Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one

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

doi:10.1021/jm00099a007

Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one

Walfred S. Saari
, John S. Wai
, Thorsten E. Fisher
, Craig M. Thomas
, Jacob M. Hoffman
, Clarence S. Rooney
, Anthony M. Smith
, James H. Jones
, Dona L. Bamberger
, Mark E. Goldman
, Julie A. O'Brien
, 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

105 Scopus citations

Abstract

A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC₅₀ values as low as 19 nM in the enzyme assay using rC-dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methylpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.

Original language	English
Pages (from-to)	3792-3802
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	35
Issue number	21
DOIs	https://doi.org/10.1021/jm00099a007
State	Published - Oct 1 1992

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/jm00099a007

Cite this

Saari, W. S., Wai, J. S., Fisher, T. E., Thomas, C. M., Hoffman, J. M., Rooney, C. S., Smith, A. M., Jones, J. H., Bamberger, D. L., Goldman, M. E., O'Brien, J. A., Nunberg, J. H., Quintero, J. C., Schleif, W. A., Emini, E. A., & Anderson, P. S. (1992). Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one. Journal of Medicinal Chemistry, 35(21), 3792-3802. https://doi.org/10.1021/jm00099a007

@article{94a5c38fdd874b29907bf888a48abcd5,

title = "Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one",

abstract = "A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC-dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methylpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95\% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.",

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

year = "1992",

month = oct,

day = "1",

doi = "10.1021/jm00099a007",

language = "English",

volume = "35",

pages = "3792--3802",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

number = "21",

}

Saari, WS, Wai, JS, Fisher, TE, Thomas, CM, Hoffman, JM, Rooney, CS, Smith, AM, Jones, JH, Bamberger, DL, Goldman, ME, O'Brien, JA, Nunberg, JH, Quintero, JC, Schleif, WA, Emini, EA & Anderson, PS 1992, 'Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one', Journal of Medicinal Chemistry, vol. 35, no. 21, pp. 3792-3802. https://doi.org/10.1021/jm00099a007

TY - JOUR

T1 - Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one

AU - Saari, Walfred S.

AU - Wai, John S.

AU - Fisher, Thorsten E.

AU - Thomas, Craig M.

AU - Hoffman, Jacob M.

AU - Rooney, Clarence S.

AU - Smith, Anthony M.

AU - Jones, James H.

AU - Bamberger, Dona L.

AU - Goldman, Mark E.

AU - O'Brien, Julie A.

AU - Nunberg, Jack H.

AU - Quintero, Julio C.

AU - Schleif, William A.

AU - Emini, Emilio A.

AU - Anderson, Paul S.

PY - 1992/10/1

Y1 - 1992/10/1

N2 - A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC-dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methylpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.

AB - A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC-dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methylpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.

UR - https://www.scopus.com/pages/publications/0026489556

U2 - 10.1021/jm00099a007

DO - 10.1021/jm00099a007

M3 - Article

C2 - 1279173

AN - SCOPUS:0026489556

SN - 0022-2623

VL - 35

SP - 3792

EP - 3802

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 21

ER -

Synthesis and Evaluation of 2-Pyridinone Derivatives as HIV-1-Specific Reverse Transcriptase Inhibitors. 2. Analogues of 3-Aminopyridin-2(1H)-one

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this