Substituted piperazine#Benzylpiperazines

Substituted piperazines are a class of chemical compounds based on a piperazine core.{{Cite journal |last1=Laras |first1=Y. |last2=Garino |first2=C. |last3=Dessolin |first3=J. |last4=Weck |first4=C. |last5=Moret |first5=V. |last6=Rolland |first6=A. |last7=Kraus |first7=J.-L. |date=2009-02-01 |title=New N4-substituted piperazine naphthamide derivatives as BACE-1 inhibitors |url=https://doi.org/10.1080/14756360802048939 |journal=Journal of Enzyme Inhibition and Medicinal Chemistry |volume=24 |issue=1 |pages=181–187 |doi=10.1080/14756360802048939 |issn=1475-6366 |pmid=18770069|s2cid=85385527 |url-access=subscription }} Some are used as recreational drugs and some are used in scientific research.{{Cite journal |last1=Alghamdi |first1=Saad |last2=Alshehri |first2=Mohammed M. |last3=Asif |first3=Mohammad |title=The Neuropharmacological Potential of Piperazine Derivatives: A Mini- Review |url=https://www.eurekaselect.com/article/120285 |journal=Mini-Reviews in Organic Chemistry |year=2022 |language=en |volume=19 |issue=7 |pages=798–810 |doi=10.2174/1570193x19666220119120211|url-access=subscription }}

List of substituted piperazines

=Benzylpiperazines=

File:Benzylpiperazine.svg|1-Benzylpiperazine (BZP)

File:Methylbenzylpiperazine.svg|1-Methyl-4-benzylpiperazine (MBZP)

File:DBZP.svg|1,4-Dibenzylpiperazine (DBZP)

File:MDBZP.svg|3,4-Methylenedioxy-1-benzylpiperazine (MDBZP)

File:2C-B-BZP.svg|4-Bromo-2,5-dimethoxy-1-benzylpiperazine (2C-B-BZP)

File:Methoxypiperamide.png|Methoxypiperamide (MeOP, MEXP) ((4-methoxyphenyl)(4-methylpiperazin-1-yl)methanone)

File:Sunifiram.svg |Sunifiram (1-benzoyl-4-propanoylpiperazine)

File:3-Methylbenzylpiperazine structure.png|3-Methylbenzylpiperazine (3-MeBZP)

File:Befuraline.svg|Befuraline
(also produces benzylpiperazine as a metabolite)

File:Fipexide.svg|Fipexide
(also produces substituted benzylpiperazine as a metabolite)

File:Piberaline.svg|Piberaline
(also produces benzylpiperazine as a metabolite)

=Phenylpiperazines=

==''ortho''-Substituted==

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.{{cite journal | vauthors = Costa Alegre MD, Barbosa DJ, Dinis-Oliveira RJ | title = Metabolism of m-CPP, trazodone, nefazodone, and etoperidone: clinical and forensic aspects | journal = Drug Metab Rev | volume = | issue = | pages = 1–32 | date = February 2025 | pmid = 39945551 | doi = 10.1080/03602532.2025.2465482 | url = }}

==''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-Trifluoromethylphenylpiperazine (pTFMPP)

==Multiple substitutions==

File:Dichlorophenylpiperazine-ifa.png|2,3-Dichlorophenylpiperazine (2,3-DCPP)

File:3,4-DCPP_structure.svg|3,4-Dichlorophenylpiperazine (3,4-DCPP)

2,3-Dimethylphenylpiperazine (DMPP)
3-Trifluoromethyl-4-chlorophenylpiperazine (TFMCPP; PAL-179) – selective partial serotonin releasing agent

==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

Antidepressants

Antihistamines

Antiserotonergics

EGIS-7625

Antipsychotics

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

Activities

Compound	{{Abbr\|PAL #\|Phenyl Amine Library Number}}	data-sort-type="number" \| Serotonin	data-sort-type="number" \| Norepinephrine	data-sort-type="number" \| Dopamine	Type	Ref
class="wikitable sortable sticky-header" style="font-size:small;" \|+ {{Nowrap\|Monoamine release ({{Abbrlink\|EC₅₀\|half-maximal effective concentration}}, nM) of arylpiperazines}}
1-Benzylpiperazine (BZP)	{{Abbr\|ND\|No data}}	6050–>100000	62.2–68	175–600	NDRA	{{cite journal \| vauthors = Rothman RB, Baumann MH \| title = Therapeutic potential of monoamine transporter substrates \| journal = Curr Top Med Chem \| volume = 6 \| issue = 17 \| pages = 1845–1859 \| date = 2006 \| pmid = 17017961 \| doi = 10.2174/156802606778249766 \| url = }}{{cite journal \| vauthors = Nagai F, Nonaka R, Satoh Hisashi Kamimura K \| title = The effects of non-medically used psychoactive drugs on monoamine neurotransmission in rat brain \| journal = Eur J Pharmacol \| volume = 559 \| issue = 2-3 \| pages = 132–137 \| date = March 2007 \| pmid = 17223101 \| doi = 10.1016/j.ejphar.2006.11.075 \| url = https://citeseerx.ist.psu.edu/document?repid=rep1&type=pdf&doi=00665d67c36dcf1777989b70cc901c654420a0c7\| url-access = subscription }}
1-Phenylpiperazine (PP)	{{Abbr\|ND\|No data}}	880	186	2530	SNRA	{{cite journal \| vauthors = Severinsen K, Kraft JF, Koldsø H, Vinberg KA, Rothman RB, Partilla JS, Wiborg O, Blough B, Schiøtt B, Sinning S \| title = Binding of the amphetamine-like 1-phenyl-piperazine to monoamine transporters \| journal = ACS Chem Neurosci \| volume = 3 \| issue = 9 \| pages = 693–705 \| date = September 2012 \| pmid = 23019496 \| pmc = 3447394 \| doi = 10.1021/cn300040f \| url = }}
2-Me-PP (oMPP)	PAL-169	175	39.1	296–542	SNDRA	{{cite journal \| vauthors = Kohut SJ, Jacobs DS, Rothman RB, Partilla JS, Bergman J, Blough BE \| title = Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys \| journal = Psychopharmacology (Berl) \| volume = 234 \| issue = 23-24 \| pages = 3455–3465 \| date = December 2017 \| pmid = 28889212 \| pmc = 5747253 \| doi = 10.1007/s00213-017-4731-5 \| url = }}{{cite journal \| vauthors = Reith ME, Blough BE, Hong WC, Jones KT, Schmitt KC, Baumann MH, Partilla JS, Rothman RB, Katz JL \| title = Behavioral, biological, and chemical perspectives on atypical agents targeting the dopamine transporter \| journal = Drug Alcohol Depend \| volume = 147 \| issue = \| pages = 1–19 \| date = February 2015 \| pmid = 25548026 \| pmc = 4297708 \| doi = 10.1016/j.drugalcdep.2014.12.005 \| url = }}
2-OMe-PP (oMeOPP)	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}
2-TFM-PP (oTFMPP)	{{Abbr\|ND\|No data}}	570	350	11200	SNRA
2-SMe-PP (oMTPP)	{{Abbr\|ND\|No data}}	270	>10000	>10000	SRA
2-Et-PP (oEtPP)	{{Abbr\|ND\|No data}}	290	830	>10000	SNRA
2-Chloro-PP (oCPP)	{{Abbr\|ND\|No data}}	310	26	>3000	NRA
2-Bromo-PP (oBPP)	{{Abbr\|ND\|No data}}	132	33	250	SNDRA
2-Nitro-PP (oNPP)	{{Abbr\|ND\|No data}}	1870	770	>10000	SNRA
3-Chloro-PP (mCPP)	{{Abbr\|ND\|No data}}	28–39	1400–>10000	>10000–63000	SRA	{{cite journal \| vauthors = Rothman RB, Baumann MH \| title = Therapeutic and adverse actions of serotonin transporter substrates \| journal = Pharmacol Ther \| volume = 95 \| issue = 1 \| pages = 73–88 \| date = July 2002 \| pmid = 12163129 \| doi = 10.1016/s0163-7258(02)00234-6 \| url = }}{{cite journal \| vauthors = Rothman RB, Baumann MH \| title = Serotonin releasing agents. Neurochemical, therapeutic and adverse effects \| journal = Pharmacol Biochem Behav \| volume = 71 \| issue = 4 \| pages = 825–836 \| date = April 2002 \| pmid = 11888573 \| doi = 10.1016/s0091-3057(01)00669-4 \| url = }}{{cite journal \| vauthors = Rothman RB, Baumann MH, Blough BE, Jacobson AE, Rice KC, Partilla JS \| title = Evidence for noncompetitive modulation of substrate-induced serotonin release \| journal = Synapse \| volume = 64 \| issue = 11 \| pages = 862–869 \| date = November 2010 \| pmid = 20842720 \| pmc = 2941209 \| doi = 10.1002/syn.20804 \| url = }}
