Rodgers J D, Johnson B L, Wang H, Erickson-Viitanen S, Klabe R M, Bacheler L, Cordova B C, Chang C H
DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0500, USA.
Bioorg Med Chem Lett. 1998 Apr 7;8(7):715-20. doi: 10.1016/s0960-894x(98)00118-8.
Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a Ki < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.
含有3-氨基吲唑P2/P2'基团的环脲是HIV蛋白酶的极强抑制剂。母体3-氨基吲唑6的Ki<0.01 nM，但观察到酶活性向抗病毒活性的转化较差。一系列3-烷基氨基吲唑表明，随着亲脂性增加，转化得到改善。获得了与HIV蛋白酶结合的6的X射线晶体结构。
