Novel substrate of adenosine deaminase

Abstract

Some 4-aminoquinolines have a high activity in the treatment of bronchial asthma13-0 and malaria, as well as having antiarrhythmic23-0 properties. Compound

Nanoparticles for the Treatment ofAlzheimer's Disease: Theoretical Rationale, Present Status and Future Perspectives

“…line conditions, as described above. Then, the ring oxygen of 3-benzyloxyl-2-alkyl-4-pyranone was replaced by a nitrogen atom via a substitution reaction with aqueous ammonia at room temperature for 48 h. The 3-benzyloxyl-2-alkyl-4-pyridinone was silylated in hexamethyldisilazane under refluxing and nitrogen gas for 2 h. After evaporation of the solvent under vacuum, the residue was redissolved in 1,2-dichloroethane and then benzyloxyethoxymethylchloride that could be replaced by (2-acetoxyethoxy)methyl bromide [361] was added in the presence of a catalytic amount of trimethylsilyl trifluoromethanesulfonate (SnCl 4 could also be used as catalyst in the alkylation reaction, but might result in separation difficulties and low yields) [362]. The resulting mixture was stirred at room temperature for 4 h and then treated with an aqueous solution saturated with sodium bicarbonate.…”

Chemotherapeutics

“…The antiherpetic activity of acyclovir, the acyclic analogue of guanosine, was first reported along with its synthesis in 1978 [224]. The rationale for this synthesis was the previous observation that the acyclic analogue of adenosine was a substrate for adenosine deaminase [225]. Acyclovir has potent activity against several herpesviruses (herpes simplex virus types 1 and 2, Epstein -Barr virus, and varicella -zoster virus), but is not as potent against human cytomegalovirus.…”

5′Prime;-Ester Prodrugs of the Varicella-Zoster Antiviral Agent, 6-Methoxypurine Arabinoside

“…Since the intestinal mucosa has high levels of adenosine deaminase (Ho et al, 1980), a prodrug of 1 that is protected from deamination during absorption may be a more effective oral agent. Substitution of the 2 /-or 5'-hydroxyl of adenosine is known to lead to compounds resistant to the action of adenosine deaminase (Shah et al, 1965;Bloch et al, 1967;Schaeffer et al, 1971;Hampton et al, 1972). In an earlier report we described the synthesis and evaluation of a series of di-and tri-esters of 1, which indicated that the 2' ,3 /-diacetate provided enhanced bioavailability and water solubility, whereas the 2',5 /-and 3',5 /-diacetates showed enhanced bioavailability with diminished aqueous solubility (Jones et al, 1991).…”