287183-01-1

Upstream product

• 142801-55-6 N-α-(t-butyloxycarbonyl)-N'-ω'-(4-methoxy-2,3,6-trimethylbenzenesulfonyl)-L-arginine-N,O-dimethylhydroxyamide 
• 287182-91-6 C₂₈H₃₉N₅O₆S₂ 
• 201006-62-4 [(1S)-1-(2-benzothiazolylcarbonyl)-4-[[imino[[(4-methoxy-2,3,6-trimethylphenyl)sulfonyl]amino]methyl]amino]butyl]carbamic acid 1,1-dimethylethyl ester 
• 102185-38-6 Nα-(t-butyloxycarbonyl)-Nω-(4-methoxy-2,3,6-trimethylbenzenesulphonyl)-L-arginine 
• 203453-39-8 N-<4-amino-5-(1,3-benzothiazol-2-yl)-5-hydroxypentyl>-N'-<(4-methoxy-2,3,6-trimethylphenyl)sulfonyl>guanidine 
• 33996-33-7 oxaceprol 

Relevant academic research and scientific papers

Potent, small-molecule inhibitors of human mast cell tryptase. Antiasthmatic action of a dipeptide-based transition-state analogue containing a benzothiazole ketone

Inhibitors of human mast cell tryptase (EC 3.4.21.59) have therapeutic potential for treating allergic or inflammatory disorders. We have investigated transition-state mimetics possessing a heterocycle-activated ketone group and identified in particular benzothiazole ketone (2S)-6 (RWJ-56423) as a potent, reversible, low-molecular-weight tryptase inhibitor with a Ki value of 10 nM. A single-crystal X-ray analysis of the sulfate salt of (2S)-6 confirmed the stereochemistry. Analogues 12 and 15-17 are also potent tryptase inhibitors. Although RWJ-56423 potently inhibits trypsin (Ki = 8.1 nM), it is selective vs other serine proteases, such as kallikrein, plasmin, and thrombin. We obtained an X-ray structure of (2S)-6 complexed with bovine trypsin (1.9-? resolution), which depicts inter alia a hemiketal involving Ser-189, and hydrogen bonds with His-57 and Gln-192. Aerosol administration of 6 (2R,2S; RWJ-58643) to allergic sheep effectively antagonized antigen-induced asthmatic responses, with 70-75% blockade of the early response and complete ablation of the late response and airway hyperresponsiveness.