Pyrimidinylpiperazine

"1-PP" redirects here. Not to be confused with 1PP.

Pyrimidinylpiperazine

Names
Preferred IUPAC name 2-(Piperazin-1-yl)pyrimidine
Identifiers
CAS Number	20980-22-7^N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:166562
ChEMBL	ChEMBL724^Y
ChemSpider	80080^Y
ECHA InfoCard	100.040.107
EC Number	244-135-5
PubChem CID	88747
UNII	H3B5B38F56
CompTox Dashboard (EPA)	DTXSID00864967
InChI InChI=1S/C8H12N4/c1-2-10-8(11-3-1)12-6-4-9-5-7-12/h1-3,9H,4-7H2^Y Key: MRBFGEHILMYPTF-UHFFFAOYSA-N^Y InChI=1S/C8H12N4/c1-2-10-8(11-3-1)12-6-4-9-5-7-12/h1-3,9H,4-7H2 InChI=1S/C8H12N4/c1-2-10-8(11-3-1)12-6-4-9-5-7-12/h1-3,9H,4-7H2 Key: MRBFGEHILMYPTF-UHFFFAOYSA-N
SMILES n1cccnc1N2CCNCC2
Properties
Chemical formula	C8H12N4
Molar mass	164.21 g/mol
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H314, H315, H319, H335
Precautionary statements	P260, P261, P264, P271, P280, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P332+P313, P337+P313, P362, P363, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Y verify (what is ^YN ?) Infobox references

1-(2-Pyrimidinyl)piperazine (1-PP, 1-PmP) is a chemical compound and piperazine derivative. It is known to act as an antagonist of the α₂-adrenergic receptor (K_i = 7.3–40 nM)^[1] and, to a much lesser extent, as a partial agonist of the 5-HT_1A receptor (K_i = 414 nM; E_max = 54%).^[2][3] It has negligible affinity for the dopamine D₂, D₃, and D₄ receptors (K_i > 10,000 nM) and does not appear to have significant affinity for the α₁-adrenergic receptors.^{[4][additional citation(s) needed]} Its crystal structure has been determined.^[5]

Derivatives

A number of pyrimidinylpiperazine derivatives are drugs, including:

• Buspirone – anxiolytic
• Dasatinib – anticancer agent
• Eptapirone – anxiolytic
• Gepirone – anxiolytic
• Ipsapirone – anxiolytic
• Piribedil – antiparkinsonian agent
• Revospirone – anxiolytic
• Tandospirone – anxiolytic
• Tirilazad – neuroprotective agent
• Umespirone – anxiolytic
• Zalospirone – anxiolytic

The anxiolytics are also classified as azapirones due to the azaspirodecanedione moiety in their structures. 1-PP is a common metabolite of most or all of the listed agents.^[1][6] Alnespirone, binospirone, and enilospirone, despite being azapirones, are not piperazines and therefore do not metabolize to 1-PP, and while perospirone and tiospirone are piperazines, they are instead benzothiazole-substituted piperazines and do not metabolize to 1-PP either.

See also

• Substituted piperazine
• Pyridinylpiperazine
• Phenylpiperazine
• Diphenylmethylpiperazine
• Benzylpiperazine

References

1. Blier P, Curet O, Chaput Y, de Montigny C (1991). "Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine--II. Effects of acute administration of 1-PP and long-term administration of tandospirone on noradrenergic neurotransmission". Neuropharmacology. 30 (7): 691–701. doi:10.1016/0028-3908(91)90176-c. PMID 1681447. S2CID 44297577.
2. Zuideveld KP, Rusiç-Pavletiç J, Maas HJ, Peletier LA, Van der Graaf PH, Danhof M (2002). "Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats". J. Pharmacol. Exp. Ther. 303 (3): 1130–7. doi:10.1124/jpet.102.036798. PMID 12438536. S2CID 14139919.
3. Gobert A, Newman-Tancredi A, Rivet J, Audinot V, Millan M (1997). "P.1.047 Yohimbine is a potent, partial agonist at rat and cloned, human serotonin1A receptors: A comparison to buspirone and its metabolite, 1-pyrimidinylpiperazine". European Neuropsychopharmacology. 7: S149–S150. doi:10.1016/S0924-977X(97)88496-9. ISSN 0924-977X. S2CID 54355225.
4. Bergman J, Roof RA, Furman CA, Conroy JL, Mello NK, Sibley DR, Skolnick P (2013). "Modification of cocaine self-administration by buspirone (buspar®): potential involvement of D3 and D4 dopamine receptors". Int. J. Neuropsychopharmacol. 16 (2): 445–58. doi:10.1017/S1461145712000661. PMC 5100812. PMID 22827916.
5. Yamuna TS, Jasinski JP, Kaur M, Anderson BJ, Yathirajan HS (1 October 2014). "Crystal structures of 4-(pyrimidin-2-yl)piperazin-1-ium chloride and 4-(pyrimidin-2-yl)piperazin-1-ium nitrate". Acta Crystallographica Section E: Structure Reports Online. 70 (10): 203–206. Bibcode:2014AcCrE..70..203Y. doi:10.1107/S1600536814020169. PMC 4257175. PMID 25484652.
6. Astier B, Lambás Señas L, Soulière F, Schmitt P, Urbain N, Rentero N, Bert L, Denoroy L, Renaud B, Lesourd M, Muñoz C, Chouvet G (2003). "In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity". Eur. J. Pharmacol. 459 (1): 17–26. doi:10.1016/s0014-2999(02)02814-5. PMID 12505530.