Board of Trustees of the University of Illinois;The United States of America, as represented by the Secretary, Department of Health and Human Serv
发明人:
John W. Erickson,Sergei V. Gulnik,Hiroaki Mitsuya,Arun E. Ghosh
申请号：
US13933319
公开号：
US20140011815A1
申请日:
2013.07.02
申请国别(地区):
US
年份:
2014
代理人:
摘要：
The present invention provides an assay for determining the biochemical fitness of a biochemical species in a mutant replicating biological entity relative to its predecessor. The present invention further provides a continuous fluorogenic assay for measuring the anti-HIV protease activity of protease inhibitor. The present invention also provides a method of administering a therapeutic compound that reduces the chances of the emergence of drug resistance in therapy. The present invention also provides a compound of formula (I) or a pharmaceutically acceptable salt, a prodrug, a composition, or an ester thereof, wherein A is a group of formulas (A), (B), (C) or (D)； R1, R2, R3, R5 or R6 is H, or an optionally substituted and/or heteroatom-bearing alkyl, alkenyl, alkynyl, or cyclic group； Y and/or Z are CH2, O, S, SO, SO2, amino, amides, carbamates, ureas, or thiocarbonyl derivatives thereof, optionally substituted with an alkyl, alkenyl, or alkynyl group； n is from 1 to 5； X is a bond, an optionally substituted methylene or ethylene, an amino, O or S； Q is C(O), C(S), or SO2； m is from 0 to 6； R4 is OH, ═O (keto), NH2, or alkylamino, including esters, amides, and salts thereof； and W is C(O), C(S), S(O), or SO2. Optionally, R5 and R6, together with the N—W bond of formula (I), comprise a macrocyclic ring.
