13691-22-0Relevant articles and documents
Characterization of crystal water molecules in a high-affinity inhibitor and hematopoietic prostaglandin D synthase complex by interaction energy studies
Takaya, Daisuke,Inaka, Koji,Omura, Akifumi,Takenuki, Kenji,Kawanishi, Masashi,Yabuki, Yukako,Nakagawa, Yukari,Tsuganezawa, Keiko,Ogawa, Naoko,Watanabe, Chiduru,Honma, Teruki,Aritake, Kosuke,Urade, Yoshihiro,Shirouzu, Mikako,Tanaka, Akiko
, p. 4726 - 4734 (2018)
Hematopoietic prostaglandin D synthase (H-PGDS) is one of the two enzymes that catalyze prostaglandin D2 synthesis and a potential therapeutic target of allergic and inflammatory responses. To reveal key molecular interactions between a high-affinity ligand and H-PGDS, we designed and synthesized a potent new inhibitor (KD: 0.14 nM), determined the crystal structure in complex with human H-PGDS, and quantitatively analyzed the ligand–protein interactions by the fragment molecular orbital calculation method. In the cavity, 10 water molecules were identified, and the interaction energy calculation indicated their stable binding to the surface amino acids in the cavity. Among them, 6 water molecules locating from the deep inner cavity to the peripheral part of the cavity contributed directly to the ligand binding by forming hydrogen bonding interactions. Arg12, Gly13, Gln36, Asp96, Trp104, Lys112 and an essential co-factor glutathione also had strong interactions with the ligand. A strong repulsive interaction between Leu199 and the ligand was canceled out by forming a hydrogen bonding network with the adjacent conserved water molecule. Our quantitative studies including crystal water molecules explained that compounds with an elongated backbone structure to fit from the deep inner cavity to the peripheral part of the cavity would have strong affinity to human H-PGDS.
Copper-Catalyzed Coupling Reaction of (Hetero)Aryl Chlorides and Amides
De, Subhadip,Yin, Junli,Ma, Dawei
supporting information, p. 4864 - 4867 (2017/09/23)
Cu2O/N,N′-bis(thiophen-2-ylmethyl)oxalamide is established to be an effective catalyst system for Goldberg amidation with inferior reactive (hetero)aryl chlorides, which have not been efficiently documented by Cu-catalysis to date. The reaction is well liberalized toward a variety of functionalized (hetero)aryl chlorides and a wide range of aromatic and aliphatic primary amides in good to excellent yields. Furthermore, the arylation of lactams and oxazolidinones is achieved. The present catalytic system also accomplished an intramolecular cross-coupling product.
Heterogeneous CuII-catalysed solvent-controlled selective N-arylation of cyclic amides and amines with bromo-iodoarenes
Kundu, Debasish,Bhadra, Sukalyan,Mukherjee, Nirmalya,Sreedhar, Bojja,Ranu, Brindaban C.
, p. 15759 - 15768 (2013/11/19)
A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalysed by CuII/Al2O3 has been achieved. This protocol has been employed for the synthesis of a library of arenes bearing a cyclic amide and an amine moiety at two ends, including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed electron paramagnetic resonance (EPR) spectroscopy, X-ray photoelectron spectroscopy (XPS), UV diffuse reflectance spectroscopy (DRS) and inductively coupled plasma-mass spectrometry (ICP-MS) studies of the catalyst at different stages of the reaction. The CuII/Al2O 3 catalyst was recovered and recycled for subsequent reactions. One over the other: A selective N-arylation of cyclic amides and amines in DMF and water, respectively, catalyzed by CuII/Al2O3 has been achieved (see scheme). This protocol has been employed for the synthesis of a library of arenes bearing cyclic amide and amine moieties at two ends including a few scaffolds of therapeutic importance. The mechanism has been established based on detailed spectroscopic studies (FG=functional group). Copyright
