Fostedil

Fostedil
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
IUPAC name
  • diethyl [4-(1,3-benzothiazol-2-yl)benzyl]phosphonate
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18NO3PS
Molar mass341.24 g·mol−1
3D model (JSmol)
SMILES
  • O=P(OCC)(OCC)Cc3ccc(c1nc2ccccc2s1)cc3

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

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

References

  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): 820–825. doi:10.1021/jm00155a037. PMID 3701791.
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