Solid support synthesis of 14-membered macrocycles containing the thioether bridge via SNAr methodology

Kiselyov, Alexander S.; Eisenberg, Shawn; Luo, Ying

doi:10.1016/s0040-4020(98)00598-5

Cited by 23 publications

(8 citation statements)

References 33 publications

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“…After another Fmoc deprotection step, the cyclization linker 2-fluoro-5-nitrobenzoic acid was incorporated into the backbone. TBDMS deprotection was then removed with triethylamine trihydrofluoride (TREAT-HF), and the structure was cyclized by a base-induced S N Ar reaction. , The aryl nitro group was reduced with tin(II) chloride, and then functionalized. The macrocycles were cleaved from solid support with TFA to provide library members in >85% purity, according to LC−MS analysis.…”

Section: Chemistrymentioning

confidence: 99%

New Inhibitors of Bacterial Protein Synthesis from a Combinatorial Library of Macrocycles

et al. 2002

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A mixture-based combinatorial library of 14-membered macrocycles was synthesized to target ribosomal RNA and uncover a new class of antibacterial agents. High-throughput screening identified a macrocyclic mixture that inhibited cell-free-coupled transcription/translation in Escherichia coli-derived extracts, with an IC(50) value in the 25-50 microM range. In a follow-up library of 64 single macrocycles, 8 gave IC(50) values ranging from 12 to 50 microM in the cell-free protein synthesis inhibition assay. Some of the macrocycles were screened in a translation inhibition assay, and IC(50) values generally paralleled those obtained in the uncoupled transcription/translation assay. Additional analogues were prepared in a preliminary structure-activity relationship study, and more potent macrocycles were identified with low micromolar activity (IC(50) values = 2-3 microM). Some of these macrocycles displayed antibacterial activity against lipopolysaccharide mutant E. coli bacterial cells (IC(50) values = 12-50 microM).

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Section: Chemistrymentioning

confidence: 99%

New Inhibitors of Bacterial Protein Synthesis from a Combinatorial Library of Macrocycles

et al. 2002

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“…Because many more libraries are published annually without associated biological data and are of equal interest to the combinatorial and medicinal chemical communities, a compilation of these types of constructs is included in this review. In 1998, there were 247 libraries of this genus. − …”

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confidence: 99%

Comprehensive Survey of Combinatorial Library Synthesis: 1998

Dolle¹,

Nelson²

1999

J. Comb. Chem.

286

133

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An exhaustive compilation of biologically active libraries covering the years 1992-1997 was presented in a previous review [1a]. In that review, libraries were divided among 4 major categories, including those active against proteases, non-proteolytic enzymes, Gprotein coupled receptors, and non-G-protein coupled receptors. A generic structure for each library was provided as well as the structure of the most active member. The number of biologically active libraries reported in the literature during this time period (86 total) represents <25% of the total number of published library constructs. Disclosure of library synthesis without accompanying screening data is a more common occurrence. Because these types of libraries are equally important to the practicing combinatorial chemist, it was thought that a comprehensive listing of such libraries spanning the years 1992-1997 would be a useful supplement to the previous review [1a,b].Library constructs [2-248] listed herein are relegated to one of five tables. Table 1 is entitled 'Scaffold derivatization' and includes all constructs in which a multi-functional scaffold is modified in some fashion to create a library. An example of a construct found in Table 1 would be the sequential addition of three nucleophiles to trichloropyrimidine. Table 2, entitled 'Acyclic synthesis', lists all linear constructs such as those derived from multi-component Ugi condensations.

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“…In addition, preparation of diverse 2-(alkylamino)benzamide was difficult with the reported method; therefore, we decided to prepare 2-(alkylamino)-benzamides from 2-fluoro-5-nitrobenzamides through S N Ar reaction. The key building block, 2-fluoro-5-nitrobenzoic acid, was successfully applied to the solid-phase synthesis of various heterocycles, such as benzimidazoles, 10 benzopiperazinones, 11 macrocycles, 12 1,4-benzothiazepin-5-ones, 13 quinazoline-2,4-diones, 3d 2-thioxoquinazolin-4-ones. 3c Here, we report the solid-phase synthesis of 2,1,3-benzothiadiazin-4-one 2-oxides.…”

mentioning

confidence: 99%

Efficient Solid-phase Synthesis of 2,1,3-Benzothiadiazin-4-one 2-Oxides with SynPhase™ Lanterns

Makino¹,

Nakanishi²,

Tsuji³

2003

Bulletin of the Korean Chemical Society

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Solid support synthesis of 14-membered macrocycles containing the thioether bridge via SNAr methodology

Cited by 23 publications

References 33 publications

New Inhibitors of Bacterial Protein Synthesis from a Combinatorial Library of Macrocycles

New Inhibitors of Bacterial Protein Synthesis from a Combinatorial Library of Macrocycles

Comprehensive Survey of Combinatorial Library Synthesis: 1998

Efficient Solid-phase Synthesis of 2,1,3-Benzothiadiazin-4-one 2-Oxides with SynPhase™ Lanterns

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