7269-58-1Relevant academic research and scientific papers
Evidence for the existence of a specific gprotein-coupled receptor activated by guanosine
Volpini, Rosaria,Marucci, Gabriella,Buccioni, Michela,DalBen, Diego,Lambertucci, Catia,Lammi, Carmen,Mishra, Ram C.,Thomas, Ajiroghene,Cristalli, Gloria
, p. 1074 - 1080 (2012/01/06)
Guanosine, released extracellularly from neurons and glial cells, plays important roles in the central nervous system, including neuroprotection. The innovative DELFIA Eu-GTP binding assay was optimized for characterization of the putative guanosine receptor binding site at rat brain membranes by using a series of novel and known guanosine derivatives. These nucleosides were prepared by modifying the purine and sugar moieties of guanosine at the 6- and 5'-positions, respectively. Results of these experiments prove that guanosine, 6-thioguanosine, and their derivatives activate a Gprotein-coupled receptor that is different from the well-characterized adenosine receptors. Catching the elusive guanosine receptor: The innovative DELFIA Eu-GTP binding assay was applied to characterize the guanosine binding site by using novel and known guanosine derivatives. Some of the tested compounds, which proved to be full agonists with EC50 values in the low nanomolar range, could be useful tools for further characterization of the putative guanosine receptor.
ANTIPARASITIC COMPOUNDS AND COMPOSITIONS
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Page/Page column 37, (2010/11/29)
Disclosed is use of a compound having a structure according to general formula (I) defined below, in the manufacture of a medicament to treat and/or prevent a parasitic infection or infestation in a mammalian subject wherein X1 = N or CH or C=O (X2 = NH) or C=S (X2 = NH) or C-OR1 or C-halogen or C-azide; X2 = N or CR1 or C-halogen or CS(O)nR1 where n = 0-2 or a (C)m linker where m = 1-3 between X2 and X6 or C-X5X6 (in which case X5X6 at C6 (purine numbering) is replaced by H or NHR1 or O or OR1 or S or SR1); X3 = N or CH or C-NO2; X4 = N or CH or C-NO2 or C-NR1R2 or an amidine derivative or a guanidinium derivative; X5 = O or NR1 or CR1R2; X6 = OR1 or O-acyl or 0-S(O)nR1 or NR1R2 or NH-acyl or N(Acyl)2 or NH-OS(O)2R1 or NH-S(O)nR1 where n = 0-2 or a hydrazone derivative or an oxime derivative, but if X5 = O, X6 cannot = O or X5X6 is an amidine or an N-substituted pyridine or substituted guanidine; Y = H or NH2 or NR1R2 or -O (X3 = NH) or OR1 or F or Cl or Br or I or CR1R2R3 or S(O)nR1 where n = 0-2 or azide or X5X6 (in which case X5X6 at C6 (purine numbering) is replaced by H or NHR1 or O or OR1 or S or SR1); R1, R2, R3 are independently selected from the group consisting of H or (optionally substituted), alkyl, alkenyl or alkynyl or aryl or aralkyl where the substituents may be selected from H, OH, NH2, halogen, N3, CN, CHO, COOR', C0NR'2, OR, NE'2, SR', NR'NR'2, NR'OR', NO2 and R' is alkyl, alkenyl, alkynyl, aralkyl, acyl, sulfonyl; Z = H or substituted (alkyl or alkenyl or alkynyl or aralkyl) or a sugar derivative of general formula (II) in the β-configuration where: B is the nucleobase from Formula (I); X7 = CH2 or O or NR1 or S; R4 = H or OH or OR1 or halogen or azide or a phosphate derivative; R5 = H or F or CH3; R6 = H or OH or OR1 or halogen or azide or a phosphate derivative; and R7 = H or halogen or R1 or a derivative of an amino acid or PO3H2 or P2O6H3 or P3O9H4 or a methylene derivative of P2O6H3 or P3O9H4 or a masked phosphate or a phosphonate derivative (5'-O replaced with CH2).
