A5071656156- Computational Drug Discovery Methods
- Cancer Genomics and Diagnostics
- Hepatitis C virus research
- Lung Cancer Treatments and Mutations
- HIV/AIDS drug development and treatment
- Molecular Biology Techniques and Applications
- HER2/EGFR in Cancer Research
- Asymmetric Synthesis and Catalysis
- Cancer-related molecular mechanisms research
- Carbohydrate Chemistry and Synthesis
- Synthetic Organic Chemistry Methods
- Oxidative Organic Chemistry Reactions
- Click Chemistry and Applications
- Biochemical and Molecular Research
- Sarcoma Diagnosis and Treatment
- Biosimilars and Bioanalytical Methods
- Synthesis of Organic Compounds
- RNA modifications and cancer
- Hepatitis B Virus Studies
- Synthesis of β-Lactam Compounds
- Crystallization and Solubility Studies
- Cancer therapeutics and mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
National Cancer Institute
2020-2023
Center for Cancer Research
2023
Secretaría Nacional de Ciencia, Tecnología e Innovación
2022
Frederick National Laboratory for Cancer Research
2020
Bristol-Myers Squibb (United States)
2007-2017
Instituto de Investigación Biomédica de Málaga
2017
Texas Christian University
2014
Mexican Social Security Institute
2003
Hospital General De Zona
2003
The University of Texas at Austin
1999-2003
The biphenyl derivatives 2 and 3 are prototypes of a novel class NS5A replication complex inhibitors that demonstrate high inhibitory potency toward panel clinically relevant HCV strains encompassing genotypes 1–6. However, these compounds exhibit poor systemic exposure in rat pharmacokinetic studies after oral dosing. structure–activity relationship investigations improved the properties parent bis-phenylimidazole chemotype, culminating identification highly potent inhibitor daclatasvir...
Lead inhibitors that target the function of hepatitis C virus (HCV) nonstructural 5A (NS5A) protein have been identified by phenotypic screening campaigns using HCV subgenomic replicons. The demonstration antiviral activity in HCV-infected subjects NS5A replication complex inhibitor (RCI) daclatasvir (1) spawned considerable interest this mechanistic approach. In Perspective, we summarize medicinal chemistry studies led to discovery 1 and other chemotypes for which resistance maps provide...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTGeneral Strategies for the Synthesis of Major Classes C-Aryl GlycosidesDavid E. Kaelin, Omar D. Lopez, and Stephen F. MartinView Author Information Department Chemistry Biochemistry The University Texas, Austin, Texas 78712 Cite this: J. Am. Chem. Soc. 2001, 123, 28, 6937–6938Publication Date (Web):June 22, 2001Publication History Received3 April 2001Published online22 June inissue 1 July...
Abstract The NCI-60 human tumor cell line panel has proved to be a useful tool for the global cancer research community in search novel chemotherapeutics. publicly available characterization and compound screening data from assay have significantly contributed understanding of cellular mechanisms targeted by new oncology agents. Signature sensitivity/resistance patterns generated given chemotherapeutic agent against long served as fingerprint presentations that encompass target information...
A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and 1b (G-1b) replicon inhibition selectivity against BVDV cytotoxicity. SAR emerging an examination prolinamide cap region revealed 11 be a selective NS5A inhibitor exhibiting submicromolar potency both G-1a G-1b replicons. Additional structural refinements resulted in identification 30 as potent, dual G-1a/1b inhibitor.
A medicinal chemistry campaign that was conducted to address a potential genotoxic liability associated with an aniline-derived scaffold in series of HCV NS5A inhibitors dual GT-1a/-1b inhibitory activity is described. Anilides 3b and 3c were used as vehicles explore structural modifications retained antiviral potency while removing the for metabolism-based unmasking embedded aniline. This effort resulted discovery highly potent biarylimidazole chemotype established benchmark replicon...
