rolziracetam
{{Short description|Chemical compound}}
{{cs1 config|mode=cs1|name-list-style=vanc|display-authors=6}}
{{Drugbox
| Verifiedfields = changed
| verifiedrevid = 464383434
| IUPAC_name = dihydro-1H-pyrrolizine-3,5(2H,6H)-dione
| image = Rolziracetam structure.svg
| width = 180
| image2 = Rolziracetam3d.png
| tradename =
| pregnancy_category =
| legal_AU = S4
| legal_US = Unscheduled
| routes_of_administration = Oral
| bioavailability =
| metabolism =
| excretion =
| CAS_number_Ref = {{cascite|changed|??}}
| CAS_number = 18356-28-0
| ATC_prefix = none
| PubChem = 71893
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 64906
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = RES9I0LGG5
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 51396
| C=7 | H=9 | N=2 | O=2
| smiles = O=C2N1C(=O)CCC1CC2
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C7H9NO2/c9-6-3-1-5-2-4-7(10)8(5)6/h5H,1-4H2
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = IEZDOKQWPWZVQF-UHFFFAOYSA-N
| synonyms = 2,6,7,8-tetrahydro-1H-pyrrolizine-3,5-dione, CI 911 & Lukes-Šorm dilactam.
}}
Rolziracetam is a nootropic drug of the racetam family.
Rolziracetam was found to improve performance on a delayed-response task in aged rhesus monkeys. It has a wide margin of safety in animals and has been evaluated for use in cognitively impaired human subjects.{{cite journal | vauthors = Butler DE, Leonard JD, Caprathe BW, L'Italien YJ, Pavia MR, Hershenson FM, Poschel PH, Marriott JG | title = Amnesia-reversal activity of a series of cyclic imides | journal = Journal of Medicinal Chemistry | volume = 30 | issue = 3 | pages = 498–503 | date = March 1987 | pmid = 3820221 | doi = 10.1021/jm00386a010 }}
Synthesis
The nitro group of dimethyl 4-nitropimelate (1) is reduced by palladium-catalysed hydrogenation to an amino group, which cyclises to give a mixture of the lactam ester (2) and its corresponding acid (3). The mixture is hydrolysed using sodium hydroxide to convert all of the ester to the acid, and this material is cyclised to give rolziracetam using acetic anhydride.{{cite journal | vauthors = Leonard NJ, Hruda LR, Long FW | title = The synthesis of pyrrolizidines | journal = Journal of the American Chemical Society | volume = 69 | issue = 3 | pages = 690–692 | date = March 1947 | pmid = 20289459 | doi = 10.1021/ja01195a067 }}{{cite patent |country=US |number=4663464 |inventor = Hoekstra MS |title=Process for the preparation of dihydro-1H-pyrrolizine-3,5-(2H,6H)-dione |status=patent |gdate=1987-05-05 |fdate=1986-03-21 |pridate=1986-03-21 |assign1=Warner Lambert Co LLC}}