Compounds and their methods of use
Inventors
Reddy, Kiran • MARTINEZ BOTELLA, Gabriel • Griffin, Andrew Mark • Marron, Brian Edward
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11773099-B2
Publication Date
2023-10-03
Expiration Date
Abstract
The present invention is directed to, in part, fused heteroaryl compounds and compositions useful for preventing and/or treating a disease or condition relating to aberrant function of a voltage-gated, sodium ion channel, for example, abnormal late/persistent sodium current. The fused heteroaryl compounds of the disclosure are represented by Formula (I): wherein X, Y, Z, A, R1 and R2 are as defined in the specification. Methods of treating a disease or condition relating to aberrant function of a sodium ion channel including Dravet syndrome or epilepsy are also provided herein.
Core Innovation
The invention relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, with X and Z both CH and Y as N. The scaffold specifies A as phenyl or 5-6 membered heteroaryl, optionally substituted by one or more R3.
The compounds are defined by multiple variable substituent groups, including R1, R2, R3, Rc, R4, R5, and R6, with nested optional substitution patterns. R1, R2, R3, Rc, R4, R5, and R6 are each selected from explicitly defined sets of hydrogen, alkyl, carbocyclyl, heterocyclyl, phenyl, heteroaryl, halo, cyano, nitro, and —ORc or —OH, as applicable.
The document also describes fluorinated imidazo[1,5-c]pyrimidine derivatives and related intermediates and compounds, including substituted aryl and heteroaryl motifs on the imidazo[1,5-c]pyrimidine scaffold. Specific fluorinated substituent types referenced include trifluoromethoxy, trifluoromethyl, and difluoromethyl substituents, and related functional group variants.
Claims Coverage
The independent claim coverage centers on a Formula (I) compound family with a fixed ring relationship and a detailed set of substituent constraints. One independent claim family is present across the inputs, covering the scaffold and its permitted variable groups.
Formula (I) compound scaffold with fixed X, Y, and Z positions
A compound of Formula (I) or a pharmaceutically acceptable salt thereof, wherein X and Z are both CH and Y is N.
Phenyl or 5-6 membered heteroaryl group A optionally substituted by R3
A is phenyl or 5-6 membered heteroaryl, and the phenyl or 5-6 membered heteroaryl group is optionally substituted by one or more R3.
Substituent R1 constrained to defined groups
R1 is independently selected from hydrogen, C1-6 alkyl, C3-8 carbocyclyl, 3-10 membered heterocyclyl, halo, and cyano, with optional substitution by R4.
Substituent R2 limited to defined groups
R2 is independently selected from hydrogen, C1-6 alkyl, halo, and cyano, with C1-6 alkyl optionally substituted by one or more R4.
Substituent R3 defined over optional substitution sets
R3 is independently selected from C1-6 alkyl, C3-8 carbocyclyl, 3-10 membered heterocyclyl, halo, cyano, nitro, and —ORc, with optional substitution by R5 on selected groups.
Substituent Rc and its allowed substituent family
Rc is independently selected from hydrogen, C1-6 alkyl, phenyl, C3-8 carbocyclyl, 3-10 membered heterocyclyl, and 5-6 membered heteroaryl, with optional substitution by R6 on selected groups.
Substituent R4, R5, and R6 allowed functional sets
R4 and R5 are each independently selected from C1-6 alkyl, C3-8 carbocyclyl, 3-10 membered heterocyclyl, phenyl, 5-6 membered heteroaryl, halo, cyano, nitro, and —ORc, and R6 is independently selected from C1-6 alkyl, C3-8 carbocyclyl, 3-10 membered heterocyclyl, halo, cyano, nitro, and —OH.
The claim coverage centers on a Formula (I) imidazo[1,5-c]pyrimidine scaffold with fixed X, Y, and Z positions, A selected as phenyl or 5-6 membered heteroaryl, and tightly defined substituent sets for R1, R2, R3, Rc, R4, R5, and R6.
Stated Advantages
Preventing and/or treating diseases related to aberrant voltage-gated sodium ion channel function.
Treating or preventing disease related to abnormal late/persistent sodium current (INaL).
Use for Dravet syndrome and epilepsy.
Documented Applications
Preventing and/or treating diseases related to aberrant voltage-gated sodium ion channel function, particularly abnormal late/persistent sodium current (INaL).
Preventing and/or treating Dravet syndrome.
Preventing and/or treating epilepsy.
Modulating late sodium current (INaL) in Nav1.6 (hNav1.6) using PatchXpress, with inhibition categories A/B/C reported across multiple compounds in Table 1.
Interested in licensing this patent?