综述了腺苷(P1)和ATP(P2)受体的SAR,重点是最近开发的选择性激动剂和拮抗剂。这些包括部分(例如,N6-乙基-8-环戊基氨基腺苷)和全A1激动剂(例如,NNC21-0136,2-氯-N6-[(R)-(苯并噻唑基硫基-2-丙基]腺苷),A2拮抗剂(例如,非黄嘌呤类:SCH58261,5-氨基-7-(苯乙基)-2-(2-呋喃基)-吡唑并[4,3-e]1,2,4-三唑并[1,5-c]嘧啶和ZM241385,4-(2-[7-氨基-2-(2-呋喃基)[1,2,4]三唑并[1,3,3,3-氨基和A3激动剂(例如,CI-IB-MECA,2-氯-N6-(3-碘苄基)-腺苷-5'-N-甲基乌隆-酰胺)。新型腺苷受体拮抗剂(例如,BTH4,3-苄基硫基-4,5,6,7-四氢-苯并[c]噻吩-4-酮-1-羧酸乙酯)已通过筛选天然产物和杂环衍生物的文库发现。待鉴定的第一个A3选择性拮抗剂包括黄酮衍生物(MRS1067),1,4-二氢吡啶(MRS1097),三唑并萘啶(L-249313),和噻唑并嘧啶(L-268605)。强效P2受体激动剂是已知的。例如,2-己基硫代AMP是C6神经胶质瘤细胞中尚未克隆的P2Y受体的高效激动剂。苏拉明是一种弱且非选择性的P2阻断剂,虽然是截断的导数,NF023似乎对P2X受体具有选择性。更具选择性的P2拮抗剂正在开发中,这些受体的克隆。[35S]ATP-γS已用作放射性配体,用于直接标记克隆的P2X受体(P2X1-P2X4)的几种亚型。
The SAR at adenosine (P1) and ATP (P2) receptors is reviewed, with emphasis on recently developed selective
agonists and antagonists. These include partial (e.g., N6-ethyl-8-cyclopentylaminoadenosine) and full A1
agonists (e.g., NNC 21-0136, 2-chloro-N6-[(R)-(benzothiazolylthio-2-propyl]adenosine), A2 antagonists (e.g., the non-xanthines: SCH58261, 5-amino-7-(phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine and ZM241385, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3a][1,3,5]triazinyl-amino]ethyl)-phenol; and the 1-propargyl-8-styrylxanthines), and A3
agonists (e.g., CI-IB-MECA, 2-chloro-N6-(3-iodobenzyl)-adenosine-5\'-N-methyluron-amide). Novel adenosine receptor antagonists (e.g., BTH4, ethyl 3-benzylthio-4,5,6,7-tetrahydro-benzo[c]thiophen-4-one-1-carboxylate) have been discovered through screening libraries of natural products and heterocyclic derivatives. The first A3 selective antagonists to be identified include derivatives of flavones (MRS 1067), 1,4-dihydropyridines (MRS 1097), triazolonaphthyridine (L-249313), and thiazolopyrimidine (L-268605). Potent P2 receptor
agonists are known. For example, 2-HexylthioAMP is a highly potent agonist at the yet uncloned P2Y receptor in C6 glioma cells. Suramin is a weak and non-selective P2 blocker, while a truncated derivative, NF023, appears to be selective for P2X receptors. More selective P2 antagonists are under development, with the cloning of these receptors. [35S]ATP-γS has been used as a radioligand for the direct labeling of several subtypes of cloned P2X receptors (P2X1-P2X4).