Synthesis of 2-Chloro-N6-Substituted-4'-thioadenosine-5'-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists | Zendy

Won Jun Choi | Zendy; H W Lee | Zendy; X. Hou | Zendy; H. O. Kim | Zendy; Kenneth A. Jacobson | Zendy; Lak Shin Jeong | Zendy

Open Access

Synthesis of 2-Chloro-N6-Substituted-4'-thioadenosine-5'-N, N-dialkyluronamides as Potent and Selective A3 Adenosine Receptor Antagonists

Author(s) -

Won Jun Choi,

H W Lee,

X. Hou,

H. O. Kim,

Kenneth A. Jacobson,

Lak Shin Jeong

Publication year - 2008

Publication title -

nucleic acids symposium series

Language(s) - English

Resource type - Journals

eISSN - 1746-8272

pISSN - 0261-3166

DOI - 10.1093/nass/nrn326

Subject(s) - agonist , chemistry , receptor , stereochemistry , adenosine receptor , derivative (finance) , affinities , thio , adenosine , hydrogen bond , alkyl , biochemistry , molecule , organic chemistry , financial economics , economics

The highly selective A(3) receptor agonist, 4'-thio-Cl-IB-MECA was successfully converted into selective A(3) receptor antagonists by appending a second N-alkyl group on the 5'-uronamide position. This result indicates that the hydrogen bonding ability of the 5'-uronamide is essential for the conformational change required for the receptor activation. Among compounds tested, a N(6)-(3-bromobenzyl) derivative with 5'-dimethyluronamide exhibited the highest binding affinity (K(i) = 9.32 nM) at the human A(3) AR with very low binding affinities to other AR subtypes.

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