3-Fluoro-PP (mFPP)	{{Abbr\|ND\|No data}}	115	340	2400	SNRA
3-Me-PP (mMPP)	{{Abbr\|ND\|No data}}	110	>20000	>20000	SRA
3-OMe-PP (mMeOPP)	{{Abbr\|ND\|No data}}	650	>10000	>10000	SRA
3-OH-PP (mOHPP)	{{Abbr\|ND\|No data}}	230	174	2500	SNRA
3-TFM-PP (TFMPP)	{{Abbr\|ND\|No data}}	121	>10000	>10000	SRA	{{cite journal \| vauthors = Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB \| title = N-substituted piperazines abused by humans mimic the molecular mechanism of 3,4-methylenedioxymethamphetamine (MDMA, or 'Ecstasy') \| journal = Neuropsychopharmacology \| volume = 30 \| issue = 3 \| pages = 550–560 \| date = March 2005 \| pmid = 15496938 \| doi = 10.1038/sj.npp.1300585 \| url = }}{{cite journal \| vauthors = Baumann MH, Clark RD, Budzynski AG, Partilla JS, Blough BE, Rothman RB \| title = Effects of "Legal X" piperazine analogs on dopamine and serotonin release in rat brain \| journal = Ann N Y Acad Sci \| volume = 1025 \| issue = \| pages = 189–197 \| date = October 2004 \| pmid = 15542717 \| doi = 10.1196/annals.1316.024 \| url = }}{{cite book \| vauthors = Blough B \| chapter = Dopamine-releasing agents \| veditors = Trudell ML, Izenwasser S \| title = Dopamine Transporters: Chemistry, Biology and Pharmacology \| pages = 305–320 \| date = July 2008 \| isbn = 978-0-470-11790-3 \| oclc = 181862653 \| ol = OL18589888W \| publisher = Wiley \| location = Hoboken [NJ] \| doi = \| url = https://books.google.com/books?id=QCagLAAACAAJ \| chapter-url = https://bitnest.netfirms.com/external/Books/Dopamine-releasing-agents_c11.pdf }}
4-Chloro-PP (pCPP)	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}
4-Fluoro-PP (pFPP)	{{Abbr\|ND\|No data}}	230	3200	>10000	SRA
4-Me-PP (pMPP)	PAL-233	220	>10000	>20000	SRA
4-OMe-PP (pMeOPP)	{{Abbr\|ND\|No data}}	3200	440–1500	6300–11000	SNDRA
4-TFM-PP (pTFMPP)	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}
4-Ac-PP (pAcPP)	{{Abbr\|ND\|No data}}	50	150	3000	SNRA
4-CN-PP (pCNPP)	{{Abbr\|ND\|No data}}	36	6300	>10000	SRA
4-Phenyl-PP (pPhPP)	{{Abbr\|ND\|No data}}	>10000	1520	5200	NDRA
4-OH-PP (pOHPP)	{{Abbr\|ND\|No data}}	>10000	230	850	NDRA
4-Nitro-PP (pNPP)	PAL-175	19–43	>10000	>10000	SRA
2,3-Dichloro-PP (2,3-DCPP)	{{Abbr\|ND\|No data}}	10	36	108	SNDRA
2,3-DiMe-PP (2,3-DMPP)	PAL-218	24–26	13.7–56	1207–1320	SNRA	{{cite journal \| vauthors = Rothman RB, Partilla JS, Baumann MH, Lightfoot-Siordia C, Blough BE \| title = Studies of the biogenic amine transporters. 14. Identification of low-efficacy "partial" substrates for the biogenic amine transporters \| journal = J Pharmacol Exp Ther \| volume = 341 \| issue = 1 \| pages = 251–262 \| date = April 2012 \| pmid = 22271821 \| doi = 10.1124/jpet.111.188946 \| url = \| pmc = 3364510 }}
2,4-Difluoro-PP (2,4-DFPP)	{{Abbr\|ND\|No data}}	470	2300	>10000	SNRA
3,4-Dichloro-PP (3,4-DCPP)	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}	{{Abbr\|ND\|No data}}
3,4-Difluoro-PP (3,4-DFPP)	{{Abbr\|ND\|No data}}	76	9200	>10000	SRA
3-TFM-4-Cl-PP (TFMCPP)	PAL-179	33	>10000	>10000	SRA
class="sortbottom" \| colspan="9" style="width: 1px; background-color:#eaecf0; text-align: center;" \| Notes: Assays were done using rat brain synaptosomes.

References

External links

{{Cite web | url = https://www.euda.europa.eu/publications/drug-profiles/bzp_en | publisher = European Union Drugs Agency (EUDA) | title = BZP/piperazines}}

Category:Arylpiperazines

Category:Benzylamines

Category:Chemical classes of psychoactive drugs

Category:Designer drugs