Chloro adenosine

FIGURE 4.18 Affinity of adenosine receptor agonists in whole cells (dark bars) and membranes (cross-hatched bars, high-affinity binding site). Data shown for (1) 2-phenylaminoadenosine, (2) 2-chloro adenosine, (3) 5 -N-ethylcarboxamidoadenosine, (4) N6-cyclohexyladenosine, (5) (-)-(R)-N6-phenylisopropyladenosine, and (6) N6-cyclopentyladenosine. Data redrawn from [15],... 

FIGURE 9.14 Effects of adenosine receptor agonist 2-chloro-adenosine on vascular perfusion pressure of isolated perfused rat kidneys. Minor effects seen in untreated kidneys (filled circles) and pronounced vasoconstriction while vasodilatation in kidneys coperfused with subthreshold concentrations of a-adrenoceptor vasoconstrictor methoxamine and vasodilatatory activation of adenylyl cyclase with forskolin (open circles). Redrawn from [49]. 

A total synthesis of ascamycin results from the 5 -aminosulphat-ion of a 2-chloro-adenosine derivative followed by acylation of the resulting amino-group with alanine.The synthesis of bredinin has... 

Chloroadenosine binding to placental microsomes reached equilibrium at approximately 20 minutes with a Ti of 4 minutes. The observec forward rate constant was 0.24 min l giving a second order rate constant (kj ) of 0.71 X 10. At equilibrium, the addition of 10 pM chloroadenosine resulted in a rapid displacement of pH] chloro adenosine which was completed by 5 minutes. The first order rate constant (k2) for the reversal of [ H]chloroadenosine binding was -1.17 min . The kd calculated from the reverse rate constant was 17 nM which was the same order of magnitude as the Kd estimated from equilibrium data (56 nM). 

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

C15H11ClN3Pt+ C10H13N5O7P- -2.25 H20 Chloro(terpyridyl)platinum(Il)adenosine 5 -monophosphate, TPTAMP 43 373... 

Cyclic-3, 5 -adenosine monophosphate [3I I]-2-Chloro-/V6-cyclopentyladenosine Chinese hamster ovary Acetonitrile... 

Aminophthalate anion Atmospheric pressure active nitrogen Analyte pulse perturbation-chemiluminescence spectroscopy Arthromyces rasomus peroxidase Ascorbic acid Adenosine triphosphate Avalanche photodiode 5-Bromo-4-chloro-3-indolyl 2,6-Di-t< r/-bu(yl-4-mclhyl phenol Bioluminescence Polyoxyethylene (23) dodecanol Bovine serum albumin Critical micelle concentration Calf alkaline phosphatase Continuous-addition-of-reagent Continuous-addition-of-reagent chemiluminescence spectroscopy Catecholamines Catechol... 

The interesting observation has been made that 3 -amino-3 -deoxy-adenosine as a suspension in phosphoryl chloride-triethyl phosphate at 4° is converted into the 5 -chloro-5 -deoxy derivative in 80% yield, but that predissolution of the nucleoside in triethyl phosphate, followed by treatment with phosphoryl chloride at 0°, yields the 5 -phosphate in 62% yield.382... 

In contrast to uridine,389 cytidine does not yield a 5 -chloro-5 -deoxy derivative on reaction with N,N-dimethyl(chlorometh-animinium) chloride instead 2,2 -anhydrocytidine is formed.395 However, thionyl chloride or bromide in hexamethylphosphor-amide at room temperature achieves this selective replacement of the primary hydroxyl group of halogen in cytidine, and also in adenosine, in respective yields of 80 and 75% for the chloro compounds, and 55 and 30% for the bromo analogs.396... 

Adenosine analogues where the furanose ring was replaced with alternative dihydro- and tetrahydrofurans were prepared from 6-chloro-9-(4-methylenetetrahydrofuran-3-yl)-9/7-purine <2002T4865>. Of particular interest was the transformation of the exocyclic alkene on the THF ring first by dihydroxylation, then elimination to yield (4-(6-aminopurin-9-yl)-2,5-dihydrofuran-3-yl)methanol after amination of the purine ring at C-6. This A-alkenylpurine was reduced (Pd/C, H2, 25 psi, 73% yield) to provide the tetrahydrofuran-3-yl derivative. 

Mengel and Robins14811 reported that treatment of 2, 3 -0-(l-meth-oxyethylidene)adenosine with pivaloyl chloride in hot pyridine gives 9-(2-0-acetyl-3-chloro-5-0-pivaloyl-/3-D-xylofuranosyl)-6-(pivalamido)-purine. 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

Vitamin B12s reacts rapidly with alkyl iodides (e.g., methyl iodide or a 5 -chloro derivative of adenosine) via nucleophilic displacement to form the alkyl cobalt forms of vitamin B12 (Eq. 16-31). These reactions provide a convenient way of preparing isotopically labeled alkyl cobalamins, including those selectively... 

Ge Z-D, Peart JN, Kreckler LM, Wan TC, Jacobson MA, Gross GJ, Auchampach JA (2006) (Cl-IB-MECA (2-chloro-((lV5-(3-iodobenzyl)adenosine)-5 - /V-methyl carboxamide) reduces ischemia/reperfusion injury in mice by activating the Aj adenosine receptor. J Pharmacol Exp Ther 319 1200-1210... 

Thus N6-(3-iodobenzyl)adenosine (MRS541, structure not shown) acts as partial agonist (46% A3 efficacy) while the 2-chloro-N6-(3-iodobenzyl)adenosine (MRS542, structure not shown) behaves as potent but non selective A3 AR antagonists (K. A3 = 1.8 nM, EC50 A2B > 10,000 nM, K A2a = 197 nM, K A, = 16.8 nM) (Gao et al. 2006). It has to be remarked that the efficacy of the latter compound is completely restored by the replacement of the 4 -hydroxymethylene group with a 5 -methyluronamide function (Cl-IB-MECA). 

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