The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones

Fred L. Ciske; Michael R. Barbachyn; Michael J. Genin; Kevin C. Grega; Chi Sing Lee; Lester A. Dolak; Eric P. Seest; William Watt; Wade J. Adams; Janice M. Friis; Charles W. Ford; Gary E. Zurenko

doi:10.1016/j.bmcl.2003.07.029

The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones

Fred L. Ciske
, Michael R. Barbachyn^*
, Michael J. Genin
, Kevin C. Grega
, Chi Sing Lee
, Lester A. Dolak
, Eric P. Seest
, William Watt
, Wade J. Adams
, Janice M. Friis
, Charles W. Ford
, Gary E. Zurenko

^*Corresponding author for this work

Department of Chemistry

Research output: Contribution to journal › Journal article › peer-review

28 Citations (Scopus)

Abstract

The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 μg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of α-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.

Original language	English
Pages (from-to)	4235-4239
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	13
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2003.07.029
Publication status	Published - 1 Dec 2003

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Ciske, F. L., Barbachyn, M. R., Genin, M. J., Grega, K. C., Lee, C. S., Dolak, L. A., Seest, E. P., Watt, W., Adams, W. J., Friis, J. M., Ford, C. W., & Zurenko, G. E. (2003). The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones. Bioorganic and Medicinal Chemistry Letters, 13(23), 4235-4239. https://doi.org/10.1016/j.bmcl.2003.07.029

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title = "The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones",

abstract = "The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 μg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of α-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.",

author = "Ciske, \{Fred L.\} and Barbachyn, \{Michael R.\} and Genin, \{Michael J.\} and Grega, \{Kevin C.\} and Lee, \{Chi Sing\} and Dolak, \{Lester A.\} and Seest, \{Eric P.\} and William Watt and Adams, \{Wade J.\} and Friis, \{Janice M.\} and Ford, \{Charles W.\} and Zurenko, \{Gary E.\}",

note = "Publisher Copyright: {\textcopyright} 2003 Published by Elsevier Ltd.",

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month = dec,

day = "1",

doi = "10.1016/j.bmcl.2003.07.029",

language = "English",

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Ciske, FL, Barbachyn, MR, Genin, MJ, Grega, KC, Lee, CS, Dolak, LA, Seest, EP, Watt, W, Adams, WJ, Friis, JM, Ford, CW & Zurenko, GE 2003, 'The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones', Bioorganic and Medicinal Chemistry Letters, vol. 13, no. 23, pp. 4235-4239. https://doi.org/10.1016/j.bmcl.2003.07.029

TY - JOUR

T1 - The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones

AU - Ciske, Fred L.

AU - Barbachyn, Michael R.

AU - Genin, Michael J.

AU - Grega, Kevin C.

AU - Lee, Chi Sing

AU - Dolak, Lester A.

AU - Seest, Eric P.

AU - Watt, William

AU - Adams, Wade J.

AU - Friis, Janice M.

AU - Ford, Charles W.

AU - Zurenko, Gary E.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 μg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of α-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.

AB - The oxazolidinones are promising agents for the treatment of infections caused by gram-positive bacteria, including multidrug-resistant strains. In ongoing studies we have discovered that a strategically placed chiral center of appropriate absolute configuration improves the antibacterial activity of indolinyl oxazolidinone analogues (gram-positive MIC's<0.5 μg/mL for the most potent congeners). The design, synthesis, antibacterial activity and pharmacokinetic profile of a selected series of α-methylated indoline derivatives and a related set of tetrahydroquinolyl and dihydrobenzoxazinyl analogues are discussed.

UR - https://www.scopus.com/pages/publications/10744222171

U2 - 10.1016/j.bmcl.2003.07.029

DO - 10.1016/j.bmcl.2003.07.029

M3 - Journal article

C2 - 14623008

AN - SCOPUS:10744222171

SN - 0960-894X

VL - 13

SP - 4235

EP - 4239

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

The effect of remote chirality on the antibacterial activity of indolinyl, tetrahydroquinolyl and dihydrobenzoxazinyl oxazolidinones

Abstract

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