FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2022658237> ?p ?o ?g. }

• W2022658237 endingPage "4987" @default.
• W2022658237 startingPage "4974" @default.
• W2022658237 abstract "Preference for the northern (N) ring conformation of the ribose moiety of adenine nucleotide 3',5'-bisphosphate antagonists of P2Y(1) receptors was established by using a ring-constrained methanocarba (a bicyclo[3.1.0]hexane) ring as a ribose substitute (Nandanan et al. J. Med. Chem. 2000, 43, 829-842). We have now combined the ring-constrained (N)-methanocarba modification with other functionalities at the 2-position of the adenine moiety. A new synthetic route to this series of bisphosphate derivatives was introduced, consisting of phosphorylation of the pseudoribose moiety prior to coupling with the adenine base. The activity of the newly synthesized analogues was determined by measuring antagonism of 2-methylthio-ADP-stimulated phospholipase C (PLC) activity in 1321N1 human astrocytoma cells expressing the recombinant human P2Y(1) receptor and by using the radiolabeled antagonist [(3)H]2-chloro-N(6)-methyl-(N)-methanocarba-2'-deoxyadenosine 3',5'-bisphosphate 5 in a newly developed binding assay in Sf9 cell membranes. Within the series of 2-halo analogues, the most potent molecule at the hP2Y(1) receptor was an (N)-methanocarba N(6)-methyl-2-iodo analogue 12, which displayed a K(i) value in competition for binding of [(3)H]5 of 0.79 nM and a K(B) value of 1.74 nM for inhibition of PLC. Thus, 12 is the most potent antagonist selective for the P2Y(1) receptor yet reported. The 2-iodo group was substituted with trimethyltin, thus providing a parallel synthetic route for the introduction of an iodo group in this high-affinity antagonist. The (N)-methanocarba-2-methylthio, 2-methylseleno, 2-hexyl, 2-(1-hexenyl), and 2-(1-hexynyl) analogues bound less well, exhibiting micromolar affinity at P2Y(1) receptors. An enzymatic method of synthesis of the 3',5'-bisphosphate from the corresponding 3'-monophosphate, suitable for the preparation of a radiophosphorylated analogue, was explored." @default.
• W2022658237 created "2016-06-24" @default.
• W2022658237 creator A5006225135 @default.
• W2022658237 creator A5007763690 @default.
• W2022658237 creator A5010450034 @default.
• W2022658237 creator A5020099959 @default.
• W2022658237 creator A5030808105 @default.
• W2022658237 creator A5047815614 @default.
• W2022658237 creator A5053282863 @default.
• W2022658237 creator A5057548461 @default.
• W2022658237 creator A5058569231 @default.
• W2022658237 creator A5085368172 @default.
• W2022658237 date "2003-10-14" @default.
• W2022658237 modified "2023-10-03" @default.
• W2022658237 title "2-Substitution of Adenine Nucleotide Analogues Containing a Bicyclo[3.1.0]hexane Ring System Locked in a Northern Conformation: Enhanced Potency as P2Y₁ Receptor Antagonists" @default.
• W2022658237 cites W1516729867 @default.
• W2022658237 cites W1608256683 @default.
• W2022658237 cites W1632825286 @default.
• W2022658237 cites W1847464474 @default.
• W2022658237 cites W1967907440 @default.
• W2022658237 cites W1972309874 @default.
• W2022658237 cites W1975489625 @default.
• W2022658237 cites W1975596197 @default.
• W2022658237 cites W1986775812 @default.
• W2022658237 cites W1991341552 @default.
• W2022658237 cites W1996100625 @default.
• W2022658237 cites W2001777306 @default.
• W2022658237 cites W2002360659 @default.
• W2022658237 cites W2003977457 @default.
• W2022658237 cites W2005786584 @default.
• W2022658237 cites W2005970127 @default.
• W2022658237 cites W2010335799 @default.
• W2022658237 cites W2015188445 @default.
• W2022658237 cites W2025321711 @default.
• W2022658237 cites W2026271678 @default.
• W2022658237 cites W2029044628 @default.
• W2022658237 cites W2029100084 @default.
• W2022658237 cites W2030204779 @default.
• W2022658237 cites W2030345023 @default.
• W2022658237 cites W2035453340 @default.
• W2022658237 cites W2037935243 @default.
• W2022658237 cites W2050417355 @default.
• W2022658237 cites W2051626166 @default.
• W2022658237 cites W2054047850 @default.
• W2022658237 cites W2064566190 @default.
• W2022658237 cites W2070582319 @default.
• W2022658237 cites W2076840783 @default.
• W2022658237 cites W2078966490 @default.
• W2022658237 cites W2082262457 @default.
• W2022658237 cites W2086468552 @default.
• W2022658237 cites W2088530528 @default.
• W2022658237 cites W2102223391 @default.
• W2022658237 cites W2135828647 @default.
• W2022658237 cites W2166646331 @default.
• W2022658237 cites W2208774673 @default.
• W2022658237 cites W2564994229 @default.
• W2022658237 cites W2950689316 @default.
• W2022658237 cites W2952734518 @default.
• W2022658237 doi "https://doi.org/10.1021/jm030127+" @default.
• W2022658237 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3408611" @default.
• W2022658237 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/14584948" @default.
• W2022658237 hasPublicationYear "2003" @default.
• W2022658237 type Work @default.
• W2022658237 sameAs 2022658237 @default.
• W2022658237 citedByCount "104" @default.
• W2022658237 countsByYear W20226582372012 @default.
• W2022658237 countsByYear W20226582372013 @default.
• W2022658237 countsByYear W20226582372014 @default.
• W2022658237 countsByYear W20226582372015 @default.
• W2022658237 countsByYear W20226582372016 @default.
• W2022658237 countsByYear W20226582372017 @default.
• W2022658237 countsByYear W20226582372018 @default.
• W2022658237 countsByYear W20226582372019 @default.
• W2022658237 countsByYear W20226582372020 @default.
• W2022658237 countsByYear W20226582372021 @default.
• W2022658237 countsByYear W20226582372022 @default.
• W2022658237 countsByYear W20226582372023 @default.
• W2022658237 crossrefType "journal-article" @default.
• W2022658237 hasAuthorship W2022658237A5006225135 @default.
• W2022658237 hasAuthorship W2022658237A5007763690 @default.
• W2022658237 hasAuthorship W2022658237A5010450034 @default.
• W2022658237 hasAuthorship W2022658237A5020099959 @default.
• W2022658237 hasAuthorship W2022658237A5030808105 @default.
• W2022658237 hasAuthorship W2022658237A5047815614 @default.
• W2022658237 hasAuthorship W2022658237A5053282863 @default.
• W2022658237 hasAuthorship W2022658237A5057548461 @default.
• W2022658237 hasAuthorship W2022658237A5058569231 @default.
• W2022658237 hasAuthorship W2022658237A5085368172 @default.
• W2022658237 hasBestOaLocation W20226582372 @default.
• W2022658237 hasConcept C114373084 @default.
• W2022658237 hasConcept C181199279 @default.
• W2022658237 hasConcept C185592680 @default.
• W2022658237 hasConcept C202751555 @default.
• W2022658237 hasConcept C24961977 @default.
• W2022658237 hasConcept C2776568683 @default.
• W2022658237 hasConcept C2779461342 @default.
• W2022658237 hasConcept C55493867 @default.
• W2022658237 hasConcept C71240020 @default.

• next