Click modification in the N6 region of A3 adenosine receptor-selective carbocyclic nucleosides for dendrimeric tethering that preserves pharmacophore recognition.

ABSTRACT: Adenosine derivatives were modified with alkynyl groups on N(6) substituents for linkage to carriers using Cu(I)-catalyzed click chemistry. Two parallel series, both containing a rigid North-methanocarba (bicyclo[3.1.0]hexane) ring system in place of ribose, behaved as A(3) adenosine receptor (AR) agonists: (5'-methyluronamides) or partial agonists (4'-truncated). Terminal alkynyl groups on a chain at the 3 position of a N(6)-benzyl group or simply through a N(6)-propargyl group were coupled to azido derivatives, which included both small molecules and G4 (fourth-generation) multivalent poly(amidoamine) (PAMAM) dendrimers, to form 1,2,3-triazolyl linkers. The small molecular triazoles probed the tolerance in A(3)AR binding of distal, sterically bulky groups such as 1-adamantyl. Terminal 4-

SUBMITTER: Tosh DK 

PROVIDER: S-EPMC3291892 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature