US 2026/0209180 A1 · PROTEASE INHIBITORS FOR TREATING OR PREVENTING CORONAVIRUS INFECTION

Abstract

The present invention provides a compound of Formula I wherein R1, R2, R3, R4, R5, R6, R7, and subscripts X and n are as described herein and pharmaceutical compositions comprising one or more said compounds, and methods for using said compounds for the treatment, inhibition, or amelioration of one or more disease states that could benefit from inhibition of a coronavirus, including SARS-CoV, MERS-CoV and SARS-CoV-2. The compounds of this invention could further be used in combination with other therapeutically effective agents, including but not limited to, other drugs useful for the treatment of coronavirus infection. The invention furthermore relates to processes for preparing compounds of Formula I, and pharmaceutical compositions which comprise compounds of Formula I and pharmaceutically acceptable salts thereof.

A compound of formula I

or a pharmaceutically acceptable salt thereof, wherein:
R1 is H, (C3-C6)cycloalkyl, (C1-C6)alkyl, (C1-C6)alkyl-OH, phenyl, (C1-C6)alkyl-phenyl, (C4-C6) heterocycloalkyl containing 1 to 3 heteroatom(s) independently selected from N, O, or S, (C1-C6)alkyl-(C4-C6) heterocycloalkyl containing 1 to 3 heteroatom(s) independently selected from N, O, or S, (C1-C6)alkyl-(C5-C6) heteroaryl containing 1 to 3 heteroatom(s) independently selected from N, O, or S, (C5-C6) heteroaryl containing 1 to 3 heteroatom(s) independently selected from N, O, or S;
R2 is (C1-C6)alkyl;
(C1-C6)alkyl-CF3;
(C1-C6)alkyl-OH;
(C1-C6)alkyl-O—CH3;
(C1-C6)alkyl-O—CF3;
(C1-C6)alkyl-O—(C3-C10)cycloalkyl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(CF2)-phenyl;
(C1-C6)alkyl-phenyl;
(C3-C10)cycloalkyl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C3-C10)cycloalkyl optionally substituted by a OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C4-C10) heterocycle including up to 3 heteroatoms independently selected from N, O, and S and optionally substituted by a carbonyl, OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C4-C10) heterocycle including up to 3 heteroatoms independently selected from N, O, and S and optionally substituted by a carbonyl, OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C6-C10) aryl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C6-C10) aryl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C5-C10) heteroaryl including up to 4 heteroatoms independently selected from N, O, and S and optionally substituted by an OH, CN, CHF2, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, —(C3-C6)cycloalkyl, O—(C1-C6)alkyl, O—CF3, O—(C3-C6)cycloalkyl, or up to 3 halogen;
(C1-C6)alkyl-(C5-C10) heteroaryl including up to 4 heteroatoms independently selected from N, O, and S and optionally substituted by an OH, CN, CHF2, (C3-C6)cycloalkyl, O—(C3-C6)cycloalkyl, —(C1-C6)alkyl, O—(C1-C6)alkyl, CF3, O—CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
—O—(C1-C6)alkyl;
—O—(C1-C6)alkyl-(C3-C6)cycloalkyl optionally substituted by an OH, CF3, —(C1-C6)alkyl, —(C1-C6)alkyl-CF3, or up to 3 halogen;
—O—(C3-C6)cycloalkyl optionally substituted by an OH, CF3, —(C1-C6)alkyl, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-N—CHO—O(C1-C6)alkyl;
CHF2;
CF3;
or N(R7)2;
R3 is H, F, Cl, or (C1-C6)alkyl;
R4 is H, F, Cl, or (C1-C6)alkyl;
R5 is H, F, Cl, CN, CF3, O—CHF2, O—CF3, —(C1-C6)alkyl-CF3, CHF2, CF3, (C1-C6)alkyl, (C3-C6)cycloalkyl, —O—(C3-C6)cycloalkyl, O—(C1-C6)alkyl;
R6 is H, F, Cl, or (C1-C6)alkyl;
R7 is independently H, (C1-C6)alkyl, (C3-C10)cycloalkyl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C3-C10)cycloalkyl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C4-C10) heterocycle including up to 3 heteroatoms selected from N, O, and S and optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C4-C10) heterocycle including up to 3 heteroatoms selected from N, O, and S and optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C6-C10) aryl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C6-C10) aryl optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C5-C10) heteroaryl including up to 3 heteroatoms selected from N, O, and S and optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
(C1-C6)alkyl-(C5-C10) heteroaryl including up to 3 heteroatoms selected from N, O, and S and optionally substituted by an OH, —(C1-C6)alkyl, CF3, —(C1-C6)alkyl-CF3, or up to 3 halogen;
A is C or N;
B is C or N,
D is C or N, provided that only 1 of A, B, or D can be N and that if A, B, or D is N then the respective R3, R4, or R6 is absent;
X is H or F.

38 more elements

Protease inhibitors for treating or preventing coronavirus infection

Life of this patent

Protease inhibitors for treating or preventing coronavirus infection

Life of this patent

Abstract

Claims26