Tosifen

Tosifen
Clinical data
Other names	Sch 11973
Identifiers
	IUPAC name 1-(4-methylphenyl)sulfonyl-3-[(2S)-1-phenylpropan-2-yl]urea;
CAS Number	32295-18-4;
PubChem CID	36102;
ChemSpider	33207;
UNII	OK1IHO7PG8;
ChEMBL	ChEMBL2105565;
CompTox Dashboard (EPA)	DTXSID3046118 ;
ECHA InfoCard	100.046.333
Chemical and physical data
Formula	C17H20N2O3S
Molar mass	332.42 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CC1=CC=C(C=C1)S(=O)(=O)NC(=O)N[C@@H](C)CC2=CC=CC=C2;
	InChI InChI=1S/C17H20N2O3S/c1-13-8-10-16(11-9-13)23(21,22)19-17(20)18-14(2)12-15-6-4-3-5-7-15/h3-11,14H,12H2,1-2H3,(H2,18,19,20)/t14-/m0/s1; Key:XILWEASNBDKGSA-AWEZNQCLSA-N;

Tosifen is a drug candidate for use as an antiarrhythmic agent. Tosifen was synthesized originally in a series of compounds whose basic structural moiety, the sulfonylurea nucleus, was of interest for potential hypoglycemic action. But tosifen is only a weak hypoglycemic agent. It is a potential antianginal and antiarrhythmic agent. The duration of action of tosifen was considerably longer than nitroglycerin and its lack of side effects considerably greater than propranolol. No long-term harmful effects have been observed during 13-week toxicity studies in animals. Tosifen differed from standard antianginal agents which may act via beta-adrenergic blocking activity or alteration of cardiac or circulatory dynamics since no acute pharmacological changes were observed after tosifen was administered. Tosifen was readily absorbed in both rats and dogs. The rates of absorption, metabolism, and urinary excretion were higher in the rat than in the dog.

Attribution:^[1] Review:^[2] Pharmacology:^[3] ADME:^[4]

Synthesis

Synthesis of tosifen is by ester-amide displacement between Tosylurethane [5577-13-9] (1) and dextroamphetamine [51-64-9] (2) gives tosifen (3).^[5]^[6]

Tosylurethane has dual use in the synthesis of Tolazamide.

References

^ "NCATS Inxight Drugs — TOSIFEN".
^ Castañer J, Weetman D (1978). "Tosifen". Drugs of the Future. 3 (7): 553. doi:10.1358/dof.1978.003.07.998266. ISSN 0377-8282.
^ Zitowitz L, Stimson J, Wohl AJ, Ehrreich SJ (1977). "PHARMACOLOGY OF SCH 11973, N-(2-PHENYLISOPROPYL)-N-p-TOLUENE SULFONYL UREA, A POTENTIAL NEW ANTIANGINAL AGENT". Japanese Journal of Pharmacology. 27 (6): 769–779. doi:10.1254/jjp.27.769. ISSN 0021-5198. PMID 24776.
^ Lin C, Foester R, Lim J, Hsu T, Morton JB, Symchowicz S (1978). "Absorption, metabolism, and excretion of 14C-tosifen in the dog and rat". Drug Metabolism and Disposition: The Biological Fate of Chemicals. 6 (1): 50–58. doi:10.1016/S0090-9556(25)06310-X. PMID 23274.
^ Lester Zitowitz, Lewis A. Walter, Arnold J. Wohl, U.S. patent 4,016,291 (1977 to Schering Corporation).
^ Lednicer, D., Mitscher, L. A. (1984). The organic chemistry of drug synthesis. 3. Wiley. ISBN 9780471092506.

[1] "NCATS Inxight Drugs — TOSIFEN".

[2] Castañer J, Weetman D (1978). "Tosifen". Drugs of the Future. 3 (7): 553. doi:10.1358/dof.1978.003.07.998266. ISSN 0377-8282.

[3] Zitowitz L, Stimson J, Wohl AJ, Ehrreich SJ (1977). "PHARMACOLOGY OF SCH 11973, N-(2-PHENYLISOPROPYL)-N-p-TOLUENE SULFONYL UREA, A POTENTIAL NEW ANTIANGINAL AGENT". Japanese Journal of Pharmacology. 27 (6): 769–779. doi:10.1254/jjp.27.769. ISSN 0021-5198. PMID 24776.

[Lin_1978-4] Lin C, Foester R, Lim J, Hsu T, Morton JB, Symchowicz S (1978). "Absorption, metabolism, and excretion of 14C-tosifen in the dog and rat". Drug Metabolism and Disposition: The Biological Fate of Chemicals. 6 (1): 50–58. doi:10.1016/S0090-9556(25)06310-X. PMID 23274.

[5] Lester Zitowitz, Lewis A. Walter, Arnold J. Wohl, U.S. patent 4,016,291 (1977 to Schering Corporation).

[6] Lednicer, D., Mitscher, L. A. (1984). The organic chemistry of drug synthesis. 3. Wiley. ISBN 9780471092506.

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