Heterocyclic compounds for the treatment of arenavirus

Inventors

Plewe, Michael • Brown, Eric • Gantla, Vidyasagar • Henkel, Gregory • McCormack, Kenneth • Sokolova, Nadzeda V. • Shin, Young-Jun

Assignees

Arisan Therapeutics Inc

Abstract

The invention relates to compounds of structural formula Iwherein A, D, and E are independently N or C—R3, G, H, and J are independently N or C, K is N or C—H, L is N, N—R3 or C—R3, and A, D, E, G, H, J, K, and L together cannot have more than 4 N, R1 is selected from (C6 to C10) aryl, (C2 to C9) heteroaryl, and 5-indolyl, wherein each of the said (C6 to C10) aryl and (C2 to C9) heteroaryl is substituted with at least one R4a group, and wherein said (C2 to C9) heteroaryl is C-attached, and R2 is selected from the group consisting of

Core Innovation

The invention relates to compounds defined by Structural Formula I, including pharmaceutically acceptable salts, and pharmaceutical compositions containing a therapeutically effective amount of one of the Structural Formula I compounds. The Structural Formula I definition constrains ring and substitution parameters, including that G and H are C, J and L are N, and K is C—H, and that A, D, and E are independently C—R3. The scope further specifies that R1 is selected from (C6 to C10) aryl and (C2 to C9) heteroaryl, with each selected aryl or C-attached heteroaryl substituted with at least one R4a group and subject to a proviso excluding numerous named R1 options.

The Structural Formula I constraints additionally define substituent-variable ranges for R2, R3, R4a, R4b, R5, R6a/R6b/R6c, R7, R8, R9a/R9b/R9c, and m and n. R4b is selected from a group listing specific alkoxy and related substituents, including isopropoxy, cyclopropoxy, tert-butoxy, cyclopropylmethoxy, difluoromethoxy, methoxyethoxy, acetyl, and related alkyl, cycloalkyl, and acyl-type variants. R6a and R6b may be taken together with the nitrogen atom to form a 4 to 8 membered cycloheteroalkyl ring having 1 to 3 ring heteroatoms selected from N, O, and S.

The invention further provides methods for relieving or alleviating arenavirus infection by administering a therapeutically effective amount of a compound of Structural Formula I, with the same Structural Formula I constraints. Pharmaceutical compositions include a therapeutically effective amount of the Structural Formula I compound together with a pharmaceutically acceptable carrier, diluent, or vehicle. The document also contemplates administration of optional co-therapeutic agents selected from antivirals, RNA-targeting agents such as small interfering RNAs and microRNAs, vaccines, and immunomodulators.

Claims Coverage

The provided claim set includes five independent claims: one compound claim (Structural Formula I), one claim selecting a compound from a specified group, one pharmaceutical composition claim, and two method claims directed to relieving and alleviating arenavirus infection. Across these independent claims, the core inventive coverage is the defined Structural Formula I scaffold with extensive substitution rules and explicit exclusions for R1, the compound-selected claim, and compositions and infection-treatment contexts.

Overall, the independent claims cover Structural Formula I compounds with extensive substitution variability and explicit exclusion of a listed R1 set, a compound-selected claim, and compositions and methods for relieving or alleviating arenavirus infection via administration of a therapeutically effective amount. Dependent claims narrow the structural options by fixing particular substituents and may add co-administration of specified therapeutic agent categories.

Stated Advantages

Documented Applications