Substituted piperazine

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

See also: Benzylpiperazine § Chemical derivatives

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

See also: Phenylpiperazine

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

• Ranolazine
• Trimetazidine

Antidepressants

• Amoxapine
• Befuraline
• Buspirone
• Flesinoxan
• Gepirone
• Ipsapirone
• Nefazodone
• Piberaline
• Tandospirone
• Trazodone
• Vilazodone
• Vortioxetine
• Zalospirone

Antihistamines

• Buclizine
• Cetirizine
• Cinnarizine
• Cyclizine
• Hydroxyzine
• Levocetirizine
• Meclizine
• Niaprazine

Antiserotonergics

• EGIS-7625

Antipsychotics

• Typical
  • Flupentixol
  • Fluphenazine
  • Perphenazine
  • Prochlorperazine
  • Thiothixene
  • Trifluoperazine
  • Zuclopenthixol
  • Acetophenazine
  • Carfenazine
• Atypical
  • Amperozide
  • Aripiprazole
  • Clozapine
  • Lurasidone
  • Olanzapine
  • Perospirone
  • Ziprasidone
  • Quetiapine
  • Cariprazine

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

• Sildenafil
• Vardenafil

Others

• 6-Nitroquipazine
• Antrafenine
• Diethylcarbamazine
• Diphenazine
• Fipexide
• Imatinib
• NSI-189
• Pipobroman (antineoplastic agent)
• Quipazine
• Sunifiram (nootropic)
• Tolpiprazole (tranquilizer)

Activities

Monoamine release (EC₅₀Tooltip half-maximal effective concentration, nM) of arylpiperazines

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