BIOMAT Database Logo BIOMAT Database Logo

Synthesis and anti-HIV activity of 2-, 3-, and 4-substituted analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT). 1991

H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.

Several analogues of a new lead for anti-HIV-1 agents, 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT), in which the C-2, N-3, or C-4 position was modified were synthesized. These involve 2-thiothymine (11), 2-thiouracil (12), 4-thiothymine (17), 4-thiouracil (18), 5-methylcytosine (27), and cytosine (28) derivatives. Preparation of N-3-substituted derivatives (29 and 30) of HEPT was also carried out. Among these analogues, compound 11 exhibited excellent activity against HIV-1 HTLV-IIIB strain with an EC50 value of 0.98 microM, which is 7-fold more potent than that of HEPT. Removal of the 5-methyl group in compound 11 results in total loss of activity. Other compounds did not show any anti-HIV-1 activity. The 4-thio derivatives 17 and 18 were found to be rather cytotoxic. When compound 11 was evaluated for its inhibitory effects on another HIV-1 strain, HTLV-IIIRE, and two HIV-2 strains, LAV-2ROD and LAV-2EHO, it proved equally inhibitory to HTLV-IIIRF, whereas both HIV-2 strains were insensitive to the compound.

UI MeSH Term Description Entries
D007202 Indicators and Reagents Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant & Hackh's Chemical Dictionary, 5th ed, p301, p499) Indicator,Reagent,Reagents,Indicators,Reagents and Indicators
D008213 Lymphocyte Activation Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION. Blast Transformation,Blastogenesis,Lymphoblast Transformation,Lymphocyte Stimulation,Lymphocyte Transformation,Transformation, Blast,Transformation, Lymphoblast,Transformation, Lymphocyte,Activation, Lymphocyte,Stimulation, Lymphocyte
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D009682 Magnetic Resonance Spectroscopy Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING). In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
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

Related Publications

H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Synthesis and potent anti-HIV-1 activity of novel 6-benzyluracil analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine.
June 1996, Journal of medicinal chemistry,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Synthesis and anti-HIV activity of novel N-1 side chain-modified analogs of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).
June 1997, Journal of medicinal chemistry,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Conformational study of the HIV-1 reverse transcriptase inhibitor 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT).
February 1999, Biological chemistry,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Structure-Based design of [(2-Hydroxyethoxy)methyl]-6-(phenylthio)-thymine derivatives as nonnucleoside HIV-1 reverse transcriptase Inhibitors: From HEPTs to Sulfinyl-substituted HEPTs.
September 2022, Bioorganic chemistry,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Human immunodeficiency virus type 1 drug-resistance patterns with different 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives.
October 1993, Molecular pharmacology,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Thorough evaluation of OECD principles in modelling of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives using QSARINS.
October 2020, SAR and QSAR in environmental research,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Resistance to 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives is generated by mutations at multiple sites in the HIV-1 reverse transcriptase.
June 1995, Virology,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Differential activities of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine derivatives against different human immunodeficiency virus type 1 mutant strains.
April 1995, Antimicrobial agents and chemotherapy,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Nonnucleoside HIV-1 reverse-transcriptase inhibitors, part 5. Synthesis and anti-HIV-1 activity of novel 6-naphthylthio HEPT analogues.
August 2005, Chemical & pharmaceutical bulletin,
H Tanaka, and M Baba, and M Ubasawa, and H Takashima, and K Sekiya, and I Nitta, and S Shigeta, and R T Walker, and E De Clercq, and T Miyasaka
Synthesis and biological activity of 4-substituted 1-[1-(2-hydroxyethoxy)-methyl-1,2,3-triazol-(4 & 5)-ylmethyl]-1H-pyrazolo[3,4-d]pyrimidines.
January 2001, Nucleosides, nucleotides & nucleic acids,
Copied contents to your clipboard!