Abstract Microsporidia comprises a diverse group of obligate, intracellular, and spore-forming parasites that infect wide range animals. Among them, Enterocytozoon bieneusi is the most frequently reported species in humans other mammals birds. Data on epidemiology E. wildlife are limited. Hence, was investigated eight wild ungulate present Spain (genera Ammotragus, Capra, Capreolus, Cervus, Dama, Ovis, Rupicapra, Sus) by molecular methods. Faecal samples were collected from free-ranging (n =...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTEndo-Selective Reactions of .alpha.,.beta.-Unsaturated Hexacarbonyldiiron Bridging Acyl Complexes with NitronesScott R. Gilbertson, David P. Dawson, Omar D. Lopez, and Kenneth Lee MarshallCite this: J. Am. Chem. Soc. 1995, 117, 15, 4431–4432Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April...
Daclatasvir is a first-in-class, potent, and selective inhibitor of the hepatitis C virus nonstructural protein 5A replication complex. In support nonclinical studies during discovery exploratory development, liquid chromatography–tandem mass spectrometry nuclear magnetic resonance were used in connection with synthetic radiosynthetic approaches to investigate biotransformation daclatasvir vitro cynomolgus monkeys, dogs, mice, rats. The results these indicated that disposition was...
<p>Analytical Data</p>
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSynthesis of and Asymmetric Cycloaddition with Chiral Diiron Acyl ComplexesScott R. Gilbertson Omar D. LopezView Author Information Department Chemistry Washington University St. Louis, Missouri 63130 Cite this: J. Am. Chem. Soc. 1997, 119, 14, 3399–3400Publication Date (Web):April 9, 1997Publication History Received5 December 1996Published online9 April 1997Published inissue 1...
Kinetic resolution is achieved in the reaction of racemic diiron complexes like 1 with chiral nitrone (−)-2. Oxidative removal metal and reductive cleavage N−O bond provides β-amino acids. This sequence was used synthesis acids as well corresponding β-lactams 4 (via 3).
Abstract In this article, 5-aza-4′-thio-2′-β-fluoro-2′-deoxycytidine (F-aza-T-dCyd, NSC801845), a novel cytidine analog, is first disclosed and compared with T-dCyd, F-T-dCyd, aza-T-dCyd in cell culture mouse xenograft studies HCT-116 human colon carcinoma, OVCAR3 ovarian NCI-H23 NSCLC HL-60 leukemia, the PDX BL0382 bladder carcinoma. three of five lines (HCT-116, HL-60, BL-0382), F-aza-T-dCyd was more efficacious than aza-T-dCyd. Comparable activity observed for these two agents against...
ABSTRACT Daclatasvir (DCV) is a first-in-class hepatitis C virus (HCV) nonstructural 5A replication complex inhibitor (NS5A RCI) that clinically effective in interferon-free combinations with direct-acting antivirals (DAAs) targeting alternate HCV proteins. Recently, we reported NS5A RCI enhance inhibitory potential vitro , defining new class of inhibitors termed synergists (J. Sun, D. R. O’Boyle II, A. Fridell, Langley, C. Wang, S. Roberts, P. Nower, B. M. Johnson F. Moulin, J. Nophsker, Y....
An efficient large-scale synthesis of acid 1, a penultimate precursor to the HCV NS5A inhibitor BMS-986097, along with final API step are described. Three routes were devised for 1 at various stages program. The third generation route, one that proved scalable and is main subject this paper, features one-step Michael addition t-butyl 2-((diphenylmethylene)amino)acetate (24) (E)-benzyl 4-(1-hydroxycyclopropyl)but-2-enoate (28) followed by cyclization chiral separation form 27c, core skeleton...
The lack of effective methods to perform direct β-selective glycosylation reactions with 2-deoxy-1,4-dithio-D-erythro-pentofuranosides has long been a significant stumbling block for the multi-gram synthesis 4'-thio-2'-deoxy nucleosides. In addition, previously reported preparation appropriately substituted have proven problematic large scale synthesis. To address these issues, herein we describe modification and optimization allow convenient benzyl...
<p>Analytical Data</p>