131607-27-7

Upstream product

• 191474-13-2 5'-O-(4,4'-dimethoxytrityl)-2,3'-anhydrothymidine 
• 40615-36-9 4,4'-dimethoxytrityl chloride 
• 16053-52-4 threothymidine 
• 220928-53-0 1-(5-O-(4,4'-dimethoxytrityl)-3-C-benzoyl-2-deoxy-β-D-threo-pentofuranosyl)thymine 
• 220928-58-5 5'-O-(4,4'-dimethoxytrityl)-3'-C-(benzoyl)thymidine 
• 114079-04-8 5'-dimethoxytritylthymidine-3'-diisopropylaminomethylphosphonoamidite 
• 115393-52-7 5'-O-dimethoxytritylthymidine-3'-O-β-cyanoethoxymethylphosphonite 
• 50-89-5 C₁₀H₁₄N₂O₅ 
• 65-71-4 thymin 
• 26879-47-0 1-(β-L-ribofuranosyl)thymine 
• 220928-41-6 1-(5-O-(4,4'-dimethoxytrityl)-3-C-acetyl-2-deoxy-β-D-threo-pentofuranosyl)thymine 
• 220928-40-5 5'-O-(4,4'-dimethoxytrityl)-3'-C-(acetyl)thymidine 
• 111647-36-0 5'-O-(4,4'-dimethoxytrityl)-3'-mesyl-2',3'-dideoxythymidine 
• 271248-27-2 3',5'-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-5-methyl-2'-O-(phenoxythiocarbonyl)-L-uridine 

Downstream Products

• 136090-71-6 1-<2'-deoxy-5'-O-(4,4'-dimethoxytriphenylmethyl)-β-D-threo-pentafuranosyl>thymine 3'-(3-carboxypropanoate) 
• 143527-01-9 1-(2'-deoxy-3'-O-mesyl-5'-O-4,4'-dimethoxytrityl-β-D-threo-pentofuranosyl)-thymine 
• 198637-82-0 1-[(2R,4R,5R)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-(2-thioxo-3-oxa-1-thia-2λ⁵-phospha-spiro[4.5]dec-2-yloxy)-tetrahydro-furan-2-yl]-5-methyl-1H-pyrimidine-2,4-dione 
• 16053-52-4 threothymidine 
• 854389-48-3 [(2R,3R,5R)-2-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-(5-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-tetrahydro-furan-3-yloxymethyl]-phosphonic acid monomethyl ester 
• 198637-93-3 C₄₃H₄₇N₄O₁₄PS 
• 1150314-64-9 C₃₆H₃₈N₂O₉ 
• 290371-78-7 5'-O-(4,4'-dimethoxytrityl)-3'-deoxy-3'-fluorothymidine 
• 25526-93-6 alovudine 
• 149666-71-7 1-{5-[bis(4-methoxyphenyl)phenyl-methoxymethyl]-2,5-dihydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione 

Relevant academic research and scientific papers

Probing the binding requirements of modified nucleosides with the dna nuclease snm1a

SNM1A is a nuclease that is implicated in DNA interstrand crosslink repair and, as such, its inhibition is of interest for overcoming resistance to chemotherapeutic crosslinking agents. However, the number and identity of the metal ion(s) in the active site of SNM1A are still unconfirmed, and only a limited number of inhibitors have been reported to date. Herein, we report the synthesis and evaluation of a family of malonate-based modified nucleosides to investigate the optimal positioning of metal-binding groups in nucleoside-derived inhibitors for SNM1A. These compounds include ester, carboxylate and hydroxamic acid malonate derivatives which were installed in the 5′-position or 3′-position of thymidine or as a linkage between two nucleosides. Evaluation as inhibitors of recombinant SNM1A showed that nine of the twelve compounds tested had an inhibitory effect at 1 mM concentration. The most potent compound contains a hydroxamic acid malonate group at the 5′-position. Overall, our studies advance the understanding of requirements for nucleoside-derived inhibitors for SNM1A and indicate that groups containing a negatively charged group in close proximity to a metal chelator, such as hydroxamic acid malonates, are promising structures in the design of inhibitors.

MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF

The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside. An oligomeric compound comprising a modified oligonucleotide consisting of 12-30 linked nucleosides, wherein at least one nucleoside of the modified oligonucleotide is a stereo-non-standard nucleoside; and wherein the oligomeric compound is selected from among an RNAi compound, a modified CRISPR compound, and an artificial mRNA compound.

