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1.
J Enzyme Inhib Med Chem ; 19(6): 511-9, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15662955

ABSTRACT

A series of 2',3'-didehydro-2',3'-dideoxynucleosides substituted with an alkynylhydroxy- (6, 7, 12 and 13) and alkynylamino- (20) groups at the C-5 position were synthesized. All these five target modified nucleosides were tested for anti-human immunodeficiency virus type 1 activity in CEM-SS and MT-4 cells and unfortunately displayed no improvement in antiviral activity.


Subject(s)
Alkynes/chemistry , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Reverse Transcriptase Inhibitors/chemical synthesis , Reverse Transcriptase Inhibitors/pharmacology , Stavudine , Anti-HIV Agents/chemistry , Cell Line , Cell Line, Tumor , Drug Evaluation, Preclinical , HIV-1/drug effects , HIV-1/physiology , Humans , Microbial Sensitivity Tests , Molecular Structure , Reverse Transcriptase Inhibitors/chemistry , Stavudine/analogs & derivatives , Stavudine/chemical synthesis , Stavudine/pharmacology , Structure-Activity Relationship , Virus Replication/drug effects
2.
Article in English | MEDLINE | ID: mdl-12484448

ABSTRACT

A series of eleven heterodimers containing both a nucleoside analogue (d4U, d4T) and a non-nucleoside type inhibitor (Trovirdine analogue) were synthesized and evaluated for their ability to inhibit HIV replication. Unfortunately, the (N-3)d4U-Trovirdine conjugates (9a-e) and (N-3)d4T-Trovirdine conjugates (10a-f) were found to be inactive suggesting that the two individual inhibitor compounds do not bind simultaneously in their respective sites.


Subject(s)
Dideoxynucleosides/chemical synthesis , HIV Reverse Transcriptase/antagonists & inhibitors , Pyridines/chemical synthesis , Reverse Transcriptase Inhibitors/chemical synthesis , Stavudine/chemical synthesis , Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Dideoxynucleosides/chemistry , Dideoxynucleosides/pharmacology , Dimerization , Drug Evaluation, Preclinical , HIV-1/drug effects , HIV-1/enzymology , Humans , Lymphocytes/drug effects , Lymphocytes/enzymology , Lymphocytes/virology , Pyridines/chemistry , Pyridines/pharmacology , Reverse Transcriptase Inhibitors/chemistry , Reverse Transcriptase Inhibitors/pharmacology , Stavudine/chemistry , Stavudine/pharmacology , Tumor Cells, Cultured , Zidovudine/pharmacology
3.
Nucleosides Nucleotides Nucleic Acids ; 20(9): 1655-70, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11580192

ABSTRACT

The target compounds 5-[N-(6-amino-hexyl)-acrylamide]-2',3'-didehydro-2',3'-dideoxy-uridine (12) and 5-[N-[5-(methoxycarbonyl)-pentyl]-acrylamide]-2',3'-didehydro-2',3'- dideoxy-uridine (15) were prepared by the palladium acetate-triphenylphosphine-catalyzed reaction of the 5'-O-acetyl-5-iodo-d4T analogue (3). These compounds 12 and 15 can be used to prepare nucleotide probes carrying fluorescent labels and were nevertheless screened for their anti-HIV activity. The biological data demonstrated that none of them were active against HIV-1.


Subject(s)
Palladium/chemistry , Stavudine/analogs & derivatives , Stavudine/chemical synthesis , Uridine/analogs & derivatives , Uridine/chemical synthesis , Catalysis/drug effects , Cell Line , Chromatography, Thin Layer , HIV-1/drug effects , HIV-1/enzymology , HIV-1/physiology , Humans , Magnetic Resonance Spectroscopy , Palladium/pharmacology , RNA-Directed DNA Polymerase/metabolism , Spectroscopy, Fourier Transform Infrared , Stavudine/chemistry , Stavudine/pharmacology , Uridine/chemistry , Uridine/pharmacology , Zidovudine/pharmacology
4.
Nucleosides Nucleotides Nucleic Acids ; 19(9): 1441-61, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11092314

