SOCE inhibitors and therapeutic uses thereof
The present invention provides SOCE inhibitors that are useful as therapeutic agents in a variety of applications. The present invention also relates to pharmaceutical compositions, products and kits comprising such SOCE inhibitors, and methods of using the SOCE inhibitors in the treatment of a variety of diseases.
1 . An aromatic azole compound,
(1) wherein said aromatic azole compound has chemical formula (I):
wherein:
R 1 is one, two, three, four or five substituents, wherein each of the substituents is independently selected from H, OH, a halogen, NH 2 , an alkoxy, an aryloxy, OCH 2 OR, wherein R is an alkyl group, and O-THP, wherein THP is tetrahydropyranyl;
A is CH 2 or O;
if A is CH 2 , then n=0, 1 or 2, and if A is O, then n=2 or 3;
Z is O, NH, NHCO or CONH, NR, wherein R is an alkyl group, NHSO 2 or SO 2 NH;
X is one of the following groups:
wherein:
R 2 is H, Cl, Br or CF 3 ; and
R 3 is one, two, three or four substituents, wherein each of the substituents is independently selected from H, OH, CF 3 , F, CI, NH 2 , COOH, and CONH 2 ;
or a pharmaceutically acceptable salt thereof, or
(2) wherein said aromatic azole compound has the chemical formula of one of the following compounds:
2 . The aromatic azole compound according to claim 1 , wherein the aromatic azole compound of chemical formula (I) has the chemical formula (II):
3 . The aromatic azole compound according to claim 2 , wherein the aromatic azole compound of chemical formula (I) has the chemical formula (III):
4 . The aromatic azole compound according to claim 1 , wherein the aromatic azole compound of chemical formula (I) has the chemical formula of one of the following compounds:
5 . The aromatic azole compound according to claim 4 , wherein the aromatic azole compound is selected from the group consisting of:
6 . A pharmaceutical composition comprising an effective amount of at least one aromatic azole compound according to claim 1 , and a pharmaceutically acceptable carrier or excipient.
7 . A method for treating a disease associated with SOCE dysregulation or dysfunction in a subject, the method comprising a step of administering to the subject a therapeutically effective amount of an aromatic azole compound according to claim 1 or a pharmaceutical composition thereof, wherein the disease associated with SOCE dysregulation or dysfunction is selected from the group consisting of immunodeficiency diseases, allergies, cardiovascular diseases, cardiorespiratory diseases, vascular diseases, skeletal muscle diseases, and thromboses;
or
wherein the disease associated with SOCE dysregulation or dysfunction is:
an inflammatory disease selected from the group consisting of inflammatory diseases of the musculoskeletal system, of the pulmonary system, of the cardiovascular system, of the gastrointestinal system, of the skin, of the neurologic system, of the central nervous system, of the hematologic system, and of the renal system;
or
a cancer selected from the group consisting of breast, prostate, liver, lung, colon, cervical, ovarian, kidney, bladder, nasopharyngeal, epidermoid, esophageal, stomach, pancreatic, cervical, thyroid, neck cancer, skin, head and neck cancers, malignant tumors of the central and peripheral nervous system, hematopoietic tumors of the lymphoid lineage, and hematopoietic tumors of myeloid lineage.
8 . The method according to claim 7 , wherein the disease associated with SOCE dysregulation or dysfunction is selected from the group consisting of inflammatory bowel diseases, pancreatitis, rheumatoid arthritis, multiple sclerosis, asthma, psoriasis, liver cancers and pancreatic cancers.