PDE4B inhibitors and uses therefor

A compound having the chemical structure

• or a salt thereof,
• wherein:
• X is selected from the group consisting of O and S;
• R3 is selected from the group consisting of cyano, nitro, —C(Z)R8, —S(O2)NR9R10, —S(O2)R11, and optionally substituted lower alkyl;
• R1, R2, R4, R5, R7, R9 and R10 are independently selected from the group consisting of hydrogen, acyl, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycle, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl,
• provided, however, that R1 and R2, or R4 and R5, or R9 and R10, or R2 and R3 can combine to form an optionally substituted heterocycle;
• Y and Z are independently selected from the group consisting of O and S;
• R8 is selected from the group consisting of, hydroxy, alkoxy, thioalkoxy, optionally substituted amine, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, and optionally substituted heterocycle;
• and
• R11 is selected from the group consisting of hydroxy, alkoxy, thioalkoxy, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• R6 is
• Z1, Z2, Z3, and Z4 are independently selected from the group consisting of —O—, —S—, —CR6a—, —CR6b—, —CR6c—, and —NR6d—, wherein:
• at least one of Z1, Z2, Z3, and Z4 is a heteroatom;
• and
• Z1, Z2, Z3, and Z4 are selected to produce a stable compound;
• R6a, R6b, and R6c are independently selected from the group consisting of hydrogen, halo hydroxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, acyloxy, optionally substituted aryl, amino, amido, amidino, urea optionally substituted with alkyl, aryl, heteroaryl or heterocyclyl groups, aminosulfonyl optionally N-mono- or N,N-di-substituted with alkyl, aryl or heteroaryl groups, alkylsulfonylamino, arylsulfonylamino, heteroarylsulfonylamino, alkylcarbonylamino, arylcarbonylamino, heteroarylcarbonylamino, carboxyl, optionally substituted heterocycle, optionally substituted hetaryl, nitro, cyano, thiol, sulfonamido, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted alkynyl, attached at any available point to produce a stable compound;
• or
• R6a, R6b, and R6c can, in combination with the five-membered ring comprising Z1, Z2, Z3, and Z4, combine to form an optionally substituted fused heterocyclic ring system;
• and
• R6d is optionally present, and when present is selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heterocycle, optionally substituted heteroaryl, acyl, sulfonyl, amido, thioamido, and sulfonamido;
• provided, however, that
• when R6 is thiophen-2-yl, then R1 and R2 are not selected from the group consisting of phenyl, lower alkyl, and lower alkenyl;
• when R6 is furan-2-yl, then R1 and R2 are not selected from the group consisting of optionally substituted phenyl and optionally substituted phenylalkyl;
• and
• when R1 or R2 is furan-2-yl-methylene or furan-2-yl-ethylene, then R6 is not optionally substituted phenyl.