PDE4B inhibitors

A compound having the chemical structure

• all salts, prodrugs, tautomers and isomers thereof,
• wherein:
• k is selected from the group consisting of —CR6R7R19, —C(Z)R8, —C(Z)NR12R13, —S(O)2NR12R13, and —S(O)2R14;
• Z is O, S, or NR9;
• t is CH;
• y is N or CH;
• one of u, v, w, and x is C-A and the others of u, v, w and x are CH;
• A has a structure selected from the group consisting of
• R6 and R7 are independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylakyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• R8 at each occurrence is independently selected from the group consisting of —OR9, optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R8 is alkenyl, no alkene carbon thereof is bound to C(Z), optionally substituted lower alkynyl, provided, however, that when R8 is alkynyl, no alkyne carbon thereof is bound to C(Z), optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• R9 at each occurrence is independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R9 is alkenyl, no alkene carbon thereof is bound to O, N or S, optionally substituted lower alkynyl, provided, however, that when R9 is alkynyl, no alkyne carbon thereof is bound to O, N or S, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• R10 and R11 at each occurrence are independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R10 and/or R11 are alkenyl, no alkene carbon thereof is bound to nitrogen, optionally substituted lower alkynyl, provided, however, that when R10 and/or R11 are alkynyl, no alkyne carbon thereof is bound to nitrogen, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, —C(Z)R8, —C(Z)NR12R13, —S(O)2NR12R13, and —S(O)2R14;
• or
• R10 and R11 together with the nitrogen to which they are attached form a 5-7 membered optionally substituted heterocycloalkyl or optionally substituted heteroaryl ring;
• R12 and R13 at each occurrence are independently selected from the group consisting of hydrogen, optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R12 and/or R13 are alkenyl, no alkene carbon thereof is bound to nitrogen, optionally substituted lower alkynyl, provided, however, that when R12 and/or R13 are alkynyl, no alkyne carbon thereof is bound to nitrogen, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• or R12 and R13 together with the nitrogen to which they are attached form a 5-7 membered optionally substituted heterocycloalkyl or optionally substituted heteroaryl ring;
• R14 at each occurrence is independently selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R14 is alkenyl, no alkene carbon thereof is bound to —S(O)2—, optionally substituted lower alkynyl, provided, however, that when R14 is alkynyl, no alkyne carbon thereof is bound to —S(O)2—, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• R15 at each occurrence is independently selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl, provided, however, that when R15 is alkenyl, no alkene carbon thereof is bound to oxygen, optionally substituted lower alkynyl, provided, however, that when R15 is alkynyl, no alkyne carbon thereof is bound to oxygen, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, —C(Z)R8, and —C(Z)NR12R13;
• R16 is selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl provided, however, that when R16 is alkenyl, no alkene carbon thereof is bound to oxygen, optionally substituted lower alkynyl provided, however, that when R16 is alkynyl, no alkyne carbon thereof is bound to oxygen, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkyl alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, —C(Z)R8, and —C(Z)NR12R13;
• R17 is selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl provided, however, that when R17 is alkenyl, no alkene carbon thereof is bound to N, O, or S, optionally substituted lower alkynyl, provided, however, that when R17 is alkynyl, no alkyne carbon thereof is bound to N, O, or S, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl;
• R18 is selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, —C(Z)R8, —OR9, —SR9, —NR10R11, —C(Z)NR12R13, —S(O)2NR12R13, and —S(O)2R14;
• R19 is selected from the group consisting of optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocycloalkyl, optionally substituted heterocycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, and optionally substituted heteroaralkyl.