Store overload-induced calcium release inhibitors and methods for producing and using the same

A compound of the formula:

• R1—X1-L-X2—R2
• wherein
• R1 is selected from the group consisting of:
• carbazolyl;
• 2,3,4,9-tetrahydro-1H-carbazolyl;
• 9H-fluorenyl;
• dibenzo[b,d]furanyl;
• (phenylamino)phenyl;
• 10H-phenothiazinyl;
• naphthalenyl;
• adamantanyl;
• (adamantanyl)alkyl;
• N-acyl-9H-cabazolyl;
• 10H-5,5-dioxide-phenothiazinyl;
• 2-oxo-1,2,3,4,4a,8a-hexahydroquinolinyl;
• 1H-indolyl, and 1H-indazolyl, each of which is optionally substituted;
• X1 is O or NR3;
• L is a linker having 3 to 9 atoms in the chain with at least two heteroatom substituents in which each of heteroatom is independently selected from the group consisting of O and N, wherein two heteroatoms in the linker optionally form a heterocyclic ring, or a heteroatom of linker L is attached to R2 and together with X2 form a heterocyclic ring, or a heteroatom of linker L and X2 together form a heterocyclic ring;
• X2 is alkylene, O, S, or NR4, or when X2 is O, S, or NR4, then X2 together with a substituent in R2 can form a heterocyclic ring;
• R2 is selected from the group consisting of phenyl;
• benzyl;
• pyridyl;
• benzo[d]oxazolyl, and benzofuranyl, each of which is optionally substituted;
• and
• each of R3 and R4 is independently selected from the group consisting of hydrogen;
• alkyl, and a nitrogen protecting group,
• provided
• when R1 is optionally substituted carbazol-4yl, then R2 is optionally substituted benzyl or pyridyl;
• or one of the two heteroatoms in linker L is N, which is located closer to R1 relative to the other heteroatom in linker L;
• or one of the two heteroatoms in linker L is carbonyl;
• or a heteroatom of linker L is attached to R2 and together with X2 form a heterocyclic ring;
• when R1 is unsubstituted carbazol-3-yl, then linker L has at least 7 atoms in the chain;
• or two heteroatoms in the linker form a heterocyclic ring;
• and
• when R1 is unsubstituted carbazol-2-yl, then linker L has at least 7 atoms in the chain;
• or two heteroatoms in the linker form a heterocyclic ring;
• or R2 is benzo[d]oxazolyl, benzofuranyl, or phenyl substituted with a substituent comprising halide, haloalkyl, or a combination thereof.