Practical Synthesis and Application of Halogen-Doped Pyrrole Building Blocks

Cotman, Andrej Emanuel; Guérin, Thomas; Kovačević, Ivana; Tiz, Davide Benedetto; Durcik, Martina; Fulgheri, Federica; Možina, Štefan; Secci, Daniela; Sterle, Maša; Ilaš, Janez; Zega, Anamarija; Zidar, Nace; Mašič, Lucija Peterlin; Tomašič, Tihomir; Leroux, Frédéric R.; Hanquet, Gilles; Kikelj, D.

doi:10.1021/acsomega.1c00331

Cited by 10 publications

(16 citation statements)

References 29 publications

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“…Synthetically, given the high electronegativity of fluorine, the design of electrophilic fluorine source (F + ) has been more challenging over the years with respect to bromine and chlorine sources. In this sense, Selectfluor ® [ 18 ] ( Figure 2 ) has been groundbreaking, allowing several transformations on alkanes [ 19 ] and aromatic scaffolds [ 20 ]. In regard to the aromatic substrates, electron-donating substituents are known to increase the rate of the formation and yield of fluorinated compounds, obviously [ 21 ].…”

Section: Fluorine and Chlorine In Medicinal Chemistrymentioning

confidence: 99%

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

et al. 2022

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This review describes the recent Food and Drug Administration (FDA)-approved drugs (in the year 2021) containing at least one halogen atom (covalently bound). The structures proposed throughout this work are grouped according to their therapeutical use. Their synthesis is presented as well. The number of halogenated molecules that are reaching the market is regularly preserved, and 14 of the 50 molecules approved by the FDA in the last year contain halogens. This underlines the emergent role of halogens and, in particular, of fluorine and chlorine in the preparation of drugs for the treatment of several diseases such as viral infections, several types of cancer, cardiovascular disease, multiple sclerosis, migraine and inflammatory diseases such as vasculitis.

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Section: Fluorine and Chlorine In Medicinal Chemistrymentioning

confidence: 99%

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

et al. 2022

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“…4 6-carboxylate (22s19). A suspension of 3,4-dichloro-5-(phthalimidomethyl)-1H-pyrrole-2-carboxylic acid 36 (63 mg, 0.186 mmol) in SOCl 2 (1 mL) was refluxed for 1 h; then, the reaction mixture was concentrated under reduced pressure to get a red tinted white solid. To this, crude acyl chloride 20s18 (81 mg, 0.186 mmol) and toluene (64 mL) were added and the resulting suspension was refluxed overnight.…”

Section: Methyl 4-(benzyloxy)-2-(methylamino)benzo[d]mentioning

confidence: 99%

“…Prepared according to the typical procedure D from 2-aminobenzothiazole 32s36 (250 mg, 0.605 mmol); light pink solid (150 mg, 42% yield). 1 H NMR (400 MHz, DMSO-d 6 ): δ 12.27 (s, 2H), 8.18 (s,1H),3H),7.35 (app t,J = 7.5 Hz,2H),7.26 (t,J = 7.4 Hz,1H),5.86 (dd,J = 7.9,3.8 Hz,1H),3.81 (s,3H),4H) thiazole-6-carboxylic Acid (36). Prepared according to the typical procedure E from methyl ester 33s36 (75 mg, 0.127 mmol); light pink solid (60 mg, 82% yield).…”

Section: -(34-dichloro-5-methyl-1h-pyrrole-2-carboxamido)-4-(1-phenyl...mentioning

confidence: 99%

“…Prepared according to the typical procedure C from aniline 4s48 (1.06 g, 4.50 mmol); light yellow powder (724 mg, 55% yield). 1 36,166.13,147.78,147.17,132.15,122.21,115.73,112.75,78.23,51.93,19.53,16.76,3.82,thiazole -6-carboxylate (6s48). Prepared according to the typical procedure D from 2aminobenzothiazole 5s48 (250 mg, 0.854 mmol); white solid (40 mg, 10% yield).…”

Section: Methyl 4-amino-3-(1-cyclopropylethoxy)benzoate (4s48)mentioning

confidence: 99%

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Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumannii and Pseudomonas aeruginosa

et al. 2023

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We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from A. baumannii and P. aeruginosa, a 10-fold decreased inhibition of human topoisomerase IIα, and no cross-resistance to novobiocin. Cocrystal structures of 1 in complex with Escherichia coli GyrB24 and (S)-27 in complex with A. baumannii GyrB23 and P. aeruginosa GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit. In further optimization steps, solubility, plasma free fraction, and other ADME properties of 27 were improved by fine-tuning of lipophilicity. In particular, analogs of 27 with retained anti-Gram-negative activity and improved plasma free fraction were identified. The series was found to be nongenotoxic, nonmutagenic, devoid of mitochondrial toxicity, and possessed no ion channel liabilities.

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“…Halogenation is one of the most important modifications in organic synthesis because of its extremely wide applications. Halogen derivatives are useful building blocks in organic synthesis for the construction of complicated, high-activity molecules [ 1 , 2 , 3 ]. Moreover, as halogenation can be applied to a wide variety of organic compounds without altering their basic structures, halogen-substituted compounds have become popular intermediates for transformation to create different functional groups [ 4 , 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Visible-Light-Induced Catalytic Selective Halogenation with Photocatalyst

2021

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Halide moieties are essential structures of compounds in organic chemistry due to their popularity and wide applications in many fields such as natural compounds, agrochemicals, and pharmaceuticals. Thus, many methods have been developed to introduce halides into various organic molecules. Recently, visible-light-driven reactions have emerged as useful methods of organic synthesis. Particularly, halogenation strategies using visible light have significantly improved the reaction efficiency and reduced toxicity, as well as promoted reactions under mild conditions. In this review, we have summarized recent studies in visible-light-mediated halogenation (chlorination, bromination, and iodination) with photocatalysts.

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Practical Synthesis and Application of Halogen-Doped Pyrrole Building Blocks

Cited by 10 publications

References 29 publications

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

New Halogen-Containing Drugs Approved by FDA in 2021: An Overview on Their Syntheses and Pharmaceutical Use

Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumannii and Pseudomonas aeruginosa

Visible-Light-Induced Catalytic Selective Halogenation with Photocatalyst

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