A5036268218- Synthesis of heterocyclic compounds
- Receptor Mechanisms and Signaling
- Synthesis and Characterization of Heterocyclic Compounds
- Neuropeptides and Animal Physiology
- Chemical Reaction Mechanisms
- Synthesis and Biological Evaluation
- Synthesis and Reactivity of Heterocycles
- Chemical Synthesis and Analysis
- Regulation of Appetite and Obesity
- Peptidase Inhibition and Analysis
- interferon and immune responses
- Diabetes Treatment and Management
- Pancreatic function and diabetes
- Quinazolinone synthesis and applications
- Pneumocystis jirovecii pneumonia detection and treatment
- Coordination Chemistry and Organometallics
- Asymmetric Synthesis and Catalysis
- Cancer Research and Treatments
- Inflammasome and immune disorders
- Systemic Lupus Erythematosus Research
- Synthesis and Catalytic Reactions
- Biochemical Analysis and Sensing Techniques
- Click Chemistry and Applications
- Monoclonal and Polyclonal Antibodies Research
- Alzheimer's disease research and treatments
Novo Nordisk (Denmark)
2003-2021
Technische Universität Dresden
1998-2001
A hallmark of the pancreatic hormone amylin is its high propensity toward formation amyloid fibrils, which makes it a challenging drug design effort. The analogue pramlintide commercially available for diabetes treatment as an adjunct to insulin therapy but requires three daily injections due short half-life. We report here development stable, lipidated long-acting cagrilintide (23) and some structure–activity efforts that led selection this clinical with obesity indication. Cagrilintide...
Peptides are notoriously known to display very short in vivo half-lives often measured minutes which many cases greatly reduces or eliminates sufficient efficacy. To obtain long allowing for up once-weekly dosing regimen, fatty acid acylation (lipidation) have been used non-covalently associate the peptide serum albumin thus serving as a circulating depot. This approach is generally considered scientific and patent community standard protract almost any given peptide. However, it not trivial...
Cholecystokinin (CCK) is a regulator of appetite and energy intake in man. The aim this study was to determine the effect NN9056, long-acting CCK-1 receptor-selective CCK analogue, on food body weight (BW) obese Göttingen Minipigs. Tolerability NN9056 acute effects intake, pancreas histology, amylase lipase levels were assessed lean domestic pigs doses up 100 nmol/kg (n = 3–4). Subsequently, Minipigs treated subcutaneously (s.c.) once daily for 13 weeks with vehicle, low dose (regulated from...
We report in vitro and vivo data of new α-melanocyte-stimulating hormone (α-MSH) analogues which are N-terminal modified with a long chain fatty acid derivative. While keeping the pharmacophoric motif (d-Phe-Arg-Trp) fixed, we tried to improve selectivity physicochemical parameters like solubility stability these by replacing amino acids further away from motif. Receptor specific changes binding affinity melanocortin receptors were observed between acetyl derivatives analogues. Furthermore,...
A group of peptide-based, long-acting, stable, highly selective cholecystokinin 1 receptor (CCK-1R) agonists with the potential to treat obesity has been identified and characterized, based on systematic investigation synthetic CCK-8 analogues N-terminal linkage fatty acids. Sulfated Tyr in such compounds was stable neutral buffer. CCK-1R selectivity achieved mostly by introducing d-N-methyl-Asp instead Asp at penultimate position CCK-8. Our compound 9 (NN9056) showed similar vitro potency...
Abstract Versatile 2‐thioxopyrimidine‐type building blocks ethyl 3‐(2‐ethoxy‐2‐oxoethyl)‐ 4 ‐oxo‐2‐thioxo‐1,2,3,4,5,6,7,8‐octahydropyrido[4′,3′:4,5]thieno[2,3‐ d ]pyrimidine‐7‐carboxylate ( ) and 4‐oxo‐2‐thioxo‐1,2,3,4,5,6,7,8‐octahydropyrido[4′,3′:4,5]thieno[2,3‐ 8 were synthesized from diethyl 2‐amino‐4,5,6,7‐tetrahydrothieno[2,3‐ c ]pyridine‐3,6‐dicarboxylate 1 ). Derivatives of linear angular heterocyclic systems having the imidazole 1,2,4‐triazole ring obtained key intermediates , respectively.
Bicyclic 2-aminothiophenes 2, which are available by the Gewald reaction of 2,2,6,6-tetramethyl-4-piperidone (triacetonamine, 1), were employed in cyclizations to give new tricyclic thienopyridine and thienopyrimidine derivatives, without protection piperidine nitrogen, whereas methylation 2 occurred exclusively at nitrogen. Acylation presence a tertiary amine yielded N-thienyl imides, due high NH acidity intermediate amides. Similarly, benzylation an amide proceeded readily sodium ethoxide...
Abstract Pharmacological activation of the STING pathway is being assessed as a strategy to stimulate both innate and adaptive arms immune system trigger an anti-tumor response in so-called "cold" tumors. Although first generation agonists dosed intratumorally showed strong preclinical models, positive clinical data has so far been limited, potentially due reduced efficacy non-injected Newer classes that are delivered systemically expected deliver more consistent predictable levels...
<h3>Background:</h3> Type I interferonopathies are a group of rare monogenic diseases causing over-activation signaling pathways ultimately leading to increased type Interferon (IFN) in the plasma and immune system. AGS is inflammatory disease with onset at birth or early infancy that principally caused by mutations genes encoding proteins cytosolic nuclease activity e.g., RNAseH2A, -B -C Trex1. Mutations Trex1 lead accumulation DNA cytosol which activates canonical DNA-sensing cGAS-STING...
A cascade-like ring transformation of a thieno [2,3-d]pyridine derivative is reported and mechanistically explained.The product novel heterocyclic system consisting thiophene peri-fused with pyrido[2,3-d]pyrimidine moiety.Various derivatives the new were prepared.
Reaction of a lithiated imine derivative 2,2,6,6-tetramethyl-4-piperidone (triacetonamine, 1) with activated or less reactive alkyl halides styrene oxide and subsequent hydrolysis afforded 3-alkylated triacetonamine derivatives. Thus, 3-benzyl-2,2,6,6-tetramethyl-4-piperidone (3), 3-(n-butyl)-2,2,6,6-tetramethyl-4-piperidone (4), 3-(3-chloropropyl)-2,2,6,6-tetramethyl-4-piperidone (5), 2,2,3,6,6-pentamethyl-4-piperidone (6) two diastereomers...
Summary Cholecystokinin receptors, CCK A R and B R, are important neuro-intestinal peptide hormone receptors play a vital role in food intake appetite regulation. Here we report three crystal structures of the human complex with different ligands, including one agonist two small-molecule antagonists, as well cryo-electron microscopy R–gastrin G i2 q , respectively. These reveal recognition pattern ligand types molecular basis selectivity cholecystokinin receptor family. By comparing...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”