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2005
Pyrazine derivatives
R 0550
Novel Pyrazinone Inhibitors of Mast Cell Tryptase: Synthesis and SAR Evalua— The synthesis of the pyrazinone core structure (VI) is achieved under modified
03- 153 tion.
Strecker conditions to yield the nitrile amino ester (IV) and subsequent cyclization of
(IV) with oxalyl chlorides (V). P4 Group optimization provides bulky, polar substituents as substituents of choice. P1 Group optimization affords a meta-substituted benzylamino amide as the optimal substituent. Thus, P4 and P1 chain modifications of the
pyrazinone nucleus identifies (XIb) as potent inhibitor of mast cell tryptase. —
(HOPKINS*, C. R.; et al.; Bioorg. Med. Chem. Lett. 14 (2004) 19, 4819-4823; Dep.
Med. Chem., Aventis Pharm., Bridgewater, NJ 08807, USA; Eng.) —
H. Hoennerscheid
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