Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Pyrimidinylpiperazine: Difference between pages

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc}}

{{redirect-distinguish|1-PP|1PP}}

| verifiedrevid = 464377285

| PIN = 2-(Piperazin-1-yl)pyrimidine

|Section1={{Chembox Identifiers

| InChI = 1S/C8H12N4/c1-2-10-8(11-3-1)12-6-4-9-5-7-12/h1-3,9H,4-7H2

| CASNo_Ref = {{cascite|changed|CAS}}

| CASNo = 20980-22-7

| ChEBI = 166562

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 724

| EC_number = 244-135-5

| UNII = H3B5B38F56

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 80080

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = MRBFGEHILMYPTF-UHFFFAOYSA-N

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C8H12N4/c1-2-10-8(11-3-1)12-6-4-9-5-7-12/h1-3,9H,4-7H2

}}

|Section2={{Chembox Properties

| Formula = C₈H₁₂N₄

| MolarMass = 164.21 g/mol

| Appearance =

| Density =

| MeltingPt =

| BoilingPt =

| Solubility =

}}

|Section3={{Chembox Hazards

| GHSPictograms = {{GHS05}}{{GHS07}}

| GHSSignalWord = Danger

| HPhrases = {{H-phrases|314|315|319|335}}

| PPhrases = {{P-phrases|260|261|264|271|280|301+330+331|302+352|303+361+353|304+340|305+351+338|310|312|321|332+313|337+313|362|363|403+233|405|501}}

| MainHazards =

| FlashPt =

| AutoignitionPt =

}}

'''1-(2-Pyrimidinyl)piperazine''' ('''1-PP''', '''1-PmP''') is a [[chemical compound]] and [[piperazine]] [[chemical derivative|derivative]]. It is known to act as an [[receptor antagonist|antagonist]] of the [[α2-adrenergic|α₂-adrenergic receptor]] (K_i = 7.3–40&nbsp;nM)<ref name="pmid1681447">{{cite journal | vauthors = Blier P, Curet O, Chaput Y, de Montigny C | title = 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 | journal = Neuropharmacology | volume = 30 | issue = 7 | pages = 691–701 | year = 1991 | pmid = 1681447 | doi = 10.1016/0028-3908(91)90176-c| s2cid = 44297577 }}</ref> and, to a much lesser extent, as a [[partial agonist]] of the [[5-HT1A receptor|5-HT_1A receptor]] (K_i = 414&nbsp;nM; [[intrinsic activity|E_max]] = 54%).<ref name="pmid12438536">{{cite journal | vauthors = Zuideveld KP, Rusiç-Pavletiç J, Maas HJ, Peletier LA, Van der Graaf PH, Danhof M | title = Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats | journal = J. Pharmacol. Exp. Ther. | volume = 303 | issue = 3 | pages = 1130–7 | year = 2002 | pmid = 12438536 | doi = 10.1124/jpet.102.036798 | s2cid = 14139919 }}</ref><ref name="GobertNewman-Tancredi1997">{{cite journal|last1=Gobert|first1=A.|last2=Newman-Tancredi|first2=A.|last3=Rivet|first3=J.M.|last4=Audinot|first4=V.|last5=Millan|first5=M.J.|title=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|journal=European Neuropsychopharmacology|volume=7|year=1997|pages=S149–S150|issn=0924-977X|doi=10.1016/S0924-977X(97)88496-9|s2cid=54355225}}</ref> It has negligible [[affinity (pharmacology)|affinity]] for the [[dopamine receptor|dopamine]] [[D2 receptor|D₂]], [[D3 receptor|D₃]], and [[D4 receptor|D₄ receptor]]s (K_i > 10,000&nbsp;nM) and does not appear to have significant affinity for the [[α1-adrenergic|α₁-adrenergic receptor]]s.<ref name="pmid22827916">{{cite journal | vauthors = Bergman J, Roof RA, Furman CA, Conroy JL, Mello NK, Sibley DR, Skolnick P | title = Modification of cocaine self-administration by buspirone (buspar®): potential involvement of D3 and D4 dopamine receptors | journal = Int. J. Neuropsychopharmacol. | volume = 16 | issue = 2 | pages = 445–58 | year = 2013 | pmid = 22827916 | pmc = 5100812 | doi = 10.1017/S1461145712000661 }}</ref>{{Additional citation needed|date=September 2017}} Its crystal structure has been determined.<ref>{{cite journal |last1=Yamuna |first1=T. S. |last2=Jasinski |first2=J. P. |last3=Kaur |first3=M. |last4=Anderson |first4=B. J. |last5=Yathirajan |first5=H. S. |title=Crystal structures of 4-(pyrimidin-2-yl)piperazin-1-ium chloride and 4-(pyrimidin-2-yl)piperazin-1-ium nitrate |journal=Acta Crystallographica Section E: Structure Reports Online |date=1 October 2014 |volume=70 |issue=10 |pages=203–206 |doi=10.1107/S1600536814020169|pmid=25484652 |pmc=4257175 |bibcode=2014AcCrE..70..203Y }}</ref>

==Derivatives==

A number of pyrimidinylpiperazine derivatives are [[drug]]s, including:

* [[Buspirone]]{{snd}} [[anxiolytic]]

* [[Dasatinib]]{{snd}} anticancer agent

* [[Eptapirone]]{{snd}} anxiolytic

* [[Gepirone]]{{snd}} anxiolytic

* [[Ipsapirone]]{{snd}} anxiolytic

* [[Piribedil]]{{snd}} antiparkinsonian agent

* [[Revospirone]]{{snd}} anxiolytic

* [[Tandospirone]]{{snd}} anxiolytic

* [[Tirilazad]]{{snd}} neuroprotective agent

* [[Umespirone]]{{snd}} anxiolytic

* [[Zalospirone]]{{snd}} anxiolytic

The [[anxiolytic]]s are also classified as [[azapirone]]s due to the [[azaspirodecanedione]] moiety in their structures. 1-PP is a common [[metabolite]] of most or all of the listed agents.<ref name="pmid1681447" /><ref name="pmid12505530">{{cite journal | vauthors = 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 | title = In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity | journal = Eur. J. Pharmacol. | volume = 459 | issue = 1 | pages = 17–26 | year = 2003 | pmid = 12505530 | doi = 10.1016/s0014-2999(02)02814-5}}</ref> [[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==

{{reflist}}

{{Adrenergic receptor modulators}}

{{Serotonin receptor modulators}}

{{Piperazines}}

[[Category:5-HT1A agonists]]

[[Category:Alpha-2 blockers]]

[[Category:Human drug metabolites]]

[[Category:1-Piperazinyl compounds]]

[[Category:Aminopyrimidines]]

[[Category:Guanidines]]

{{Nervous-system-drug-stub}}