Zaprinast

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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
37762-06-4 N
ChEMBL ChEMBL28079 YesY
ChemSpider 5520 YesY
2919
Jmol interactive 3D Image
PubChem 5722
UNII GXT25D5DS0 YesY
Properties
C13H13N5O2
Molar mass 271.28 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is YesYN ?)
Infobox references

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] - however the clinical significance of this has yet to be determined.

References[edit]

  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. 
  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. 
  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: 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.