Organic Process Research & Development最新文献_第2页

Determining the Influence of Particle Size and Surface Area on the Measured Minimum Ignition Energy of Pharmaceutical Powders 测定粒径和表面积对药粉最小点火能的影响

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-15 DOI: 10.1021/acs.oprd.5c00052

Rafaela Costa Carmona, Rachel Duong, John F. Gamble, Lauren N. Grant, Helen Hughes, Simon Shun Wang Leung, Michael Tobyn, Linda Zheng

{"title":"Determining the Influence of Particle Size and Surface Area on the Measured Minimum Ignition Energy of Pharmaceutical Powders","authors":"Rafaela Costa Carmona, Rachel Duong, John F. Gamble, Lauren N. Grant, Helen Hughes, Simon Shun Wang Leung, Michael Tobyn, Linda Zheng","doi":"10.1021/acs.oprd.5c00052","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00052","url":null,"abstract":"Dust explosions constitute a significant risk in many industries. To identify materials for which mitigation strategies are required, information about the relative risk for each material is required. Such information will include characteristics such as the minimum ignition energy (MIE), but material availability represents a significant challenge for the pharmaceutical industry at early stages of development. These challenges contrast with the relatively high material requirements for risk characterization. To this end, there is significant interest in the application of models to predict MIE. The aims of this study were 2-fold. The first stage was to assess the predictive strength of a published MIE prediction model for a range of pharmaceutical powders. The second stage of the study was to investigate the role of particle size for a series of samples of ‘constant chemistry’ and varying size. The results demonstrate that the model provided ‘safe’ results for half the materials tested while the accuracy of the model was unsatisfactory. The results showed that the risk was often overestimated; thereby, the work required for safety mitigation would not add value to the process, or underestimated, raising the risk of inadequate safety mitigation. When the chemistry of the materials was maintained constant, significant differences in the relationship of particle size and surface area with the measured MIE were demonstrated. Overall, the work suggests that the relative influence of chemistry and particle properties on MIE shows notable differences between materials, thereby affecting the ability of the assessed model to accurately predict MIE.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"53 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Concise Flow Synthesis of the IKZF2 Glue Degrader DKY709 IKZF2型胶水降解剂DKY709的简洁流动合成

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-15 DOI: 10.1021/acs.oprd.4c00476

Xu You, Xu-Lun Huang, Hailong Ren, Chunrui Wu, Dahai Wang

引用次数: 0

Development of a Manufacturing Process for S-892216 Part II: Improvements Toward Commercially Feasible Process S-892216制造工艺的开发，第二部分：对商业可行工艺的改进

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-15 DOI: 10.1021/acs.oprd.5c00072

Thien Phuc Le, Takahiro Kawajiri, Naoto Sahara, Go Kato, Masahiro Hosoya, Tadashi Oohara, Kazushi Agura, Takafumi Ohara, Satoshi Goda

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Cu-Catalyzed Coupling of Aryl Halides Utilizing Ammonia and Hydroxypicolinamide Ligands 利用氨和羟基喹啉酰胺配体铜催化芳基卤化物的偶联

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-15 DOI: 10.1021/acs.oprd.5c00101

David J. Bernhardson, Ian Hotham, Liam S. Sharninghausen, Robert A. Singer, Daniel W. Widlicka

引用次数: 0

Enabling the First Scale-Up of the Selective HER2 Inhibitor BI-4142 选择性HER2抑制剂BI-4142的首次规模化应用

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-14 DOI: 10.1021/acs.oprd.5c00127

Eugene Chong, Ruoshi Li, Weitong Dong, Maxim Chevliakov, Thomas G. Tampone, Yongda Zhang, Bo Qu, Nizar Haddad, Jon C. Lorenz, Max Sarvestani, Thuraya Omar, Huayu Li, Joe J. Gao, Donghong A. Gao, Scott Pennino, Ling Wu, Earl Spinelli, Steven Yao, Heewon Lee, Frederic Buono, Jinhua J. Song, Birgit Wilding

