Chemistry:Substituted piperazine
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Short description: Class of chemical compounds
Substituted piperazines are a class of chemical compounds based on a piperazine core.[1] Some are used as recreational drugs and some are used in scientific research.[2]
List of substituted piperazines
Benzylpiperazines
Chemical structures of selected benzylpiperazines
-
1-Benzylpiperazine (BZP) -
1-Methyl-4-benzylpiperazine (MBZP) -
1,4-Dibenzylpiperazine (DBZP) -
3,4-Methylenedioxy-1-benzylpiperazine (MDBZP) -
4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP) -
Methoxypiperamide (MeOP, MEXP) ((4-methoxyphenyl)(4-methylpiperazin-1-yl)methanone) -
Sunifiram (1-benzoyl-4-propanoylpiperazine) -
3-Methylbenzylpiperazine (3-MeBZP) -
Befuraline
(also produces benzylpiperazine as a metabolite) -
Fipexide
(also produces substituted benzylpiperazine as a metabolite) -
Piberaline
(also produces benzylpiperazine as a metabolite)
Phenylpiperazines
ortho-Substituted
- 2-Chlorophenylpiperazine (oCPP)
- 2-Methylphenylpiperazine (oMPP)
- 2-Methoxyphenylpiperazine (oMeOPP)
- Mefeclorazine
- Vortioxetine
Enpiprazole is known to produce oCPP as a metabolite. It was initially anticipated to produce oMeOPP as a metabolite, but this proved not to be the case.
meta-Substituted
- 3-Chlorophenylpiperazine (mCPP)
- 3-Methoxyphenylpiperazine (mMeOPP)
- 3-Trifluoromethylphenylpiperazine (TFMPP)
- 1-(3-Chlorophenyl)-4-(2-phenylethyl)piperazine (3C-PEP)
Trazodone, nefazodone, etoperidone, mepiprazole, and others produce mCPP as a metabolite.[3]
para-Substituted
- 4-Chlorophenylpiperazine (pCPP)
- 4-Fluorophenylpiperazine (pFPP)
- 4-Methylphenylpiperazine (pMPP)
- 4-Methoxyphenylpiperazine (pMeOPP, MeOPP)
- 4-Nitrophenylpiperazine (pNPP; PAL-175) – selective partial serotonin releasing agent[4]
- 4-Trifluoromethylphenylpiperazine (pTFMPP)
Multiple substitutions
- 2,3-Dichlorophenylpiperazine (2,3-DCPP)
- 3,4-Dichlorophenylpiperazine (3,4-DCPP)
- 2,3-Dimethylphenylpiperazine (DMPP)
- 3-Trifluoromethyl-4-chlorophenylpiperazine (TFMCPP; PAL-179) – selective partial serotonin releasing agent[4]
Others
- 1-Phenylpiperazine (PP)
Other arylpiperazines
- 1-(1-Naphthyl)piperazine (1-NP)
- 1-(2-Pyrimidinyl)piperazine (1-PP)
- ORG-12962 (1-(5-trifluoromethyl-6-chloropyridin-2-yl)piperazine)
- Quipazine (2-piperazin-1-ylquinoline)
Many azapirones such as buspirone, gepirone, and tandospirone produce 1-PP as a metabolite.
