2. Academic Validation
  3. Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists

Structure-activity relationships of 2-chloro-N6-substituted-4'-thioadenosine-5'-N,N-dialkyluronamides as human A3 adenosine receptor antagonists

  • Bioorg Med Chem Lett. 2008 Mar 1;18(5):1612-6. doi: 10.1016/j.bmcl.2008.01.070.
Lak Shin Jeong 1,  Hyuk Woo Lee,  Hea Ok Kim,  Dilip K Tosh,  Shantanu Pal,  Won Jun Choi,  Zhan-Guo Gao,  Amit R Patel,  Wanda Williams,  Kenneth A Jacobson,  Hee-Doo Kim
Affiliations

Affiliation

  • 1 Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Republic of Korea. [email protected]
PMID: 18255292 DOI: 10.1016/j.bmcl.2008.01.070
Abstract

On the basis of potent and selective A(3) Adenosine Receptor (AR) antagonist, 2-chloro-N(6)-(3-iodobenzyl)-4'-thioadenosine-5'-N,N-dimethyluronamide, structure-activity relationships were studied for a series of 5'-N,N-dialkyluronamide derivatives, synthesized from D-gulonic gamma-lactone. From this study, it was revealed that removal of the hydrogen bond-donating ability of the 5'-uronamide was essential for the pure A(3)AR antagonism. 5'-N,N-Dimethyluronamide derivatives exhibited higher binding affinity than larger 5'-N,N-dialkyl or 5'-N,N-cycloalkylamide derivatives, indicating that steric factors are crucial in binding to the human A(3)AR. A N(6)-(3-bromobenzyl) derivative 6c (K(i)=9.32 nM) exhibited the highest binding affinity at the human A(3)AR with very low binding affinities to Other AR subtypes.

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