A simple synthetic route to the preparation of 2-(1-phosphonoalkoxy)ethyl derivatives of heterocyclic bases as novel nucleotide analogs related to PMEA

1996 ◽  
Vol 61 (s1) ◽  
pp. 81-84 ◽  
Author(s):  
Ivan Rosenberg ◽  
Šárka Králíková
Keyword(s):  
Synthetic Route ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA II. Racemic cis-Configured Derivatives

1996 ◽  
Vol 61 (5) ◽  
pp. 778-790 ◽  
Author(s):  
Radek Liboska ◽  
Milena Masojídková ◽  
Ivan Rosenberg
Keyword(s):  
Ring Opening ◽  
Nucleoside Analogs ◽  
Mitsunobu Reaction ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Racemic N-(cis-2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of adenine- (6a, 6b), uracil- (6c) and cytosine- (6d) containing carbocyclic phosphonates is based on the reaction of cis-2-hydroxycycloalkyl derivatives of protected nucleobases with diisopropyl tosyloxymethanephosphonate. The starting purine-containing nucleoside analogs 5a-5f were prepared by the Mitsunobu reaction of protected nucleobases with trans-2-benzyloxycycloalkanols, whereas pyrimidine-containing nucleoside analogs 5g-5k were obtained by configurational inversion at C-2' of the corresponding 1-(trans-2-hydroxycycloalkyl)pyrimidines via ring opening of their 2,2'-anhydro derivatives.

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA. I. Racemic trans-Configured Derivatives

1996 ◽  
Vol 61 (2) ◽  
pp. 313-332 ◽  
Author(s):  
Radek Liboska ◽  
Milena Masojídková ◽  
Ivan Rosenberg
Keyword(s):  
Ring Opening ◽  
Oxirane Ring ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Racemic trans-N-(2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of fully protected adenine- (5), hypoxanthine- (7), guanine- (11), thymine- (13), uracil- (16) and cytosine-containing (18) carbocyclic nucleotide analogs is based on the reaction of trans-2-hydroxycycloalkyl derivatives of N-protected nucleobases (2, 10, 12, 14, 17) with diisopropyl tosyloxymethanephosphonate. Deprotection of these compounds afforded the title nucleotide analogs. The starting nucleoside derivatives have been prepared via nucleophilic oxirane ring opening of cycloalkene oxides with various protected or free nucleobases.

Synthesis and Biological Effects of N-(2-Phosphonomethoxyethyl) Derivatives of Deazapurine Bases

1993 ◽  
Vol 58 (6) ◽  
pp. 1419-1429 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý
Keyword(s):  
Biological Effects ◽  
Sodium Hydride ◽  
Cesium Carbonate ◽  
Cytostatic Effect ◽  
Phosphonic Acids ◽  
Dna Viruses ◽  
Purine Bases ◽  
Heterocyclic Bases ◽  
L 1210 Leukemia ◽  
Derivatives Of

Analogs of antiviral 9-(2-phosphonomethoxyethyl)adenine (PMEA,II), containing modified purine bases 1-deazaadenine (VII, 3-deazapurine (XI), 7-deaza-7-cyanoadenine (XIIIb) and 3-deazaguanine (XXIb) were prepared by alkylation of the heterocyclic bases with bis(2-propyl) 2-chloroethoxymethylphosphonate (V) in dimethylformamide in the presence of sodium hydride or cesium carbonate. The obtained protected derivatives were deblocked with bromotrimethylsilane to give the phosphonic acids. 3-DeazaPMEG (XXIb) is active against DNA viruses and exhibits a marked cytostatic effect against L-1210 leukemia.