By drug class
Antianginals
- Amoxapine
- Befuraline
- Buspirone
- Flesinoxan
- Gepirone
- Ipsapirone
- Nefazodone
- Piberaline
- Tandospirone
- Trazodone
- Vilazodone
- Vortioxetine
- Zalospirone
Antiserotonergics
Recreational Drugs
- 4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)
- 1-Benzylpiperazine (BZP)
- 2,3-Dichlorophenylpiperazine (DCPP)
- 1,4-Dibenzylpiperazine (DBZP)
- 4-Methyl-1-benzylpiperazine (MBZP)
- 3-Chlorophenylpiperazine (mCPP)
- 3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)
- 4-Methoxyphenylpiperazine (MeOPP)
- Methoxypiperamide (MeOP or MEXP)
- 4-Chlorophenylpiperazine (pCPP)
- 4-Fluorophenylpiperazine (pFPP)
- 3-Trifluoromethylphenylpiperazine (TFMPP)
Urologicals
Others
- 6-Nitroquipazine
- Antrafenine
- Diethylcarbamazine
- Diphenazine
- Fipexide
- Imatinib
- NSI-189
- Pipobroman (antineoplastic agent)
- Quipazine
- Sunifiram (nootropic)
- Tolpiprazole (tranquilizer)
Activities
| Compound | PAL # | Serotonin | Norepinephrine | Dopamine | Type | Ref | ||
|---|---|---|---|---|---|---|---|---|
| 1-Benzylpiperazine (BZP) | ND | 6050–>100000 | 62.2–68 | 175–600 | NDRA | [5][6][7][8][9][10] | ||
| 1-Phenylpiperazine (PP) | ND | 880 | 186 | 2530 | SNRA | [11] | ||
| 2-Me-PP (oMPP) | PAL-169 | 175 | 39.1 | 296–542 | SNDRA | [11][12][10] | ||
| 2-OMe-PP (oMeOPP) | ND | ND | ND | ND | ND | ND | ||
| 2-TFM-PP (oTFMPP) | ND | 570 | 350 | 11200 | SNRA | [11] | ||
| 2-SMe-PP (oMTPP) | ND | 270 | >10000 | >10000 | SRA | [11] | ||
| 2-Et-PP (oEtPP) | ND | 290 | 830 | >10000 | SNRA | [11] | ||
| 2-Chloro-PP (oCPP) | ND | 310 | 26 | >3000 | NRA | [11] | ||
| 2-Bromo-PP (oBPP) | ND | 132 | 33 | 250 | SNDRA | [11] | ||
| 2-Nitro-PP (oNPP) | ND | 1870 | 770 | >10000 | SNRA | [11] | ||
| 3-Chloro-PP (mCPP) | ND | 28–39 | 1400–>10000 | >10000–63000 | SRA | [6][13][14][15] | ||
| 3-Fluoro-PP (mFPP) | ND | 115 | 340 | 2400 | SNRA | [11] | ||
| 3-Me-PP (mMPP) | ND | 110 | >20000 | >20000 | SRA | [11] | ||
| 3-OMe-PP (mMeOPP) | ND | 650 | >10000 | >10000 | SRA | [11] | ||
| 3-OH-PP (mOHPP) | ND | 230 | 174 | 2500 | SNRA | [11] | ||
| 3-TFM-PP (TFMPP) | ND | 121 | >10000 | >10000 | SRA | [8][7][9] | ||
| 4-Chloro-PP (pCPP) | ND | ND | ND | ND | ND | ND | ||
| 4-Fluoro-PP (pFPP) | ND | 230 | 3200 | >10000 | SRA | [11] | ||
| 4-Me-PP (pMPP) | PAL-233 | 220 | >10000 | >20000 | SRA | [11][10] | ||
| 4-OMe-PP (pMeOPP) | ND | 3200 | 440–1500 | 6300–11000 | SNDRA | [11][6] | ||
| 4-TFM-PP (pTFMPP) | ND | ND | ND | ND | ND | ND | ||
| 4-Ac-PP (pAcPP) | ND | 50 | 150 | 3000 | SNRA | [11] | ||
| 4-CN-PP (pCNPP) | ND | 36 | 6300 | >10000 | SRA | [11] | ||
| 4-Phenyl-PP (pPhPP) | ND | >10000 | 1520 | 5200 | NDRA | [11] | ||
| 4-OH-PP (pOHPP) | ND | >10000 | 230 | 850 | NDRA | [11] | ||
| 4-Nitro-PP (pNPP) | PAL-175 | 19–43 | >10000 | >10000 | SRA | [11][4] | ||
| 2,3-Dichloro-PP (2,3-DCPP) | ND | 10 | 36 | 108 | SNDRA | [11] | ||
| 2,3-DiMe-PP (2,3-DMPP) | PAL-218 | 24–26 | 13.7–56 | 1207–1320 | SNRA | [11][4][10] | ||
| 2,4-Difluoro-PP (2,4-DFPP) | ND | 470 | 2300 | >10000 | SNRA | [11] | ||
| 3,4-Dichloro-PP (3,4-DCPP) | ND | ND | ND | ND | ND | ND | ||
| 3,4-Difluoro-PP (3,4-DFPP) | ND | 76 | 9200 | >10000 | SRA | [11] | ||
| 3-TFM-4-Cl-PP (TFMCPP) | PAL-179 | 33 | >10000 | >10000 | SRA | [4] | ||
| Notes: Assays were done using rat brain synaptosomes. | ||||||||
See also
- Substituted α-alkyltryptamine
- Substituted amphetamine
- Substituted cathinone
- Substituted methylenedioxyphenethylamine
- Substituted phenethylamine
- Substituted phenylmorpholine
- Substituted tryptamine
References
- ↑ Laras, Y.; Garino, C.; Dessolin, J.; Weck, C.; Moret, V.; Rolland, A.; Kraus, J.-L. (2009-02-01). "New N4-substituted piperazine naphthamide derivatives as BACE-1 inhibitors". Journal of Enzyme Inhibition and Medicinal Chemistry 24 (1): 181–187. doi:10.1080/14756360802048939. ISSN 1475-6366. PMID 18770069. https://doi.org/10.1080/14756360802048939.
