A5081270560- Synthetic Organic Chemistry Methods
- Cancer Treatment and Pharmacology
- Respiratory viral infections research
- Asymmetric Synthesis and Catalysis
- Oxidative Organic Chemistry Reactions
- Plant Virus Research Studies
- Organic Chemistry Cycloaddition Reactions
- Virus-based gene therapy research
- Tuberculosis Research and Epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Bioactive Compounds and Antitumor Agents
- Virology and Viral Diseases
- Viral Infectious Diseases and Gene Expression in Insects
- Advanced Synthetic Organic Chemistry
- Influenza Virus Research Studies
- Synthesis and Biological Activity
- Mycobacterium research and diagnosis
- Synthesis of Organic Compounds
- Synthesis and Biological Evaluation
- Pneumocystis jirovecii pneumonia detection and treatment
- Traditional and Medicinal Uses of Annonaceae
- RNA and protein synthesis mechanisms
- Antimicrobial Resistance in Staphylococcus
- Click Chemistry and Applications
- Phytochemical compounds biological activities
Blinn College
2020-2022
Texas A&M International University
2018-2022
Bristol-Myers Squibb (United States)
1995-2014
Novartis (United States)
2013-2014
Alcon (United States)
2013-2014
Novartis (Switzerland)
2014
Bristol-Myers Squibb (Germany)
2000-2007
The Ohio State University
1991-2000
University of Kansas
1989-1995
ABSTRACT BMS-433771 was found to be a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. It exhibited excellent potency against multiple laboratory and clinical isolates both group A B viruses, with an average 50% effective concentration 20 nM. Mechanism-of-action studies demonstrated that inhibits the fusion lipid membranes during early entry stage late-stage syncytium formation. After isolation resistant resistance mapped series single amino acid mutations F1...
The discovery of BMS-605339 (35), a tripeptidic inhibitor the NS3/4A enzyme, is described. This compound incorporates cyclopropylacylsulfonamide moiety that was designed to improve potency carboxylic acid prototypes through introduction favorable nonbonding interactions within S1′ site protease. identification 35 enabled optimization and balance critical properties including pharmacokinetics (PK). achieved modulation P2* subsite which identified isoquinoline ring system as key template for...
BMS-433771 is a potent inhibitor of respiratory syncytial virus (RSV) replication in vitro. Mechanism action studies have demonstrated that halts entry through inhibition F protein-mediated membrane fusion. also exhibited vivo efficacy following oral administration mouse model RSV infection (C. Cianci, K. Y. Yu, Combrink, N. Sin, B. Pearce, A. Wang, R. Civiello, S. Voss, G. Luo, Kadow, E. Genovesi, Venables, H. Gulgeze, Trehan, J. James, L. Lamb, I. Medina, Roach, Z. Yang, Zadjura, Colonno,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFormal 2 + and 3 cycloaddition reactions of 2H-chromenes with 2-alkoxy-1,4-benzoquinones: regioselective synthesis substituted pterocarpansThomas A. Engler, Jayachandra P. Reddy, Keith D. Combrink, David Vander VeldeCite this: J. Org. Chem. 1990, 55, 4, 1248–1254Publication Date (Print):February 1, 1990Publication History Published online1 May 2002Published inissue 1 February...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereoselective 3 + 2 and stereospecific cycloaddition reactions of alkenes quinonesThomas A. Engler, Keith D. Combrink, James E. RayCite this: J. Am. Chem. Soc. 1988, 110, 23, 7931–7933Publication Date (Print):November 1, 1988Publication History Published online1 May 2002Published inissue 1 November 1988https://doi.org/10.1021/ja00231a084RIGHTS & PERMISSIONSArticle Views510Altmetric-Citations41LEARN ABOUT THESE METRICSArticle Views are the...
