Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10556893-B2
Publication Date
2020-02-11
Expiration Date
Abstract
The present invention provides compounds having the general structural formula (I) (I) and pharmaceutically acceptable derivatives thereof, as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases involving fibrosis and proliferation, and where anti-fibrotic or anti-proliferative activity is beneficial.
Core Innovation
The invention relates to CYP26-inhibiting benzo[d]thiazole-triazole compounds, where the active compounds are selected from a defined group of benzo[d]thiazole-benzoic acid derivatives bearing a triazole substituent on a substituted butyl linker and optionally substituted benzoic acid ring groups. The disclosed compounds include variants with different triazole forms and optional substitution patterns such as 2-chloro, 2-fluoro, or 2-(trifluoromethyl) on the benzoic acid ring.
A central concept is the use of the disclosed compounds to modulate ATRA levels and inhibit CYP26 in a subject, with the therapeutic intent of lessening the severity of a condition or disease associated with ATRA level modulation. The disclosure addresses diverse diseases and conditions in which modulation of ATRA levels and CYP26 inhibition are relevant targets.
The disclosure also presents pharmaceutical compositions comprising the compounds with a pharmaceutically acceptable carrier, together with pharmaceutical formulation and administration routes described as oral, rectal, and parenteral. The patent content further indicates potential combination therapy concepts that include all-trans retinoic acid analogs, and it describes a treatment kit concept in addition to the compound and composition.
Claims Coverage
The claim coverage includes 6 inventive features. It centers on specific benzo[d]thiazole-benzoic acid derivatives and methods that inhibit CYP26 and modulate ATRA levels, with treatment scope extending to multiple disease contexts.
Defined benzo[d]thiazole-benzoic acid-triazole compound group
A compound selected from a group consisting of specific benzo[d]thiazol-2-yl benzoic acid derivatives bearing a 2-ethyl substituted butyl linker and a triazole substituent in either 1H-1,2,4-triazol-1-yl or 4H-1,2,4-triazol-4-yl form, with optional 2-chloro/2-fluoro/2-(trifluoromethyl) substitution on the benzoic acid ring.
CYP26 inhibition by administering the compound or composition
A method of inhibiting CYP26 in a subject by administering a compound selected from the group of claim 1 or a pharmaceutical composition thereof.
ATRA level modulation to lessen severity of a condition or disease
A treatment method for lessening the severity of a condition or disease by administering a compound of claim 1 or a pharmaceutical composition thereof to modulate ATRA levels in a subject in need thereof.
Fibrosis and dysproliferative disease treatment
A method of treating fibrosis and dysproliferative diseases, including cancers, by administering a compound or pharmaceutical composition thereof.
Ichthyosis treatment
A method for treating ichthyosis by administering a compound or pharmaceutical composition thereof.
Combination therapy and treatment kit
Potential combination therapy concepts that include all-trans retinoic acid analogs, and a treatment kit concept.
The claim coverage is anchored by the defined set of benzo[d]thiazole-benzoic acid-triazole derivatives, and it extends through methods that inhibit CYP26 and modulate ATRA levels to lessen disease severity, with treatment scope expressly including fibrosis, dysproliferative diseases including cancers, and ichthyosis.
Stated Advantages
Lessens the severity of a condition or disease associated with modulation of ATRA levels.
Inhibits CYP26 in a subject.
CYP26 inhibition is described as potent and selective versus other evaluated CYP enzymes.
Prevention and treatment of fibrosis.
Anti-proliferative treatment of dysproliferative diseases, including cancers.
Treatment of ichthyosis.
Documented Applications
Wound healing and acceleration of wound healing.
Improved vascularization in damaged or ischemic organs.
Amelioration of ischemia-reperfusion injury, including in the brain, heart, liver, and kidney.
Normalization of myocardial perfusion after chronic cardiac ischemia or myocardial infarction.
Enhanced collateral vessel development after vascular occlusion to ischemic tissues or organs.
Prevention and treatment of fibrosis, including hepatic fibrosis, lung fibrosis, and fibrosis-related conditions affecting the kidney and renal failure.
Treatment of radiocontrast nephropathy.
Treatment of diabetes mellitus-related renal failure and other renal failure related to chronic diabetes and/or hypertension.
Treatment of stroke (cerebral infarction).
Treatment of transplanted or grafted tissue vascularization.
Treatment of dysproliferative diseases including cancer.
Treatment of psoriasis.
Treatment of multiple neurodegenerative disorders, including Parkinson’s disease, Alzheimer’s disease, amyotrophic lateral sclerosis, muscular dystrophy, scleroderma, chronic obstructive pulmonary disease, multiple sclerosis, and other conditions described.
Treatment of skin disorders and ichthyosis, with specified ichthyosis types.
Interested in licensing this patent?