| 摘要 |
Antiviral protease inhibitors, including macrocylic transition state inhibitors and peptidomimetics are disclosed, along with related antiviral compounds, and methods of using the same to treat or prevent viral infection and disease. The compounds possess broad-spectrum activity against viruses that belong to the picornavirus-like supercluster, which include important human and animal pathogens including noroviruses, sapoviruses, enteroviruses, poliovirus, foot-and-mouth disease virus, hepatitis A virus, human rhinovirus (cause of common cold), human coronavirus (another cause of common cold), transmissible gastroenteritis virus, murine hepatitis virus, feline infectious peritonitis virus, and severe acute respiratory syndrome coronavirus. |
| 主权项 |
1. An antiviral compound comprising:or the pharmaceutically-acceptable salts thereof, where:
each X is selected from the group consisting of aldehydes; bisulfate salts; ketoamides; α-hydroxyphosphonates; sulfonamides; and ketones; each R0 is —CH— or —N—; each R1 is a natural or non-naturally occurring amino acid side chain such as branched or unbranched alkyl, cycloalkyl, aryl, arylalkyl, or a combination thereof; each R2 is selected from the group consisting of —C(O)OR8, where R8 is alkyl, cycloalkyl, or substituted or unsubstituted: aryl, arylalkyl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or aromatic heterocyclic ring; —C(O)NHR9, where R9 is alkyl, cycloalkyl, or substituted or unsubstituted: aryl, arylalkyl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or aromatic heterocyclic ring; and —SO2R10, where R10 is alkyl, cycloalkyl, or substituted or unsubstituted: aryl, arylalkyl, aryloxy, heteroaryloxy, arylalkoxy, heteroarylalkoxy, or aromatic heterocyclic ring; each R3 is selected from the group consisting ofand
—(CH2)2C(O)NR14R15, where R14 is alkyl, cycloalkyl, or arylalkyl, and R15 is H or alkyl, or R14 and R15 are tethered together to form a cyclic amine; each W is selected from the group consisting of —(CH2)x—, where x is 4 to 10; —CH2Q(CH2)z—, where Q is S or O, and z is 4 to 8; —(CH2)mC(O)NR11(CH2)p—, where R11 is H or methyl, m is 1 to 2, and p is 3 to 6; —CH2Im(CH2)t—, where Im is imidazole and r is 3 to 6; —(CH2)sTr(CH2)s—, where Tr is a 1,4- or 1,5-substituted triazole and each s is 1 to 4; and —(CH2)tR12(CH2)t—, where R12 is a phenyl or heterocyclic ring, and each t is 1 to 4; and each Y is —CH2— or NR13, where R13 is H, alkyl, cycloalkyl, or arylalkyl. |
