Fostedil (A-53,986, KB-944) is a vasodilator acting as a calcium channel blocker which was under development for the treatment of heart conditions such as angina pectoris but was never marketed.[1][2][3][4] It has antihypertensive and antiarrhythmic effects.[5][6][7]
 | |
| Clinical data | |
|---|---|
| Routes of administration | Oral |
| ATC code |
|
| Legal status | |
| Legal status |
|
| Identifiers | |
| |
| CAS Number | |
| PubChem CID | |
| ChemSpider | |
| UNII | |
| KEGG | |
| ChEMBL | |
| CompTox Dashboard (EPA) | |
| Chemical and physical data | |
| Formula | C18NO3PS |
| Molar mass | 341.24 g·mol−1 |
| 3D model (JSmol) | |
| |
Synthesis
edit
- Treatment of benzanilide with phosphorus pentasulfide or Lawesson's reagent gives thioamide.
- Oxidative ring formation by reaction with potassium ferricyanide and base (presumably involving a free radical intermediate) constructs the benzothiazole ring.
- Bromination of this compound with N-bromosuccinimide produces bromomethyl intermediate.
- The synthesis of fostedil concludes with a Michaelis-Arbuzov reaction with triethyl phosphite.
See also
editReferences
edit- ^ Triggle DJ (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 0-412-46630-9.
- ^ Khurmi NS, Bowles MJ, O'Hara MJ, Lahiri A, Raftery EB (November 1985). "Ambulatory monitoring and exercise testing in the evaluation of a new long-acting calcium ion antagonist KB-944 (Fostedil) for the treatment of exertional angina pectoris". International Journal of Cardiology. 9 (3): 289–302. doi:10.1016/0167-5273(85)90027-0. PMID 3902675.
- ^ Morita T, Yoshino K, Kanazawa T, Ito K, Nose T (1982). "Vasodilator action of KB-944, a new calcium antagonist". Arzneimittel-Forschung. 32 (9): 1037–1042. PMID 6890822.
- ^ Morita T, Kanazawa T, Ito K, Nose T (1982). "Vasodilator mechanism of KB-944, a new calcium antagonist". Arzneimittel-Forschung. 32 (9): 1043–1046. PMID 6890823.
- ^ Morita T, Kanazawa T, Ito K, Nose T (1982). "Antihypertensive effect of KB-944, a new calcium antagonist, in conscious normotensive and hypertensive rats". Arzneimittel-Forschung. 32 (9): 1047–1052. PMID 6890824.
- ^ Morita T, Ito K, Nose T (1982). "Cardiac action of KB-944, a new calcium antagonist". Arzneimittel-Forschung. 32 (9): 1053–1055. PMID 6890825.
- ^ Yoshidomi M, Sukamoto T, Morita T, Ito K, Nose T (1982). "Antiarrhythmic effect of KB-944, a new calcium antagonist. A comparison with verapamil and diltiazem". Arzneimittel-Forschung. 32 (9): 1056–1059. PMID 6890826.
- ^ Yoshino K, Kohno T, Uno T, Morita T, Tsukamoto G (May 1986). "Organic phosphorus compounds. 1. 4-(Benzothiazol-2-yl)benzylphosphonate as potent calcium antagonistic vasodilator". Journal of Medicinal Chemistry. 29 (5): 820–825. doi:10.1021/jm00155a037. PMID 3701791.