A5017766903- Computational Drug Discovery Methods
- Innovative Microfluidic and Catalytic Techniques Innovation
- Analytical Chemistry and Chromatography
- Synthesis and Biological Evaluation
- Bioactive Compounds and Antitumor Agents
- Chemical Synthesis and Analysis
- Microbial Natural Products and Biosynthesis
- Carcinogens and Genotoxicity Assessment
- Optimal Experimental Design Methods
- Synthetic Organic Chemistry Methods
- Service-Oriented Architecture and Web Services
- Biochemical and Molecular Research
- Genetically Modified Organisms Research
- HIV/AIDS drug development and treatment
- Drug Transport and Resistance Mechanisms
- Business Process Modeling and Analysis
- Asthma and respiratory diseases
- Chemical Synthesis and Reactions
- Fault Detection and Control Systems
- Renal Transplantation Outcomes and Treatments
- Chemical Reactions and Isotopes
- Chemistry and Chemical Engineering
- Nanomaterials for catalytic reactions
- Asymmetric Hydrogenation and Catalysis
- Analytical Methods in Pharmaceuticals
Vertex Pharmaceuticals (United States)
2006-2019
Sterling Research Group
2001
Yale University
2000-2001
The ICH M7 guidance provides a series of flexible control options for the (potentially) mutagenic impurities (PMIs) that fully align with key risk-based principles. This includes option 4, which leverages existing process knowledge and/or data to justify PMIs without need routine analytical release testing during manufacturing. One such technique highlighted uses systematic, semiquantitative calculations define degree "purge" within synthetic route an active pharmaceutical ingredient (API)...
A strategy for the risk assessment of potentially genotoxic impurities is described that utilizes Quality by Design in an effort to furnish greater process and analytical understanding, ultimately leading a determination impurity criticality. By identifying risks parameters most influence those risks, enhancement both product control attained mitigates potential impact these impurities. This approach calls use toxicological testing where necessary, chemical fate arguments when possible,...
A process for the manufacture of merimepodib (VX-497), an inosine monophosphate dehydrogenase (IMPDH) inhibitor, has been developed and efficiently scaled to produce clinical supply. The comprises five steps, incorporating simple robust chemistry that ultimately yielded 96.5 kg with a purity 100% (by HPLC analysis) 99.7% w/w assay. Highlights are effective use production-scale phosgene, manipulation Schotten−Baumann reaction conditions give low pH procedure avoids critical impurity, online...
The scale-up of a prototype HCV protease inhibitor (1) from gram scale in the laboratory to kilogram pilot plant is described. Key features optimization included synthesis bulk quantities exomethylene proline intermediate 6, separation diastereomers spirocycle 2 without chromatography, isolation precursor 1 purge byproducts that might raise genotoxic structural alerts, and purification an amorphous drug substance via crystalline acetic acid solvate.
This paper describes using real-time mid-IR, heat flow, and gas uptake data to optimize the hydrogenation of a nitroaromatic an aniline that had been difficult control during previous campaign in pilot plant. A bimetallic Pt/V catalyst was identified eliminated buildup reaction intermediates consequently resulted inherently more controllable process. The analytics were then used rapidly conditions develop strategies for controlling rate plant should unexpected deviation occur.
Lead time and cost are important factors for any pharmaceutical API. However, these issues become even more when the drug substance contains an isotope such as deuterium, which has a natural abundance of only ∼0.016% all hydrogen. Fewer suppliers logistical barriers both play role in driving up cost. These can challenge supply route used to manufacture d9-ivacaftor (17), requiring investigation into alternative routes. By adapting work from Pettus et al., synthetic approach utilizing...
ADVERTISEMENT RETURN TO ISSUEPREVLetterNEXTFormation of 9,10-Unsaturation in the Mitomycins: Facile Fragmentation β-Alkyl-β-aryl-α-oxo-γ-butyrolactonesFrederick E. Ziegler, Michael Y. Berlin, Kyungae Lee, and Adam R. LookerView Author Information Sterling Chemistry Laboratory, Yale University, New Haven, Connecticut 06511-8118 Cite this: Org. Lett. 2000, 2, 23, 3619–3621Publication Date (Web):October 25, 2000Publication History Received25 August 2000Published online25 October inissue 1...
ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to "Development of Manufacturing Process for an HCV Protease Inhibitor Candidate Molecule"Benjamin J. Littler*, Michael Aizenberg, Narendra B. Ambhaikar, Todd A. Blythe, Timothy T. Curran, Vadims Dvornikovs, Young C. Jung, Valdas Jurkauskas, Elaine Lee, Adam R. Looker, Hoa Luong, Theodore Martinot, David Miller, Bobbianna Neubert-Langille, Pieter Otten, Peter Rose, and Piero L....
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