Zaprinast

Last updated
Zaprinast
Zaprinast.svg
Names
IUPAC name
5-(2-Propoxyphenyl)-1H-[1,2,3]triazolo[4,5-d]pyrimidin-7(4H)-one
Other names
M&B 22,948
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.048.760 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C13H13N5O2/c1-2-7-20-9-6-4-3-5-8(9)11-14-12-10(13(19)15-11)16-18-17-12/h3-6H,2,7H2,1H3,(H2,14,15,16,17,18,19) Yes check.svgY
    Key: REZGGXNDEMKIQB-UHFFFAOYSA-N Yes check.svgY
  • O=C1C2=C(N=NN2)NC(C3=CC=CC=C3OCCC)=N1
Properties
C13H13N5O2
Molar mass 271.280 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Zaprinast was an unsuccessful clinical drug candidate that was a precursor to the chemically related PDE5 inhibitors, such as sildenafil (Viagra), which successfully reached the market. It is a phosphodiesterase inhibitor, [1] selective for the subtypes PDE5, PDE6, PDE9 and PDE11. IC50 values are 0.76, 0.15, 29.0, and 12.0 μM, respectively. [2] [3]

Zaprinast inhibits the growth of asexual blood-stage malaria parasites (P. falciparum) in vitro with an ED50 value of 35 μM, and inhibits PfPDE1, a P. falciparum cGMP-specific phosphodiesterase, with an IC50 value of 3.8 μM. [4]

Zaprinast has also been shown to activate the orphan G-protein coupled receptor known as GPR35, both in rats and humans, [5] and to inhibit the mitochondrial pyruvate carrier. [6]

References

  1. ↑ Choi, SH; Choi, DH; Song, KS; Shin, KH; Chun, BG (2002). "Zaprinast, an inhibitor of cGMP-selective phosphodiesterases, enhances the secretion of TNF-alpha and IL-1beta and the expression of iNOS and MHC class II molecules in rat microglial cells". Journal of Neuroscience Research. 67 (3): 411–21. doi:10.1002/jnr.10102. PMID   11813247. S2CID   24513289.
  2. ↑ Taniguchi, Y.; Tonaikachi, H.; Shinjo, K. (2006). "Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35". FEBS Letters. 580 (21): 5003–5008. doi:10.1016/j.febslet.2006.08.015. PMID   16934253. S2CID   43142927.
  3. ↑ Keswani, A. N.; Peyton, K. J.; Durante, W.; Schafer, A. I.; Tulis, D. A. (2009). "The Cyclic GMP Modulators YC-1 and Zaprinast Reduce Vessel Remodeling Through Antiproliferative and Proapoptotic Effects". Journal of Cardiovascular Pharmacology and Therapeutics. 14 (2): 116–124. doi:10.1177/1074248409333266. PMC   2702762 . PMID   19342499.
  4. ↑ Keizo Yuasa; Fumika Mi-Ichi; Tamaki Kobayashi; Masaya Yamanouchi; Jun Kotera; Kiyoshi Kita; Kenji Omori (2005). "PfPDE1, a novel cGMP-specific phosphodiesterase from the human malaria parasite Plasmodium falciparum". Biochem. J. 392 (Pt 1): 221–9. doi:10.1042/BJ20050425. PMC   1317681 . PMID   16038615.
  5. ↑ Yasuhito Taniguchi; Hiroko Tonai-Kachi; Katsuhiro Shinjo (2006). "Zaprinast, a well-known cyclic guanosine monophosphate-specific phosphodiesterase inhibitor, is an agonist for GPR35". FEBS Letters. 580 (21): 5003–5008. doi:10.1016/j.febslet.2006.08.015. PMID   16934253. S2CID   43142927.
  6. ↑ Jianhai Du; Whitney M Cleghorn; Laura Contreras; Ken Lindsay; Austin M Rountree; Andrei O Chertov; Sally J Turner; Ayse Sahaboglu; Jonathan Linton; Martin Sadilek; Jorgina Satrustegui; Ian R Sweet; Francois Paquet-Durand; James B Hurley (2013). "Inhibition of mitochondrial pyruvate transport by zaprinast causes massive accumulation of aspartate at the expense of glutamate in the retina". J Biol Chem. 288 (50): 36129–36140. doi: 10.1074/jbc.M113.507285 . PMC   3861660 . PMID   24187136. S2CID   9429684.


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