Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues

Jacob M. Hoffman; Anthony M. Smith; Clarence S. Rooney; Thorsten E. Fisher; John S. Wai; Craig M. Thomas; Dona L. Bamberger; James L. Barnes; Theresa M. Williams; James H. Jones; Brandon D. Olson; Julie A. O'Brien; Mark E. Goldman; Jack H. Nunberg; Julio C. Quintero; William A. Schleif; Emilio A. Emini; Paul S. Anderson

doi:10.1021/jm00060a002

Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues

Jacob M. Hoffman, Anthony M. Smith, Clarence S. Rooney, Thorsten E. Fisher, John S. Wai, Craig M. Thomas, Dona L. Bamberger, James L. Barnes, Theresa M. Williams, James H. Jones, Brandon D. Olson, Julie A. O'Brien, Mark E. Goldman, Jack H. Nunberg, Julio C. Quintero, William A. Schleif, Emilio A. Emini, Paul S. Anderson

Montana Biotechnology Center

Merck

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94 Scopus citations

Abstract

A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalimido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain III_B One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H-one (9, L-696,229), which was a highly selective antagonist of the RT enzyme (IC₅₀ = 23 nM) and which inhibited the spread of HIV-1 III_B infection by >95% in MT4 human T-lymphoid cell culture (CIC₉₅ = 50–100 nM), was selected for clinical evaluation as an antiviral agent.

Original language	English
Pages (from-to)	953-966
Number of pages	14
Journal	Journal of Medicinal Chemistry
Volume	36
Issue number	8
DOIs	https://doi.org/10.1021/jm00060a002
State	Published - 1993

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Hoffman, J. M., Smith, A. M., Rooney, C. S., Fisher, T. E., Wai, J. S., Thomas, C. M., Bamberger, D. L., Barnes, J. L., Williams, T. M., Jones, J. H., Olson, B. D., O'Brien, J. A., Goldman, M. E., Nunberg, J. H., Quintero, J. C., Schleif, W. A., Emini, E. A., & Anderson, P. S. (1993). Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues. Journal of Medicinal Chemistry, 36(8), 953-966. https://doi.org/10.1021/jm00060a002

@article{c3d1a56e0a27489f9cad8506130e3a99,

title = "Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues",

abstract = "A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalimido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H-one (9, L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by >95\% in MT4 human T-lymphoid cell culture (CIC95 = 50–100 nM), was selected for clinical evaluation as an antiviral agent.",

author = "Hoffman, \{Jacob M.\} and Smith, \{Anthony M.\} and Rooney, \{Clarence S.\} and Fisher, \{Thorsten E.\} and Wai, \{John S.\} and Thomas, \{Craig M.\} and Bamberger, \{Dona L.\} and Barnes, \{James L.\} and Williams, \{Theresa M.\} and Jones, \{James H.\} and Olson, \{Brandon D.\} and O'Brien, \{Julie A.\} and Goldman, \{Mark E.\} and Nunberg, \{Jack H.\} and Quintero, \{Julio C.\} and Schleif, \{William A.\} and Emini, \{Emilio A.\} and Anderson, \{Paul S.\}",

year = "1993",

doi = "10.1021/jm00060a002",

language = "English",

volume = "36",

pages = "953--966",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "8",

}

Hoffman, JM, Smith, AM, Rooney, CS, Fisher, TE, Wai, JS, Thomas, CM, Bamberger, DL, Barnes, JL, Williams, TM, Jones, JH, Olson, BD, O'Brien, JA, Goldman, ME, Nunberg, JH, Quintero, JC, Schleif, WA, Emini, EA & Anderson, PS 1993, 'Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues', Journal of Medicinal Chemistry, vol. 36, no. 8, pp. 953-966. https://doi.org/10.1021/jm00060a002

Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues. / Hoffman, Jacob M.; Smith, Anthony M.; Rooney, Clarence S. et al.
In: Journal of Medicinal Chemistry, Vol. 36, No. 8, 1993, p. 953-966.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues

AU - Hoffman, Jacob M.

AU - Smith, Anthony M.

AU - Rooney, Clarence S.

AU - Fisher, Thorsten E.

AU - Wai, John S.

AU - Thomas, Craig M.

AU - Bamberger, Dona L.

AU - Barnes, James L.

AU - Williams, Theresa M.

AU - Jones, James H.

AU - Olson, Brandon D.

AU - O'Brien, Julie A.

AU - Goldman, Mark E.

AU - Nunberg, Jack H.

AU - Quintero, Julio C.

AU - Schleif, William A.

AU - Emini, Emilio A.

AU - Anderson, Paul S.

PY - 1993

Y1 - 1993

N2 - A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalimido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H-one (9, L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by >95% in MT4 human T-lymphoid cell culture (CIC95 = 50–100 nM), was selected for clinical evaluation as an antiviral agent.

AB - A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalimido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H-one (9, L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by >95% in MT4 human T-lymphoid cell culture (CIC95 = 50–100 nM), was selected for clinical evaluation as an antiviral agent.

UR - https://www.scopus.com/pages/publications/0027229213

U2 - 10.1021/jm00060a002

DO - 10.1021/jm00060a002

M3 - Article

C2 - 7683054

AN - SCOPUS:0027229213

SN - 0022-2623

VL - 36

SP - 953

EP - 966

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 8

ER -

Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and Analogues

Abstract

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