- ↑ Alghamdi, Saad; Alshehri, Mohammed M.; Asif, Mohammad (2022). "The Neuropharmacological Potential of Piperazine Derivatives: A Mini- Review" (in en). Mini-Reviews in Organic Chemistry 19 (7): 798–810. doi:10.2174/1570193x19666220119120211. https://www.eurekaselect.com/article/120285.
- ↑ "Metabolism of m-CPP, trazodone, nefazodone, and etoperidone: clinical and forensic aspects". Drug Metab Rev 57 (2): 115–146. February 2025. doi:10.1080/03602532.2025.2465482. PMID 39945551.
- ↑ 4.0 4.1 4.2 4.3 4.4 "Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters". J Pharmacol Exp Ther 341 (1): 251–262. April 2012. doi:10.1124/jpet.111.188946. PMID 22271821.
- ↑ "Therapeutic potential of monoamine transporter substrates". Curr Top Med Chem 6 (17): 1845–1859. 2006. doi:10.2174/156802606778249766. PMID 17017961.
- ↑ 6.0 6.1 6.2 "The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain". Eur J Pharmacol 559 (2–3): 132–137. March 2007. doi:10.1016/j.ejphar.2006.11.075. PMID 17223101. https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=00665d67c36dcf1777989b70cc901c654420a0c7.
- ↑ 7.0 7.1 "Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain". Ann N Y Acad Sci 1025: 189–197. October 2004. doi:10.1196/annals.1316.024. PMID 15542717. Bibcode: 2004NYASA1025..189B.
- ↑ 8.0 8.1 "N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy')". Neuropsychopharmacology 30 (3): 550–560. March 2005. doi:10.1038/sj.npp.1300585. PMID 15496938.
- ↑ 9.0 9.1 "Dopamine-releasing agents". Dopamine Transporters: Chemistry, Biology and Pharmacology. Hoboken [NJ]: Wiley. July 2008. pp. 305–320. ISBN 978-0-470-11790-3. OCLC 181862653. https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf.
- ↑ 10.0 10.1 10.2 10.3 "Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter". Drug Alcohol Depend 147: 1–19. February 2015. doi:10.1016/j.drugalcdep.2014.12.005. PMID 25548026.
- ↑ 11.00 11.01 11.02 11.03 11.04 11.05 11.06 11.07 11.08 11.09 11.10 11.11 11.12 11.13 11.14 11.15 11.16 11.17 11.18 11.19 11.20 11.21 11.22 11.23 "Binding of the amphetamine-like 1-phenyl-piperazine to monoamine transporters". ACS Chem Neurosci 3 (9): 693–705. September 2012. doi:10.1021/cn300040f. PMID 23019496.
- ↑ "Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys". Psychopharmacology (Berl) 234 (23–24): 3455–3465. December 2017. doi:10.1007/s00213-017-4731-5. PMID 28889212.
- ↑ "Therapeutic and adverse actions of serotonin transporter substrates". Pharmacol Ther 95 (1): 73–88. July 2002. doi:10.1016/s0163-7258(02)00234-6. PMID 12163129.
- ↑ "Serotonin releasing agents. Neurochemical, therapeutic and adverse effects". Pharmacol Biochem Behav 71 (4): 825–836. April 2002. doi:10.1016/s0091-3057(01)00669-4. PMID 11888573.
- ↑ "Evidence for noncompetitive modulation of substrate-induced serotonin release". Synapse 64 (11): 862–869. November 2010. doi:10.1002/syn.20804. PMID 20842720.
External links
- "BZP/piperazines". European Union Drugs Agency (EUDA). https://www.euda.europa.eu/publications/drug-profiles/bzp_en.
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