Pyrazine Chemistry. I. Derivatives of 3-Aminopyrazinoic Acid

Ellingson, Rudolph C.; Henry, Robert L.; McDonald, Francis G.

doi:10.1021/ja01226a028

Cited by 20 publications

(5 citation statements)

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“…Interestingly, the analogous 1,3benzodioxole ester 17b, prepared by esterification of 17a, afforded the unopened amine in high yield upon treatment with SnCl 2 ‚2H 2 O in refluxing MeOH, suggesting that ring strain may not be the only factor to influence the cleavage process. Finally, cyclization of 22 afforded the novel dioxolo [4,5-h] 28,29 (31) 30,31 which was initially hydrolyzed to the corresponding acid 36. Treatment with EDCI/HOBT followed by 13 effected simultaneous coupling and N-deacetylation to afford the amino thioacetal 37.…”

Section: C3-o-butyl Ethersmentioning

confidence: 99%

Effect of A-Ring Modifications on the DNA-Binding Behavior and Cytotoxicity of Pyrrolo[2,1-c][1,4]benzodiazepines

et al. 1999

J. Med. Chem.

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Several A-ring-modified analogues of the DNA-binding antitumor agent DC-81 (5) have been synthesized in order to study structure-reactivity/cytotoxicity relationships. For two molecules (23 and 30) the modifications required the addition of a fourth ring to give the novel dioxolo[4,5-h]- and dioxano[5,6-h]pyrrolo[2,1-c][1, 4]benzodiazepin-11-one (PBD) ring systems, respectively. Another three analogues (34, 38, and 48) have the native benzenoid A-ring replaced with pyridine, diazine, or pyrimidine rings to give the novel pyrrolo[2,1-c][1,4]pyridodiazepine, pyrrolo[2,1-c][1, 4]diazinodiazepine, and pyrrolo[2,1-c][1,4]pyrimidinodiazepine systems, respectively. The other new analogues (16a,b) have extended chains at the C8-position of the DC-81 structure. During the synthesis of these compounds, a novel tin-mediated regiospecific cleavage reaction of the dioxole intermediate 18 was discovered, leading to the previously unknown iso-DC-81 (20). In addition, an unusual simultaneous nitration-oxidation reaction of 4-(3-hydroxypropoxy)-3-methoxybenzoic acid (8) was found to produce 3-(4-carboxy-2-methoxy-5-nitrophenoxy)propanoic acid (9), a key intermediate, in high yield. In general, the results of cytotoxicity and DNA-binding studies indicated that none of the changes made to the A-ring of the PBD system significantly improved either binding affinity or cytotoxicity in comparison to DC-81. This result suggests that the superior potency of natural products such as anthramycin (1), tomaymycin (2), and sibiromycin (3) is due entirely to differences in C-ring structure, and in particular exo or endo unsaturation at the C2-position and C2-substituents containing unsaturation. This study also provided information regarding the influence of A-ring substitution pattern on the relative stability of the interconvertible N10-C11 carbinolamine, carbinolamine methyl ether, and imine forms of PBDs.

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Section: C3-o-butyl Ethersmentioning

confidence: 99%

Effect of A-Ring Modifications on the DNA-Binding Behavior and Cytotoxicity of Pyrrolo[2,1-c][1,4]benzodiazepines

et al. 1999

J. Med. Chem.

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“…The synthesis of pteridine-liked compounds are described in Scheme 2. The intermediates 7-10 can be obtained by the reported methods [29][30][31]. The key intermediates 12a-c were prepared by the alkoxylation of 10, followed by chlorination of the resulting 6-alkoxy-4pteridinone 11a-c with thionyl chloride under catalytic amount of DMF.…”

Section: Resultsmentioning

confidence: 99%

ChemInform Abstract: Synthesis of N‐Substituted‐6‐alkoxypteridin‐4‐amine

et al. 2013

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“…The synthesis of pteridine‐liked compounds are described in Scheme . The intermediates 7 , 8 , 9 , 10 can be obtained by the reported methods . The key intermediates 12a , 12b , 12c were prepared by the alkoxylation of 10 , followed by chlorination of the resulting 6‐alkoxy‐4‐pteridinone 11a , 11b , 11c with thionyl chloride under catalytic amount of DMF.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of N‐Substituted‐6‐alkoxypteridin‐4‐amine

Duan

Jia

Zhu

et al. 2012

Journal of Heterocyclic Chem

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A novel seven‐step methodology for the synthesis of N‐substituted‐6‐alkoxypteridin‐4‐amine has been developed with the total yields of 35.4–41%. Twenty new compounds were synthesized by heterocyclization of easily prepared 3‐amino‐6‐bromopyrazine‐2‐carboxamide, subsequent alkoxylation, chlorination, and nucleophilic substitution. Their structures were confirmed by 1H‐NMR, 13C‐NMR, ESI‐MS, and elemental analysis. The structure of N‐(3‐chloro‐4‐fluorophenyl)‐6‐ethoxypteridin‐4‐amine was further determined by X‐ray crystallographic analysis. It was found that different chlorinating reagents gave different products. The possible chlorination mechanism was discussed.

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Pyrazine Chemistry. I. Derivatives of 3-Aminopyrazinoic Acid

Cited by 20 publications

References 0 publications

Effect of A-Ring Modifications on the DNA-Binding Behavior and Cytotoxicity of Pyrrolo[2,1-c][1,4]benzodiazepines

Effect of A-Ring Modifications on the DNA-Binding Behavior and Cytotoxicity of Pyrrolo[2,1-c][1,4]benzodiazepines

ChemInform Abstract: Synthesis of N‐Substituted‐6‐alkoxypteridin‐4‐amine

Synthesis of N‐Substituted‐6‐alkoxypteridin‐4‐amine

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