Hydroxysteroid compounds, their intermediates, process of preparation, composition and uses thereof

1. A compound of formula (I):

or a salt thereof, wherein:

is independently either a single bond, a double bond or a cyclopropyl ring, provided that adjacent double bonds are not allowed;

A 1 and A 3 are absent or are independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, halogen, and C 1 -C 6 alkyl;

A 2 is selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, halogen, and C 1 -C 6 alkyl;

B is H and C is selected from the group consisting of hydroxyl, halogen, —OR 6 , —COR 6 , —COOR 6 , —OCOR 6 , —CH 2 OH, —CH 2 OR 6 , —C(OH)R 6 R 7 , —NHR 6 , —NR 6 R 7 , C 1 -C 12 straight or branched chain alkyl, 5-6 membered heterocycloalkyl, C(O)heteroaryl, C(O)heterocyclyl, —NR 5 CONHR 6 and —NR 6 COOR 7 ;

R 1 and R 2 are independently selected from the group consisting of hydrogen, deuterium, hydroxyl, halogen, ═O, —OR 6 , —NR 6 R 7 , —COR 6 , —COOR 6 , —OCOR 6 , —CONR 6 R 7 , C 1 -C 6 alkyl, and Otert-butyldimethylsilyl;

R 3 is hydroxyl;

wherein R 3 is in a beta configuration;

R 4 is selected from the group consisting of hydrogen, deuterium, hydroxyl, halogen, —OR 6 , —NR 6 R 7 , —COR 6 , —COOR 6 , —OCOR 6 , —CONR 6 R 7 , C 1 -C 6 alkyl, and -Otert-butyldimethylsilyl;

R 5 is selected from the group consisting of hydrogen, hydroxyl, halogen, and OR 6 ;

R 6 and R 7 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1 -C 12 alkyl, —NH 2 , —(CH 2 ) n NH 2 , 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, and 5-6 membered heteroaryl;

X is NR 6 ; and

n is 0 to 3.

2. The compound of claim 1 , wherein A 1 and A 2 are hydrogen.

3. The compound of claim 1 , wherein the compound has formula (II):

or a salt thereof, wherein:

is independently either a single bond, a double bond or a cyclopropyl ring, provided that adjacent double bonds are not allowed;

A 1 and A 2 are independently selected from the group consisting of hydrogen, hydroxyl, hydroxymethyl, halogen, and C 1 -C 6 alkyl;

B is H and C is selected from the group consisting of C(O)heteroaryl, C(O)heterocyclyl, —NR 5 CONHR 6 and —NR 6 NCOOR 7 ;

R 1 is selected from the group consisting of hydrogen, deuterium, hydroxyl, halogen, ═O, —OR 6 , —NR 6 R 7 , —COR 6 , —COOR 6 , —OCOR 6 , —CONR 6 R 7 , C 1 -C 6 alkyl, and -Otert-butyldimethylsilyl;

R 4 is selected from the group consisting of hydrogen, deuterium, hydroxyl, halogen, —OR 6 , —NR 6 R 7 ,

—COR 6 , —COOR 6 , —OCOR 6 , —CONR 6 R 7 , C 1 -C 6 alkyl, and -Otert-butyldimethylsilyl;

R 6 and R 7 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C 1 -C 12 alkyl, —NH 2 , —(CH 2 ) n NH 2 , 3-6 membered cycloalkyl, 4-6 membered heterocycloalkyl, 5-6 membered heteroaryl; and

n is 0 to 3.

4. A pharmaceutical composition comprising a compound as claimed in claim 1 , or a pharmaceutically acceptable salt thereof.

5. A method of treating a disease or disorder pertaining to mitochondrial biogenesis, selected from the group consisting of skeletal or cardiac muscle diseases associated with ischemia, or impaired or inadequate blood flow, diseases associated with genetic disorders that directly or indirectly affect the number, structure, or function of mitochondria, diseases associated with impaired neurological function associated with decreased mitochondrial number or function, diseases associated with loss of number, loss of function, or loss of correct internal organization of skeletal muscle cells or cardiac muscle cells, metabolic diseases, and conditions associated with liver cell injury and altered fatty acid metabolism, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

6. A method of treating a mitochondrial biogenesis-mediated disease selected from the group comprising acute coronary syndrome, myocardial infarction, angina, renal injury, renal ischemia, diseases of the aorta and its branches, injuries arising from medical interventions, atherosclerosis, trauma, diabetes, hyperlipidemia, vascular stenosis, peripheral arterial disease, vasculopathy, vasculitis, Friedreich's ataxia, muscular dystrophy, Duchenne muscular dystrophy, Becker muscular dystrophy, limb girdle muscular dystrophy, congenital muscular dystrophy, facioscapulohumeral muscular dystrophy, myotonic muscular dystrophy, oculopharyngeal muscular dystrophy, distal muscular dystrophy, spinal muscular atrophy, Emery-Dreifuss muscular dystrophy, Huntington's disease, Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis, sarcopenia, congestive heart failure, aging, myocarditis, myositis, polymyalgia rheumatic, polymyositis, HIV, cancer and/or the side effects of chemotherapy targeting the cancer, malnutrition, aging, inborn errors of metabolism, trauma, and stroke or other types of neurological impairment, hepatic steatosis, hepatic fibrosis, cirrhosis, and hepatocyte or stellate cell injury, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

7. A method of treating or preventing the adverse effects of administration of compounds which exhibit mitochondrial toxicity, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

8. A method for enhancing sports performance and endurance, building muscle shape and strength, or facilitating recovery from the muscle related side effects of training or competition, the method comprising administering to a subject in need thereof an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.