9-Benzyl-6-(dimethylamino)-9H-purines with antirhinovirus activity

Kelley, James L.; Linn, James A.; Krochmal, Mark P.; Selway, J. W. T.

doi:10.1021/jm00118a025

Cited by 25 publications

(17 citation statements)

References 1 publication

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“…Synthetic protocols and representative 1 H NMR chemical shift data are included as Additional file 1. Briefly, aryl amines were coupled to a PMB-protected 2,6 dichloro-9H-purine starting reagent at the 6-position, followed by addition at the 2-position using a modified Buchwald-Hartwig amination to yield analogues 10-25 [25,26]. Analogues 26 and 27 were synthesized by modifying a synthetic protocol described in the patent literature [27].…”

Section: Methodsmentioning

confidence: 99%

A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants

et al. 2012

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BackgroundThe recently approved anti-AIDS drug rilpivirine (TMC278, Edurant) is a nonnucleoside inhibitor (NNRTI) that binds to reverse transcriptase (RT) and allosterically blocks the chemical step of DNA synthesis. In contrast to earlier NNRTIs, rilpivirine retains potency against well-characterized, clinically relevant RT mutants. Many structural analogues of rilpivirine are described in the patent literature, but detailed analyses of their antiviral activities have not been published. This work addresses the ability of several of these analogues to inhibit the replication of wild-type (WT) and drug-resistant HIV-1.ResultsWe used a combination of structure activity relationships and X-ray crystallography to examine NNRTIs that are structurally related to rilpivirine to determine their ability to inhibit WT RT and several clinically relevant RT mutants. Several analogues showed broad activity with only modest losses of potency when challenged with drug-resistant viruses. Structural analyses (crystallography or modeling) of several analogues whose potencies were reduced by RT mutations provide insight into why these compounds were less effective.ConclusionsSubtle variations between compounds can lead to profound differences in their activities and resistance profiles. Compounds with larger substitutions replacing the pyrimidine and benzonitrile groups of rilpivirine, which reorient pocket residues, tend to lose more activity against the mutants we tested. These results provide a deeper understanding of how rilpivirine and related compounds interact with the NNRTI binding pocket and should facilitate development of novel inhibitors.

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Section: Methodsmentioning

confidence: 99%

A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants

et al. 2012

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“…They act as hormones and neurotransmitters and are present in some coenzymes . Purine derivatives have been used as the intermediate structure for synthesis of some heterocyclic compounds with variety of pharmacological properties such as antirhinovirus , anti‐HIV‐1 , antimicrobial, antibacterial, antifungal , antiviral, and antitumor activity as kinase inhibitors . Pteridines are also important heterocyclic compounds for many biological processes, such as amino acid metabolism, nucleic acid synthesis, cancer, and neurotransmitter and dihydrofolic acid synthesis in many microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Solvent‐free Synthesis of 2,6‐Dihydroxy‐9H‐purin and Pteridine Derivatives

Nami

Tizkar

Zardost

2017

Journal of Heterocyclic Chem

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5,6‐Diaminopyrimidin‐2,4‐diol 1 was reacted with 1,4‐d‐gluconolactone 2, 6‐chloro‐4‐cyclopropyl‐7‐floro‐1,4‐dihydro‐1‐oxonaphthalen‐2‐carboxilic acid 4, (3S)‐9,10‐difloro‐3,7‐dihydro‐3‐methyl‐7‐oxo‐2H‐[1,4]oxazino[2,3,4‐ij]quinolin‐6‐carboxylic acid 6, and dimethylacetylendicarboxylate to afford 1‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐sorbitol 3, 7‐chloro‐1‐cyclopropyl‐6‐flouro‐3‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)quinoline‐4(1H)‐one 5, 9,10‐difluoro‐2,3‐dihydro‐6‐(2,6‐dihydroxy‐9H‐purin‐8‐yl)‐3‐methyl‐[1,4]oxazine[2,3,4‐ij]quinoline‐7‐one 7, and (2,4‐dihydroxy‐6‐oxo‐5,8‐dihydro‐6H‐pteridine‐7‐yiliden)‐acetic acid methyl ester 9, respectively. The synthesized compounds characterized by IR, 1H‐NMR, 13C‐NMR, GC‐mass, and elemental analysis.

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“…1 For example, purine derivatives are reported to act as nucleotide binding proteins that play a significant role in many biological processes. 2 Other representatives of this class have antirhinovirus 3 or antitumor activity as kinase inhibitors. 4 Consequently, a large number of purine libraries have been synthesized in solution 5 or using solid polymer supports.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and screening of 2,6-diamino-substituted purine derivatives as potential cardiomyogenesis inducing agents

Koley¹,

König²,

Hilber³

et al. 2010

Arkivoc

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The synthesis of 2,6-diamino-substituted purines is reported starting from 2,6-dichloropurine via two subsequent selective nucleophilic substitution reactions. The first substitution takes place selectively in 6-, the second in 2-position. The compounds were synthesized as structural analogs of reversine, a substance which was reported to possess the ability to de-differentiate lineagecommitted cells into progenitor cells which then can be differentiated into other cell types such as adipocytes or osteoblasts. The obtained compounds were tested regarding their potential to support cardiomyogenic cell differentiation based on preliminary findings that reversine also showed some activity in this regard.

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9-Benzyl-6-(dimethylamino)-9H-purines with antirhinovirus activity

Cited by 25 publications

References 1 publication

A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants

A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants

Solvent‐free Synthesis of 2,6‐Dihydroxy‐9H‐purin and Pteridine Derivatives

Synthesis and screening of 2,6-diamino-substituted purine derivatives as potential cardiomyogenesis inducing agents

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