Suritozole

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 ;
PubChem CID	25431;
ChemSpider	23743 ;
UNII	3H7H68317X;
KEGG	D05980 ;
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 ; Key:IWDUZEHNLHFBRZ-UHFFFAOYSA-N ;
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Suritozole (MDL 26,479) is an investigational cognition enhancer. It acts as a partial inverse agonist at the benzodiazepine receptor site on the GABA_A ion channel complex, but does not have either anxiogenic or convulsant effects, unlike other BZD inverse agonists such as DMCM.^[1] It was investigated for the treatment of depression and Alzheimer's disease,^[2] but clinical development seems to have been discontinued.

Synthesis

Synthesis:^[3]^[4] ~85%:^[5] Patents:^[6]^[7] etc

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

^ 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-3 H -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).

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[pmid1330168-1] 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.

[pmid9158880-2] 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.

[3] 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.

[4] 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.

[5] 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-3 H -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.

[6] US5856350 idem Christopher Robin Dalton, John Michael Kane, John Herr Kehne, WO 1996033177 (1999 to Hoechst Marion Roussel, Inc.).

[7] US5723624 idem Sandra K. Stolz-Dunn, David H. Louks, Yolanda M. Puga, Christian T. Goralski, WO 1996001812 (1998 to Merrell Pharmaceuticals Inc).

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[2]

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[5]

[6]

[7]

Suritozole

Synthesis

See also

References

zproxy.org

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
PubChem CID	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)