Methods and agents for treating disease
Inventors
Panicker, Bijoy • Oehlen, Lambertus J. W. M.
Assignees
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Publication Number
US-10287282-B2
Publication Date
2019-05-14
Expiration Date
Abstract
The present invention provides compounds having the general structural formula (I) [formula should be inserted here] 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 elevated levels of aldosterone or abnormal or excessive fibrosis, such as kidney disease and hypertension.
Core Innovation
The invention relates to compounds of Formula (I), including pharmaceutically acceptable derivatives, for treating diseases associated with elevated aldosterone and/or fibrosis. The compounds lower aldosterone through aldosterone synthase (CYP11B2) inhibition with selectivity over CYP11B1.
The disclosed compound framework is defined by substituent variables R1–R7 and R8–R9, including optional substituent definitions and stereochemical considerations. The disclosure further includes pharmaceutical compositions containing the compounds and pharmaceutically acceptable derivatives for therapeutic use in disease states involving aldosterone dysregulation and fibrotic pathology.
The background addresses treatment of diseases associated with elevated aldosterone and/or fibrosis, including chronic kidney disease and hypertension, and multiple fibrotic diseases. The document links therapeutic effects to anti-fibrotic and renal-protective outcomes in several disease models.
Claims Coverage
The independent claim coverage includes two main categories: a Formula (I) compound, salt, or enantiomer with detailed substituent definitions and an explicit structural exclusion, and a pharmaceutical composition comprising the Formula (I) compound with a pharmaceutically acceptable carrier, diluent, or excipient.
Formula (I) compound with R1–R7/R8–R9 substituent framework
A compound as described in Formula (I) or a salt or enantiomer thereof, with R1, R2, R3, R4, R5, R6, R7, R8, and R9 defined by the specified independent selection lists, and the compound not being benzo[d]thiazol-2-yl(pyridin-3-yl)methanol.
Pharmaceutical composition with pharmaceutically acceptable carrier, diluent, or excipient
A pharmaceutical composition comprising the compound of Formula (I) together with a pharmaceutically acceptable carrier, diluent, or excipient.
Overall, the claim coverage centers on Formula (I) compounds defined by detailed substituent-selective variable definitions and exclusion of a specific benzo[d]thiazol-2-yl(pyridin-3-yl)methanol structure, and on pharmaceutical compositions that incorporate those compounds with pharmaceutically acceptable carrier, diluent, or excipient.
Stated Advantages
Aldosterone synthase (CYP11B2) inhibition with selectivity over CYP11B1 for aldosterone lowering.
Anti-fibrotic and renal-protective effects reported in fibrosis/renal function models, including reduced kidney collagen/hydroxyproline/Sirius Red and improved renal function readouts.
Documented Applications
Treating diseases associated with elevated aldosterone and/or fibrosis, including chronic kidney disease and hypertension.
Treatment for multiple fibrotic diseases including renal, liver, lung, and cardiac fibrotic diseases.
Treatment contexts explicitly listed include ischemia-reperfusion injury and stroke-related outcomes.
Treatment for polycystic kidney disease (including PCK rat) is explicitly described.
Treatment for unilateral ureteral obstruction (UUO) is explicitly described.
Treatment for 5/6 nephrectomy models is explicitly described.
Treatment for scleroderma is explicitly described (bleomycin skin model).
Treatment for liver fibrosis is explicitly described (including hepatic stellate cells (LX2)).
Treatment for bleomycin-induced lung fibrosis model is explicitly described.
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