4-(3-Methylsulfonylphenyl)-1-propylpiperidine

• CAT Number: R006885
• CAS Number: 346688-38-8
• Molecular Formula: C15H23NO2S
• Molecular Weight: 281.414
• Purity: ≥95%
• Synonyms: 4-[3-(Methylsulfonyl)phenyl]-1-propylpiperidine; ACR 16; ASP 2314; FR 310826; Pridopidine
• Target: Neuronal Signaling
• Storage: -20°C
• IUPAC Name: 4-(3-methylsulfonylphenyl)-1-propylpiperidine
• InChI: InChI=1S/C15H23NO2S/c1-3-9-16-10-7-13(8-11-16)14-5-4-6-15(12-14)19(2,17)18/h4-6,12-13H,3,7-11H2,1-2H3
• InChIKey: YGKUEOZJFIXDGI-UHFFFAOYSA-N
• SMILES: CCCN1CCC(CC1)C2=CC(=CC=C2)S(=O)(=O)C

Pridopidine, also known as ACR16, is a dopamine stabilizer, which improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. Huntington disease (HD) is a neurodegenerative disorder for which new treatments are urgently needed. Pridopidine is a new dopaminergic stabilizer, recently developed for the treatment of motor symptoms associated with HD.

Reference

1: Squitieri F, de Yebenes JG. Profile of pridopidine and its potential in the treatment of Huntington disease: the evidence to date. Drug Des Devel Ther. 2015 Oct 28;9:5827-33. doi: 10.2147/DDDT.S65738. eCollection 2015. PubMed PMID: 26604684; PubMed Central PMCID: PMC4629959.2: Rabinovich-Guilatt L, Siegler KE, Schultz A, Halabi A, Rembratt A, Spiegelstein O. The effect of mild and moderate renal impairment on the pharmacokinetics of pridopidine, a new drug for Huntington/’s disease. Br J Clin Pharmacol. 2016 Feb;81(2):246-55. doi: 10.1111/bcp.12792. Epub 2015 Nov 25. PubMed PMID: 26407011.3: Shannon KM, Fraint A. Therapeutic advances in Huntington/’s Disease. Mov Disord. 2015 Sep 15;30(11):1539-46. doi: 10.1002/mds.26331. Epub 2015 Jul 30. Review. PubMed PMID: 26226924.4: Sahlholm K, Sijbesma JW, Maas B, Kwizera C, Marcellino D, Ramakrishnan NK, Dierckx RA, Elsinga PH, van Waarde A. Pridopidine selectively occupies sigma-1 rather than dopamine D2 receptors at behaviorally active doses. Psychopharmacology (Berl). 2015 Sep;232(18):3443-53. doi: 10.1007/s00213-015-3997-8. Epub 2015 Jul 11. PubMed PMID: 26159455; PubMed Central PMCID: PMC4537502.5: Squitieri F, Di Pardo A, Favellato M, Amico E, Maglione V, Frati L. Pridopidine, a dopamine stabilizer, improves motor performance and shows neuroprotective effects in Huntington disease R6/2 mouse model. J Cell Mol Med. 2015 Nov;19(11):2540-8. doi: 10.1111/jcmm.12604. Epub 2015 Jun 22. PubMed PMID: 26094900; PubMed Central PMCID: PMC4627560.6: Waters S, Ponten H, Klamer D, Waters N. Co-administration of the Dopaminergic Stabilizer Pridopidine and Tetrabenazine in Rats. J Huntingtons Dis. 2014;3(3):285-98. doi: 10.3233/JHD-140108. PubMed PMID: 25300332.7: Waters S, Ponten H, Edling M, Svanberg B, Klamer D, Waters N. The dopaminergic stabilizers pridopidine and ordopidine enhance cortico-striatal Arc gene expression. J Neural Transm (Vienna). 2014 Nov;121(11):1337-47. doi: 10.1007/s00702-014-1231-1. Epub 2014 May 11. PubMed PMID: 24817271.8: Reilmann R. The pridopidine paradox in Huntington/’s disease. Mov Disord. 2013 Sep;28(10):1321-4. doi: 10.1002/mds.25559. Epub 2013 Jul 11. PubMed PMID: 23847099.9: Gronier B, Waters S, Ponten H. The dopaminergic stabilizer pridopidine increases neuronal activity of pyramidal neurons in the prefrontal cortex. J Neural Transm (Vienna). 