RTI-13951-33 hydrochloride

• CAT Number: I046235
• Molecular Formula: C28H35Cl2N3O3
• Molecular Weight: 532.50
• Purity: ≥95%
• Synonyms: (1R,2R)-N-[(2R,3R)-2-amino-3-methoxybutyl]-N-[4-[4-(methoxymethyl)phenyl]phenyl]-2-pyridin-2-ylcyclopropane-1-carboxamide;dihydrochloride
• InChI: InChI=1S/C28H33N3O3.2ClH/c1-19(34-3)26(29)17-31(28(32)25-16-24(25)27-6-4-5-15-30-27)23-13-11-22(12-14-23)21-9-7-20(8-10-21)18-33-2;;/h4-15,19,24-26H,16-18,29H2,1-3H3;2*1H/t19-,24-,25-,26-;;/m1../s1
• InChIKey: YEUXFGDNARDKIP-DBJQVROASA-N
• SMILES: CC(C(CN(C1=CC=C(C=C1)C2=CC=C(C=C2)COC)C(=O)C3CC3C4=CC=CC=N4)N)OC.Cl.Cl

RTI-13951-33 hydrochloride is a potent, selective, and brain-penetrant GPR88 agonist, with an EC50 of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 hydrochloride reduces alcohol reinforcement and intake behaviors in rats[1].
RTI-13951-33 is a potent, selective, and brain-penetrant GPR88 agonist, with an EC50 of 25 nM in GPR88 cAMP functional assay. RTI-13951-33 elevates [35S]-GTPγS binding (EC50, 535 nM) in mouse striatal membranes but not in membranes from GPR88 KO mice[1].
RTI-13951-33 has weak affinities at kappa opioid receptor (KOR; Ki, 2.29 μM), vesicular monoamine transporter (VMAT; Ki, 4.23 μM), and moderate affinity at serotonin transporter (SERT; Ki, 0.75 μM), however, RTI-13951-33 poorly inhibits SERT (IC50, 25.1±2.7 μM)[1].
RTI-13951-33 (10 and 20 mg/kg, i.p.) dose-dependently decreases alcohol lever responses in a rat model of alcohol self-administration[1].
RTI-13951-33 (10 mg/kg, i.p.) has sufficient brain penetration, with t1/2 of 48 min and 87 min in rat plasma and brain[1].

Reference

[1]. Jin C, et al. Discovery of a Potent, Selective, and Brain-Penetrant Small Molecule that Activates the Orphan Receptor GPR88 and Reduces Alcohol Intake. J Med Chem. 2018 Aug 9;61(15):6748-6758.
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