Forasartan

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Forasartan.svg
Systematic (IUPAC) name
5-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-[2-(2H-tetrazol-5-yl)phenyl]pyridine
Clinical data
Pregnancy
category
  • Not assigned
Legal status
  • Development halted, never marketed[1]
Routes of
administration		 Oral
Pharmacokinetic data
Biological half-life 1–2 hours
Identifiers
CAS Number 145216-43-9
ATC code C09CA (WHO)
PubChem CID: 132706
DrugBank DB01342
ChemSpider 117146
UNII 065F7WPT0B
KEGG D04243
ChEBI CHEBI:239233
ChEMBL CHEMBL315021
Synonyms SC-52458
Chemical data
Formula C23H28N8
Molecular mass 416.522 g·mol−1
  • CCCCC1=NN(C(=N1)CCCC)CC2=CN=C(C=C2)C3=CC=CC=C3C4=NNN=N4
  • InChI=1S/C23H28N8/c1-3-5-11-21-25-22(12-6-4-2)31(28-21)16-17-13-14-20(24-15-17)18-9-7-8-10-19(18)23-26-29-30-27-23/h7-10,13-15H,3-6,11-12,16H2,1-2H3,(H,26,27,29,30)
  • Key:YONOBYIBNBCDSJ-UHFFFAOYSA-N

Forasartan, otherwise known as the compound SC-52458, is a nonpeptide angiotensin II receptor antagonist (ARB, AT1 receptor blocker).[2][3][4][5]

Indications

Forasartan is indicated for the treatment of hypertension [6] and, similar to other ARBs, it protects the kidneys from kidney blood vessel damage caused by increased kidney blood pressure by blocking renin-angiotensin system activation.[7]

Administration

Forasartan is administered in the active oral form [6] which means that it must go through first pass metabolism in the liver. The dose administered ranges between 150 mg-200 mg daily.[6] Increasing to more than 200 mg daily does not offer significantly greater AT1 receptor inhibition.[6] Forasartan is absorbed quickly in the GI, and within an hour it becomes significantly biologically active.[6] Peak plasma concentrations of the drug are reached within one hour.[6]

Contraindications

Negative side effects of Forasartan are similar to other ARBs, and include hypotension and hyperkalemia.[8] There are no drug interactions identified with forasartan.[6]

Pharmacology

The angiotensin II receptor, type 1

Angiotensin II binds to AT1 receptors, increases contraction of vascular smooth muscle, and stimulates aldosterone resulting in sodium reabsorption and increase in blood volume.[9] Smooth muscle contraction occurs due to increased calcium influx through the L-type calcium channels in smooth muscle cells during the plateau component, increasing the intracellular calcium and membrane potential which sustain depolarization and contraction.[10]

Effects of forasartan

Forasartan is a competitive and reversible ARB that competes with the angiotensin II binding site on AT1 [11] and relaxes vascular smooth muscle,[10] resulting in decreased blood pressure. Forasartan has a high affinity for the AT1 receptor (IC50=2.9 +/- 0.1nM).[12] In dogs, it was found to block the pressor response of Angiotensin II with maximal inhibition, 91%.[10] Forasartan administration selectively inhibits L-type calcium channels in the plateau component of the smooth muscle cells, favoring relaxation of the smooth muscle.[10] Forasartan also decreases heart rate by inhibiting the positive chronotropic effect of high frequency preganglionic stimuli.[13]

Scarce use of Forasartan

Even though experiments have been conducted on rabbits,[6] guinea pigs,[10] dogs [14] and humans,[6][13] forasartan is not a popular drug of choice for hypertension due to its short duration of action; forasartan is less effective than losartan.[6] Research demonstrates that forasartan is also significantly less potent than losartan.[6]

Synthesis

Forasartan synthesis:[15]

N.B. Same journal issue contains many similar analogs.

See also

References

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