Tolazamide

Tolazamide
Clinical data
Trade names	Tolinase
AHFS/Drugs.com	Monograph
MedlinePlus	a682482
License data	US FDA: Tolazamide;
Pregnancy; category	AU: C; ;
Routes of; administration	Oral
ATC code	A10BB05 (WHO) ;
Legal status
Legal status	US: ℞-only;
Pharmacokinetic data
Bioavailability	?
Metabolism	metabolized in the liver to active metabolites
Elimination half-life	7 hours
Excretion	Renal (85%) and fecal (7%)
Identifiers
	IUPAC name N-[(azepan-1-ylamino)carbonyl]-4-methylbenzenesulfonamide;
CAS Number	1156-19-0;
PubChem CID	5503;
IUPHAR/BPS	6847;
DrugBank	DB00839 ;
ChemSpider	5302 ;
UNII	9LT1BRO48Q;
KEGG	D00379 ;
ChEBI	CHEBI:9613;
ChEMBL	ChEMBL817 ;
CompTox Dashboard (EPA)	DTXSID3021358 ;
ECHA InfoCard	100.013.262
Chemical and physical data
Formula	C14H21N3O3S
Molar mass	311.40 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=S(=O)(c1ccc(cc1)C)NC(=O)NN2CCCCCC2;
	InChI InChI=1S/C14H21N3O3S/c1-12-6-8-13(9-7-12)21(19,20)16-14(18)15-17-10-4-2-3-5-11-17/h6-9H,2-5,10-11H2,1H3,(H2,15,16,18) ; Key:OUDSBRTVNLOZBN-UHFFFAOYSA-N ;
	(verify)

Tolazamide is an oral blood glucose lowering drug used for people with Type 2 diabetes. It is part of the sulfonylurea family (ATC A10BB).

Synthesis

The reaction between p-toluenesulfonamide (1) and ethyl chloroformate (2) in the presence of base gives tosylurethane [5577-13-9] (3). Heating that intermediate with azepane (4) leads to the displacement of the ethoxy group and the formation of tolazemide (5).^[1]^[2]^[3]^[4]^[5]

Azepane proper would lead to [13078-23-4].

References

^ Vardanyan, Ṛuben, Hruby, V. J. (2006). Synthesis of essential drugs. Elsevier. ISBN 9780444521668.
^ Wright JB, Willette RE (July 1962). "Antidiabetic Agents. N4-Arylsulfonylsemicarbazides". Journal of Medicinal and Pharmaceutical Chemistry. 91 (4): 815–22. doi:10.1021/jm01239a016. PMID 14056414.
^ John B Wright, U.S. patent 3,063,903 (1962 to Upjohn Co).
^ Wright John Brenton, GB 887886 (1962 to Upjohn).
^ DE1196200 idem Korger Gerhard, Weber Helmut, Aumuller Walter, U.S. patent 3,248,384 (1966 to Hoechst Ag).

External links

"Tolazamide". Medline Plus. U.S. National Library of Medicine.

[1] Vardanyan, Ṛuben, Hruby, V. J. (2006). Synthesis of essential drugs. Elsevier. ISBN 9780444521668.

[Wright_1962-2] Wright JB, Willette RE (July 1962). "Antidiabetic Agents. N4-Arylsulfonylsemicarbazides". Journal of Medicinal and Pharmaceutical Chemistry. 91 (4): 815–22. doi:10.1021/jm01239a016. PMID 14056414.

[3] John B Wright, U.S. patent 3,063,903 (1962 to Upjohn Co).

[4] Wright John Brenton, GB 887886 (1962 to Upjohn).

[5] DE1196200 idem Korger Gerhard, Weber Helmut, Aumuller Walter, U.S. patent 3,248,384 (1966 to Hoechst Ag).

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