90596-75-1Relevant articles and documents
Medicinal compositions for treating eye diseases
-
, (2008/06/13)
Medicinal compositions for treating eye diseases which contain as the active ingredient 2-alkynyladenosine derivatives having an acetylene union at the 2-position of adenine base. Having a long-lasting and remarkable effect of lowering ocular tension, the
Nucleosides and nucleotides. 107. 2-(cycloalkylalkynyl)adenosines: Adenosine A2 receptor agonists with potent antihypertensive effects
Abiru,Miyashita,Watanabe,Yamaguchi,Machida,Matsuda
, p. 2253 - 2260 (2007/10/02)
Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosine (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100 μg/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3 position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.
Nucleosides and nucleotides. 103. 2-Alkynyladenosines: A novel class of selective adenosine A2 receptor agonists with potent antihypertensive effects
Matsuda,Shinozaki,Yamaguchi,Homma,Nomoto,Miyasaka,Watanabe,Abiru
, p. 241 - 252 (2007/10/02)
The synthesis and receptor-binding activities at A1 and A2 adenosine receptors for a series of 2-alkynyladenosines are described. The palladium- catalyzed cross-coupling reaction of 2-iodoadenosine (4a) with various terminal alkynes
2-Alkynyl derivatives of adenosine and adenosine-5'-N-ethyluronamide as selective agonists at A2 adenosine receptors
Cristalli,Eleuteri,Vittori,Volpini,Lohse,Klotz
, p. 2363 - 2368 (2007/10/02)
In the search for more selective A2-receptor agonists and on the basis that appropriate substitution at C2 is known to impart selectivity for A2 receptors, 2-alkynyladenosines 2a-d were resynthesized and evaluated in radioligand binding, adenylate cyclase, and platelet aggregation studies. Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited by compounds 2a-d with K(i) values ranging from 2.8 to 16.4 nM. 2- Alkynyladenosines also exhibited high-affinity binding at solubilized A2 receptors from human platelet membranes. Competition of 2-alkynyladenosines 2a-d for the antagonist radioligand [3H]DPCPX and for the agonist [3H]CCPA gave K(i) values in the nanomolar range, and the compounds showed moderate A2 selectivity. In order to improve this selectivity, the corresponding 2- alkynyl derivatives of adenosine-5'-N-ethyluronamide 8a-d were synthesized and tested. As expected, the 5'-N-ethyluronamide derivatives retained the A2 affinity whereas the A1 affinity was attenuated, resulting in an up to 10- fold increase in A2 selectivity. A similar pattern was observed in adenylate cyclase assays and in platelet aggregation studies. A 30- to 45-fold selectivity for platelet A2 receptors compared to A1 receptors was found for compounds 8a-c in adenylate cyclase studies.