A library of compounds were prepared by reacting 2-(bromomethyl)-1, 2-benzisothiazol-3(2H)-one 1,1-dioxide (5) with commercially available carboxylic acids in the presence potassium carbonate or a tertiary amine base. From this library, (1,1-dioxido-3-oxo-1, 2-benzisothiazol-2(3H)-yl)methyl N-[(phenylmethoxy)carbonyl]-beta-alanate (7b) emerged as potent inhibitor human mast cell tryptase (IC50 = 0.85 microM). Extension side chain 7b two carbons gave (1,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStereospecific Lewis Acid-Promoted Reactions of Styrenyl Systems with 2-Alkoxy-(6-Alkyl)-1,4-Benzoquinones: Scope, Limitations, and Synthetic ApplicationsThomas A. Engler, Keith D. Combrink, Michael Letavic, Kenneth O. Lynch Jr., James E. RayCite this: J. Org. Chem. 1994, 59, 22, 6567–6587Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November...
The cysteine protease adenain is the essential of adenovirus and, as such, represents a promising target for treatment ocular and other adenoviral infections. Through concise two-pronged hit discovery approach we identified tetrapeptide nitrile 1 pyrimidine 2 complementary starting points inhibition. These hits enabled first high-resolution X-ray cocrystal structures with inhibitors bound revealed binding mode 2. screening were optimized by structure-guided medicinal chemistry strategy into...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImpact of substituent modifications on the atropselectivity characteristics an anionic oxy-Cope ring expansionLeo A. Paquette, Keith D. Combrink, Steven W. Elmore, and Robin RogersCite this: J. Am. Chem. Soc. 1991, 113, 4, 1335–1344Publication Date (Print):February 1, 1991Publication History Published online1 May 2002Published inissue 1 February 1991https://pubs.acs.org/doi/10.1021/ja00004a040https://doi.org/10.1021/ja00004a040research-articleACS...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRegioselective Lewis Acid-Directed Reactions of 2-Alkoxy-5-alkyl-1,4-benzoquinones with Styrenes: Synthesis Burchellin and Guianin NeolignansThomas A. Engler, Dong Donna Wei, Michael Letavic, Keith D. Combrink, Jayachandra P. ReddyCite this: J. Org. Chem. 1994, 59, 22, 6588–6599Publication Date (Print):November 1, 1994Publication History Published online1 May 2002Published inissue 1 November...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSelective control of the various cycloaddition products from reactions styrenes and 1,4-benzoquinones: optimization formal 5 + 2 cycloadductsThomas A. Engler, Michael Letavic, Keith D. Combrink, Fusao TakusagawaCite this: J. Org. Chem. 1990, 55, 23, 5810–5812Publication Date (Print):November 1, 1990Publication History Published online1 May 2002Published inissue 1 November...
Infections caused by Mycobacterium abscessus are difficult to treat due its intrinsic resistance most antibiotics. Formation of biofilms and the capacity M. survive inside host phagocytes further complicate eradication. Herein, we explored whether addition a carbamate-linked group at C25 position rifamycin SV blocks enzymatic inactivation ArrMab, an ADP-ribosyltransferase conferring rifampicin (RMP). Unlike RMP, 5j, benzyl piperidine derivative with morpholino substituted C3 naphthoquinone...
Abstract The feasibility of the titled reactions for rapid, enantioselective synthesis cis ‐tricyclo[9.3.1.0 3,8 ]pentadecane precursors to taxusin and taxol has been examined. catalysts most well suited inducing appropriate 1,2‐shifts have identified. To a great extent, rearrangement products are formed as direct consequence structural features (kinetic phenomenon) strain minimization (thermodynamic driving force). Complementary MM2 calculations global minimum in each series provided...
Abstract The key elements associated with the synthetic elaboration of functionalized trans ‐tricyclo‐[9.3.1.0 3,8 ]pentadecanes carrying either a bridgehead H or OH substituent are detailed. Starting 12 , ketone available in two steps from ( R )‐2‐oxo‐7,7‐dimethyl‐l‐vinylbicyclo[2.2.1]heptane, it proved possible to introduce ‐B/C ring juncture configuration as 16 five steps. This advanced intermediate constitutes point bifurcation. pathway taxusin precursor 23 was attained by stereospecific...