2013 Sep;120(9):1281-94. doi: 10.1007/s00702-013-1002-4. Epub 2013 Mar 7. PubMed PMID: 23468085.10: Huntington Study Group HART Investigators. A randomized, double-blind, placebo-controlled trial of pridopidine in Huntington/’s disease. Mov Disord. 2013 Sep;28(10):1407-15. doi: 10.1002/mds.25362. Epub 2013 Feb 28. PubMed PMID: 23450660.11: Squitieri F, Landwehrmeyer B, Reilmann R, Rosser A, de Yebenes JG, Prang A, Ivkovic J, Bright J, Rembratt A. One-year safety and tolerability profile of pridopidine in patients with Huntington disease. Neurology. 2013 Mar 19;80(12):1086-94. doi: 10.1212/WNL.0b013e3182886965. Epub 2013 Feb 27. PubMed PMID: 23446684.12: Ponten H, Kullingsjö J, Sonesson C, Waters S, Waters N, Tedroff J. The dopaminergic stabilizer pridopidine decreases expression of L-DOPA-induced locomotor sensitisation in the rat unilateral 6-OHDA model. Eur J Pharmacol. 2013 Jan 5;698(1-3):278-85. doi: 10.1016/j.ejphar.2012.10.039. Epub 2012 Nov 2. PubMed PMID: 23127496.13: Lindskov Krog P, Osterberg O, Gundorf Drewes P, Rembratt Å, Schultz A, Timmer W. Pharmacokinetic and tolerability profile of pridopidine in healthy-volunteer poor and extensive CYP2D6 metabolizers, following single and multiple dosing. Eur J Drug Metab Pharmacokinet. 2013 Mar;38(1):43-51. doi: 10.1007/s13318-012-0100-2. Epub 2012 Sep 5. PubMed PMID: 22948856.14: Ruiz C, Casarejos MJ, Rubio I, Gines S, Puigdellivol M, Alberch J, Mena MA, de Yebenes JG. The dopaminergic stabilizer, (-)-OSU6162, rescues striatal neurons with normal and expanded polyglutamine chains in huntingtin protein from exposure to free radicals and mitochondrial toxins. Brain Res. 2012 Jun 12;1459:100-12. doi: 10.1016/j.brainres.2012.04.021. Epub 2012 Apr 21. PubMed PMID: 22560595.15: Helldén A, Panagiotidis G, Johansson P, Waters N, Waters S, Tedroff J, Bertilsson L. The dopaminergic stabilizer pridopidine is to a major extent N-depropylated by CYP2D6 in humans. Eur J Clin Pharmacol. 2012 Sep;68(9):1281-6. doi: 10.1007/s00228-012-1248-z. Epub 2012 Mar 8. PubMed PMID: 22399238.16: Sahlholm K, Århem P, Fuxe K, Marcellino D. The dopamine stabilizers ACR16 and (-)-OSU6162 display nanomolar affinities at the σ-1 receptor. Mol Psychiatry. 2013 Jan;18(1):12-4. doi: 10.1038/mp.2012.3. Epub 2012 Feb 21. PubMed PMID: 22349783.17: Neurodegenerative disease: Pridopidine for Huntington disease falls short of primary efficacy end point in phase III trial. Nat Rev Neurol. 2011 Dec 26;8(1):4. doi: 10.1038/nrneurol.2011.208. PubMed PMID: 22198402.18: de Yebenes JG, Landwehrmeyer B, Squitieri F, Reilmann R, Rosser A, Barker RA, Saft C, Magnet MK, Sword A, Rembratt A, Tedroff J; MermaiHD study investigators. Pridopidine for the treatment of motor function in patients with Huntington/’s disease (MermaiHD): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2011 Dec;10(12):1049-57. doi: 10.1016/S1474-4422(11)70233-2. Epub 2011 Nov 7. PubMed PMID: 22071279.19: Feigin A. Pridopidine in treatment of Huntington/’s disease: beyond chorea? Lancet Neurol. 2011 Dec;10(12):1036-7. doi: 10.1016/S1474-4422(11)70247-2. Epub 2011 Nov 7. PubMed PMID: 22071278.20: Esmaeilzadeh M, Kullingsjö J, Ullman H, Varrone A, Tedroff J. Regional cerebral glucose metabolism after pridopidine (ACR16) treatment in patients with Huntington disease. Clin Neuropharmacol. 2011 May-Jun;34(3):95-100. doi: 10.1097/WNF.0b013e31821c31d8. PubMed PMID: 21586914.