Ion channel antagonists/blockers and uses thereof

A compound or a pharmaceutically acceptable salt, a solvate, or a stereoisomer thereof,

• wherein
• the compound is a compound of formula (IIh);
• wherein
• R1 is —O—, or —S—;
• R3 is selected from the group consisting of:
• —O—, —S—, —N(Ra)—, and —C(Rb)2—;
• wherein Ra is selected from the group consisting of H, and C1-C4 alkyl, and Rb is each independently selected from the group consisting of H and C1-C6 alkyl;
• L1 is substituted or unsubstituted C3-C8 cycloalkyl or unsubstituted C1-C6 alkylene group;
• R7 is selected from the group consisting of:
• H, —OH, halogen, Rf—, Rf—O—, Rf—S—, Rf—C(O)O—, Rf—S(O)2—, Rf—S(O)—, Rf—C(O)—, NHRf, NH(SO2)Rf, and —R1a-L1a-Rda, wherein Rf is selected from the group consisting of:
• H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C3-C6 cycloalkyl;
• R1a is —O—, or —S—;
• L1a is unsubstituted C1-C6 alkylene group, or substituted or unsubstituted C3-C8 cycloalkyl;
• each R2 is independently selected from the group consisting of:
• H, and substituted or unsubstituted C1-C6 alkyl;
• or two R2 and the nitrogen atom to which they are attached form a substituted or unsubstituted 4 to 10 membered heterocyclic group, and the heterocyclyl contains 1 or 2 N atoms and 0, 1, or 2 O or S heteroatoms;
• Rc, Rd and Rda are each independently selected from the group consisting of —OH, nitro, cyano, sulfonyl, R″, —N(R″)2—, R″—O—, R″—S—, R″—S(O)2—, R″—S(O)—, R″—C(O), R″—C(O)O—, and R″—OC(O)—;
• n1 and n2 are each independently 0, 1, or 2;
• each of m is independently 0, 1, 2 or 3;
• and
• unless otherwise specified, the term “substituted” refers to one or more hydrogens in the group is replaced with an R′ group;
• each R′ is independently selected from the group consisting of D, halogen, —OH, nitro, cyano, sulfonyl, R″, —N(R″), R″—O—, R″—S—, R″—S(O)2—, R″—S(O)—, R″—C(O), R″—C(O)O—, R″—OC(O)—, and oxo (O═);
• or when two R′ attached to the same carbon atom, the two R′ and the carbon atom to which they are attached form substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C10 aryl, substituted or unsubstituted 4 to 7 membered heterocyclic group or 5 to 7-membered heteroaryl;
• R″ is each independently selected from the group consisting of H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C6-C10 aryl, 4- to 7-membered heterocycloalkyl, 5- to 7-membered heteroaryl, -C1-C4 alkylene-C3-C6 cycloalkyl, -C1-C4 alkylene-C6-C10 aryl, -C1-C4 alkylene-(4 to 7-membered heterocycloalkyl), and -C1-C4 alkylene-(5 to 7-membered heteroaryl);
• and in R″, the alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl or heteroaryl, as a whole group or a partial group, is optionally substituted by a substituent selected from the group consisting of:
• halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, —OH, nitro, cyano, sulfonyl, and amino;
• or the compound is selected from the following table:
• Compd
• Example
• ID
• No.
• Structure
• A234
• 85
• TJU-A234
• A235
• 85
• TJU-A235
• A139-2
• 74
• TJU-A139-2
• A262
• 26
• TJU-A262
• A271
• 92
• TJU-A271
• A279
• 93
• TJU-A279
• A286
• 95
• TJU-A286
• A191
• 80
• TJU-A191