γ-diketones as WNT/β-catenin signaling pathway activators
The present disclosure provides γ-diketones or analogs thereof, that activate Wnt/β-catenin signaling and thus treat or prevent diseases related to signal transduction, such as osteoporosis and osteoarthropathy; osteogenesis imperfecta, bone defects, bone fractures, periodontal disease, otosclerosis, wound healing, craniofacial defects, oncolytic bone disease, traumatic brain injuries or spine injuries, brain atrophy/neurological disorders related to the differentiation and development of the central nervous system, including Parkinson's disease, strokes, ischemic cerebral disease, epilepsy, Alzheimer's disease, depression, bipolar disorder, schizophrenia; otic disorders like cochlear hair cell loss; eye diseases such as age related macular degeneration, diabetic macular edema or retinitis pigmentosa and diseases related to differentiation and growth of stem cell, such as hair loss, hematopoiesis related diseases and tissue regeneration related diseases.
1. A compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein:
Ring A is a 7-12 membered heteroaryl, wherein a carbon atom on the ring is attached to the carbonyl carbon;
Ring B is phenyl;
R 1 is a substituent attached to Ring A and is independently selected at each occurrence from the group consisting of H, unsubstituted —C 1-6 alkyl, —C 1-3 haloalkyl, halide, —OR 3 , CF 3 , and CN;
R 2 is a substituent attached to Ring B and is independently selected at each occurrence from the group consisting of H, unsubstituted —C 1-6 alkyl, —CH 2 OH, —CH 2 N(R 3b ) 2 , —C 1-3 haloalkyl, halide, —OR 3 , CF 3 , and CN;
each R 3 is independently selected from the group consisting of H, unsubstituted —C 1-6 alkyl, —C 1-3 haloalkyl, and CF 3 ;
each R 3b is independently selected from the group consisting of H and unsubstituted —C 1-3 alkyl;
each n is an integer of 1 to 10; and
each m is an integer of 1 to 5;
with the proviso that the compound of Formula I is not a compound selected from the group consisting of:
2. The compound of claim 1 , wherein the compound of Formula I is selected from the group consisting of:
3. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.