Pulmonary Arterial Hypertension.Tran TA,Kramer B,Shin YJ,Vallar P,Boatman PD,Zou N,Sage CR,Gharbaoui T,Krishnan A,Pal B,Shakya SR,Garrido Montalban A,Adams JW,Ramirez J,Behan DP,Shifrina A,Blackburn A,Leakakos T,Shi Y,Morgan M,Sadeque A,Chen W,Unett DJ,Gaidarov I,Chen X,Chang S,Shu HH,Tung SF,Semple G, PMID: 28072531 DOI: 10.1021/acs.jmedchem.6b00871 </br><span>Abstract:</span> The design and synthesis of a new series of potent non-prostanoid IP receptor agonists that showed oral efficacy in the rat monocrotaline model of pulmonary arterial hypertension (PAH) are described. Detailed profiling of a number of analogues resulted in the identification of 5c (ralinepag) that has good selectivity in both binding and functional assays with respect to most members of the prostanoid receptor family and a more modest 30- to 50-fold selectivity over the EP3 receptor. In our hands, its potency and efficacy are comparable or superior to MRE269 (the active metabolite of the clinical compound NS-304) with respect to in vitro IP receptor dependent cAMP accumulation assays. 5c had an excellent PK profile across species. Enterohepatic recirculation most probably contributes to a concentration-time profile after oral administration in the cynomolgus monkey that showed a very low peak-to-trough ratio. Following the identification of an acceptable solid form, 5c was selected for further development for the treatment of PAH. |
