Conformational restriction of cyclic dinucleotides with triazole-linked cyclophane analogues

Fujino, Tomoko; Okada, Koudai; Isobe, Hiroyuki

doi:10.1016/j.tetlet.2014.03.026

Cited by 19 publications

(11 citation statements)

References 19 publications

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“…The DFT energies of stereoisomers (Δ E , Figure 6) emerging from the R/S and E/Z geometries are summarized in two-dimensional profiles shown in Figures 10 and S16. 46,47 The stereoisomers are mapped so that the adjacent isomers are interconvertible through bond rotations at a single biaryl linkage (hereafter denoted as single-linkage rotation). 48 The isomeric structures on the x -axis of the profiles cover all possible structures arising from the R/S -geometries.…”

Section: Resultsmentioning

confidence: 99%

Stereoisomerism in Nanohoops with Heterogeneous Biaryl Linkages of E/Z- and R/S-Geometries

et al. 2016

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The stereochemistry of cycloarylene nanohoops gives rise to unique cyclostereoisomerism originating from hoop-shaped molecular shapes. However, cyclostereoisomerism has not been well understood despite the ever-increasing number of structural variants. The present work clarifies the cyclostereoisomerism of a cyclophenanthrenylene nanohoop possessing both E/Z- and R/S-geometries at the biaryl linkages. Involvement of the R/S axial chirality in the nanohoop leads to the deviation of the structure from a coplanar belt shape and allows for structural variations with 51 stereoisomers with E/Z- and R/S-geometries. Experimental investigations of the dynamic behaviors of the cyclophenanthrenylene nanohoop revealed the presence of two-stage isomerization processes taking place separately at the E/Z- and R/S-linkages. Consequently, despite the presence of E/Z-fluctuations, the R/S axial chirality resulted in a separable pair of enantiomers. The structural information reported here, such as geometric descriptors and anomalous dynamics, may shed light on the common structures of various nanohoops.

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Section: Resultsmentioning

confidence: 99%

Stereoisomerism in Nanohoops with Heterogeneous Biaryl Linkages of E/Z- and R/S-Geometries

et al. 2016

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“…In this review, derivatives derived from the modification of the phosphorothioate, lipid/fluorine substitution, nucleobase change, and locked nucleic acid strategy are discussed. Other modifications such as CDNs analogs with a triazole, thiourea, urea, carbodiimide, and guanidinium linkages also have been studied. But their STING pathway activity remains unknown.…”

Section: Sting Agonistsmentioning

confidence: 99%

Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy

Zhao

et al. 2019

Medicinal Research Reviews

114

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Since being discovered in 2008, the STING (stimulator of interferon genes) pathway has gradually been recognized as a central and promising target for immunotherapy. The STING pathway can be stimulated by cyclic dinucleotides (CDNs), leading to the type I interferons (IFN) production for immunotherapy for cancer or other diseases. However, the negative charges, hydrophilicity, and instability of CDNs have hindered their further applications. In addition, chronic activation of the STING pathway has been found to be involved in autoimmune diseases as IFN overproduction.Thus, research and development of STING agonists and inhibitors has been a hot field for the treatment of several diseases. The past several years, especially 2018, has seen increasingly rapid advances in this field. Here, this review summarizes the synthesis and modification of CDNs, the identification of nonnucleotide agonists, the recent progress in delivery systems and the medical applications, such as personalized vaccine adjuvants, in detail. In addition, in this review, we summarize the STING inhibitors' advances from two aspects, covalent, and noncovalent inhibitors. K E Y W O R D S agonist, cyclic dinucleotides, immunotherapy, inhibitor, STING

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“…It was observed that these compounds exhibited anti‐HIV activity and cell toxicity. Isobe and co‐workers reported the synthesis of triazole‐linked cyclic nucleoside analogues J (Figure ) containing guanine and adenine through click chemistry . It was observed that the conformational restriction induced by the triazole units helped to maintain a structure similar to the open conformers of natural nucleosides.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anti‐Proliferative Activity of a Triazole‐Fused Thymidine Analogue

et al. 2020

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Here we report the synthesis of two-an acyclic and a macrocyclic-analogues of thymidine linked to a triazole moiety. The new molecules were synthesized through an intramolecular 1,3-dipolar cycloaddition reaction of the diazido derivative of thymidine with a suitable alkyne. The acyclic nucleoside showed dose dependent cytotoxicity against glioblastoma and breast cancer cells by causing significant cellular damage as studied with confocal laser scanning microscopy. In silico induced fit molecular docking studies showed poly(ADP-ribose) polymerase 1 (PARP1) as a potential target of the acyclic nucleoside. On the other hand, both the analogues showed no toxicity against normal fibroblast cells. ChemistrySelectCommunications

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Conformational restriction of cyclic dinucleotides with triazole-linked cyclophane analogues

Cited by 19 publications

References 19 publications

Stereoisomerism in Nanohoops with Heterogeneous Biaryl Linkages of E/Z- and R/S-Geometries

Stereoisomerism in Nanohoops with Heterogeneous Biaryl Linkages of E/Z- and R/S-Geometries

Agonists and inhibitors of the STING pathway: Potential agents for immunotherapy

Synthesis and Anti‐Proliferative Activity of a Triazole‐Fused Thymidine Analogue

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