Nuclear transport modulators and uses thereof
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10709706-B2
Publication Date
2020-07-14
Expiration Date
Abstract
The present invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising the compounds of formula (I) or their pharmaceutically acceptable salts, and methods of using said compounds, salts and compositions in the treatment of various disorders associated with CRM1 activity.
Core Innovation
The disclosure relates to nuclear transport modulators comprising heteroaryl compounds of structural formula (Ia), (Ib), or (Ic), related specific structures, and pharmaceutically acceptable salts thereof. These compounds encompass substituted pyrimidine- and pyrazine-based acrylamides and heteroaryl carboxamides with defined substituents, including aryl, heteroaryl, sulfonamide groups, and 3,5-bis(trifluoromethyl)phenyl moieties, with specified values of n. The disclosure also identifies pharmaceutical compositions comprising these compounds or salts and pharmaceutically acceptable carriers.
The compounds function as CRM1 (exportin-1/XPO1) inhibitors for treating CRM1-associated disorders and conditions associated with abnormal nuclear transport, while the problem being solved is not explicitly described in patent. Disclosed therapeutic applications encompass proliferative disorders, inflammatory conditions, viral infections, ophthalmological diseases, neurodegenerative disorders, disorders of abnormal tissue growth, food intake disorders, allergic disorders, and respiratory disorders. Biological evaluations report antiproliferative testing in MM1S multiple-myeloma cells and Z138 leukemia cells, alongside combination therapy applications.
Claims Coverage
The claim information identifies three independent claims, comprising claims 1, 25, and 26, directed to compounds or pharmaceutically acceptable salts thereof across three inventive features.
Compounds of structural formula (Ia), (Ib), or (Ic) with defined substituents
Claim 1 covers a compound of structural formula (Ia), (Ib), or (Ic), or a pharmaceutically acceptable salt thereof, with defined substituent ranges for R1, R2, Rb, R3, R4, R5, R6, and R7, and n specified as 0, 1, 2, 3, 4, or 5.
Compounds represented by recited structural formulas
Claim 25 covers a compound represented by any one of the recited structural formulas in the claim, or a pharmaceutically acceptable salt thereof.
Compounds represented by additional recited structural formulas
Claim 26 covers a compound represented by any one of the recited structural formulas in the claim, or a pharmaceutically acceptable salt thereof.
The independent claims cover compounds defined by three sets of structural formulas and pharmaceutically acceptable salts, with claim 1 specifying broad substituent definitions and ranges for n.
Stated Advantages
The description reports synergistic effects in combination therapies with doxorubicin or bortezomib.
The compounds are described for use as radiosensitizers.
Documented Applications
Pharmaceutical compositions comprising a claimed compound or pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
Treatment of CRM1-associated disorders and conditions associated with abnormal nuclear transport, including proliferative disorders (such as relapsed or refractory multiple myeloma), viral infections, ophthalmological disorders, neurodegenerative disorders, inflammatory and autoimmune disorders, disorders of abnormal tissue growth, disorders related to food intake, allergic disorders, respiratory disorders, and wounds.
Combination therapy with doxorubicin or bortezomib, and use in combination with radiation therapy.
Evaluation of antiproliferative activity in MM1S multiple-myeloma cells, Z138 leukemia cells, and 3T3 fibroblasts.
Interested in licensing this patent?