ALPHA HELIX MIMETICS AND METHODS RELATING THERETO

摘要

Alpha-helix mimetic structures and compounds represented by the formula (I) wherein the general formula and the definition of each symbol are as defined in the specification, a chemical library relating thereto, and methods relating thereto, are disclosed. Applications of these compounds in the treatment of medical conditions, e.g., cancer diseases, fibrotic diseases, and pharmaceutical compositions comprising the mimetics are further disclosed.

主权项

1. A compound having the following general formula (I):wherein
is single bond or double bond; A is —CHR7—,
wherein
R7 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl or optionally substituted heterocycloalkylalkyl; E is —CHR5—, —O— or —NR8—,
whereinR5 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl, andR8 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl; B is void or optionally substituted monocyclic ring formed together with G and Y; D is void or optionally substituted spiro ring formed together with Y; with the proviso that B and D are not both present, when B is present, then G and Y are independently carbon atom or nitrogen atom, when D is present, then Y is carbon atom and G is —NR6—, —O—, —CHR6— or —C(R6)2—, when both B and D are void, then G and Y are the same or different and each is —NR6—, —O—, —CHR6— or —C(R6)2—,
wherein
each R6 is independently hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted arylalkyl or optionally substituted heteroarylalkyl; R1 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted arylalkyl, optionally substituted heteroarylalkyl, optionally substituted cycloalkylalkyl or optionally substituted heterocycloalkylalkyl; R2 is —W21—W22—Rb—R20,
whereinW21 is —(CO)— or —(SO2)—,W22 is bond, —O—, —NH— or optionally substituted lower alkylene,Rb is bond or optionally substituted alkylene, andR20 is optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl or optionally substituted heterocycloalkyl; and R3 is hydrogen, optionally substituted alkyl, optionally substituted alkenyl or optionally substituted alkynyl; or a pharmaceutically acceptable salt thereof.