145899-46-3

Upstream product

• 530-62-1 1,1'-carbonyldiimidazole 
• 145878-49-5 3-(N-Hydroxycarbamimidoyl)-phenyl-carbamic acid tert-butyl ester 
• 145878-49-5 3-Boc-amino-N-hydroxybenzamidine 
• 24468-13-1 2-Ethylhexyl chloroformate 
• 145878-50-8 3-(3-tert-butoxycarbonylamino)benzonitrile 

Downstream Products

• 503469-36-1 3-(3-aminophenyl)-1,2,4-oxadiazol-5(4H)-one 
• 476362-72-8 3-(5-oxo-4,5-dihydro[1,2,4]oxadiazol-3-yl)benzenesulfonyl chloride 
• 503469-36-1 3-(3-amino-phenyl)-2H-[1,2,4]oxadiazol-5-one 

Relevant academic research and scientific papers

Design of pentapeptidic BACE1 inhibitors with carboxylic acid bioisosteres at P1′ and P4 positions

We previously reported potent BACE1 inhibitors KMI-420 and KMI-570 possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Acidic moieties at the P1′ and P4 positions of KMI inhibitors are thought to be unfavorable in terms of membrane permeability across the blood-brain barrier. Herein, we replaced acidic moieties at the P4 position with hydrogen bond accepting groups and acidic moieties at the P1′ position with less acidic and similar molecular-size moieties (carboxylic acid or tetrazole bioisosteres). These inhibitors exhibited improved BACE1 inhibitory activities and a thorough quantitative structure-activity relationship study was performed.

PROCESS FOR THE PREPARATION OF BENZOTRIAZEPINE DERIVATIVES

The present invention is directed to a novel process for the preparation of benzo[e][1,2,4]triazepin-2-one derivatives, useful in the preparation of gastrin and cholecystokinin receptor ligands.

Design and synthesis of potent β-secretase (BACE1) inhibitors with P1′ carboxylic acid bioisosteres

Recently, we reported potent and small-sized β-secretase (BACE1) inhibitors KMI-420 and KMI-429 in which we replaced the Glu residue at the P4 position of KMI-260 and KMI-360, respectively, with a 1H-tetrazole-5-carbonyl DAP (l-α,β-diaminopropi

Identification of potent and selective small-molecule inhibitors of caspase-3 through the use of extended tethering and structure-based drug design

The design, synthesis, and in vitro activities of a series of potent and selective small-molecule inhibitors of caspase-3 are described. From extended tethering, a salicylic acid fragment was identified as having binding affinity for the S4 pocket of caspase-3. X-ray crystallography and molecular modeling of the initial tethering hit resulted in the synthesis of 4, which reversibly inhibited caspase-3 with a Ki = 40 nM. Further optimization led to the identification of a series of potent and selective inhibitors with Ki values in the 20-50 nM range. One of the most potent compounds in this series, 66b, inhibited caspase-3 with a Ki = 20 nM and selectivity of 8-500-fold for caspase-3 vs a panel of seven caspases (1, 2, and 4-8). A high-resolution X-ray cocrystal structure of 4 and 66b supports the predicted binding modes of our compounds with caspase-3.