Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol

Charlotte Uldahl Jansen; Katja Egeskov Grier; Jens Bo Andersen; Louise Dahl Hultqvist; Martin Nilsson; Claus Moser; Michael Graz; Tim Tolker-Nielsen; Michael Givskov; Katrine Qvortrup

doi:10.3390/ijms25126737

Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol

Charlotte Uldahl Jansen, Katja Egeskov Grier, Jens Bo Andersen, Louise Dahl Hultqvist, Martin Nilsson, Claus Moser, Michael Graz, Tim Tolker-Nielsen, Michael Givskov, Katrine Qvortrup^*

^*Corresponding author for this work

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

2 Downloads (Pure)

Abstract

This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound E, as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.

Original language	English
Article number	6737
Journal	International Journal of Molecular Sciences
Volume	25
Issue number	12
Number of pages	8
ISSN	1661-6596
DOIs	https://doi.org/10.3390/ijms25126737
Publication status	Published - 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

biofilm
c-di-GMP
dispersal
dust analysis
flow chemistry
large-scale synthesis
preclinical
Pseudomonas aeruginosa
pyrazole
safety

Access to Document

10.3390/ijms25126737Licence: CC BY

FulltextFinal published version, 1.17 MBLicence: CC BY

Cite this

Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol. / Jansen, Charlotte Uldahl; Grier, Katja Egeskov; Andersen, Jens Bo ; Hultqvist, Louise Dahl ; Nilsson, Martin ; Moser, Claus; Graz, Michael; Tolker-Nielsen, Tim ; Givskov, Michael; Qvortrup, Katrine.

In: International Journal of Molecular Sciences, Vol. 25, No. 12, 6737, 2024.

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

Jansen, Charlotte Uldahl ; Grier, Katja Egeskov ; Andersen, Jens Bo ; Hultqvist, Louise Dahl ; Nilsson, Martin ; Moser, Claus ; Graz, Michael ; Tolker-Nielsen, Tim ; Givskov, Michael ; Qvortrup, Katrine. / Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol. In: International Journal of Molecular Sciences. 2024 ; Vol. 25, No. 12.

@article{86340c8498894feaad320dea2af0d342,

title = "Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol",

abstract = "This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound E, as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.",

keywords = "biofilm, c-di-GMP, dispersal, dust analysis, flow chemistry, large-scale synthesis, preclinical, Pseudomonas aeruginosa, pyrazole, safety",

author = "Jansen, {Charlotte Uldahl} and Grier, {Katja Egeskov} and Andersen, {Jens Bo} and Hultqvist, {Louise Dahl} and Martin Nilsson and Claus Moser and Michael Graz and Tim Tolker-Nielsen and Michael Givskov and Katrine Qvortrup",

note = "Publisher Copyright: {\textcopyright} 2024 by the authors.",

year = "2024",

doi = "10.3390/ijms25126737",

language = "English",

volume = "25",

journal = "International Journal of Molecular Sciences (Online)",

issn = "1661-6596",

publisher = "MDPI AG",

number = "12",

}

TY - JOUR

T1 - Upscaling and Risk Evaluation of the Synthesis of the 3,5-Diamino-1H-Pyrazole, Disperazol

AU - Jansen, Charlotte Uldahl

AU - Grier, Katja Egeskov

AU - Andersen, Jens Bo

AU - Hultqvist, Louise Dahl

AU - Nilsson, Martin

AU - Moser, Claus

AU - Graz, Michael

AU - Tolker-Nielsen, Tim

AU - Givskov, Michael

AU - Qvortrup, Katrine

PY - 2024

Y1 - 2024

N2 - This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound E, as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.

AB - This paper presents the work performed to transition a lab-scale synthesis (1 g) to a large-scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol, a new pharmaceutical for treatment of antibiotic-resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab-scale synthesis was transformed to a safe and easy-to-handle flow chemistry step. Additionally, the paper presents an OSHA-recommended safety assessment of active compound E, as performed by Fauske and Associates, LLC, Burr Ridge, IL, USA.

KW - biofilm

KW - c-di-GMP

KW - dispersal

KW - dust analysis

KW - flow chemistry

KW - large-scale synthesis

KW - preclinical

KW - Pseudomonas aeruginosa

KW - pyrazole

KW - safety

U2 - 10.3390/ijms25126737

DO - 10.3390/ijms25126737

M3 - Journal article

C2 - 38928443

AN - SCOPUS:85197119622

VL - 25

JO - International Journal of Molecular Sciences (Online)

JF - International Journal of Molecular Sciences (Online)

SN - 1661-6596

IS - 12

M1 - 6737

ER -