BORONIC ACID INHIBITORS OF HIV PROTEASE

摘要

Protease inhibitors, particularly aspartyl protease inhibitors, and more particularly HIV protease inhibitors which are boronated to enhance activity or to enhance entry into cells. Compounds, prodrugs and salts thereof of this invention contain phenylboronate groups, in particular p-B(OH)2-phenyl groups, benzoxaborole groups or borono-pyridyl groups or analogous groups in which the boronate group is protected. Methods for treating AIDS and ARC as well as providing a method for treating or preventing HIV infection

主权项

1. A compound of formula: or a salt, ester, solvate or hydrate thereof, wherein: x is 0 or 1 to show the presence or absence of —XX—, —XX— when present is —O—, —CO2—, —SO2, —CO—CO—, —O—CO—, —O—SO2—, —NR10—SO2—, —NR10—CO— or —NR10—CO—CO—; where each R10 is independently H, C1-C4 alkyl or C1-C4 alkyl substituted with C3-C7 cycloalkyl; R20, R20A and R20B are independently selected from C1-C4 alkyl, C3-C6 cycloalkyl, C5-C6-cycloalkenyl, phenyl, C1-C4 alkyl substituted with one or more phenyl, or C3-C6 cycloalkyl groups, a C3-C6 cycloalkyl group substituted with or fused to phenyl or a C5-C6 cycloalkyl group substituted with or fused to a phenyl; R21 is selected H; —PO3(R3)2; or —PO3R3H or —PO3H2 or pharmaceutically acceptable salts thereof; or an acyl group (—CO—R22), where R22 is selected from C1-C4 alkyl, C2-C4 alkenyl, or C2-C10 alkyl wherein one or more —CH2— groups are replaced with —O—; or a C2-C10 alkyl wherein one or more —CH2— groups are replaced with —NH— or one or more —CH3 groups are replaced with —NR23, where R23 is H or a C1-C4 alkyl; and A is selected from H; Het; C6-C10 aryl; C3-C7 cycloalkyl; C5-C7 cycloalkenyl; C1-C4 alkyl; C2-C4 alkenyl; C1-C4 alkyl substituted with one or more C1-C4 alkoxy, C3-C7 cycloalkyl, C5-C7 cycloalkenyl, C6-C10 aryl, or a Het group, wherein Het is selected from a 5-10 membered saturated, partially saturated or unsaturated cyclic group containing one or more heteroatoms or moieties selected from —N═; —N(R24)—; —O—; —S—, —SO—; —SO2—, or —CO—, where R24 is selected from H, C1-C4 alkyl, C1-C4 alkyl substituted with a C3-C7 cycloalkyl group, or C1-C4 alkyl substituted with a C6-C10 aryl group; wherein each R20, R22, R23, R24, A or Het group is optionally substituted with one or more oxo, C1-C3-alkoxy, —OH, —C1-C3 alkyl, —CO—R25, —N(R25)2, —CO2R25 (or when R25 is H, pharmaceutically acceptable salts thereof), —NR25—CO—R25, —CO—N(R25)2, —(CH2)r—OH (where r is 1 or 2), —CN, —NO2, halo or —CF3, and R25 is selected from H or C1-C3 alkyl, and wherein BBB is a boronated aryl, heteroaryl group or boronate protected derivative thereof selected from: is any one of: