title: Synthesis and structure-activity relationships of selective ligands for P3 purinoceptor-like protein (P3LP).
abstract: We examined the structure-activity relationship of various 5'-N-substituted-carboxamidoadenosine derivatives toward P3 purinoceptor-like protein (P3LP), which has affinity for both adenine nucleosides and nucleotides. We discovered a hydrophobic binding region near the 5'-N-substituted-carboxamide group. From the linear alkyl N-substituted derivatives, 1-(adenin-9-yl)-1-deoxy-N-n-pentyl-beta-D-ribofuranuronamide (6) was found to be the most potent ligand. In the series of the N-cycloalkyl derivatives, 1-(adenin-9-yl)-1-deoxy-N-cyclohexyl-beta-D-ribofuranuronamide (8) was the strongest ligand. We also examined the receptor selectivity for the selected nucleosides 6 and 8 with 1 (HAK2701) and N-ethylcarboxamidoadenosine (NECA) versus P1 purinoceptor subtypes, such as adenosine A1, A2A, A2B, and A3 receptors and found 8 is the most selective ligand for P3LP.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Umino
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
authors.forename: Y
authors.initials: Y
authors.lastname: Saitoh
authors.forename: N
authors.initials: N
authors.lastname: Minakawa
authors.forename: H
authors.initials: H
authors.lastname: Nakata
authors.forename: A
authors.initials: A
authors.lastname: Matsuda
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands; D011983:Receptors, Purinergic / Q000145:classification / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D011983:Receptors, Purinergic; D018047:Receptors, Purinergic P1; D000241:Adenosine