Indole, benzimidazole, and benzolactam boronic acid compounds, analogs thereof and methods of use thereof

A method of inhibiting phosphodiesterase in a subject in need thereof, the method comprising administering to the subject a compound selected from the group consisting of:

• (a) a compound of Formula I or Formula II
• (b) a compound of Formula III, Formula IV, or Formula V:
• (c) a compound of Formula VI:
• wherein:
• A is N or C in compounds of Formula I and II, subject to the proviso that R5 is absent when A is N;
• A is S, O, SO2 or NR in compounds of Formula VI;
• X is —C(O)—, —S(O)2—, or a covalent bond;
• Y is alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, alkyloxyalkyl, aryl, alkylaryl, alkylarylalkyl, arylalkyl, cycloalkylalkyl, alkylheterocycle, heterocyclealkyl, alkylheterocyclealkyl, heterocycle, aminoalkyl, oxyalkyl, aminoaryl, oxyaryl;
• Z is selected from the group consisting of —B(OR1)OR2, —CON(R1)OR2, and —N(OR1)COR2;
• R1 and R2 are each independently H, loweralkyl, or together form C2-C4 alkylene;
• and
• R3, R4, R5, R6, and R7 and, if present, R, R8, R9, and R10 are each independently selected from the group consisting of:
• H, halo, loweralkyl, haloloweralkyl, haloloweralkoxy, loweralkoxy, hydroxy, loweralkoxycarbo, cycloalkyl, alkylcycloalkyl, carboxylic acid, acyl, azido, mercapto, alkylthio, amino, heterocycleamino, alkylamino, dialkylamino, acylamino, aminoacyl, arylamino, arylalkyl, arylalkylamino, aryloxy, cyano, sulfonamide, aminosulfonyl, sulfone, nitro;
• arylalkyloxy, cycloalkyloxy, cycloalkylalkoxy, cycloalkylamino, urea, cycloalkylalkylamino, cycloalkyl, alkylcycloalkyl, hydroxyamino, alkoxyacylamino, and arylthio;
• and 5- or 6-membered organic rings containing 0 to 4 heteroatoms selected from the group consisting of N, O and S, which rings may be unsubstituted or substituted from 1 to 4 times with halo, loweralkyl, haloloweralkyl, haloloweralkyloxy, loweralkoxy, hydroxy, loweralkoxycarbo, carboxylic acid, acyl, azido, mercapto, alkylthio, amino, heterocycleamino, alkylamino, dialkylamino, acylamino, aminoacyl, arylamino, arylalkyl, arylalkylamino, aryloxy, cyano, sulfonamide, aminosulfonyl, sulfone, nitro;
• and oxoheterocyclic groups;
• or R8 and R9, if present, together are ═O or ═S;
• or a pharmaceutically acceptable salt or prodrug thereof, in an amount effective to inhibit phosphodiesterase.

A method of treating an inflammatory disease in a subject in need thereof, the method comprising administering to the subject a compound selected from the group consisting of:

