A5063863508- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Marine Sponges and Natural Products
- Carbohydrate Chemistry and Synthesis
- Chemical synthesis and alkaloids
- Plant biochemistry and biosynthesis
- Catalytic C–H Functionalization Methods
- PARP inhibition in cancer therapy
- Natural product bioactivities and synthesis
- Cancer therapeutics and mechanisms
- DNA Repair Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Pesticide Exposure and Toxicity
- Computational Drug Discovery Methods
- Oxidative Organic Chemistry Reactions
- Radical Photochemical Reactions
- Cyclopropane Reaction Mechanisms
- Metal-Catalyzed Oxygenation Mechanisms
- Pharmacological Effects of Natural Compounds
Freie Universität Berlin
2017-2024
Princeton University
2023
Bayer (Germany)
2020-2021
University of Nebraska Medical Center
1997
The ATR kinase plays a key role in the DNA damage response by activating essential signaling pathways of repair, especially to replication stress. Because and stress are major sources genomic instability, selective inhibition has been recognized as promising new approach cancer therapy. We now report identification preclinical evaluation novel, clinical inhibitor BAY 1895344. Starting from quinoline 2 with weak inhibitory activity, lead optimization efforts focusing on potency, selectivity,...
Organophosphate-inhibited cholinesterases can be reactivated by nucleophilic compounds. Sometimes phosphylated (phosphorylated or phosphonylated) become progressively refractory to reactivation; this result from different reactions. The most frequent process, termed ‘aging’, involves the dealkylation of an alkoxy group on phosphyl moiety through a carbocation mechanism. In attempting determine amino acid residues involved in aging butyrylcholinesterase (BuChE), human BuChE gene was mutated...
Eukaryotes have evolved two major pathways to repair potentially lethal DNA double-strand breaks. Homologous recombination represents a precise, DNA-template-based mechanism available during the S and G2 cell cycle phase, whereas non-homologous end joining, which requires DNA-dependent protein kinase (DNA-PK), allows for fast, cycle-independent but less accurate repair. Here, we report discovery of BAY-8400, novel selective inhibitor DNA-PK. Starting from triazoloquinoxaline, had been...
The first chemical synthesis of pentacyclic onocerane triterpenoids (+)-cupacinoxepin and (+)-onoceranoxide is described.
An efficient strategy for the synthesis of potent phospholipase A2 inhibitors spongidine A and D is presented. The tetracyclic core natural products was assembled via an intramolecular hydrogen atom transfer initiated Minisci reaction. divergent late-stage functionalization ring system also used to achieve a concise petrosaspongiolide L methyl ester.
The replacement of benzene rings with sp3-hybridized bioisosteres in drug candidates generally improves pharmacokinetic properties while retaining biological activity. Rigid, strained frameworks such as bicyclo[1.1.1]pentane and cubane are particularly well-suited since the ring strain imparts high bond strength thus metabolic stability on its C–H bonds. Cubane is ideal bioisostere it provides closest geometric match to benzene. At present, however, all cubanes design, like almost...
Abstract Onoceroids are a rare family of triterpenes. One representative onoceroid is ambrein, which the main component ambergris used as traditional medicine. We have previously identified synthase, BmeTC, in Bacillus megaterium and succeeded creating ambrein synthase by introducing mutations into BmeTC. Owing to structural similarity vitamin D, molecule with diverse biological activities, we hypothesized that some activities may be induced binding D receptor (VDR). demonstrated VDR ability...
An efficient strategy for the synthesis of potent phospholipase A2 inhibitors spongidine A and D is presented. The tetracyclic core natural products was assembled via an intramolecular hydrogen atom transfer‐initiated Minisci reaction. divergent late‐stage functionalization ring system also used to achieve a concise petrosaspongiolide L methyl ester.
<div>An efficient strategy for the synthesis of potent phospholipase A2 inhibitors spongidine A and D is presented. The tetracyclic core natural products was assembled via an intramolecular hydrogen atom transfer‐initiated Minisci reaction. divergent late‐stage functionalization ring system also used to achieve a concise petrosaspongiolide L methyl ester.</div>