MRS5698

• CAT Number: I008194
• CAS Number: 1377273-00-1
• Molecular Formula: C28H23ClF2N6O3
• Molecular Weight: 564.978
• Purity: ≥95%
• Target: A3 adenosine receptor agonist
• Solubility: Soluble in DMSO
• Storage: 0 - 4 °C for short term, or -20 °C for long term
• IUPAC Name: (1S,2R,3S,4R,5S)-4-[6-[(3-chlorophenyl)methylamino]-2-[2-(3,4-difluorophenyl)ethynyl]purin-9-yl]-2,3-dihydroxy-N-methylbicyclo[3.1.0]hexane-1-carboxamide
• InChI: InChI=1S/C28H23ClF2N6O3/c1-32-27(40)28-11-17(28)22(23(38)24(28)39)37-13-34-21-25(33-12-15-3-2-4-16(29)9-15)35-20(36-26(21)37)8-6-14-5-7-18(30)19(31)10-14/h2-5,7,9-10,13,17,22-24,38-39H,11-12H2,1H3,(H,32,40)(H,33,35,36)/t17-,22-,23+,24+,28+/m1/s1
• InChIKey: LYLLLJJYBWLGHW-CIZVZKTGSA-N
• SMILES: CNC(=O)C12CC1C(C(C2O)O)N3C=NC4=C3N=C(N=C4NCC5=CC(=CC=C5)Cl)C#CC6=CC(=C(C=C6)F)F

MRS5698 (Cat.No:I008194) is a high affinity and selective A3 adenosine receptor agonist (Ki ~ 3 nM) protects against chronic neuropathic pain. MRS5698 displays >1000-fold selectivity over A1 and A2A adenosine receptors. MRS5698 reverses mechanoallodynia in several neuropathic pain models in vivo.

Reference

1:Purinergic Signal. 2015 Sep;11(3):371-87. doi: 10.1007/s11302-015-9459-2. Epub 2015 Jun 27. Efficient, large-scale synthesis and preclinical studies of MRS5698, a highly selective A3 adenosine receptor agonist that protects against chronic neuropathic pain.Tosh DK,Padia J,Salvemini D,Jacobson KA, PMID: 26111639 PMCID: PMC4529848 DOI: 10.1007/s11302-015-9459-2 Abstract: We reported that 2-(3,4-difluorophenylethynyl)-N (6)-3-chlorobenzyl (N)-methanocarba adenosine derivative 1 (MRS5698) binds selectively to human and mouse A3 adenosine receptors (A3ARs, K i 3 nM). It is becoming an important pharmacological tool for defining A3AR effects and is orally active in a chronic neuropathic pain model. Here, we introduce a new synthetic route for MRS5698 from D-ribose, suitable for a scale-up on a multi-gram scale, and we measure in vitro and in vivo ADME-Tox parameters. MRS5698 was very stable in vitro, failed to inhibit CYPs at <10 μM, and was largely bound to plasma proteins. It was well tolerated in the rat at doses of ≤200 mg/kg i.p. A 1 mg/kg i.p. dose in the mouse displayed t 1/2 of 1.09 h and plasma Cmax of 204 nM at 1 h with an AUC of 213 ng × h/mL. CACO-2 bidirectional transport studies suggested intestinal efflux of MRS5698 (efflux ratio 86). Although the oral %F is only 5 %, the beneficial effect to reverse pain lasted for at least 2 h in the CCI model in rats, using the same vehicle for oral administration of a high dose. The stability, low toxicity, lack of CYP interaction, pharmacokinetic half-life, and in vivo efficacy suggest that MRS5698 is a preferred compound for further consideration as a treatment for neuropathic pain.