Fostedil

Last updated
Fostedil
Fostedil structure.png
Clinical data
Routes of
administration
Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • diethyl [4-(1,3-benzothiazol-2-yl)benzyl]phosphonate
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)
  • 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]

Contents

Synthesis

Fostedil synthesis: Fostedil synthesis.png
Fostedil synthesis:
  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

Related Research Articles

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References

  1. Triggle DJ (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): 1037–1042. 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): 1043–1046. 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): 1047–1052. PMID   6890824.
  6. Morita T, Ito K, Nose T (1982). "Cardiac action of KB-944, a new calcium antagonist". Arzneimittel-Forschung. 32 (9): 1053–1055. 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): 1056–1059. PMID   6890826.
  8. 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.