A5001004870- Innovative Microfluidic and Catalytic Techniques Innovation
- Crystallization and Solubility Studies
- Cyclopropane Reaction Mechanisms
- Drug Transport and Resistance Mechanisms
- X-ray Diffraction in Crystallography
- Synthesis and Catalytic Reactions
- Asymmetric Synthesis and Catalysis
- Nanomaterials for catalytic reactions
- Asymmetric Hydrogenation and Catalysis
- Adenosine and Purinergic Signaling
- Microfluidic and Capillary Electrophoresis Applications
- Liver Disease Diagnosis and Treatment
- Systemic Lupus Erythematosus Research
- Hepatitis C virus research
- PARP inhibition in cancer therapy
- Integrated Circuits and Semiconductor Failure Analysis
- Analytical Chemistry and Chromatography
- Toxin Mechanisms and Immunotoxins
- Synthesis and Biological Evaluation
- HIV/AIDS drug development and treatment
- Enzyme Catalysis and Immobilization
- Complement system in diseases
- Glycogen Storage Diseases and Myoclonus
- Steroid Chemistry and Biochemistry
- Process Optimization and Integration
Novartis (Switzerland)
2013-2024
University of Perugia
2008-2022
Universidad de Montevideo
2022
Clínica Santa María
2022
EsSALUD
2022
Total (France)
2022
Nini Hospital
2022
Nema Research (United States)
2022
Basildon Hospital
2022
Fondazione Roma
2022
In this article we demonstrate how a combination of enabling technologies such as flow synthesis, solid-supported reagents and scavenging resins utilised under fully automated software control can assist in typical medicinal chemistry programmes. particular continuous methods have greatly assisted the optimisation reaction conditions facilitated scale up operations involving hazardous chemical materials. Overall collection twenty diverse analogues casein kinase I inhibitor has been...
A platform for conducting organolithium chemistry in continuous flow mode, covering the scales from medicinal to later phase process development, is described. The use of this setup, which mimics concept flash on scale, has been demonstrated by exemplary, large-scale preparation (4-fluoro-2-(trifluoromethyl)phenyl)boronic acid following a reaction sequence halogen/lithium exchange, borylation, and semibatch workup. Furthermore, key factors corresponding practical assessments required...
Hydrogen peroxide is showcased in a range of oxidations, operating continuous-flow equipment to deliver practical and risk-minimized procedures.
Abstract PARP‐1 and PARP‐2 are members of the family poly(ADP‐ribose)polymerases, which involved in maintenance genomic integrity under conditions genotoxic stimuli. The different roles two isoforms pathophysiological have not yet been fully clarified, this is partially due to lack selective inhibitors. We report herein synthesis preliminary pharmacological evaluation a large series isoquinolinone derivatives as PARP‐1/PARP‐2 Among them, we identified 5‐benzoyloxyisoquinolin‐1(2 H )‐one...
LCZ696 is a novel treatment for patients suffering from heart failure that combines the two active pharmaceutical ingredients sacubitril and valsartan in single chemical compound. While an established drug substance, new manufacturing process suitable large-scale commercial production had to be developed sacubitril. The use of chemocatalysis, biocatalysis, flow chemistry as state-of-the-art technologies allowed efficiently build up structure achieve defined performance targets.
Grounding on our former 3D QSAR studies, a knowledge-based screen of natural bile acids from diverse animal species has led to the identification avicholic acid as selective but weak TGR5 agonist. Chemical modifications this compound resulted in disclosure 6α-ethyl-16-epi-avicholic that shows enhanced potency at and FXR receptors. The synthesis, biological appraisals, structure-activity relationships series compounds are herein described. Moreover, thorough physicochemical characterization...
Ethyl diazo(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)acetate was prepared by aldol-type condensation of ethyl diazoacetate with isatin. A systematic and mechanistic study on the Lewis acid induced decomposition reaction this valuable diazo precursor carried out aim to gain new insights into aspects as well further understand factors experimental conditions which affect relative product distribution. The reaction, may proceed via cationic noncationic mechanisms, found be significantly...
