Side-chain derivatives of biologically active nucleosides. Part 1. Side-chain analogs of 3'-azido-3'-deoxythymidine (AZT)

1-(3′-Fluoro-2′,3′,6′-trideoxy-β-D-allofuranosyl)thymine [7] and 1-(3′-fluoro-2′,3′,6′-trideoxy-α-L-talofuranosyl) thymine [8] were synthesized starting from the corresponding 2,3′-anhydro nucleoside derivatives. The fluorine was introduced stereoselectively by opening of the anhydro bridge in the presence of HF/AIF3. The 5′-C-methyl derivatives, [7] and [8], of 3′-fluoro-3′-deoxythymidine (FLT) were evaluated for their inhibitory effect against human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). The compounds [7] and [8] had antiviral activity which was three orders of magnitude lower than the reference compound 3′-fluoro-3′-deoxythymidine. None of the compounds showed appreciable activity against other RNA or DNA viruses at subtoxic concentrations.

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SOME DIRECTIONS IN THE MODIFICATION OF AZOLES

SERIES CHEMISTRY AND TECHNOLOGY ◽

10.32014/2020.2518-1491.84 ◽

2020 ◽

Vol 5 (443) ◽

pp. 85-91

Author(s):

Ibrayev M.K., ◽

◽

Takibayeva A.T., ◽

Fazylov S.D., ◽

Rakhimberlinova Zh.B., ◽

...

Keyword(s):

13C Nmr Spectroscopy ◽

Biologically Active Compounds ◽

Biologically Active ◽

Active Compounds ◽

Synthesis Conditions ◽

Alkaloid Cytisine ◽

Azole Ring ◽

Cyclic Compounds ◽

New Compounds ◽

Derivatives Of

This article presents studies on the targeted search for new derivatives of azoles, such as benzthiazole, 3,5-dimethylpyrazole, 1,3,4-oxadiazole-2-thione, 1,3,4-thiadiazole. The possibility of combining in one molecule of the azole ring with other cyclic compounds: the alkaloid cytisine, morpholine, furan and some arenes has been studied. To obtain new compounds, the reactions of bromination, acylation, and interaction with isothiocyanates were studied. Optimal synthesis conditions were studied for all reactions. It was found that the reaction of 4-bromo-3,5-dimethylpyrazole with isothiocyanates, in contrast to the previously written derivatives of anilines, takes a longer time and requires heating the reaction mixture. The combination of a pirasol fragment with halide substituents often results in an enhanced therapeutic effect. The synthesized 2-bromine-N-(6-rodanbenzo[d]thiazole-2-yl)acetamide, due to the alkylbromide group, is an important synth in the synthesis of new benzthiazole derivatives. Its derivatives combine in one molecule the rest of rhodanbenzthiazole with alkaloid cytisine and biogenic amine morpholine and are potentially biologically active compounds, since the molecule structure contains several pharmacophoric fragments: benzthiazole and alkaloid (amine) heterocycles, rhodane and urea groups. The mechanism of formation of 1,3,4-oxadiazole-2-tyons from hydrazides under action on them by carbon disulfide was studied and assumed. It was shown that dithiocarbamates in acidic medium decompose with the release of hydrogen sulfide and the formation of highly reactive isothiocyanate group. Then, intra-molecular cyclization occurs, with the formation of end products - 1,3,4-oxadiazole-2-thions. The structures of the synthesized compounds were studied by 1H and 13C NMR spectroscopy. All synthesized substances are potentially biologically active compounds, since they contain several pharmacophore fragments in their structure.

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Absolute configuration at C(20) of the derivatives of 21-nor-5α-cholane-20,24-diol

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19802443 ◽

1980 ◽

Vol 45 (9) ◽

pp. 2443-2451

Author(s):

Vladimír Pouzar ◽

Miroslav Havel

Keyword(s):

Absolute Configuration ◽

Side Chain ◽

Chemical Correlation ◽

The Absolute ◽

Derivatives Of

Derivatives of 21-nor-5α-cholane-20,24-diol XI and XIX were prepared by stepwise construction of the side-chain in the position 17β. Their absolute configuration at C(20) was determined on the basis of chemical correlation with the derivatives of 21-nor-5α-cholan-20-ol, XVI and XXIV. The absolute configuration of alcohols XVI and XXIV was determined from the ratio of the yields in which they are formed during the reduction of ketone X and using the benzoate rule. To compounds XI-XVIII the configuration 20R and to compounds XIX-XXVI the configuration 20S has been assigned.

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Analogues of the cholecystokinin octapeptide modified in the central part of the molecule

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc19911963 ◽

1991 ◽

Vol 56 (9) ◽

pp. 1963-1970 ◽

Cited By ~ 3

Author(s):

Jan Hlaváček ◽

Václav Čeřovský ◽

Jana Pírková ◽

Pavel Majer ◽

Lenka Maletínská ◽

...

