Methods and compositions useful in treating cancer and reducing Wnt mediated effects in a cell
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-11834446-B2
Publication Date
2023-12-05
Expiration Date
Abstract
Provided herein are novel compounds, pharmaceutical compositions for use, inter alia, in methods of reducing Wnt-mediated effects and treating cancer.
Core Innovation
The disclosure provides a class of compounds and pharmaceutically acceptable salts defined by a broad structural formula. The compounds include variable substituents L1, R2, R4/R4A/R4B, R5/R5A/R5B, R6/R6A/R6B, R10/R11, and R12/R12A/R12B, together with ring/linkage parameters z and w, and additional substituent groups that may be joined to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.
L1 is —NH—C(O)— or —C(O)—NH—, and the substituents are described through extensive options including hydrogen, halogen, —CN, —CF3, substituted or unsubstituted alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl. The structural definition further includes z and w as integers from 0 to 4.
The patent also states Wnt-pathway inhibition for reducing Wnt-mediated cellular effects and for treating cancer, and includes methods of contacting cells or administering the disclosed compounds, together with pharmaceutical compositions comprising the compound and a pharmaceutically acceptable excipient.
Claims Coverage
The claims cover one broad independent structural formula for compounds or pharmaceutically acceptable salts, with multiple inventive feature areas involving the L1 linkage, multi-position substituent variability, ring/joining parameters, and formulation coverage. Dependent claims further specify labeled structural embodiments, a connectivity exclusion, and pharmaceutical composition coverage.
Broad structural formula with variable substituents
A compound having the formula, or a pharmaceutically acceptable salt thereof, wherein L1 is —NH—C(O)— or —C(O)—NH—, and R2, R4/R4A/R4B, R5/R5A/R5B, R6/R6A/R6B, R10/R11, and R12/R12A/R12B are defined by the listed substituent options, with z and w each an integer from 0 to 4.
Joined ring and linkage parameters
R10 and R11 are joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl, and R2 and R5 may also be optionally joined together to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.
Specific structural embodiments via labeled formula depictions
The compound of claim 1, or a pharmaceutically acceptable salt, having the specific structural formula shown in the claim images (XIIB/XIIA).
Connectivity exclusion for R2 and R5
The compound of claim 1, or a pharmaceutically acceptable salt, in which R2 and R5 are not connected to form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl.
Pharmaceutical composition with pharmaceutically acceptable excipient
A pharmaceutical composition including the compound of claim 1, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable excipient.
Claim coverage centers on a broad structural formula with an L1 linkage, extensive substituent variability at multiple positions, and ring/joining parameters, including optional joining of R2 and R5 and joined R10/R11 groups. The dependent claims narrow or specify the formula through labeled embodiments, a connectivity exclusion, and pharmaceutical composition coverage.
Stated Advantages
Reduces Wnt-mediated effects, as indicated by altered degradation/activity markers including Pygopus, β-catenin, Axin, Myc, CD44, Axin2, Bcl-9, and cyclin D.
Can treat cancer by administration of the compounds in an effective amount.
Reducing Wnt-mediated cellular effects.
Treating cancer.
Documented Applications
Treating cancer by administering a compound defined by the formula or a pharmaceutically acceptable salt in an effective amount.
Use of pharmaceutical compositions that include the compound or pharmaceutically acceptable salt together with pharmaceutically acceptable excipients.
Reducing Wnt-mediated cellular effects by contacting cells with the disclosed compound or pharmaceutically acceptable salt.
Treating cancer in a subject by administering an effective amount of the disclosed compound or pharmaceutically acceptable salt.
Interested in licensing this patent?