A5051036224- Hepatitis C virus research
- HIV/AIDS drug development and treatment
- Asymmetric Synthesis and Catalysis
- Quinazolinone synthesis and applications
- Catalytic Alkyne Reactions
- Catalytic C–H Functionalization Methods
- Cyclopropane Reaction Mechanisms
- Organic Chemistry Cycloaddition Reactions
- Catalytic Cross-Coupling Reactions
- Chemical Synthesis and Analysis
- Asymmetric Hydrogenation and Catalysis
- Hepatitis B Virus Studies
- Coordination Chemistry and Organometallics
- Biochemical and Molecular Research
- Synthesis and Catalytic Reactions
- Crystallization and Solubility Studies
- Inorganic and Organometallic Chemistry
- X-ray Diffraction in Crystallography
- Synthetic Organic Chemistry Methods
- Organometallic Compounds Synthesis and Characterization
- Toxin Mechanisms and Immunotoxins
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Click Chemistry and Applications
- Immune Response and Inflammation
- Phosphorus compounds and reactions
AbbVie (United States)
2013-2020
Abbott Fund
2002-2012
Kiel University
2010
Wayne State University
1992-2008
Stanford University
1996
Universität Hamburg
1989
We describe here N-phenylpyrrolidine-based inhibitors of HCV NS5A with excellent potency, metabolic stability, and pharmacokinetics. Compounds 2S,5S stereochemistry at the pyrrolidine ring provided improved genotype 1 (GT1) potency compared to 2R,5R analogues. Furthermore, attachment substituents 4-position central N-phenyl group resulted in compounds potency. Substitution tert-butyl, as compound 38 (ABT-267), low-picomolar EC50 values superior It was discovered that a pan-genotypic...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTOn the Question of Asymmetric Induction with Acyclic Allylic Substrates. An Synthesis (+)-Polyoxamic AcidBarry M. Trost, A. Chris Krueger, Richard C. Bunt, and Jorge ZambranoView Author Information Department Chemistry, Stanford University Stanford, California 94305 Cite this: J. Am. Chem. Soc. 1996, 118, 27, 6520–6521Publication Date (Web):July 10, 1996Publication History Received1 April 1996Published online10 July inissue 1 January...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal-promoted higher-order cycloaddition reactions. Stereochemical, regiochemical, and mechanistic aspects of the [6.pi. + 4.pi.] reactionJames H. Rigby, Humy S. Ateeq, Nelly R. Charles, Stephane V. Cuisiat, Mark D. Ferguson, James A. Henshilwood, Chris Krueger, Cyprian O. Ogbu, Kevin M. Short, J. HeegCite this: Am. Chem. Soc. 1993, 115, 4, 1382–1396Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published...
Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component these is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the inhibitors, do not exhibit equivalent efficacy against genotypes 1–6. In particular, first inhibitors tend to select viral drug resistance. Ombitasvir inhibitor included as key Viekira Pak treatment with...
7 resin acids, 3 symbolically prepared derivatives and the neutral fraction of Chinese colophony were studied by experimental sensitization using a modified FCA method. 4 laevopimaric. abietic. podocarpic tetrahydroabietic. proved to be weak sensitizers Neoabietic, dehydroabietic, isopimarie acid larixol remained negative. However, derivative, methyl abietate calcium abietate. shown moderate sensitizers. maleic‐modified adduct strong sensitizer. As laevopimaric plays only minor rote in...
Tumor necrosis factor α (TNFα) is a soluble cytokine that directly involved in systemic inflammation through the regulation of intracellular NF-κB and MAPK signaling pathways. The development biologic drugs inhibit TNFα has led to improved clinical outcomes for patients with rheumatoid arthritis other chronic autoimmune diseases; however, proven be difficult drug small molecules. Herein, we present two-phase, fragment-based discovery (FBDD) effort which first identified isoquinoline...
ABT-072 is a non-nucleoside HCV NS5B polymerase inhibitor that was discovered as part of program to identify new direct-acting antivirals (DAAs) for the treatment infection. This compound identified during medicinal chemistry effort improve on an original lead, 1, which we described in previous publication. Replacement amide linkage 1 with trans-olefin resulted improved permeability and solubility provided much better pharmacokinetic properties preclinical species. dihydrouracil N-linked...
The hepatitis C virus (HCV) NS5B polymerase is essential for viral replication and has been a prime target drug discovery research. Our efforts directed toward the of HCV inhibitors resulted in identification unsymmetrical dialkyl-hydroxynaphthalenoyl-benzothiadiazines 2 3. most active compound displayed activity genotypes 1a 1b replicon cell culture inhibition assays at subnanomolar low nanomolar concentrations, respectively. It also an excellent pharmacokinetic profile rats, with plasma...
α-Lithiodihydrothiepin-1,1-dioxide is prepared by treatment of the parent heterocycle with n-BuLi. Alkylation this species a wide range electrophiles has been achieved. Subsequent thermal extrusion sulfur dioxide affords corresponding terminally alkylated hexatrienes.
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Abstract The synthesis of various pyridopyrimidine derivatives (X) is described.