Synthesis and evaluation of 3′-[18F]fluorothymidine-5′-squaryl as a bioisostere of 3′-[18F]fluorothymidine-5′-monophosphate

The squaryl moiety has emerged as an important phosphate bioisostere with reportedly greater cell permeability. It has been used in the synthesis of several therapeutic drug molecules including nucleoside and nucleotide analogues but is yet to be evaluated in the context of positron emission tomography (PET) imaging. We have designed, synthesised and evaluated 3′-[18F]fluorothymidine-5′-squaryl ([18F]SqFLT) as a bioisostere to 3′-[18F]fluorothymidine-5′-monophosphate ([18F]FLTMP) for imaging thymidylate kinase (TMPK) activity. The overall radiochemical yield (RCY) was 6.7 ± 2.5% and radiochemical purity (RCP) was >90%. Biological evaluationin vitroshowed low tracer uptake (?1) but significantly discriminated between wildtype HCT116 and CRISPR/Cas9 generated TMPK knockdown HCT116shTMPK?. Evaluation of [18F]SqFLT in HCT116 and HCT116shTMPK?xenograft mouse models showed statistically significant differences in tumour uptake, but lacked an effective tissue retention mechanism, making the radiotracer in its current form unsuitable for PET imaging of proliferation.

MODIFIED OLIGOMERIC COMPOUNDS AND USES THEREOF

The present disclosure provides oligomeric compounds comprising a modified oligonucleotide having at least one stereo-non-standard nucleoside.

Red light-controlled polymerase chain reaction

A 23-mer DNA "caged" at its 3′-terminus with a 9-anthracenyl moiety was prepared. It can be uncaged in the presence of photosensitizer (In(pyropheophorbide-a)chloride)-containing DNAs (9-12 mers) and upon irradiation with red light. This mixture of DNAs was used to design red-light controlled polymerase chain reaction.

Radiolabeled cyclosaligenyl monophosphates of 5-iodo-2′-deoxyuridine, 5-iodo-3′-fluoro-2′,3′-dideoxyuridine, and 3′-fluorothymidine for molecular radiotherapy of cancer: Synthesis and biological evaluation

Targeted molecular radiotherapy opens unprecedented opportunities to eradicate cancer cells with minimal irradiation of normal tissues. Described in this study are radioactive cyclosaligenyl monophosphates designed to deliver lethal doses of radiation to cancer cells. These compounds can be radiolabeled with SPECT- and PET-compatible radionuclides as well as radionuclides suitable for Auger electron therapies. This characteristic provides an avenue for the personalized and comprehensive treatment strategy that comprises diagnostic imaging to identify sites of disease, followed by the targeted molecular radiotherapy based on the imaging results. The developed radiosynthetic methods produce no-carrier-added products with high radiochemical yield and purity. The interaction of these compounds with their target, butyrylcholinesterase, depends on the stereochemistry around the P atom. IC50 values are in the nanomolar range. In vitro studies indicate that radiation doses delivered to the cell nucleus are sufficient to kill cells of several difficult to treat malignancies including glioblastoma and ovarian and colorectal cancers.

STABILISATION OF RADIOPHARMACEUTICAL PRECURSORS

The invention relates to a method for improving stability of radiopharmaceutical precursors, and in particular non radiolabelled nucleoside derivatives which are used as precursors for production of radiolabelled nucleoside derivatives for use in in vivo imaging procedures such as positron emission tomography (PET). The invention further includes formulations of radiopharmaceutical precursors, and cassettes for automated synthesis apparatus comprising the same.

Radiologic Agents for Monitoring Alzheimer's Disease Progression and Evaluating a Response to Therapy and Processes for the Preparation of Such Agents

Disclosed are certain cycloSalingenyl pyrimidine nucleoside monophosphates comprising positron emitters or gamma-emitting radiohalides, uses thereof for monitoring Alzheimer's disease progression and evaluating response to therapy and process for their preparation.

Nucleosidyl-O-methylphosphonates: A pool of monomers for modified oligonucleotides

An unique set of 5′-O- and 3′-O-phosphonomethyl derivatives of four natural 2′-deoxyribonucleosides, 1-(2-deoxy-β-D-threo- pentofuranosyl)thymine, 5′-O- and 2′-O-phosphonomethyl derivatives of 1-(3-deoxy-β-D-erythro-pentofuranosyl)thymine, and 1-(3-deoxy-β-D- threo-pentofuranosyl)thymine has been synthesized as a pool of monomers for the synthesis of modified oligonucleotides. The phosphonate moiety was protected with 4-methoxy-1-oxido-2-pyridylmethyl ester group, serving also as an intramolecular catalyst in the coupling step.

TT dinucleotides containing an isoxazoline moiety: Synthesis and binding affinity study

We have prepared four diastereomers of TT dinucleotides containing an isoxazoline moiety and four dodecanucleotides incorporating these TT dinucleotides in the middle of the DNA sequence. We also have determined the melting temperatures of these modified oligonucleotides (Tm values) by measuring change in UV absorbance.