A5065679786- Synthesis and Biological Evaluation
- Trace Elements in Health
- Plant Micronutrient Interactions and Effects
- Catalytic C–H Functionalization Methods
- Cytokine Signaling Pathways and Interactions
- Molecular spectroscopy and chirality
- Biochemical and Molecular Research
- Chronic Lymphocytic Leukemia Research
- Adenosine and Purinergic Signaling
- Molecular Spectroscopy and Structure
- Melanoma and MAPK Pathways
- Cyclopropane Reaction Mechanisms
- Animal Nutrition and Physiology
- Synthesis and Reactions of Organic Compounds
- Advanced Chemical Physics Studies
- Systemic Lupus Erythematosus Research
- Quinazolinone synthesis and applications
- Bat Biology and Ecology Studies
- ATP Synthase and ATPases Research
- Nonlinear Optical Materials Research
- Blood Pressure and Hypertension Studies
- Bioactive Compounds and Antitumor Agents
- Genetic and rare skin diseases.
- Synthesis of β-Lactam Compounds
- Selenium in Biological Systems
University of Auckland
2022
Bristol-Myers Squibb (United States)
2002-2021
Bristol-Myers Squibb (Germany)
2002-2010
DuPont (United States)
1997-1998
Texas A&M University – Kingsville
1997
Wilmington University
1997
University of Virginia
1974-1991
St. Vincent's Birmingham
1981
Saint Vincent's Catholic Medical Center
1981
University of Georgia
1964-1967
Small molecule JAK inhibitors have emerged as a major therapeutic advancement in treating autoimmune diseases. The discovery of isoform selective that traditionally target the catalytically active site this kinase family has been formidable challenge. Our strategy to achieve high selectivity for TYK2 relies on targeting pseudokinase (JH2) domain. Herein we report late stage optimization efforts including structure-guided design and water displacement led BMS-986165 (11) affinity JH2 ligand...
Summary and conclusionsLarge areas around surgically imposed wounds developed parakeratosis in zinc-deficient calves. The regions involved normally do not develop parakeratosis. Thus secondary factors such as mild trauma appear to determine the location of This also indicates that basic condition skin a zinc deficiency is same throughout body. Reducing total amount feed consumed, either by or limited feeding, substantially retarded rate generation new following surgical removal skin. effects...
Necroptosis has been implicated in a variety of disease states, and RIPK3 is one the kinases identified to play critical role this signaling pathway. In an effort identify kinase inhibitors with novel profile, mechanistic studies were incorporated at hit triage stage. Utilization these assays enabled identification Type II DFG-out inhibitor for RIPK3, which was confirmed by protein crystallography. Structure-based drug design on targeting previously unreported conformation enhancement...
Sodium is considered the mineral most limiting to growth and reproduction of mammalian herbivores worldwide. Notwithstanding large database on physiological adaptations low sodium intake, information maintenance requirements dynamics mammals depauperate. We measured intake output in adult, nonreproductive white-tailed deer (n = 15) over four seasons estimate daily for a seasonal an annual basis. Dietary content was based best available predictions requirements. With regression techniques, we...
The four members of the Janus family nonreceptor tyrosine kinases play a significant role in immune function. JAK kinase inhibitor, tofacitinib 1, has been approved United States for use rheumatoid arthritis (RA) patients. A number inhibitors with variety selectivity profiles are currently clinical trials. Our goal was to identify that were functionally selective JAK1 and JAK3. Compound 22 prepared desired functional profile, but it suffered from poor absorption related physical properties....
IRAK4 is an attractive therapeutic target for the treatment of inflammatory conditions. Structure guided optimization a nicotinamide series inhibitors has been expanded to explore front pocket. This resulted in identification compounds such as 12 with improved potency and selectivity. Additionally demonstrated activity pharmacokinetics/pharmacodynamics (PK/PD) model. Further efforts led highly kinome selective 21, which robust PD effect efficacy TLR7 driven model murine psoriasis.
Abstract The chiroptical properties of L ‐3‐methyl‐2,5‐diketopiperazine ( ‐alanylglycyl anhydride) are examined on a theoretical model in which the electronic wave functions obtained from semi‐empirical all‐valence‐shell molecular orbital calculations. INDO is used to perform SCF‐MO calculations ground states six conformation isomers and two chiral conformational unsubstituted 2,5‐diketopiperazine. Excited‐state constructed virtual orbital‐configuration interaction approximation. rotatory...
The chiroptical properties associated with the n→π* transition of dissymmetric saturated γ- and δ-lactones are calculated relationships between observables stereochemical electronic structural features these systems examined. calculations based on INDOMO model for structure molecular excited states constructed in virtual orbital-configuration interaction approximation. highest second occupied orbitals each 17 structures studied are, respectively, in-plane n out-of-plane π* nonbonding...
Abstract For see ChemInform in Full Text.
On their way to IkB kinase β inhibitors, BMS scientists developed a convenient route azaindoles as reported herein. The first approach involving Sonogashira coupling and subsequent annulation required isolation of intermediates. In this with no C2-substitution complex mixtures were obtained; furthermore, trying follow direct C2-arylation was unsuccessful. Additionally, the palladium-catalyzed enamine Heck only successful ethyl pyruvate, tandem gem-dichloroolefins substrates having few or...
Aim Obesity as a major risk factor for childhood hypertension necessitates careful blood pressure (BP) monitoring of those affected. This study aimed to compare BP classification in cohort children affected by obesity using tables versus digital calculations two sets guidelines. Methods was secondary analysis data collected from randomised clinical trial multidisciplinary life‐style assessment and intervention program. Baseline 237 with body mass index >99th percentile or >91st...
Abstract For see ChemInform in Full Text.