- 5'-N-substituted carboxamidoadenosines as agonists for adenosine receptors
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Novel as well as known 5'-N-substituted carboxamidoadenosines were prepared via new routes that provided shorter reaction times and good yields. Binding affinities were determined for rat A1 and A(2A) receptors and human A3 receptors. EC50 values were determined for cyclic AMP production in CHO cells expressing human A(2B) receptors. On all receptor subtypes relatively small substituents on the carboxamido moiety were optimal. Selectivity for the A3 receptor was found for several analogues (1a, 1d, 1h, and 1k). On A1 receptors a number of compounds, but not 5'-N-ethylcarboxamidoadenosine (NECA, 1b), showed small GTP shifts, which could be indicative of lower intrinsic activities at the A1 receptor. At the A(2B) receptor, derivatives 1i-k with modified ethyl substituents had reduced activities compared to the A(2B) reference agonist NECA (1b). Thiocarboxamido derivatives (8b and 8c) displayed considerable although decreased A(2B) receptor activity. The X-ray structure determination of compound 8b was carried out. Due to intramolecular hydrogen bonding between the carboxamido NH and the purine N3 in the crystal structure, the ribose moiety of this compound is in a syn conformation. However, theoretical calculations support that NECA (1b), and less so 8b, can readily adopt both the syn and the anti conformation, therefore not excluding the proposed anti mode of binding to the receptor.
- De Zwart, Maarten,Kourounakis, Angeliki,Kooijman, Huub,Spek, Anthony L.,Link, Regina,Von Frijtag Drabbe Künzel, Jacobien K.,IJzerman, Ad P.
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- An efficient convergent synthesis of adenosine-5′-N-alkyluronamides
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Herein we report an efficient synthesis of adenosine-5′-N-alkyluronamides in which an enzyme-mediated deacetylation reaction is a key to the selective modification of the 5′-N-position, prior to coupling the ribose and purine components via a microwave-as
- Devine, Shane M.,Scammells, Peter J.
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p. 1772 - 1777
(2008/09/18)
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- Nucleosides and nucleotides. 200. Reinvestigation of 5′-N-ethylcarboxamidoadenosine derivatives: Structure-activity relationships for P3 purinoceptor-like proteins
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The non-P1 and non-P2 muscle relaxant effect of ATP in rabbit thoracic aorta has recently been attributed to a putative P3 purinoceptor, which is activated by either adenosine or ATP. Since the physiological roles of this
- Umino,Yoshioka,Saitoh,Minakawa,Nakata,Matsuda
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p. 208 - 214
(2007/10/03)
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- Inactivation of S-adenosyl-L-homocysteine hydrolase by amide and ester derivatives of adenosine-5'-carboxylic acid
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S-Adenosyl-L-homocysteine (AdoHcy) hydrolase has been shown to have (576') hydrolytic activity with vinyl (5') or homovinyl (6') halides derived from adenosine (Ado). This hydrolyric activity is independent of its 3'- oxidative activity. The vinyl (or hom
- Wnuk, Stanislaw F.,Liu, Siming,Yuan, Chong-Sheng,Borchardt, Ronald T.,Robins, Morris J.
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p. 4162 - 4166
(2007/10/03)
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- Modification of the 5' Position of Purine Nucleosides. 2. Synthesis and Some Cardiovascular Properties of Adenosine-5'-(N-substituted)carboxamides
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We have shown previously that the esters of adenosine-5'-carboxylic acid (10) represent a new class of potent nontoxic coronary vasodilators.For example, the ethyl ester (12), which is active by an intraduodenal or intravenous route in dogs, causes a larg
- Prasad, Raj Nandan,Bariana, Dilbagh S.,Fung, Anthony,Savic, Milica,Tietje, Karin,et al.
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p. 313 - 319
(2007/10/02)
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- Adenosine-5'-carboxylic acid amides
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Adenosine-5'-carboxylic acid amides represented by the formula STR1 wherein R1 and R2 are each selected from the group consisting of hydrogen, loweralkyl, lowerhaloalkyl, lowerhydroxyalkyl, lowercycloalkyl, loweralkylcycloalkyl, loweralkenyl, lowerhaloalkenyl, lowerhydroxyalkenyl, loweralkynyl, lowerhaloalkynyl, benzylamino, phenyl, loweralkylphenyl, loweralkoxyloweralkyl, substituted phenyl, 2-methylfuran or di(C1 -C4)alkylamino(C1 -C4)alkyl, adamantyl or R1 and R2 taken together form a 5 or 6 membered heterocyclic moiety; R3 and R4 are hydrogen or acyl, or taken together form an isopropylidene or a benzylidene group; or a pharmaceutically acceptable acid addition salt thereof.
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