BIOMAT Database Logo BIOMAT Database Logo

Highly potent and selective inhibition of human immunodeficiency virus type 1 by a novel series of 6-substituted acyclouridine derivatives. 1991

M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Department of Bacteriology, Fukushima Medical College, Japan.

In the search for novel derivatives of 1-[2-(hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), we have found that several 5-ethyl-6-(3,5-dimethylphenylthio)uracil and 5-ethyl-6-(3,5-dimethylbenzyl)uracil analogues are exquisitely potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell culture systems. Of this series, 5-ethyl-1-ethoxymethyl-6-(3,5-dimethylbenzyl)uracil (E-EBU-dM) emerged as the most active congener. Its 50% inhibitory concentration for HIV-1 (HTLV-IIIB) in MT-4 cells and peripheral blood lymphocytes is 2.2 and 0.45 nM, respectively. These concentrations are more than 10(5)-fold lower than the 50% cytotoxic concentrations of E-EBU-dM for the host cells. All compounds proved equally inhibitory to a number of clinical HIV-1 isolates, including a 3'-azido-2',3'-dideoxythymidine-resistant variant. However, as previously noted for HEPT, they do not inhibit human immunodeficiency virus type 2 replication. Reverse transcriptase assays have revealed that these HEPT derivatives act specifically on HIV-1 reverse transcriptase, according to a mechanism that is different from that of the dideoxynucleosides.

UI MeSH Term Description Entries
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000998 Antiviral Agents Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013941 Thymine One of four constituent bases of DNA. 5-Methyluracil,5 Methyluracil
D015215 Zidovudine A dideoxynucleoside compound in which the 3'-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with AIDS. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. AZT (Antiviral),Azidothymidine,3'-Azido-2',3'-Dideoxythymidine,3'-Azido-3'-deoxythymidine,AZT Antiviral,AZT, Antiviral,BW A509U,BWA-509U,Retrovir,3' Azido 2',3' Dideoxythymidine,3' Azido 3' deoxythymidine,Antiviral AZT,BWA 509U,BWA509U
D015497 HIV-1 The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte. Human immunodeficiency virus 1,HIV-I,Human Immunodeficiency Virus Type 1,Immunodeficiency Virus Type 1, Human
D018894 Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (RNA-DIRECTED DNA POLYMERASE), an enzyme that synthesizes DNA on an RNA template. Reverse Transcriptase Inhibitor,Inhibitors, Reverse Transcriptase,Inhibitor, Reverse Transcriptase,Transcriptase Inhibitor, Reverse

Related Publications

M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Potent and selective inhibition of human immunodeficiency virus type 1 transcription by piperazinyloxoquinoline derivatives.
June 1997, Antimicrobial agents and chemotherapy,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Potent and highly selective human immunodeficiency virus type 1 (HIV-1) inhibition by a series of alpha-anilinophenylacetamide derivatives targeted at HIV-1 reverse transcriptase.
March 1993, Proceedings of the National Academy of Sciences of the United States of America,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Benzophenone derivatives: a novel series of potent and selective inhibitors of human immunodeficiency virus type 1 reverse transcriptase.
May 1995, Journal of medicinal chemistry,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Thiadiazole derivatives: highly potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) replications in vitro.
January 1997, Microbiology and immunology,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Anti-human immunodeficiency virus type 1 activity of novel 6-substituted 1-benzyl-3-(3,5-dimethylbenzyl)uracil derivatives.
May 2012, Antimicrobial agents and chemotherapy,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Highly potent and selective inhibition of human immunodeficiency virus by the bicyclam derivative JM3100.
April 1994, Antimicrobial agents and chemotherapy,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Inhibition of human immunodeficiency virus type 1 integration by diketo derivatives.
October 2002, Antimicrobial agents and chemotherapy,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Selective inhibition of Human Immunodeficiency Virus type 1 (HIV-1) by a novel family of tricyclic nucleosides.
October 2011, Antiviral research,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Potent and selective inhibition of HIV-1 replication in vitro by a novel series of TIBO derivatives.
February 1990, Nature,
M Baba, and E De Clercq, and H Tanaka, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and K Umezu, and R T Walker, and S Mori
Selective inhibition of human immunodeficiency virus type 1 replication by novel fluoroalkylated oligomers in vitro.
January 1994, Journal of acquired immune deficiency syndromes,
Copied contents to your clipboard!