Abstract:
:We describe here a novel 4-amino-2-cyanopyrimidine scaffold for nonpeptidomimetic cathepsin S selective inhibitors. Some of the synthesized compounds have sub-nanomolar potency and high selectivity toward cathepsin S along with promising pharmacokinetic and physicochemical properties. The key structural features of the inhibitors consist of a combination of a spiro[2.5]oct-6-ylmethylamine P2 group at the 4-position, a small or polar P3 group at the 5-position and/or a polar group at the 6-position of the pyrimidine.
journal_name
Bioorg Med Chem Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Irie O,Yokokawa F,Ehara T,Iwasaki A,Iwaki Y,Hitomi Y,Konishi K,Kishida M,Toyao A,Masuya K,Gunji H,Sakaki J,Iwasaki G,Hirao H,Kanazawa T,Tanabe K,Kosaka T,Hart TW,Hallett Adoi
10.1016/j.bmcl.2008.07.011subject
Has Abstractpub_date
2008-08-15 00:00:00pages
4642-6issue
16eissn
0960-894Xissn
1464-3405pii
S0960-894X(08)00780-4journal_volume
18pub_type
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