Semicarbazone derivatives and their use as thrombopoietin mimetics

A method of treating of thrombocytopenia in a mammal in need thereof which comprises administering to such mammal a therapeutically effective amount of a compound of Formula (I):

• wherein:
• R1 and R2 are each independently selected from hydrogen, C1-12alkyl, aryl, substituted aryl, and alkyl substituted with one or more substituents selected from the group consisting of:
• alkoxy, acyloxy, aryl, substituted aryl, amino, N-acylamino, oxo, hydroxy, cycloalkyl, substituted cycloalkyl, —C(O)OR7, —S(O)2NR7R8, —S(O)nR6, aryloxy, nitro, cyano, halogen, and protected —OH,
• where
• R6 is selected from hydrogen, alkyl, cycloalkyl, C1-C12aryl, substituted alkyl, substituted cycloalkyl and substituted C1-C12aryl, and
• R7 and R8 are independently selected from hydrogen, cycloalkyl, aryl, substituted cycloalkyl, substituted aryl, alkyl or alkyl substituted with one or more substituents selected from the group consisting of:
• alkoxy, acyloxy, aryloxy, amino, N-acylamino, oxo, hydroxy, —C(O)OR6, —S(O)nR6, —C(O)NR6R6, —S(O)2NR6R6, nitro, cyano, cycloalkyl, substituted cycloalkyl, halogen, C1-C12aryl, substituted C1-C12aryl and protected —OH where R6 is as described above;
• and
• n is 0-3;
• or R1 and R2 taken together with the group to which they are attached represent a ring of formula (A):
• where
• R4 and R10 are each independently selected from two hydrogens, ═NR5, ═O, ═S, and ═CHR5, where R5 is C1-C12aryl or substituted C1-C12aryl;
• and m is 0 to 2;
• Z is a bond or selected from S or NR5, where R5 is C1-C12aryl or substituted C1-C12aryl;
• R3 is selected from hydrogen, C1-C10alkyl, phenyl, substituted phenyl, carboxyl or C1-C10alkoxycarbonyl;
• L is a group of formula (L):
• where
• A, B, D and E independently represent CR11 or N;
• where R11 is selected from hydrogen, halogen, —CF3, —CN, —SO3H, —SO3Na, —SO2R14, —NO2, phenyl, substituted phenyl, C1-C10alkyl, C1-C10alkoxy, C1-C10acyloxy, arylalkoxy, —COR14, —NR12R13, hydroxy or cycloalkyl;
• where R14 is selected from hydroxy, C1-C10alkyl, phenyl, amino, mono- or dialkylamino;
• R12 and R13 are independently selected from hydrogen, C1-10alkyl, C1-C12aryl, substituted C1-C12aryl, C1-10acyl or cycloalkyl;
• or either A═B or D═E alternatively represent O, S or NR12;
• where R12 is as defined above;
• Y is selected from S, O and NR15, where R15 is selected from hydrogen, C1-C10alkyl, substituted C1-C10alkyl, C1-C6alkylphenyl, substituted C1-C6alkylphenyl, C1-C10acyl, substituted C1-C10acyl, or SO2R9, where R9 is C1-C10alkyl, substituted C1-C10alkyl, C1-C12aryl or substituted C1-C12aryl;
• and
• X is selected from SR16, OR16 or NHR17;
• where R16 is hydrogen, C1-C10alkyl or substituted C1-C10alkyl;
• R17 is hydrogen, C1-C10alkyl, substituted C1-C10alkyl, C1-C6alkylphenyl, C1-C10acyl, substituted C1-C10acyl or SO2R9;
• where R9 is C1-C10alkyl, substituted C1-C10alkyl, C1-C12aryl or substituted C1-C12aryl;
• or a
• pharmaceutically acceptable salt, hydrate, solvate or ester thereof,
• provided that;
• when R1 and R2 do not form a ring and X is not —NHSO2R9, R5 is not a substituted or unsubstituted pyridyl or a substituted or unsubstituted phenyl.