Keyword(s):

Amino Acid ◽

Biological Activities ◽

Point Of View ◽

Biologically Active ◽

Side Chain ◽

Amino Acid Residues ◽

Cholecystokinin Octapeptide ◽

Biological Tests ◽

Biological Potency ◽

Biologically Active Conformation

In a series of analogues of the cholecystokinin octapeptide (CCK-8) the amino acid residues were gradually modified by substituting Gly by Pro in position 4, Trp by His in position 5, Met by Cle in position 6, or the Gly residue was inserted between Tyr and Met in positions 2 and 3 of the peptide chain, and in the case of the cholecystokinin heptapeptide (CCK-7) the Met residues were substituted by Nle or Aib. These peptides were investigated from the point of view of their biological potency in the peripheral and central region. From the results of the biological tests it follows that the modifications carried out in these analogues and in their Nα-Boc derivatives mean a suppression of the investigated biological activities by 2-3 orders of magnitude (at a maximum dose of the tested substance of 2 . 10-2 mg per animal).This means that a disturbance of the assumed biologically active conformation of CCK-8, connected with a considerable decrease of the biological potency of the molecule, takes place not only after introduction of the side chain into its centre (substitution of Gly4), but also after the modification of the side chains of the amino acids or by extension of the backbone in further positions around this central amino acid.

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Synthesis of 5'-O-phosphonomethyl derivatives of biologically active nucleosides

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc1990s125 ◽

1990 ◽

Vol 55 (s1) ◽

pp. 125-128

Author(s):

J. Brokeš ◽

A. Holý

Keyword(s):

Biologically Active ◽

Derivatives Of

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Quantum-Chemical Search for Keto Tautomers of Azulenols in Vacuo and Aqueous Solution

Symmetry ◽

10.3390/sym13030497 ◽

2021 ◽

Vol 13 (3) ◽

pp. 497

Author(s):

Ewa D. Raczyńska

Keyword(s):

Aqueous Solution ◽

Quantum Chemical ◽

Biologically Active ◽

Deprotonation Reaction ◽

Chemical Studies ◽

Quantum Chemical Studies ◽

Scanty Information ◽

Derivatives Of ◽

Common Anion ◽

Tautomeric Mixture

Keto-enol prototropic conversions for carbonyl compounds and phenols have been extensively studied, and many interesting review articles and even books appeared in the last 50 years. Quite a different situation takes place for derivatives of biologically active azulene, for which only scanty information on this phenomenon can be found in the literature. In this work, quantum-chemical studies have been undertaken for symmetrically and unsymmetrically substituted azulenols (constitutional isomers of naphthols). Stabilities of two enol (OH) rotamers and all possible keto (CH) tautomers have been analyzed in the gas phase {DFT(B3LYP)/6-311+G(d,p)} and also in aqueous solution {PCM(water)//DFT(B3LYP)/6-311+G(d,p)}. Contrary to naphthols, for which the keto forms can be neglected, at least one keto isomer (C1H, C2H, and/or C3H) contributes significantly to the tautomeric mixture of each azulenol to a higher degree in vacuo (non-polar environment) than in water (polar amphoteric solvent). The highest amounts of the CH forms have been found for 2- and 5-hydroxyazulenes, and the smallest ones for 1- and 6-hydroxy derivatives. The keto tautomer(s), together with the enol rotamers, can also participate in deprotonation reaction leading to a common anion and influence its acid-base properties. The strongest acidity in vacuo exhibits 6-hydroxyazulene, and the weakest one displays 1-hydroxyazulene, but all azulenols are stronger acids than phenol and naphthols. Bond length alternation in all DFT-optimized structures has been measured using the harmonic oscillator model of electron delocalization (HOMED) index. Generally, the HOMED values decrease for the keto tautomers, particularly for the ring containing the labile proton. Even for the keto tautomers possessing energetic parameters close to those of the enol isomers, the HOMED indices are low. However, some kind of parallelism exists for the keto forms between their relative energies and HOMEDs estimated for the entire molecules.

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Synthesis of New Derivatives of BEDT-TTF: Installation of Alkyl, Ethynyl, and Metal-Binding Side Chains and Formation of Tris(BEDT-TTF) Systems

Magnetochemistry ◽

10.3390/magnetochemistry7080110 ◽

2021 ◽

Vol 7 (8) ◽

pp. 110

Author(s):

Songjie Yang ◽

Matteo Zecchini ◽

Andrew Brooks ◽

Sara Krivickas ◽

Desiree Dalligos ◽

...

Keyword(s):

Metal Binding ◽

Tricarboxylic Acid ◽

Metal Salts ◽

Side Chain ◽

Side Chains ◽

Ethynyl Group ◽

X Ray ◽

Transition Metal Salts ◽

Alkyl Side Chains ◽

Derivatives Of

The syntheses of new BEDT-TTF derivatives are described. These comprise BEDT-TTF with one ethynyl group (HC≡C-), with two (n-heptyl) or four (n-butyl) alkyl side chains, with two trans acetal (-CH(OMe)2) groups, with two trans aminomethyl (-CH2NH2) groups, and with an iminodiacetate (-CH2N(CH2CO2−)2 side chain. Three transition metal salts have been prepared from the latter donor, and their magnetic properties are reported. Three tris-donor systems are reported bearing three BEDT-TTF derivatives with ester links to a core derived from benzene-1,3,5-tricarboxylic acid. The stereochemistry and molecular structure of the donors are discussed. X-ray crystal structures of two BEDT-TTF donors are reported: one with two CH(OMe)2 groups and with one a -CH2N(CH2CO2Me)2 side chain.

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