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US 2023/0331683 A1Published application
Inhibitors of spinster homolog 2 (spns2) for use in therapy
AssigneeUniversity of Virginia Patent Foundation
InventorsKevin R. Lynch, Yugesh Kharel, Webster L. Santos, Russell G. Fritzemeier, Ariel Louise Burgio, Christopher Shrader, Daniel Foster
Life of this patent
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Abstract
The present disclosure provides SPNS2 inhibitor compounds according to Formula (IA) and Formula (I), and their pharmaceutically acceptable salts, and/or tautomers as described in the disclosure, and the disclosure provides their pharmaceutical compositions and methods of use in therapy.
Claims37
A compound according to Formula IA:
- wherein
- X is a C6-C10-aryl or 5- to 10-membered heteroaryl (wherein 1 to 4 heteroaryl ring members are independently selected from N, O, and S);
- R1 and R2 are independently selected from the group consisting of H, C1-C6-alkyl, C1-C6. alkoxy, C1-C6-haloalkoxy, C3-C8-cycloalkyl, C1-C6-haloalkyl, CN, and halo;
- W is a bond, O, NH, —NHC(O)—, or —O—(N═)C(R)— (wherein R is H or C1-C6-alkyl);
- V is selected from the group consisting of H, C1-C14-alkyl, C2-C12-alkenyl, (C6-C10)aryl, (C6-C10)heteroaryl, -C1-C10-alkyl-(C6-C10)aryl, -C2-C12-alkenyl-(C6-C10)aryl, -C1-C10-alkyl-(C3-C8)cycloalkyl, -(3- to 14-membered heterocycloalkyl) (wherein 1-4 heterocycloalkyl members are independently selected from N, O, and S), -(C1-C10)alkyl-(3- to 14-membered heterocycloalkyl) (wherein 1-4 heterocycloalkyl members are independently selected from N, O, and S);
- T is selected from the group consisting of a bond, —C(O)—, —C(O)NRx—, —C(S)NRx—, —NRxC(O)—, —NRx—, —NRxC(O)NRx—, and —NRxC(O)O—;
- Rx in each instance is independently selected from H and C1-C6-alkyl;
- m is an integer selected from 0, 1, 2, 3, 4, 5, and 6;
- n is an integer selected from 1 and 2, wherein the sum of n and o is greater than 0;
- each “---” is a single bond that is optionally present, wherein all “---” are simultaneously present or absent, and wherein
- when “---” is present, then
- o is selected from 1, 2, and 3;
- and
- p is 0, (N)pR6 represents a bond, and U is —CH— or N, or
- p is 1 and U is —CH—;
- and
- when “---” is not present, then o is 0 and U is —CH2— or NH;
- q is an integer selected from 1, 2, and 3;
- R3 is selected from the group consisting of, H, C1-C6-alkyl, and —C(NH)NH2;
- R4 is absent when “---” is present, and when “---” is absent, then R4 is H or C1-C6-alkyl;
- each R5 is independently selected from the group consisting of H, C1-C6-alkyl, C1-C6-alkoxy, C1-C6-haloalkoxy, C3-C8-cycloalkyl, C1-C6-haloalkyl, CN, NH2, and halo;
- R6 is H or C1-C6-alkyl;
- wherein each alkyl, alkoxy, alkenyl, alkynyl, aryl, cycloalkyl, heterocycloalkyl, and heteroaryl is optionally substituted with 1 - 5 substituents independently selected from the group consisting of hydroxy, halo, C1-C6-haloalkoxy, C1-C6-haloalkyl, —NR′2, -NHC(O)(OC1-C6-alkyl), —NO2, —CN, oxo, —C(O)OH, -C(O)O(C1-C6-alkyl), -C1-C6-alkyl(C1-C6-alkoxy), —C(O)NH2, C1-C6-alkyl, -C(O)C1-C6-alkyl, -OC1-C6-alkyl, -Si(C1-C6-alkyl)3, -S(O)0-2-(C1-C6-alkyl), C6-C10-aryl, -(C1-C6-alkyl)(C6-C10-aryl), 3- to 14-membered heterocycloalkyl, and -(C1-C6-alkyl)-(3- to 14-membered heterocycle) (wherein 1-4 heterocycle members are independently selected from N, O, and S), and -O(C6-C14-aryl);
- and
- wherein each R′ is independently selected from the group consisting of C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C6-C10-aryl, 3- to 14-membered heterocycloalkyl and -(C1-C6-alkyl)-(3- to 14-membered heterocycloalkyl) (wherein 1-4 ring members are independently selected from N, O, and S), and 5- to 10-membered heteroaryl (wherein 1-4 heteroaryl members are independently selected from N, O, and S;
- or a pharmaceutically acceptable salt thereof.
23 more elements
37-42. (canceled)
Dependencies are inferred from the claim text.