• (a) a compound of Formula I or Formula II
• (b) a compound of Formula III, Formula IV, or Formula V:
• (c) a compound of Formula VI:
• wherein:
• A is N or C in compounds of Formula I and II, subject to the proviso that R5 is absent when A is N;
• A is S, O, SO2 or NR in compounds of Formula VI;
• X is —C(O)—, —S(O)2—, or a covalent bond;
• Y is alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, alkyloxyalkyl, aryl, alkylaryl, alkylarylalkyl, arylalkyl, cycloalkylalkyl, alkylheterocycle, heterocyclealkyl, alkylheterocyclealkyl, heterocycle, aminoalkyl, oxyalkyl, aminoaryl, oxyaryl;
• Z is selected from the group consisting of —B(OR1)OR2, —CON(R1)OR2, and —N(OR1)COR2;
• R1 and R2 are each independently H, loweralkyl, or together form C2-C4 alkylene;
• and
• R3, R4, R5, R6, and R7 and, if present, R, R8, R9, and R10 are each independently selected from the group consisting of:
• H, halo, loweralkyl, haloloweralkyl, haloloweralkoxy, loweralkoxy, hydroxy, loweralkoxycarbo, cycloalkyl, alkylcycloalkyl, carboxylic acid, acyl, azido, mercapto, alkylthio, amino, heterocycleamino, alkylamino, dialkylamino, acylamino, aminoacyl, arylamino, arylalkyl, arylalkylamino, aryloxy, cyano, sulfonamide, aminosulfonyl, sulfone, nitro;
• arylalkyloxy, cycloalkyloxy, cycloalkylalkoxy, cycloalkylamino, urea, cycloalkylalkylamino, cycloalkyl, alkylcycloalkyl, hydroxyamino, alkoxyacylamino, and arylthio;
• and 5- or 6-membered organic rings containing 0 to 4 heteroatoms selected from the group consisting of N, O and S, which rings may be unsubstituted or substituted from 1 to 4 times with halo, loweralkyl, haloloweralkyl, haloloweralkyloxy, loweralkoxy, hydroxy, loweralkoxycarbo, carboxylic acid, acyl, azido, mercapto, alkylthio, amino, heterocycleamino, alkylamino, dialkylamino, acylamino, aminoacyl, arylamino, arylalkyl, arylalkylamino, aryloxy, cyano, sulfonamide, aminosulfonyl, sulfone, nitro;
• and oxoheterocyclic groups;
• or R8 and R9, if present, together are ═O or ═S;
• or a pharmaceutically acceptable salt or prodrug thereof,
• in an amount effective to treat the inflammatory disease.

A method of treating a non-inflammatory disease in a subject in need thereof, the method comprising administering to the subject a compound selected from the group consisting of:

• (a) a compound of Formula I or Formula II
• (b) a compound of Formula III, Formula IV, or Formula V:
• (c) a compound of Formula VI:
• wherein:
• A is N or C in compounds of Formula I and II, subject to the proviso that R5 is absent when A is N;
• A is S, O, SO2 or NR in compounds of Formula VI;
• X is —C(O)—, —S(O)2—, or a covalent bond;
• Y is alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, alkylcycloalkylalkyl, alkyloxyalkyl, aryl, alkylaryl, alkylarylalkyl, arylalkyl, cycloalkylalkyl, alkylheterocycle, heterocyclealkyl, alkylheterocyclealkyl, heterocycle, aminoalkyl, oxyalkyl, aminoaryl, oxyaryl;
• Z is selected from the group consisting of —B(OR1)OR2, —CON(R1)OR2, and —N(OR1)COR;
• R1 and R2 are each independently H, loweralkyl, or together form C2-C4 alkylene;
• and
• R3, R4, R5, R6, and R7 and, if present, R, R8, R9, and R10 are each independently selected from the group consisting of:
• H, halo, loweralkyl, haloloweralkyl, haloloweralkoxy, loweralkoxy, hydroxy, loweralkoxycarbo, cycloalkyl, alkylcycloalkyl, carboxylic acid, acyl, azido, mercapto, alkylthio, amino, heterocycleamino, alkylamino, dialkylamino, acylamino, aminoacyl, arylamino, arylalkyl, arylalkylamino, aryloxy, cyano, sulfonamide, aminosulfonyl, sulfone, nitro;
• arylalkyloxy, cycloalkyloxy, cycloalkylalkoxy, cycloalkylamino, urea, cycloalkylalkylamino, cycloalkyl, alkylcycloalkyl, hydroxyamino, alkoxyacylamino, and arylthio;
• and 5- or 6-membered organic rings containing 0 to 4 heteroatoms selected from the group consisting of N, O and S, which rings may be unsubstituted or substituted from 1 to 4 times with halo, loweralkyl, haloloweralkyl, haloloweralkyloxy, loweralkoxy, hydroxy, loweralkoxycarbo, carboxylic acid, acyl, azido, mercapto, alkylthio, amino, heterocycleamino, alkylamino, dialkylamino, acylamino, aminoacyl, arylamino, arylalkyl, arylalkylamino, aryloxy, cyano, sulfonamide, aminosulfonyl, sulfone, nitro;
• and oxoheterocyclic groups;
• or R8 and R9, if present, together are ═O or ═S;
• or a pharmaceutically acceptable salt or prodrug thereof;
• in an amount effective to treat the non-inflammatory disease.