An efficient and scalable transformation of 3-halo-N-acyl anilines to the corresponding benzoxazoles within a continuous flow reactor is reported. This proceeds via base-mediated deprotonation, ortho-lithiation, intramolecular cyclization provide unstable lithiated benzoxazole moieties. The subsequent in-line electrophilic quench results in formation substituted high yield quality. Continuous technology allowed for accurate temperature control immediate while minimizing hold-up time...
The focus of this study was to develop a chemical reaction sequence toward key benzoxazole building block, required for clinical manufacturing lead candidate in the respiratory disease area. chemistry consisted initial low-temperature reactions with an organometallic reagent generate core, and followed by noncryogenic transformations sulfonamide substituent. With particular interest continuous-flow we attempted integrate entire on lab scale. Subsequent in-depth process research, supported...
A new method for the calorimetric characterization of high-energetic, fast reactions in flow mode was developed. The use an engineered reactor combination with a process modeling software allowed deconvolution reaction enthalpy from space-resolved temperature profiles. procedure verified comparison conventional batch calorimeter and subsequently implemented thermal organolithium process. information collected this successfully supported scale-up to pilot plant. Overall, approach resulted...
We report a novel and more efficient synthesis of S-ESBA an analysis it inhibitory activity toward recombinant human KAT II. The data are discussed in light the crystal structure II on basis conserved nonconserved residues species-specific orthologs (human, rat, mouse).
A multi-gram scale protocol for the N-acyl amidation of bile acids with glycine and taurine has been successfully developed under continuous flow processing conditions. Selecting ursodeoxycholic acid (UDCA) as model compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) condensing agent, a modular mesoreactor assisted set-up was employed to significantly speed up optimization reaction conditions scale-up synthesis. The results in terms yield, line purification, analysis, implemented...
An efficient method for the C3-glucuronidation of bile acids is developed under flow conditions. A modular mesoreactor assisted set-up was combined with statistical design experiments to speed up optimization Koenigs–Knorr reaction in terms yield, regioselectivity, costs, as well technical and practical standpoints. Using optimal conditions, selective glucuronidation naturally occurring successfully achieved offering a new, valuable route C3-glucuronidated useful biological, diagnostic...
Activation of poly(ADP-ribose) polymerase (PARP) is an important factor in controlling cell survival or death. As a consequence, therapeutic interventions with PARP-1 inhibitors are sought different pathological conditions such as cancer, cardiovascular and inflammatory diseases, well brain ischemia. In the first part this work, continuation our efforts field, we report design, synthesis biological appraisal novel potent inhibitors. A crystallization experiment carried out to ascertain mode...
In this paper we explore and propose a methodology for the scale-up of continuous biphasic liquid/liquid reactions under super-heating conditions.
The BF(3).Et(2)O-induced decomposition of ethyl 2-diazo-3-hydroxy-3,3-diarylpropanoates, prepared by the addition a series benzophenones to diazo(lithio)acetate, is reported and studied. By using acetonitrile as solvent, corresponding N-acyl beta-enamino ester derivatives are obtained in good yields with diverse regioselectivity result 1,2-aryl migration vinyl cation intermediates. factors that govern migratory aptitude well mechanistic aspects reaction discussed.
Continuous processing has been demonstrated to be a superior approach when applied fast and energetic chemical transformations. Indeed, whereas classical batch or semi-batch methods require cryogenic conditions slow addition rates of reactive species, flow technologies enable rapid mixing synthetic partners in highly controlled environment. As result, low yielding dangerous processes can performed at scale cost competitive safer continuous manner. Despite the advantages higher quality...
DFT and NMR spectroscopy studies unveil three major minima conformations of cholic acid that may affect its biological properties.
We evaluated the role of low-dose alpha-2b interferon, added to chemotherapy, for advanced colorectal cancer; we randomized patients, either a combination chemotherapy 5-fluorouracil (5-FU) and high-dose folinic acid (HDFA) or same regimen plus interferon. Between January 1990 March 1992, 100 untreated patients (PTS) with cancer, 53 men 47 women, an ECOG performance status (PS) ≤3, were HDFA 200 mg/m2 iv bolus 5FU 370 in 15-min infusion days 1-5 every 4 weeks (arm A), IFN 3 × 106 IU...