Unifiram

Unifiram
Clinical data
Other names	DM-232
Legal status
Legal status	In general: unscheduled;
Identifiers
	IUPAC name 2-[(4-Fluorophenyl)sulfonyl]hexahydropyrrolo[1,2-a]pyrazin-6(2H)-one;
CAS Number	272786-64-8;
PubChemCID	9861054;
ChemSpider	8036753;
UNII	N4024LN29G;
ChEMBL	ChEMBL140717;
CompTox Dashboard(EPA)	DTXSID00432024;
Chemical and physical data
Formula	C13H15FN2O3S
Molar mass	298.33g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C2CN1C(=O)CCC1CN2S(=O)(=O)c(cc3)ccc3F;
	InChI InChI=1S/C13H15FN2O3S/c14-10-1-4-12(5-2-10)20(18,19)15-7-8-16-11(9-15)3-6-13(16)17/h1-2,4-5,11H,3,6-9H2; Key:SNRTZFZAFBIBJP-UHFFFAOYSA-N;
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Unifiram(developmental code nameDM-232) is an experimental drug.^[1]that hasantiamnesicand other effects inanimal studieswith far greaterpotencythanpiracetam.^[2]^[3]A number of related compounds are known, such assunifiram(DM-235) and sapunifiram (MN-19).^[4]^[5]^[6]Unifiram has twoenantiomers,with the dextro form being the more active isomer.^[7]It has been shown to reduce the duration of hypnosis induced bypentobarbital,without impairing motor coordination.^[8]As of 2015^[update],no formal human studies with unifiram have been conducted. Unifiram is not patented and, despite the lack of human and long-term toxicity studies, it is commonly sold online.^[9]

Pharmacology

Unifiram, as well as sunifiram, were assayed at a wide panel of sites, including the most importantreceptors,ion channels,andtransporters,but showed noaffinityfor any of the sites.^[9]^[3]They specifically did not bind to theglutamate,GABA,serotonin,dopamine,adrenergic,histamine,acetylcholine,oropioid receptorsat concentrations of up to 1 μM.^[9]^[3]In addition, the drugs were tested on recombinantAMPA receptorsand showed no potentiation of the receptors, indicating that they do not act asAMPA receptor positive allosteric modulators.^[9]However, they were able to prevent theamnesiainduced by the AMPA receptorantagonist NBQXin the passive avoidance test, suggesting thatindirect/downstreamAMPA receptor activation may be involved in their memory-enhancing effects.^[3]

Chemistry

References

^Galeotti N, Ghelardini C, Pittaluga A, Pugliese AM, Bartolini A, Manetti D, et al. (December 2003). "AMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram)".Naunyn-Schmiedeberg's Archives of Pharmacology.368(6): 538–545.doi:10.1007/s00210-003-0812-6.PMID 14600801.S2CID 11810684.
^Ghelardini C, Galeotti N, Gualtieri F, Romanelli MN, Bucherelli C, Baldi E, Bartolini A (June 2002). "DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer".Naunyn-Schmiedeberg's Archives of Pharmacology.365(6): 419–426.doi:10.1007/s00210-002-0577-3.hdl:2158/772195.PMID 12070754.S2CID 9501712.
^^a ^b ^c ^dRomanelli MN, Galeotti N, Ghelardini C, Manetti D, Martini E, Gualtieri F (2006)."Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers".CNS Drug Reviews.12(1): 39–52.doi:10.1111/j.1527-3458.2006.00039.x.PMC6741768.PMID 16834757.
^Scapecchi S, Martini E, Manetti D, Ghelardini C, Martelli C, Dei S, et al. (January 2004). "Structure-activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs".Bioorganic & Medicinal Chemistry.12(1): 71–85.doi:10.1016/j.bmc.2003.10.025.PMID 14697772.
^Martini E, Ghelardini C, Dei S, Guandalini L, Manetti D, Melchiorre M, et al. (February 2008). "Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers".Bioorganic & Medicinal Chemistry.16(3): 1431–1443.doi:10.1016/j.bmc.2007.10.050.PMID 17981042.
^Martini E, Norcini M, Ghelardini C, Manetti D, Dei S, Guandalini L, et al. (December 2008). "Design, synthesis and preliminary pharmacological evaluation of new analogues of DM232 (unifiram) and DM235 (sunifiram) as cognition modulators".Bioorganic & Medicinal Chemistry.16(23): 10034–10042.doi:10.1016/j.bmc.2008.10.017.PMID 18954993.
^Martini E, Ghelardini C, Bertucci C, Dei S, Gualtieri F, Guandalini L, et al. (September 2005). "Enantioselective synthesis and preliminary pharmacological evaluation of the enantiomers of unifiram (DM232), a potent cognition-enhancing agent".Medicinal Chemistry.1(5): 473–480.doi:10.2174/1573406054864142.PMID 16787332.
^Ghelardini C, Galeotti N, Gualtieri F, Manetti D, Bucherelli C, Baldi E, Bartolini A (2002). "The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats".Drug Development Research.56:23–32.doi:10.1002/ddr.10055.hdl:2158/772162.S2CID 85091757.
^^a ^b ^c ^dGualtieri F (2016)."Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings".Journal of Enzyme Inhibition and Medicinal Chemistry.31(2): 187–194.doi:10.3109/14756366.2015.1021252.PMID 25831025.S2CID 207528957.

