Novel opioid compounds and uses thereof

A pharmaceutical composition, comprising a compound of Formula I:

• or a pharmaceutically acceptable salt or solvate thereof, wherein:
• R1 is H;
• alkyl optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of hydroxy, halo, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy, and alkoxycarbonyl;
• -PEG-R7;
• or a hydroxyl protecting group PG selected from the group consisting of alkyl, arylalkyl, heterocyclo, (heterocyclo)alkyl, acyl, silyl, and carbonate, any of which is optionally substituted;
• Z is C—OR2 or C(═O);
• is single bond or a double bond, provided that is a single bond when Z is C(═O) and is a double bond when Z is C—OR2;
• R2 is C(═O)R5 or -PEG-R7, wherein
• R5 is selected from the group consisting of unsubstituted C1-12 alkyl, unsubstituted C2-12 alkenyl, unsubstituted C2-12 alkynyl , —CH2—O—(CH2CH2O)m—R7, —O—(CH2CH2O)n—R7, —NH—(CH2CH2O)p—R7, phenyl, benzyl, phenethyl, pyridyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, 6-membered heterocycle, and (5- or 6-membered heterocycle)alkyl, wherein the phenyl, pyridyl, cycloalkyl, cycloalkenyl, and heterocycle moiety is optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of alkyl, hydroxy, halo, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy, and alkoxycarbonyl;
• and wherein the 6-membered heterocycle group is attached to the carbonyl carbon of R2 through a carbon atom or through a nitrogen atom;
• R3 is hydrogen, OH, —Y-PEG-R7, or —OC(═O)R6, wherein
• Y is a covalent bond or a linker;
• R6 is selected from the group consisting of unsubstituted C1-12 alkyl, unsubstituted C2-12 alkenyl, unsubstituted C2-12 alkynyl, —CH2—O—(CH2CH2O)m—R7, —O—(CH2CH2O)n—R7, —NH(CH2CH2O)p—R7, phenyl, benzyl, phenethyl, pyridyl, cycloalkyl, (cycloalkyl)alkyl, cycloalkenyl, (cycloalkenyl)alkyl, 6-membered heterocycle, and (5- or 6-membered heterocycle)alkyl, wherein the phenyl, pyridyl, cycloalkyl, cycloalkenyl, and heterocycle moiety is optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of alkyl, hydroxy, halo, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy, and alkoxycarbonyl;
• and wherein the 6-membered heterocycle group is attached to the carbonyl carbon through a carbon atom or through a nitrogen atom;
• provided that R3 is —OC(═O)R6 when Z is C(═O);
• PEG is one ethylene oxide unit or an oligomer of 2 or more ethylene oxide subunits;
• R7 is selected form the group consisting of hydrogen, C1-6 alkyl, aryl, heteroaryl, cycloalkyl, and heterocyclo, any of which is optionally substituted;
• R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, and (cycloalkyl)alkyl, any of which is optionally substituted with 1, 2, or 3 substituents, each independently selected from the group consisting of hydroxy, halo, haloalkyl, amino, alkylamino, dialkylamino, carboxy, alkoxy, and alkoxycarbonyl;
• m is an integer between 1 and 9;
• n and p are each independently an integer between 1 and 20;
• and
• provided that at least one of R2 and R3 is —C(═O)R5 and —OC(═O)R6, respectively;
• with the following provisos:
• 1) the compound is not
• 2) when R1 is unsubstituted alkyl, R3 is hydrogen, and R4 is unsubstituted alkyl, then R5 is other than optionally substituted phenyl or optionally substituted pyridyl,
• 3) when R1 is unsubstituted alkyl, R4 is unsubstituted alkyl, and R3 is OC(═O)R6, then both R5 and R6 are other than optionally substituted pyridyl,
• 4) the compound is not
• and one or more pharmaceutically acceptable carriers.