3647-71-0Relevant articles and documents
Structural Revision of the Ring-Opened Product in the ZnCl 2-Catalyzed Reactions of 1-Benzyl-2-phenylaziridine with Thiols
Furuta, Yukiko,Kumamoto, Takuya,Ishikawa, Tsutomu
, p. 362 - 364 (2004)
The reported β-amino sulfide structures for the products in the ZnCl2-catalyzed ring-opening reactions of 1-benzyl-2-phenylaziridine with thiols should be revised to 2-amino-1-phenyl-ethyl sulfides from 2-amino-2-phenylethyl sulfides.
Structure-Activity Relationship Studies of Pyrimidine-4-Carboxamides as Inhibitors of N-Acylphosphatidylethanolamine Phospholipase D
Mock, Elliot D.,Kotsogianni, Ioli,Driever, Wouter P. F.,Fonseca, Carmen S.,Vooijs, Jelle M.,Den Dulk, Hans,Van Boeckel, Constant A. A.,Van Der Stelt, Mario
, p. 481 - 515 (2021/02/05)
N-Acylphosphatidylethanolamine phospholipase D (NAPE-PLD) is regarded as the main enzyme responsible for the biosynthesis of N-acylethanolamines (NAEs), a family of bioactive lipid mediators. Previously, we reported N-(cyclopropylmethyl)-6-((S)-3-hydroxypyrrolidin-1-yl)-2-((S)-3-phenylpiperidin-1-yl)pyrimidine-4-carboxamide (1, LEI-401) as the first potent and selective NAPE-PLD inhibitor that decreased NAEs in the brains of freely moving mice and modulated emotional behavior [ Mock et al. Nat Chem. Biol., 2020, 16, 667-675 ]. Here, we describe the structure-activity relationship (SAR) of a library of pyrimidine-4-carboxamides as inhibitors of NAPE-PLD that led to the identification of LEI-401. A high-throughput screening hit was modified at three different substituents to optimize its potency and lipophilicity. Conformational restriction of an N-methylphenethylamine group by replacement with an (S)-3-phenylpiperidine increased the inhibitory potency 3-fold. Exchange of a morpholine substituent for an (S)-3-hydroxypyrrolidine reduced the lipophilicity and further increased activity by 10-fold, affording LEI-401 as a nanomolar potent inhibitor with drug-like properties. LEI-401 is a suitable pharmacological tool compound to investigate NAPE-PLD function in vitro and in vivo.
Rhodium-Catalyzed Anti-Markovnikov Hydroamination of Aliphatic and Aromatic Terminal Alkynes with Aliphatic Primary Amines
Kakiuchi, Fumitoshi,Kochi, Takuya,Morimoto, Yoshihiko
, p. 13143 - 13152 (2021/09/28)
Anti-Markovnikov hydroamination of both aliphatic and aromatic terminal alkynes with primary amines was achieved using an 8-quinolinolato rhodium catalyst to form aldimines and enamines in high yields. This catalytic system realized high functional group tolerance including hydroxy, bromo, cyano, and thioester groups.
