Acyl and sulfonyl derivatives of 6,9-disubstituted 2-(trans-1,4-diaminocyclohexyl)-purines and their use as antiproliferative agents

A compound according to the formula (I)

• 1491
• (I)
• wherein
• Z is selected from the group consisting of —S(O)2— and —C(O)—, when Z is —S(O)2—, Ra is selected from the group consisting of —R1 and —N(R1)(R3), or when Z is —C(O)—, Ra is selected from the group consisting of —R1, —OR1, —N(R1)(R3) and —SR1,
• where
• R1 is selected from the group consisting of
• —C1-C11 alkyl, wherein each carbon may be optionally substituted with one, two or three X substituents,
• —C3-C10 cycloalkyl, w herein each carbon may be optionally substituted with one or two X substituents,
• —(CH2)nQp(CH2)nW, wherein each carbon of —(CH2)n— may be optionally substituted with one or two X substituents,
• Q is O, S, or NR3,
• n is independently an integer 0-6,
• p is independently an integer 0 or 1,
• W is independently selected from the group consisting of hydrogen, C3-C10 cycloalkyl, —(C3-C10 cycloalkyl)-aromatic, and one of the following aromatic or heteroaromatic rings:
• 1492
• where B is —O—, —S—, —NR6—, where each carbon of the aromatic or heteroaromatic ring may be independently substituted by a nitrogen atom, and each carbon of the aromatic ring may be independently substituted with an X substituent;
• and —(CH2)nCHW2,
• where each X substituent is independently selected from the group consisting of hydrogen, halogen, methylenedioxy, —C1-C8 alkyl, —C3-C10 cycloalkyl, substituted or unsubstituted phenyl, —C1-C8 alkoxy, —SR3, —OH, ═O, —CY3, —OCY3, —CO2R3, —CN, —CO—NR4R5, —NO2, —COR3, —NR4R5, —NH—C(O)—R3, —NH—C(O)—(C1-C6 alkyl)-aromatic, and —NH—C(O)—(C1-C6 alkyl)-heteroaromatic;
• where each Y is independently selected from the group consisting of hydrogen and halogen;
• where each R3 is independently selected from the group consisting of hydrogen, and C1-C8 alkyl, where C1-C8 alkyl may be straight or branched, saturated or unsaturated;
• where each R4 and R5 is independently selected from the group consisting of hydrogen, and C1-C6 alkyl, where C1-C6 alkyl may be straight or branched, saturated or unsaturated, where which each carbon of C1-C6 alkyl is optionally substituted with an X substituent, or where R4 and R5 taken together with the nitrogen to which they are attached, form a heterocyclic ring of three to seven atoms including the nitrogen atom;
• where —NR6— is selected from the group consisting of an unsubstituted N, an N substituted with -hydrogen, —(C1-C6 alkyl), —C3-C10 cycloalkyl, —S(O)2—(C1-C6 alkyl), —S(O)2—(C3-cycloalkyl), —C(O)R3, —C(O)—(C0-C6 alkyl)-aromatic, and —S(O)2—(C0-C6 alkyl)-aromatic, wherein each carbon of the aromatic ring may be optionally substituted with an X substituent;
• and
• where phenyl is substituted with one to five substituents independently selected from the group consisting of hydrogen, halogen, methylenedioxy, —C1-C8 alkyl, -C3-C10 cycloalkyl, —C1-C8 alkoxy, —OH, —CY3, —OCY3, —CO2R3, —CN, —NO2, —COR3, —NR4R5, —SR3, —CO—NR4R5, and —NH—C(O)—R3;
• and
• R2 is selected from the group consisting of cyclopentyl, cyclopentenyl, and isopropyl;
• or
• a pharmaceutically acceptable salt, optical isomer, solvate or hydrate thereof.