A5041581377- Chemical Synthesis and Analysis
- Radical Photochemical Reactions
- Click Chemistry and Applications
- Sulfur-Based Synthesis Techniques
- Chemical Synthesis and Reactions
- Synthesis and biological activity
- Biochemical and Molecular Research
- Psoriasis: Treatment and Pathogenesis
- Asthma and respiratory diseases
- Synthesis and Catalytic Reactions
- Synthetic Organic Chemistry Methods
- Quinazolinone synthesis and applications
- DNA Repair Mechanisms
- Oxidative Organic Chemistry Reactions
- Retinoids in leukemia and cellular processes
- PI3K/AKT/mTOR signaling in cancer
- Synthesis and Characterization of Heterocyclic Compounds
- Chronic Lymphocytic Leukemia Research
- Synthesis and bioactivity of alkaloids
- Coccidia and coccidiosis research
- Catalytic Cross-Coupling Reactions
- Carcinogens and Genotoxicity Assessment
- Computational Drug Discovery Methods
- Protein Degradation and Inhibitors
- Synthesis and Biological Evaluation
NeRRe Therapeutics (United Kingdom)
2025
Stevenage Bioscience Catalyst
2024
Evotec (United Kingdom)
2019-2022
Galderma (Switzerland)
2021
Skin Research Center
2017-2019
AstraZeneca (France)
2012-2018
Nestlé (France)
2017-2018
Galderma (France)
2016-2018
SKiN Health
2018
Nestlé (Sweden)
2018
ATM inhibitors, such as 7, have demonstrated the antitumor potential of inhibition when combined with DNA double-strand break-inducing agents in mouse xenograft models. However, properties 7 result a relatively high predicted clinically efficacious dose. In an attempt to minimize attrition during clinical development, we sought identify inhibitors low dose (<50 mg) and focused on strategies increase both potency human pharmacokinetic half-life (predominantly through volume distribution)....
Here we report the discovery and optimization of a series bivalent bromodomain extraterminal inhibitors. Starting with observation BRD4 activity compounds from previous program, were optimized for potency physical properties. The compound this campaign exhibited excellent pharmacokinetic profile high in vitro vivo effecting c-Myc downregulation tumor growth inhibition xenograft studies. This was selected as development candidate, AZD5153. showed enhanced result binding clear correlation...
A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such 6-[6-(methoxymethyl)-3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3-quinolinecarboxamide (72) 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S)-1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) highly ATM with overall ADME properties suitable...
Radically useful: The radical addition of dithiocarbonates to branched allyl diphenylphosphine oxides can be followed by elimination a diphenylphosphinoyl radical, thereby giving rise allylated products (see scheme; Phth=phthalimido). Highly functionalized structures thus rapidly assembled under mild conditions and from cheap readily available substrates reagents. Supporting information for this article is on the WWW http://www.wiley-vch.de/contents/jc_2002/2006/z601556_s.pdf or author....
Potassium O-ethyl xanthate readily adds to α,β-unsaturated nitro compounds give stable β-nitro xanthates, which undergo tin-free elimination form olefins in good yield and E selectivity upon simple heating with lauroyl peroxide refluxing 1,2-dichloroethane.
Abstract With possible implications in multiple autoimmune diseases, the retinoic acid receptor‐related orphan receptor RORγ has become a sought‐after target pharmaceutical industry. Herein are described efforts to identify potent inverse agonist compatible with topical application for treatment of skin diseases. These culminated discovery N ‐(2,4‐dimethylphenyl)‐ ‐isobutyl‐2‐oxo‐1‐[(tetrahydro‐2 H ‐pyran‐4‐yl)methyl]‐2,3‐dihydro‐1 ‐benzo[ d ]imidazole‐5‐sulfonamide (CD12681), vivo activity...
Phototoxicity occurs when UV irradiation causes otherwise benign compounds to become irritant, sensitizers, or even genotoxic. This toxicity is particularly a concern after topical application and in dermatological programs where skin irritation can be incompatible with the desired therapeutic outcome. brief article establishes that intrinsic property forecast index (iPFI) used evaluate probability of compound being phototoxic gives medicinal chemists practical tool handle this liability.
Xanthate-mediated intermolecular radical addition, hydrogen atom transfer and sulfonyl elimination have been efficiently combined in a new convergent synthesis of ketones substituted olefins.