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

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

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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