ABSTRACT

A series of beta-D-2',3'-didehydro-2',3'-dideoxy-nucleosides bearing a tether attached at the C-5 position and their beta-L-counterparts was synthesized. Their inhibitory activities against human immunodeficiency virus (HIV) were investigated and compared to establish relationship(s) between compound structure and their antiviral activity. No significant activity was observed for beta-D- and beta-L-modified nucleosides respectively 7a-c and 14a-c, but 7d and 14d exhibited a weak activity against HIV-1.


Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Dideoxynucleosides/chemical synthesis , Dideoxynucleosides/pharmacology , HIV-1/drug effects , Thymidine/analogs & derivatives , Cell Line , Humans , Microbial Sensitivity Tests , Molecular Structure , Thymidine/chemical synthesis
5.
Nucleosides Nucleotides Nucleic Acids ; 19(5-6): 1017-31, 2000.
Article in English | MEDLINE | ID: mdl-10893719

ABSTRACT

A general strategy is reported for the preparation of C-5-methylamino- or methyldiamino-d4T analogues of "different sizes". Reactions of the 2',3'-didehydro-2',3'-dideoxy-C-5 hydroxymethyl precursor (7) with either polymethylene diamines (n = 6, 8, 10 and 12) or propargylamine proceed regioselectively via substitution reactions at the C-5 position of uracil. The compounds were evaluated for antiviral activity and cytotoxicity. No significant activity was observed for compounds 9, 11, and 13, but 10 and 12 exhibited a weak activity against HIV-1.


Subject(s)
Anti-HIV Agents/chemical synthesis , Stavudine/analogs & derivatives , Stavudine/chemical synthesis , Anti-HIV Agents/pharmacology , Cell Line/drug effects , Cells, Cultured , HIV-1/drug effects , Humans , RNA-Directed DNA Polymerase/metabolism , Stavudine/pharmacology
6.
Nucleosides Nucleotides ; 18(4-5): 883-4, 1999.
Article in English | MEDLINE | ID: mdl-10432702

ABSTRACT

This work reports the synthesis of 2',3'-didehydro-2',3'-dideoxy-thymidine analogues bearing several kinds of amino-linker arms at the C-5 position of the pyrimidine moiety. C-5 is an attractive position since a flexible chain may permit the triphosphates to be generated. The beta-D- and beta-L-d4T analogues were synthesized following a multi-step reaction from D-ribose and D-xylose, from D- and L-arabinose (towards an oxazoline ring) or from uridine and then were reacted with alkylene diamines.


Subject(s)
Anti-HIV Agents/chemical synthesis , Anti-HIV Agents/pharmacology , Stavudine/chemical synthesis , Stavudine/pharmacology , Cell Line , HIV-1/drug effects , Humans , Microbial Sensitivity Tests
9.
Article in Romanian | MEDLINE | ID: mdl-6454179

ABSTRACT

The duodenal ulcers with which the surgeon is confronted increasingly take on tumoural postbulbar forms, penetrating in the pancreas or liver pedicle. Such a duodenal stump can neither be anastomized to the residual stomach ulcer inversed safely. Therefore it has become increasingly necessary to find a tight inversion method. One of the authors (D. Gavriliu) updated mucous antrectomy + truncular vagotomy and Reichel-Polya gastrectomy, which leaves an adequate seromuscular cuff for a double closing suture of the duodenum; after ablation of the antral mucosa the patient benefits by a veritable humoral antrectomy. In point of fact the operation is increasingly applied (truncular vagotomy + antrectomy and Reichel-Polya gastrectomy), with the difference however that antrectomy only removes the mucosa, and the advantage of ensuring perfect closure of the duodenal stump.


Subject(s)
Duodenal Ulcer/surgery , Pyloric Antrum/surgery , Vagotomy , Adult , Aged , Female , Humans , Male , Middle Aged
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