57846-83-0

Upstream product

• 696-07-1 5-iodouracil 
• 79-11-8 chloroacetic acid 
• 207724-94-5 N¹-(tert-butoxycarbonylmethyl)-5-iodouracil 
• 213454-72-9 methyl 2-(5-iodo-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetate 
• 79-08-3 bromoacetic acid 

Downstream Products

• 668474-58-6 [(2-tert-butoxycarbonylamino-ethyl)-({5-[3-(4,5-dimethoxy-2-nitro-benzyloxycarbonylamino)-prop-1-ynyl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl}-acetyl)-amino]-acetic acid ethyl ester 
• 431042-68-1 [(2-tert-butoxycarbonylamino-ethyl)-({5-[3-(4-methoxy-benzylsulfanyl)-prop-1-ynyl]-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl}-acetyl)-amino]-acetic acid ethyl ester 

Relevant academic research and scientific papers

Conjugation and evaluation of small hydrophobic molecules to triazole-linked siRNAs

Short interfering RNAs (siRNAs) have tremendous potential as a new class of next-generation therapeutics; however, their progress is lagging due to issues related to stability, biodistribution, and cell-membrane permeability. To overcome these issues, there is widespread interest in chemically modifying siRNAs. In this study, siRNAs that contain a triazole-backbone unit with pyrimidine-modified hydrophobic substituents were synthesized and examined for their gene-silencing activity. In our study, we generated a library of siRNAs that target both a plasmid reporter system and an endogenous gene target, bcl-2. Our results indicate that these unique modifications are well tolerated within the RNA interference pathway. In addition, a cholesterol-modified triazole-linked siRNA targeting the exogenous target firefly luciferase was capable of gene-silencing at levels greater than 80% in the absence of a carrier complex.

New tocopherol derivatives for functionalization of amino or carboxyl groups with lipid anchors

Lipid anchors play an important biological role in natural proteins in particular in lipid membrane anchoring. This principle was extended to nonnatural nucleic acids, peptide nucleic acids (PNA) and peptides. In order to provide new lipophilic anchors for the introduction into peptide nucleic acids (PNA) or peptides, a number of new α-tocopherol derivatives were synthesized containing carboxylic acids, amino groups or alkyne groups as linking sites. Amongst them are compounds with one or with two tocopherol units. Sonogashira reaction turned out to be a useful tool in these approaches. The products were characterized by NMR-spectroscopy and MS. An unusual phenomenon was found in 2-propargylamino-4,6-difluorotriazine that exhibits two different chemical shifts in the 19F-NMR spectrum for the two fluoro atoms.

Synthesis and antitumor activity of novel substituted uracil-1′(N)-acetic acid ester derivatives of 20(S)-camptothecins

A series of novel substituted uracil-1′(N)-acetic acid esters (6–20) of camptothecins (CPTs) were synthesized by the acylation method. These new compounds were evaluated for in vitro antitumor activity against tumor cell lines, A549, Bel7402, BGC-823, HCT-8 and A2780. In vitro results showed that most of the derivatives exhibited comparable or superior cytotoxicity compare to CPT (1) and topotecan (TPT, 2), with 12 and 13 possessing the best efficacy. Four compounds, 9, 12, 13 and 16, were selected to be evaluated for in vivo antitumor activity against H22, BGC-823 and Bel-7402 in mice. In vivo testing results indicated that 12 and 13 had antitumor activity against mouse liver carcinoma H22close to Paclitaxel and cyclophosphamide. 12 had similar antitumor activity against human gastric carcinoma BGC-823 in nude mice compared to irinotecan (3) and possessed better antitumor activity against human hepatocarcinoma Bel-7402 in nude mice than 2. It is also discovered that 12 showed a similar mechanism but better inhibitory activity on topoisomerase I (Topo I) compared to 2. These findings indicate that 20(S)-O-fluorouracil-1′(N)-acetic acid ester derivative of CPTs, 12, could be developed as an antitumor drug candidate for clinical trial.

Pyrene chromophores for the photoreversal of psoralen interstrand crosslinks

Applying psoralen interstrand crosslinks for the photoactivation of nucleic acids is a new concept. To find chromophores that can efficiently stimulate crosslink repair we screened several pyrenes and appended them to peptide nucleic acids for their site-selective addressing. Even though pyrenes conjugated to uracil revealed desirable spectroscopic properties they were not effective in crosslink reversal. In contrast, bare pyrenes are well suitable for crosslink repair with 350 nm light showing an uncaging efficiency similar to classical photocaging groups.

C(5) modified uracil derivatives showing antiproliferative and erythroid differentiation inducing activities on human chronic myelogenous leukemia K562 cells

The K562 cell line has been proposed as a useful experimental system to identify anti-tumor compounds acting by inducing terminal erythroid differentiation. K562 cells exhibit a low proportion of hemoglobin-synthesizing cells under standard cell growth conditions, but are able to undergo terminal erythroid differentiation when treated with a variety of anti-tumor compounds. In this paper we report a screening study on a set of different modified C(5) uracil derivatives for the evaluation of their antiproliferative effect in connection with erythroid differentiation pathways, and for defining a new class of drug candidates for the treatment of chronic myelogenous leukemia. Activity of the derivatives tested can be classified in two effect: an antiproliferative effect linked to a high level of erythroid differentiation activity and an antiproliferative effect without activation of gamma globin genes The highest antiproliferative effect and erythroid induction was shown by compound 9, a thymine derivative bearing a n-octyl chain on nitrogen N(1), whereas thymine did not show any effect, suggesting the importance of the linear alkyl chain in position N(1). To our knowledge this compound should be considered among the most efficient inducers of erythroid differentiation of K562 cells. This work is the starting point for the quest of more effective and specific drugs for the induction of terminal erythroid differentiation, for leading new insights in the treatment of neoplastic diseases with molecules acting by inducing differentiation rather than by simply exerting cytotoxic effects.

Synthesis of new, base-modified PNA monomers

A number of N-Boc-protected peptide nucleic acids (PNA) monomers containing 5-aryl- and 5-alkynyl-uracil bases have been synthesized using different palladium-catalyzed cross-coupling reactions. Starting from the base-unprotected 5-iodo-uracil PNA monomer

The use of Sonogashira coupling for the synthesis of modified uracil peptide nucleic acid

Palladium-catalyzed Sonogashira coupling has been shown to be compatible with PNA monomers as illustrated by the reaction of 5-iodouracil peptide nucleic acid monomer (IU-PNA) with several terminal alkynes. These reactions have been performed in the solution phase and with IU-PNA linked to an insoluble polymer support. The results presented herein show that while the isolated yields from the solution phase chemistry are modest (38-53%), the yields of the resin-bound coupling reactions are essentially quantitative, at the monomer level. A selection of alkynes was used to install various additional functionality on the uracil nucleobase. Examples of a hydroxyl, protected thiol and protected amino group are given. Further, an example of derivatization of a resin-bound oligomer with a single IU insert is given.