Submission Details
Molecule(s):
CCN(CC)c1cc(NC(=O)Cc2ccc(O)cc2)c(Nc2nccc(C(N)=O)n2)cc1NCCN(C)C
Design Rationale:
Loosely based on the Cys-modifying drug osimertinib. Here the acrylamide moiety (see entry STE-LAU-835) was replaced by NH(CO)CH2Phe-OH. The compound therefore lacks the Cys-modifying group. The compound was docked using the structure generated with the x0072 fragment (pdb 5R7Y). Docking and partial minimization was performed with Nanome (virtual reality). Two clefts are occupied by the diethylamine and the ethylenediamine moieties. There are multiple H bonds to Asn142. The phenolic OH group interacts with the backbone carbonyl oxygen of Thr26. There is also an additional H bond between the backbone carbonyl oxygen of Glu166 and one of the ethylenediamine nitrogens (protonated form).