[1] Galeotti N, Ghelardini C, Pittaluga A, Pugliese AM, Bartolini A, Manetti D, et al. (December 2003). "AMPA-receptor activation is involved in the antiamnesic effect of DM 232 (unifiram) and DM 235 (sunifiram)".Naunyn-Schmiedeberg's Archives of Pharmacology.368(6): 538–545.doi:10.1007/s00210-003-0812-6.PMID 14600801.S2CID 11810684.

[2] Ghelardini C, Galeotti N, Gualtieri F, Romanelli MN, Bucherelli C, Baldi E, Bartolini A (June 2002). "DM235 (sunifiram): a novel nootropic with potential as a cognitive enhancer".Naunyn-Schmiedeberg's Archives of Pharmacology.365(6): 419–426.doi:10.1007/s00210-002-0577-3.hdl:2158/772195.PMID 12070754.S2CID 9501712.

[pmid16834757-3] Romanelli MN, Galeotti N, Ghelardini C, Manetti D, Martini E, Gualtieri F (2006)."Pharmacological characterization of DM232 (unifiram) and DM235 (sunifiram), new potent cognition enhancers".CNS Drug Reviews.12(1): 39–52.doi:10.1111/j.1527-3458.2006.00039.x.PMC6741768.PMID 16834757.

[4] Scapecchi S, Martini E, Manetti D, Ghelardini C, Martelli C, Dei S, et al. (January 2004). "Structure-activity relationship studies on unifiram (DM232) and sunifiram (DM235), two novel and potent cognition enhancing drugs".Bioorganic & Medicinal Chemistry.12(1): 71–85.doi:10.1016/j.bmc.2003.10.025.PMID 14697772.

[5] Martini E, Ghelardini C, Dei S, Guandalini L, Manetti D, Melchiorre M, et al. (February 2008). "Design, synthesis and preliminary pharmacological evaluation of new piperidine and piperazine derivatives as cognition-enhancers".Bioorganic & Medicinal Chemistry.16(3): 1431–1443.doi:10.1016/j.bmc.2007.10.050.PMID 17981042.

[6] Martini E, Norcini M, Ghelardini C, Manetti D, Dei S, Guandalini L, et al. (December 2008). "Design, synthesis and preliminary pharmacological evaluation of new analogues of DM232 (unifiram) and DM235 (sunifiram) as cognition modulators".Bioorganic & Medicinal Chemistry.16(23): 10034–10042.doi:10.1016/j.bmc.2008.10.017.PMID 18954993.

[7] Martini E, Ghelardini C, Bertucci C, Dei S, Gualtieri F, Guandalini L, et al. (September 2005). "Enantioselective synthesis and preliminary pharmacological evaluation of the enantiomers of unifiram (DM232), a potent cognition-enhancing agent".Medicinal Chemistry.1(5): 473–480.doi:10.2174/1573406054864142.PMID 16787332.

[8] Ghelardini C, Galeotti N, Gualtieri F, Manetti D, Bucherelli C, Baldi E, Bartolini A (2002). "The novel nootropic compound DM232 (UNIFIRAM) ameliorates memory impairment in mice and rats".Drug Development Research.56:23–32.doi:10.1002/ddr.10055.hdl:2158/772162.S2CID 85091757.

[pmid25831025-9] Gualtieri F (2016)."Unifi nootropics from the lab to the web: a story of academic (and industrial) shortcomings".Journal of Enzyme Inhibition and Medicinal Chemistry.31(2): 187–194.doi:10.3109/14756366.2015.1021252.PMID 25831025.S2CID 207528957.

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