RT Journal Article
T1 2-MeS-β,γ-CCl2-ATP is a Potent Agent for Reducing Intraocular Pressure
A1 Eliahu, Shay
A1 Martín Gil, Alba
A1 Perez de Lara, María Jesús
A1 Pintor Just, Jesús Jerónimo
A1 Camden, Jean
A1 Weisman, Gary
A1 Lecka, Joanna
A1 Sévigny, Jean
A1 Fischer, Bilha
AB Extracellular nucleotides can modify the production or drainage of the aqueous humor via activation of P2 receptors and therefore affect the intraocular pressure (IOP). We have synthesized slowly hydrolyzable nucleoside di- and triphosphate analogues, 1, and 8-14. Analogues 8-14 were completely resistant to hydrolysis by alkaline phosphatase over 30 min at 37 °C. In human blood serum, analogues 8-14 exhibited high stability, e.g., analogues 9 and 10-14 were only 15% and 0% degraded after 24 h, respectively. Moreover, analogues 8-14 were highly stable at pH 1.4 (t1/2 1 h-30 days). Analogues 8-14 were agonists of the P2Y1 receptor (EC50 0.57-9.54 μM). Ocular administration of most analogues into rabbits reduced IOP, e.g., analogue 9 reduced IOP by 32% (EC50 95.5 nM). Analogue 9 was more effective at reducing IOP than several common glaucoma drugs and represents a promising alternative to timolol maleate, which cannot be used for the treatment of patients suffering from asthma or cardiac problems. © 2010 American Chemical Society.
PB ASC Publications
SN 0022-2623
YR 2010
FD 2010
LK https://hdl.handle.net/20.500.14352/101266
UL https://hdl.handle.net/20.500.14352/101266
LA eng
NO Eliahu, Shay, et al. «2-MeS-β,γ-CCl2 -ATP Is a Potent Agent for Reducing Intraocular Pressure». Journal of Medicinal Chemistry, vol. 53, n.o 8, abril de 2010, pp. 3305-19. https://doi.org/10.1021/jm100030u.
DS Docta Complutense
RD 17 abr 2025