2-aminocarbonyl-9H-purine derivatives

A method of treating an inflammatory disease in a mammal, comprising administering to said mammal in need of such treatment an effective amount of a compound of formula (I)

• or a pharmaceutically acceptable salt or solvate thereof, wherein
• R1 is H, C1–C6 alkyl or fluorenyl, said C1–C6 alkyl being optionally substituted by 1 or 2 substituents each independently selected from phenyl and naphthyl, said phenyl and naphthyl being optionally substituted by C1–C6 alkyl, C1–C6 alkoxy, halo or cyano;
• (A) R2 is H or C1–C6 alkyl, R15 is H or C1–C6 alkyl, and X is either (i) unbranched C2–C3 alkylene optionally substituted by C1–C6 alkyl or C3–C8 cycloalkyl, or (ii) a group of the formula:
• —(CH2)n—W—(CH2)p—
• where W is C5–C7 cycloalkylene optionally substituted by C1–C6 alkyl, n is 0 or 1 and p is 0 or 1, or
• (B) R15 is H or C1–C6 alkyl, and R2 and X, taken together with the nitrogen atom to which they are attached, represent azetidin-3-yl, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, homopiperidin-3-yl or homopiperidin-4-yl, each being optionally substituted by C1–C6 alkyl, or
• (C) R2 is H or C1–C6 alkyl, and R15 and X, taken together with the nitrogen atom to which they are attached, represent azetidin-3-yl, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, homopiperidin-3-yl or homopiperidin-4-yl, each being optionally substituted by C1–C6 alkyl;
• either, R3 and R4, taken together with the nitrogen atom to which they are attached, represent azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, homopiperidinyl or homopiperazinyl, each being optionally substituted on a ring nitrogen or carbon atom by C1–C6 alkyl or C3–C8 cycloalkyl and optionally substituted on a ring carbon atom not adjacent to a ring nitrogen atom by —NR6R7,
• or, R3 is H, C1–C6 alkyl, C3–C8 cycloalkyl or benzyl and R4 is
• (a) azetidin-3-yl, pyrrolidin-3-yl, piperidin-3-yl, piperidin-4-yl, homopiperidin-3-yl or homopiperidin-4-yl, each being optionally substituted by C1–C6 alkyl, C3–C8 cycloalkyl, phenyl, benzyl or het, or
• (b) —(C2–C6 alkylene)—R8,
• (c) —(C1–C6 alkylene)—R13, or
• (d) C1–C6 alkyl or C3–C8 cycloalkyl;
• R5 is CH2OH or CONHR14;
• R6 and R7 are either each independently H or C1–C6 alkyl or, taken together with the nitrogen atom to which they are attached, represent azetidinyl, pyrrolidinyl or piperidinyl, said azetidinyl, pyrrolidinyl and piperidinyl being optionally substituted by C1–C6 alkyl;
• R8 is (i) azetidin-1-yl, pyrrolidin-1-yl, piperidin-1-yl, morpholin-4-yl, piperazin-1-yl, homopiperidin-1-yl, homopiperazin-1-yl or tetrahydroisoquinolin-1-yl, each being optionally substituted on a ring carbon atom by C1–C6 alkyl, C3–C8 cycloalkyl, phenyl, C1–C6 alkoxy-(C1–C6)-alkyl, R9R9N—(C1–C6 )-alkyl, fluoro-(C1–C6)-alkyl, —CONR9R9, —COOR9 or C2–C5 alkanoyl, and optionally substituted on a ring carbon atom not adjacent to a ring nitrogen atom by fluoro-(C1–C6)-alkoxy, halo, —OR9, cyano, —S(O)mR10, —NR9R9, —SO2NR9R9, —NR9COR10 or —NR9SO2R10, and said piperazin-1-yl and homopiperazin-1-yl being optionally substituted on the ring nitrogen atom not attached to the C2–C6 alkylene group by C1–C6 alkyl, phenyl, C1–C6 alkoxy-(C2–C6)-alkyl, R9R9N—(C2–C6)-alkyl, fluoro-(C1–C6)-alkyl, C2–C5 alkanoyl, —COOR10, C3–C8 cycloalkyl, —SO2R10, —SO2NR9R9 or —CONR9R9, or (ii) NR11R12;
• R9 is H, C1–C6 alkyl, C3–C8 cycloalkyl or phenyl;
• R10 is C1–C6 alkyl, C3–C8 cycloalkyl or phenyl;
• R11 is H, C1–C6 alkyl, C3–C8 cycloalkyl or benzyl;
• R12 is H, C1–C6 alkyl, C3–C8 cycloalkyl, phenyl, benzyl, fluoro-(C1–C6)-alkyl, —CONR9R9, —COOR10, C2–C5 alkanoyl or —SO2NR9R9;
• R13 is (a) phenyl, pyridin-2-yl, pyridin-3-yl or pyridin-4-yl, each being optionally substituted by C1–C6 alkyl, C1–C6 alkoxy, —(C1–C3 alkylene)—(C1–C6 alkoxy), halo, cyano, —(C1–C3 alkylene)—CN, —CO2H, —(C1–C3 alkylene)—CO2H, —CO2(C1–C6 alkyl), —(C1–C3 alkylene)—CO2(C1–C6 alkyl), —(C1–C3 alkylene)—NR14R14, —CONR14R14 or —(C1–C3 alkylene)—CONR14R14, or (b) azetidin-2-yl, azetidin-3-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl homopiperidin-2-yl, homopiperidin-3-yl or homopiperidin-4-yl, each being optionally substituted by C1–C6 alkyl, C3–C8 cycloalkyl, phenyl, benzyl or het;
• R14 is H or C1–C6 alkyl optionally substituted by cyclopropyl;
• m is 0, 1 or 2;
• Y is CO, CS, SO2 or C═N(CN);
• and
• “het”, used in the definition of R4 and R13, is a C-linked, 4- to 6-membered ring, heterocycle having either from 1 to 4 ring nitrogen heteroatoms or 1 or 2 nitrogen ring heteroatoms and 1 oxygen or 1 sulphur ring heteroatom, optionally substituted by C1–C6 alkyl, C3–C8 cycloalkyl, C1–C6 alkoxy, C3–C8 cycloalkoxy, hydroxy, oxo or halo.