引用次数: 0

Scalable Membrane Enabled One-Pot Liquid-Phase Oligonucleotide Synthesis 可扩展膜支持一锅液相寡核苷酸合成

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-13 DOI: 10.1021/acs.oprd.5c00117

Ronan Kelly, Catalina Parga, Steven Ferguson

{"title":"Scalable Membrane Enabled One-Pot Liquid-Phase Oligonucleotide Synthesis","authors":"Ronan Kelly, Catalina Parga, Steven Ferguson","doi":"10.1021/acs.oprd.5c00117","DOIUrl":"https://doi.org/10.1021/acs.oprd.5c00117","url":null,"abstract":"In this article, a new one-pot liquid-phase oligonucleotide synthesis (OP-LPOS) route enabled by organic solvent resistant (OSR) ceramic membranes is described. This approach was demonstrated through the synthesis of 6mer and 18mer 2’-OMe phosphorothioate oligonucleotides with high stepwise filtration yields (97–100%), and high crude purity (∼72% for 18mer) using just 1.5 equiv of phosphoramidites. Ceramic organic solvent nanofiltration (OSN) and ultrafiltration (OSU) membranes were used to selectively retain the growing oligonucleotide, which is reversibly tethered to a 4-arm branched PEG support, facilitating lower molecular weight reaction byproducts to permeate to waste. This is the first application of ceramic ultrafiltration membranes in such an application, which enables purification of intermediate products in just 5 diavolumes with high permeance (13 Lm–2 h–1 bar–1). We employ a one-pot approach that integrates sequential coupling, sulfurization, and detritylation steps, followed by a single membrane purification step per chain extension cycle. Analysis of the methodology indicates that the homogeneous reactions and separation performance, which use commercially available reagents and highly scalable membrane systems, represent a promising alternative to solid-phase oligonucleotide synthesis (SPOS) for large-scale manufacturing of therapeutic oligonucleotides. Furthermore, the combination of OP-LPOS with membrane separation increases intermediate product purity and yield. It reduces the number of unit operations, cycle times, and process mass intensity (PMI) compared to the previous state-of-the-art membrane-based LPOS.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"115 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Green Chemistry Articles of Interest to the Pharmaceutical Industry 制药工业感兴趣的绿色化学文章

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-10 DOI: 10.1021/acs.oprd.5c00050

Melissa A. Ashley, Miles H. Aukland, Marian C. Bryan, Megan A. Cismesia, Theresa Dutschei, Oliver D. Engl, Pascal S. Engl, Álvaro Enríquez García, Alejandro Gimenez Molina, Vanessa Harawa, George Karageorgis, Shazia Keily, Christopher B. Kelly, Alexandre Leclair, Johnny W. Lee, Wei Li, Matthew Osborne, Jan Pawlas, Paul F. Richardson, Samuel C. Scott, Alan Steven, Balaram S. Takale, Mingshuo Zeng

引用次数: 0

Preparation of Furazan Carboxylates from Enamines by a Nitrosation–Oxidative Cyclization Sequence 胺基亚硝化-氧化环化法制备呋喃唑羧酸酯

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-09 DOI: 10.1021/acs.oprd.5c00119

Connor L. Martin, Matthew E. Martinez

引用次数: 0

Development of a Broadly Applicable Enzymatic Ligation Process for the Production of Single Guide RNAs 一种广泛应用于生产单个引导rna的酶连接工艺的发展

IF 3.4 3区化学

Organic Process Research & Development Pub Date : 2025-05-05 DOI: 10.1021/acs.oprd.4c00502

Martina Bigatti, André Moser, Bas Dierssen, Shtjefen Frrokaj, Elena Covato, Christophe Pfleger, Joerg Lill, Yael Leiser, Joël Zuber, Andreas Staempfli, Filippo Sladojevich, Stefan G. Koenig

