Abstract:Since the strategy for the synthesis of 9‐, 10‐ and 11‐nitronoracronycine [3,4] could not be applied to the 8‐nitronoracronycine 9, we here report the preparation of the latter by a fusion of methyl 2‐amino‐6‐nitrobenzoate 2 and phloroglucinol 3. The fusion of 2 and 3 gave 1,3‐dihydroxy‐8‐nitro‐9(10H)‐acridinone 6. Subsequent methylation, demethylation and reaction with 2‐chloro‐2‐methyl‐3‐butyne afforded the desired 8‐nitronoracronycine 9. Compound 9, 1,3‐dimethoxy‐10‐methyl‐8‐nitro‐9(10H)‐acridinone 7 and 1,… Show more
“…In addition to analogues obtained through thermal coupling and through the traditional procedure (Scheme ), N -methylated analogues were also prepared from 1 (Scheme ). Attempts to demethylate the 3-methoxy group of 16 with boron tribromide failed; however, demethylation with hydrobromic acid was successful. 1 Thermal Coupling 2 Analogues Synthesized from 1 a a (a) MeI, Cs 2 CO 3 (b) HBr, reflux. …”
5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a novel mechanism of action for 1, although the target is not yet defined.(2) With the goal of lead optimization, analogues of 1 were synthesized in an effort to describe the structure-activity relationships between 1 and its hypothetical binding site. Modifications of key functional groups led to the identity of several features of 1 that were important for activity. In the process, a more expedient and reliable synthesis of 1 and its analogues was developed. Analogues were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell were also measured in order to assess a therapeutic index (TI) of selectivity. Several new analogues with significant antiviral activity were identified, including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of several HSV-2 strains with a mean ED(50) of 0.7 muM and a TI range of 25-60-fold.
“…In addition to analogues obtained through thermal coupling and through the traditional procedure (Scheme ), N -methylated analogues were also prepared from 1 (Scheme ). Attempts to demethylate the 3-methoxy group of 16 with boron tribromide failed; however, demethylation with hydrobromic acid was successful. 1 Thermal Coupling 2 Analogues Synthesized from 1 a a (a) MeI, Cs 2 CO 3 (b) HBr, reflux. …”
5-Chloro-1,3-dihydroxyacridone, 1, is a potent and selective inhibitor of Herpes Simplex Virus Type-1 (HSV-1).(1) Substituted 1,3-dihydroxyacridones represent a new class of nonnucleoside HSV-1 inhibitors, and biochemical studies indicate a novel mechanism of action for 1, although the target is not yet defined.(2) With the goal of lead optimization, analogues of 1 were synthesized in an effort to describe the structure-activity relationships between 1 and its hypothetical binding site. Modifications of key functional groups led to the identity of several features of 1 that were important for activity. In the process, a more expedient and reliable synthesis of 1 and its analogues was developed. Analogues were evaluated against HSV-1 and HSV-2 using a viral plaque-elimination assay for viral inhibition of HSV-1 and HSV-2, and effects on replication of the host cell were also measured in order to assess a therapeutic index (TI) of selectivity. Several new analogues with significant antiviral activity were identified, including 5-methoxy-1,3-dihydroxyacridone (11), which inhibits replication of several HSV-2 strains with a mean ED(50) of 0.7 muM and a TI range of 25-60-fold.
Natural Product Chemistry.Part 153. Synthesis and Possible Anticancer Activity of 8-Nitronoracronycine.-The title compound (V) does not show any anticancer activity. -(REISCH, J.; DZIEMBA, P.;
Two different methods for the synthesis of 4‐azaacronycine (10) have been described. One route with a fusion reaction between 1,3‐dihydroxy‐10‐methyl‐9(10H)‐acridinone (1) and 2‐amino‐2‐methyl‐3‐butyne in a glass ampoule and the other by a reaction of 3‐amino‐1‐methoxy‐10‐methyl‐9(10H)‐acridinone (9) with 2‐chloro‐2‐methyl‐3‐butyne.
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