Anthranilic sulfonamide CCK1/CCK2 dual receptor antagonists II: Tuning of receptor selectivity and in vivo efficacy

Rhodium-catalysed asymmetric hydrogenation as a valuable synthetic tool for the preparation of chiral drugs

“…Deng and co-workers at Johnson & Johnson recently applied Rh-catalysed asymmetric hydrogenation to prepare the unnatural b-aryl-a-amino acid (S)-3 0 -bromo-4 0 -fluorophenylalanine 52 (6), a major pharmaceutical chiral building block used in the synthesis of a dual CCK1/CCK2 receptor antagonist which is currently into human clinical trials for the treatment of various gastrointestinal diseases 53 (Scheme 2). The ferrocene-based bidentate phosphineaminophosphine ligand (R,S)-Me-BoPhoz [54][55][56] was the chiral ligand of choice for performing the enantioselective hydrogenation of the acrylate 4 as a free carboxylic acid derivative.…”

Benzoselenadiazole-based responsive long-lifetime photoluminescent probes for protein kinases

“…16 Oxygen-and sulphur-containing counterparts of benzoselenadiazole (benzoxadiazole and benzothiadiazole, respectively) have been widely used as fragments of ligands for several proteins. 17 Discovery of an aromatic scaffold with requested optical properties deepens the understanding of principles that have to be considered when constructing new responsive optical probes for PKs and other (non-kinase) proteins. 17 Hereto optical properties (excitation and emission wavelengths, fluorescence quantum yields, etc.)…”

“…17 Discovery of an aromatic scaffold with requested optical properties deepens the understanding of principles that have to be considered when constructing new responsive optical probes for PKs and other (non-kinase) proteins. 17 Hereto optical properties (excitation and emission wavelengths, fluorescence quantum yields, etc.) of the benzoselenadiazole luminophore can be easily varied by simple modifications of the core structure of the compound, 18 thereby further improvement of the protein-responsive probe is apparently possible.…”

Enantioselective Access to Chiral Drugs by using Asymmetric Hydrogenation Catalyzed by Rh(POP) Complexes

“…Despite the pharmacological relevance of P2 , to the best of our knowledge, the results described here constitute the first reported enantioselective synthesis of P2 by asymmetric hydrogenation. The present approach also constitutes an efficient enantioselective entry into ( S )‐ N ‐acetyl‐3‐bromo‐4‐fluorophenylalanine ( P4 , Scheme ), a key pharmaceutical building block used for the preparation of dual CCK1/CCK2 receptor antagonists14 (Scheme 4, see later), which have recently been developed for the treatment of various gastrointestinal diseases 15. A precedent for the asymmetric hydrogenation of alkene S3 was not found in the literature, but the high level of enantioselectivity achieved for its analogue S4 (96–98 % ee ) represents an improvement on the enantiomeric excess previously obtained for this type of alkene upon using a Rh complex derived from ( N ‐methyl‐ N ‐diphenylphosphino‐1‐[2‐(diphenylphosphino)ferrocenyl]ethylamine) (Me‐BoPhoz), which gave the product with 94 % ee 14b .…”