Budipine

Budipine (brand name Parkinsan) is an antiparkinson agent marketed for the treatment of Parkinson's disease.^[2]^[3]^[4]

AHFS/Drugs.comInternational Drug Names

ATC code

N04BX03 (WHO)

CAS Number

57982-78-2^Y

PubChem CID

68778

Quick facts Clinical data, AHFS/Drugs.com ...

Budipine
Clinical data

AHFS/Drugs.com	International Drug Names
ATC code	N04BX03 (WHO)
Identifiers
IUPAC name 1-tert-butyl-4,4-diphenylpiperidine^[1]
CAS Number	57982-78-2^Y
PubChem CID	68778
ChemSpider	62021^Y
UNII	L9026OPI2Z
KEGG	D07306^Y
ChEMBL	ChEMBL334491^Y
CompTox Dashboard (EPA)	DTXSID20206709
ECHA InfoCard	100.055.494
Chemical and physical data
Formula	C₂₁H₂₇N
Molar mass	293.454 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES c1(ccccc1)C3(c2ccccc2)CCN(C(C)(C)C)CC3
InChI InChI=1S/C21H27N/c1-20(2,3)22-16-14-21(15-17-22,18-10-6-4-7-11-18)19-12-8-5-9-13-19/h4-13H,14-17H2,1-3H3^Y Key:QIHLUZAFSSMXHQ-UHFFFAOYSA-N^Y
(verify)

While its exact mechanism of action is not well characterized,^[2] it is believed to be an NMDA receptor antagonist,^[5]^[6] but also promoting the synthesis of dopamine.^[7]

Because it provides additional benefits relative to existing treatments, it probably does not precisely mimic the mechanism of an existing known treatment.^[7]^[8]

It is an hERG blocker and can produce long QT syndrome as a side effect.^[9]

Analogues include prodipine and medipine.^[10]^[11]

Synthesis

Budipine can be prepared from the 1-tert-butyl-4-piperidone [1465-76-5] directly by treatment with benzene in the presence triflic acid.^[12] This method of synthesis enables a 99% yield of product.

4-Phenyl-1-t-butyl-4-piperidinol,^[14] (1)

1-t-butyl-3-benzoyl-4-phenyl-4-piperidinol [81831-81-4] (3)

References

[1]
Sweetman SC, ed. (2007). Martindale: The Complete Drug Reference (35th ed.). London: Pharmaceutical Press. ISBN 978-0-85369-687-2.
[2]
Reichmann H (October 2006). "Budipine in Parkinson's tremor". Journal of the Neurological Sciences. 248 (1–2): 53–55. doi:10.1016/j.jns.2006.05.039. PMID 16784759. S2CID 21540225.
[3]
Przuntek H, Müller T (1999). "Clinical efficacy of budipine in Parkinson's disease". Diagnosis and Treatment of Parkinson's Disease — State of the Art. Journal of Neural Transmission. Supplementa. Vol. 56. pp. 75–82. doi:10.1007/978-3-7091-6360-3_3. ISBN 978-3-211-83275-2. PMID 10370903. {{cite book}}: |journal= ignored (help)
[4]
"Budipine". AdisInsight. Springer Nature Switzerland AG.
[5]
Kornhuber J, Herr B, Thome J, Riederer P (1995). "The antiparkinsonian drug budipine binds to NMDA and sigma receptors in postmortem human brain tissue". Journal of Neural Transmission. Supplementum. 46: 131–137. PMID 8821048.
[6]
Palmer GC (September 2001). "Neuroprotection by NMDA receptor antagonists in a variety of neuropathologies". Current Drug Targets. 2 (3): 241–271. doi:10.2174/1389450013348335. PMID 11554551.
[7]
Przuntek H, Bittkau S, Bliesath H, Büttner U, Fuchs G, Glass J, et al. (May 2002). "Budipine provides additional benefit in patients with Parkinson disease receiving a stable optimum dopaminergic drug regimen". Archives of Neurology. 59 (5): 803–806. doi:10.1001/archneur.59.5.803. PMID 12020263.
[8]
Owen JC, Whitton PS (October 2006). "Effects of amantadine and budipine on antidepressant drug-evoked changes in extracellular dopamine in the frontal cortex of freely moving rats". Brain Research. 1117 (1): 206–212. doi:10.1016/j.brainres.2006.07.039. PMID 16996043. S2CID 29177107.
[9]
Scholz EP, Zitron E, Kiesecker C, Lueck S, Kathöfer S, Thomas D, Weretka S, Peth S, Kreye VA, Schoels W, Katus HA, Kiehn J, Karle CA (November 2003). "Drug binding to aromatic residues in the HERG channel pore cavity as possible explanation for acquired Long QT syndrome by antiparkinsonian drug budipine". Naunyn Schmiedebergs Arch Pharmacol. 368 (5): 404–414. doi:10.1007/s00210-003-0805-5. PMID 14557918.
[10]
Russ H, Pindur U, Przuntek H (1986). "The interaction of 1-alkyl-4,4-diphenylpiperidines with the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine receptor binding site". J Neural Transm. 65 (3–4): 157–166. doi:10.1007/BF01249078. PMID 3011983. Other representatives of this class of substances, the 1-alkyl-4,4-diphenylpiperidines, such as, e.g., the 1-isopropyl analogue (prodipine) or the 1-methyl analogue (medipine) have similar pharmacological properties including marked tremorin and reserpin antagonism (Schaefer et al., 1984). The mechanism of action of the 1-alkyl-4,4- diphenylpiperidines is not yet understood in detail.
[11]
Fonne-Pfister R, Meyer UA (October 1988). "Xenobiotic and endobiotic inhibitors of cytochrome P-450dbl function, the target of the debrisoquine/sparteine type polymorphism". Biochem Pharmacol. 37 (20): 3829–3835. doi:10.1016/0006-2952(88)90063-9. PMID 2903741. Budipine (1-t-butyl-4,4-diphenylpiperidine) (Parkinson's disease treatment); Prodipine (1-isopropyl-4,4-diphenylpiperidine); Medipine (1-methyl-4,4-diphenylpiperidine)
[12]
Klumpp, D. A., Garza, M., Jones, A., Mendoza, S. (1 September 1999). "Synthesis of Aryl-Substituted Piperidines by Superacid Activation of Piperidones". The Journal of Organic Chemistry. 64 (18): 6702–6705. doi:10.1021/jo990454i.
[13]
Schaefer H, Hackmack G, Eistetter K, Krüger U, Menge HG, Klosa J (1984). "[Synthesis, physical-chemical properties and pharmacologically-oriented screening studies on budipine and related 4,4-diphenylpiperidines]". Arzneimittel-Forschung (in German). 34 (3): 233–240. PMID 6539602.
[14]
"4-Phenyl-1-t-butyl-4-piperidinol". PubChem. U.S. National Library of Medicine. CID:20536606.

Synthesis

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