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Suritozole

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Chemical compound

Pharmaceutical compound

Suritozole
Clinical data

ATC code	none
Identifiers
IUPAC name 5-(3-fluorophenyl)-2,4-dimethyl-2,4-dihydro-3H-1,2,4-triazole-3-thione
CAS Number	110623-33-1^Y
PubChemCID	25431
ChemSpider	23743^N
UNII	3H7H68317X
KEGG	D05980^Y
CompTox Dashboard(EPA)	DTXSID10149333
Chemical and physical data
Formula	C₁₀H₁₀FN₃S
Molar mass	223.27 g·mol⁻¹
3D model (JSmol)	Interactive image
SMILES Cn1c(=S)n(C)nc1-c2cccc(F)c2
InChI InChI=1S/C10H10FN3S/c1-13-9(12-14(2)10(13)15)7-4-3-5-8(11)6-7/h3-6H,1-2H3^N Key:IWDUZEHNLHFBRZ-UHFFFAOYSA-N^N
^NY (what is this?) (verify)

Suritozole (MDL 26,479) is an investigationalcognition enhancer. It acts as a partialinverse agonist at thebenzodiazepine receptor site on the GABA_A ion channel complex, but does not have eitheranxiogenic orconvulsant effects, unlike other BZD inverse agonists such asDMCM.^[1] It was investigated for the treatment ofdepression andAlzheimer's disease in the 90s,^[2] but clinical development seems to have been discontinued.

Synthesis

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The reaction between monomethylhydrazine [60-34-4] (1) and methyl isothiocyanate (Trapex) [556-61-6] (2) gave 2,4-dimethylthiosemicarbazide [6621-75-6] (3). Amide formation with 3-fluorobenzoyl chloride [1711-07-5] (4) yielded 1-(3-fluorobenzoyl)-2,4-dimethylthiosemicarbazide [110623-52-4] (5). Cyclization to Suritozole (6).

References

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^Miller JA, Dudley MW, Kehne JH, Sorensen SM, Kane JM (September 1992)."MDL 26,479: a potential cognition enhancer with benzodiazepine inverse agonist-like properties".British Journal of Pharmacology.107 (1):78–86.doi:10.1111/j.1476-5381.1992.tb14466.x.PMC 1907590.PMID 1330168.
^Robbins DK, Hutcheson SJ, Miller TD, Green VI, Bhargava VO, Weir SJ (May 1997). "Pharmacokinetics of MDL 26479, a novel benzodiazepine inverse agonist, in normal volunteers".Biopharmaceutics & Drug Disposition.18 (4):325–334.doi:10.1002/(SICI)1099-081X(199705)18:4<325::AID-BDD21>3.0.CO;2-1.PMID 9158880.
^Miller JA, Dudley MW, Kehne JH, Sorensen SM, Wenstrup DL, Kane JM (1992). "MDL 26,479".Drugs of the Future.17 (1):21–23.doi:10.1358/dof.1992.017.01.161263.
^Kane JM, Dudley MW, Sorensen SM, Miller FP (June 1988). "2,4-Dihydro-3H-1,2,4-triazole-3-thiones as potential antidepressant agents".Journal of Medicinal Chemistry.31 (6):1253–1258.doi:10.1021/jm00401a031.PMID 3373495.
^Louks DH, Stolz-Dunn SK (2007). "Kinetics for Scale-Up of a One-Pot Pathway to 5-(3-Fluorophenyl)-2,4-dihydro-2,4-dimethyl-3H -1,2,4-triazole-3-thione Using a Hybrid Model of Parallel and Consecutive Reactions".Organic Process Research & Development.11 (5):877–884.doi:10.1021/op700101g.
^US5856350 idem Christopher Robin Dalton, John Michael Kane, John Herr Kehne,WO 1996033177 (1999 to Hoechst Marion Roussel, Inc.).
^US5723624 idem Sandra K. Stolz-Dunn, David H. Louks, Yolanda M. Puga, Christian T. Goralski,WO 1996001812 (1998 to Merrell Pharmaceuticals Inc).