{"title":"Development of a Broadly Applicable Enzymatic Ligation Process for the Production of Single Guide RNAs","authors":"Martina Bigatti, André Moser, Bas Dierssen, Shtjefen Frrokaj, Elena Covato, Christophe Pfleger, Joerg Lill, Yael Leiser, Joël Zuber, Andreas Staempfli, Filippo Sladojevich, Stefan G. Koenig","doi":"10.1021/acs.oprd.4c00502","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00502","url":null,"abstract":"In this manuscript, we present a robust chemo-enzymatic approach for the production of single guide RNAs (sgRNAs), essential reagents for CRISPR-Cas9-based cell and gene therapy applications currently under development. Our method leverages ligase-mediated assembly of two RNA fragments, each synthesized using standard solid-phase chemistry. This versatile process has been applied, without modification, to produce a variety of GMP-grade sgRNAs, supporting our clinical ex vivo cell therapy pipeline. We demonstrate that our approach consistently achieves higher purity (10–15% improvement in LC-UV area%) and significantly greater yield (3–4 times higher) compared to traditional linear solid-phase synthesis, which is commonly used for sgRNA production. Importantly, the process utilizes T4 RNA ligase 2, a natural, nonengineered enzyme, which can be easily sourced from several vendors. We believe that openly sharing this method will drive significant progress in the development of cell and gene therapies, enabling the production of higher-quality sgRNAs at lower cost, ultimately improving accessibility and treatment outcomes for patients.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"88 1","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143910237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of a Broadly Applicable Enzymatic Ligation Process for the Production of Single Guide RNAs 一种广泛应用于生产单个引导rna的酶连接工艺的发展

IF 3.1 3区化学

Organic Process Research & Development Pub Date : 2025-05-05 DOI: 10.1021/acs.oprd.4c0050210.1021/acs.oprd.4c00502

Martina Bigatti, André Moser, Bas Dierssen, Shtjefen Frrokaj, Elena Covato, Christophe Pfleger, Joerg Lill, Yael Leiser, Joël Zuber, Andreas Staempfli, Filippo Sladojevich* and Stefan G. Koenig*,

{"title":"Development of a Broadly Applicable Enzymatic Ligation Process for the Production of Single Guide RNAs","authors":"Martina Bigatti, André Moser, Bas Dierssen, Shtjefen Frrokaj, Elena Covato, Christophe Pfleger, Joerg Lill, Yael Leiser, Joël Zuber, Andreas Staempfli, Filippo Sladojevich* and Stefan G. Koenig*, ","doi":"10.1021/acs.oprd.4c0050210.1021/acs.oprd.4c00502","DOIUrl":"https://doi.org/10.1021/acs.oprd.4c00502https://doi.org/10.1021/acs.oprd.4c00502","url":null,"abstract":"In this manuscript, we present a robust chemo-enzymatic approach for the production of single guide RNAs (sgRNAs), essential reagents for CRISPR-Cas9-based cell and gene therapy applications currently under development. Our method leverages ligase-mediated assembly of two RNA fragments, each synthesized using standard solid-phase chemistry. This versatile process has been applied, without modification, to produce a variety of GMP-grade sgRNAs, supporting our clinical ex vivo cell therapy pipeline. We demonstrate that our approach consistently achieves higher purity (10–15% improvement in LC-UV area%) and significantly greater yield (3–4 times higher) compared to traditional linear solid-phase synthesis, which is commonly used for sgRNA production. Importantly, the process utilizes T4 RNA ligase 2, a natural, nonengineered enzyme, which can be easily sourced from several vendors. We believe that openly sharing this method will drive significant progress in the development of cell and gene therapies, enabling the production of higher-quality sgRNAs at lower cost, ultimately improving accessibility and treatment outcomes for patients.","PeriodicalId":55,"journal":{"name":"Organic Process Research & Development","volume":"29 5","pages":"1228–1236 1228–1236"},"PeriodicalIF":3.1,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144067686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0