Fostedil

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Fostedil
Fostedil structure.png
Systematic (IUPAC) name
diethyl [4-(1,3-benzothiazol-2-yl)benzyl]phosphonate
Clinical data
  • Uncontrolled
Oral
Identifiers
75889-62-2
None
PubChem CID 53421
ChemSpider 48253
UNII D41WS786UL YesY
KEGG D04260
ChEMBL CHEMBL39516
Chemical data
Formula C18NO3PS
361.40 g/mol

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]

Synthesis[edit]

Fostedil synthesis:[8]
  1. Treatment of benzanilide with phosphorus pentasulfide or Lawesson's reagent gives thioamide.
  2. Oxidative ring formation by reaction with potassium ferricyanide and base (presumably involving a free radical intermediate) constructs the benzothiazole ring.
  3. Bromination of this compound with N-bromosuccinimide produces bromomethyl intermediate.
  4. The synthesis of fostedil concludes with a Michaelis-Arbuzov reaction with triethyl phosphite.

See also[edit]

References[edit]

  1. ^ David J. Triggle (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 0-412-46630-9. 
  2. ^ 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. 
  3. ^ Morita T, Yoshino K, Kanazawa T, Ito K, Nose T (1982). "Vasodilator action of KB-944, a new calcium antagonist". Arzneimittel-Forschung 32 (9): 1037–42. PMID 6890822. 
  4. ^ Morita T, Kanazawa T, Ito K, Nose T (1982). "Vasodilator mechanism of KB-944, a new calcium antagonist". Arzneimittel-Forschung 32 (9): 1043–6. PMID 6890823. 
  5. ^ 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): 1047–52. PMID 6890824. 
  6. ^ Morita T, Ito K, Nose T (1982). "Cardiac action of KB-944, a new calcium antagonist". Arzneimittel-Forschung 32 (9): 1053–5. PMID 6890825. 
  7. ^ 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): 1056–9. PMID 6890826. 
  8. ^ Yoshino, K.; Kohno, T.; Uno, T.; Morita, T.; Tsukamoto, G. (1986). "Organic phosphorus compounds. 1. 4-(Benzothiazol-2-yl)benzylphosphonate as potent calcium antagonistic vasodilator". Journal of Medicinal Chemistry 29 (5): 820. doi:10.1021/jm00155a037.  edit