Methods and use of bifunctional enzyme-building clamp-shaped molecules

摘要

This invention is in the fields of cancer therapy. More particularly it concerns compounds which are useful agents for inhibiting cell proliferative disorders, especially those disorders characterized by over activity and/or inappropriate activity of a EGFR, including EGFR-related cancers, and methods for treating these disorders.

主权项

1. A compound having a structure of Formula I:wherein
R1 is independently H, optionally substituted amino, optionally substituted C1-6 alkyl, optionally substituted C1-6 alkoxy, optionally substituted C1-6 alkenyl, optionally substituted C1-6 alkynyl, optionally substituted benzyloxy, cyano, halo, hydroxy, nitro, optionally substituted phenoxy, or mono-, di-, or trifluoromethyl; n is 1, 2, or 3; R2 is independently H or C1-3-alkyl; R3A is —OR5A, —NR2R5A, —SR5A, —C(O)R5A, —C(O)OR5A, —C(O)N(R2)(R5A), —OC(O)R5A, —OC(O)OR5A, —OC(O)NR2R5A, —NR2C(O)R5A, —NR2C(O)OR5A; R4 is H, —N(R2)2, optionally substituted C1-3-alkyl, optionally substituted C1-3-alkoxy, cyano, halo, hydroxy, nitro, or mono-, di-, or trifluoromethyl; R5A is —(C1-4-alkyl)-X—R6—R7; X is O, S, or N(R2); R6 is a bond; R7 is either (i) a C1-4-alkyl substituted by at least one —OH or —C(O)OR2 or —C(O)N(R2)2, or (ii) a heteroaryl having 5 ring members, containing 1-3 heteroatoms and substituted by R2 and —X—R8; and R8 is C1-3 alkyl substituted by at least one —OH, —COOH, —C(O)O—C1-4 alkyl, —C(O)N(R2)2, or C1-5 cycloalkyl; or a pharmaceutically acceptable salt form thereof.