A Synthetic Route to Epoxyalkyl β-Laminaribiosides, Especially Suitable for Radiolabeling

1994 ◽  
Vol 47 (9) ◽  
pp. 1805 ◽  
Author(s):  
WM Best ◽  
RV Stick ◽  
DMG Tilbrook
Keyword(s):  
Synthetic Route ◽  
Benzyl Ethers ◽  
Derivatives Of

The major products in the controlled benzylation (NaH/PhCH2Cl) of allyl and but-3-enyl β-D-glucopyranosides were the 2,4,6-tri-O-benzyl ethers. Subsequent glycosidations of these tribenzyl ethers gave derivatives of allyl and but-3-enyl β- laminaribioside, the latter being subsequently transformed into 3,4-epoxybutyl β- laminaribioside.

scholarly journals α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

2019 ◽  
Vol 15 ◽  
pp. 2524-2533 ◽  
Author(s):  
Shital K Chattopadhyay ◽  
Subhankar Ghosh ◽  
Sarita Sarkar ◽  
Kakali Bhadra
Keyword(s):  
Anticancer Drug ◽  
Hela Cells ◽  
Hydroxamic Acid ◽  
Suberoylanilide Hydroxamic Acid ◽  
Oxygen Species ◽  
Synthetic Route ◽  
Metathesis Reaction ◽  
Cross Metathesis ◽  
Terminal Alkene ◽  
Derivatives Of

An alternate synthetic route to the important anticancer drug suberoylanilide hydroxamic acid (SAHA) from its α,ß-didehydro derivative is described. The didehydro derivative is obtained through a cross metathesis reaction between a suitable terminal alkene and N-benzyloxyacrylamide. Some of the didehydro derivatives of SAHA were preliminarily evaluated for anticancer activity towards HeLa cells. The administration of the analogues caused a significant decrease in the proliferation of HeLa cells. Furthermore, one of the analogues showed a maximum cytotoxicity with a minimum GI50 value of 2.5 µg/mL and the generation of reactive oxygen species (ROS) as some apoptotic features.

scholarly journals ALKOXYALKYL ESTERS OF NUCLEOTIDE ANALOGS INHIBIT POLYOMAVIRUS DNA REPLICATION AND LARGE T ANTIGEN ACTIVITIES

2020 ◽  
Author(s):  
Nichodemus O. Onwubiko ◽  
Suraya Diaz ◽  
Marcela Krecmerova ◽  
Heinz Peter Nasheuer
Keyword(s):  
Dna Replication ◽  
Tumor Antigens ◽  
Antiviral Agent ◽  
Dna Helicase ◽  
T Antigen ◽  
Nucleotide Analogs ◽  
Large Tumor ◽  
Nucleotide Analog ◽  
Derivatives Of

Polyomavirus-related infections are ubiqutious in immunocompromised individuals and in some cases are intractable and fatal. Due to lack of approved drugs to treat polyomavirus infections, cidofovir, a phosphonate nucleotide analog approved to treat cytomegalovirus infections has been repurposed as anti-polyomavirus agent. Cidofovir has been modified in various ways to improve its efficacies as broad-spectrum antiviral agent. However, the actual mechanisms and targets of cidofovir and its modified derivatives as anti-polyomavirus agents are still under research. Here, polyomavirus large tumor antigens (Tag) activities were identified as the viral target of cidofovir derivatives. The alkoxyalkyl-ester derivatives of cidofovir efficiently inhibit polyomavirus DNA replication in cell-free human extracts and a viral in vitro replication system only utilizing purified proteins. We present evidence that DNA helicase, and DNA binding activities of polyomavirus Tags are diminished in the presence of low concentrations of alkoxyalkyl-ester derivatives of cidofovir suggesting that the inhibition of viral DNA replication is at least in part mediated by inhibiting ssDNA and dsDNA binding activities of Tags. These findings show that the alkoxyalkyl-ester derivatives of cidofovir are effective in vitro without undergoing further conversions and conclude that the inhibitory mechanisms of nucleotide analog-based drugs are more complex than previously believed.

ChemInform Abstract: A Convenient Synthetic Route from Isatin N-Mannich Bases to Nitrogen-Containing Derivatives of Isoindigo.

ChemInform ◽  
2011 ◽  
Vol 42 (17) ◽  
pp. no-no
Author(s):  
Andrei V. Bogdanov ◽  
Vladimir F. Mironov ◽  
Lenar I. Musin ◽  
Rashid Z. Musin ◽  
Dmitry B. Krivolapov ◽  
...  
Keyword(s):  
Mannich Bases ◽  
Synthetic Route ◽  
Derivatives Of
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