Broad spectrum antiviral compounds targeting the ski complex
AssigneeUniversity of Maryland, Baltimore
InventorsMatthew Frieman, Alexander D. Mackerell, JR., Stuart WESTON
Life of this patent
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Abstract
Compounds and methods of using the same for treating conditions alleviated by SKI complex inhibition, viral replication inhibition, or interferon signaling inducement are provided.
Claims31
A compound of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof:
- wherein in formula (I):
- W is selected from C1-C5-alkyl and
- Y is selected from H,
- A and B are each independently selected from:
- X2 and X3 at each occurrence are independently selected from O and S;
- Z is selected from —CH2— and —C(O)—;
- R1a and R1b at each occurrence are independently C1-C5-alkyl;
- R2a, R2b, R2c, R3a, R3b, R3c, R4a, R4b, R4c, R4d, and R4e at each occurrence are independently selected from hydrogen, halo, C1-C5-alkyl, trifluoromethyl, —(C1-C5-alkyl)-OH, phenyl, thiophenyl, furyl, and —C(O)O—C1-C5-alkyl;
- and
- n is an integer selected from 1 to 5.
A compound of formula (II), or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof:
- wherein in formula (II):
- X is N or CR1d;
- R1a, R1b, R1c, and R1d are each independently selected from hydrogen, C1-C5-alkyl, —OH, C1-C5-alkoxy, C1-C5-cycloalkyl,
- Xa is at each occurrence independently selected from —CH2—, —O—, —NH—, or —N(C1-C5-alkyl)-;
- R2 is selected from hydrogen, C1-C5-alkyl, C1-C5-alkenyl, —(C1-C5-alkyl)-OH,
- Xb is at each occurrence independently selected from —CH2—, —O—, —NH—, or —N(C1-C5-alkyl)-;
- R3a and R3b are each independently selected from hydrogen, C1-C5-alkyl, —(C1-C5-alkyl)-O—(C1-C5-alkyl),
- or R3a and R3b are joined together to form
- R4 is at each occurrence independently selected from hydrogen and halo;
- R5 is at each occurrence independently selected from
A compound of formula (III), or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof:
- wherein in formula (III):
- R1a is selected from
- R1b is selected from C1-C5-alkyl and —(C1-C5-alkyl)-O—(C1-C5-alkyl);
- R2 is selected from C1-C10-alkyl, C3-C10-cycloalkyl, —(CH2)—C3-C10-cycloalkyl, and —(CH2)—C6-C10-aryl;
- X2 and X2′ at each occurrence are independently selected from O and S;
- and
- R3a, R3b, R3c, R3a′, R4a, R4b, R4c, R4d, and R4e at each occurrence are independently selected from hydrogen, halo, C1-C5-alkyl, and C1-C5-alkoxy.
A compound of formula (IV), or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof:
A compound of formula (V), or a pharmaceutically acceptable salt, solvate, hydrate, cocrystal, or prodrug thereof:
- wherein in formula (V):
- A is selected from
- V is selected from a single bond and
- W is selected from a single bond
- R1 is selected from
- R2a and R2b are each independently selected from hydrogen, —OH, and C1-C5-alkoxy, or R2a and R2b are joined to form
- R4a is selected from hydrogen and C1-C5-alkyl,
- R4b is selected from C3-C10-cycloalkyl, —(CH2)—C3-C10-cycloalkyl,
- and
- R5 is selected from hydrogen, C1-C10-alkyl, and
-57. (canceled)
Dependencies are inferred from the claim text.