Pyrrolo pyrimidines as agents for the inhibition of cystein proteases

A compound of formula I, or a pharmaceutically acceptable salt thereof

• wherein
• R is H, —R2, —OR2 or NR1R2,
• wherein R1 is H, lower alkyl or C3 to C10 cycloalkyl, and
• R2 is lower alkyl or C3 to C10 C10 cycloalkyl, and
• wherein R1 and R2 are independently, optionally substituted by halo, hydroxy, lower alkoxy, CN, NO2, or optionally mono- or di-lower alkyl substituted amino;
• X is ═C(Z)-,
• wherein Z is H, —C(O)—NR3R4, —NH—C(O)—R3, —CH2—NH—C(O)—R3, —C(O)—R3, —S(O)—R3, —S(O)2—R3,—CH2—C(O)—R3, —CH2—NR3R4, —R4, —C≡C—CH2—R5, N-heterocyclyl, N-heterocyclyl-carbonyl, or —C(P)═C(Q)-R4
• wherein
• P and Q independently are H, lower alkyl or aryl,
• R3 is aryl, aryl-lower alkyl, C3—C10cycloalkyl, C3—C10cycloalkyl-lower alkyl, heterocyclyl or heterocyclyl-lower alkyl,
• R4 is H, aryl, aryl-lower alkyl, aryl-lower-alkenyl, C3—C10cycloalkyl, C3—C10cycloalkyl-lower alkyl, heterocyclyl or heterocyclyl-lower alkyl, or
• wherein R3 and R4 together with the nitrogen atom to which they are joined form an N-heterocyclyl group,
• wherein N-heterocyclyl denotes a saturated, partially unsaturated or aromatic nitrogen containing heterocyclic moiety attached via a nitrogen atom thereof having from 3 to 8 ring atoms optionally containing further 1, 2 or 3 heteroatoms selected from N, NR6, O, S, S(O) or S(O)2 and wherein the N-heterocyclyl is optionally fused in a bicyclic structure and wherein the N-heterocyclyl is optionally linked in a spiro structure with a 3 to 8 membered cycloalkyl or heterocyclic ring wherein the heterocyclic ring has from 3 to 10 ring members and contains from 1 to 3 heteroatoms selected from N, NR6, O, S, S(O) or S(O)2
• R6 is hydrogen, optionally substituted lower alkyl, optionally substituted carboxy, formyl, optionally substituted acetyl, optionally substituted propionyl, optionally substituted benzoyl, optionally substituted amido, or optionally substituted aryl;
• wherein R3 and R4 are independently, optionally substituted by 1-3 groups, selected from halo, hydroxy, oxo, lower alkoxy, CN or NO2, amino, or optionally substituted mono- or di-lower alkyl amino, optionally substituted aryl, optionally substituted aryl-lower alkyl, optionally substituted N-heterocyclyl or optionally substituted N-heterocyclyl-lower alkyl (wherein the optional substitution comprises from 1 to 3 substituents selected from halo, hydroxy, lower alkoxy, CN, NO2, or optionally mono- or di- lower alkyl substituted amino, and
• wherein
• R5 is aryl, aryl-lower alkyl, aryloxy, aroyl or N-heterocyclyl as defined above, and
• wherein R5 is optionally substituted by R7 which represents from 1 to 5 substitutents selected from halo, hydroxy, ON, NO2 or oxo, or optionally substituted lower-alkoxy, optionally substituted lower-alkyl, optionally substituted aryl, optionally substituted aryloxy, optionally substituted aroyl, optionally substituted lower-alkylsulphonyl, optionally substituted arylsulphonyl, amino optionally substituted mono- or di-lower alkyl amino, or optionally substituted N-heterocyclyl, or optionally substituted N-heterocyclyl-lower alkyl wherein N-heterocyclyl is as defined above, and
• wherein R7 is optionally substituted by from 1 to 3 substitutents selected from halo, hydroxy, optionally mono- or di- lower-alkyl substituted amino, lower-alkyl carbonyl, lower-alkoxy or lower-alkylamido;
• R13 is lower alkyl, C3 to C10 cycloalkyl or C3—C10cycloalkyl-lower alkyl, all of which are independently optionally substituted by halo, hydroxy, CN, NO2 or optionally mono- or di-lower alkyl-substituted amino;
• and
• R14 is H or optionally substituted aryl, optionally substituted aryl-W—, optionally substituted aryl-lower alkyl-W—, optionally substituted C3 to C10 cycloalkyl, optionally substituted C3 to C10 cycloalkyl-W—, optionally substituted N-heterocyclyl or optionally substituted N-heterocyclyl-W— wherein N-heterocyclyl is as defined above, optionally substituted phthalimide, optionally substituted hydantoin, optionally substituted oxazolidinone, or optionally substituted 2,6-dioxo-piperazine,
• wherein —W— is —O—, —C(O)—, —N(R6)—, —N(R6)—C(O)—, —N(R6)—C(O)—O—, —S(O)—, —S(O)2— or —S—,
• wherein R14 is optionally substituted by R18 which represents from 1 to 10 substitutents selected from halo, hydroxy, ON, NO2, oxo, amido, carbonyl, sulphonamido, lower-alkyldioxymethylene, or optionally substituted (-lower-alkoxy, optionally substituted lower-alkyl, optionally substituted lower-alkenyl, optionally substituted lower alkynyl, optionally substituted lower alkoxy carbonyl, amino, optionally substituted mono- or di-lower alkyl amino, optionally substituted aryl, aryl-lower alkyl, aryl-lower alkenyl, aryloxy, aroyl, lower-alkylsulphonyl, arylsulphonyl, N-heterocyclyl, N-heterocyclyl-lower alkyl wherein N-heterocyclyl is as defined above, heterocyclyl or R14 comprising aryl has an aryl fused with a hetero-atom containing ring, and
• wherein R18 is optionally substituted by R19 which represents from 1 to 4 substitutents selected from halo, hydroxy, CN, NO2 or oxo, or optionally substituted lower-alkoxy, optionally substituted lower-alkyl, optionally substituted lower-alkoxy-lower-alkyl, optionally substituted C3—C10cycloalkyl, optionally substituted lower-alkoxy carbonyl, optionally substituted halo-lower alkyl, amino, optionally substituted mono- or di-lower alkyl amino, optionally substituted aryl, optionally substituted aryloxy, optionally substituted aroyl optionally substituted lower-alkyl carbonyl, optionally substituted lower-alkylsulphonyl, optionally substituted arylsulphonyl, optionally substituted N-heterocyclyl, or optionally substituted N-heterocyclyl-lower alkyl wherein N-heterocyclyl is as defined above,
• wherein R19 is optionally substituted by from 1 to 4 substitutents selected from halo, hydroxy, CN, NO2, oxo, optionally mono- or di-lower alkyl substituted amino, lower-alkyl, or lower-alkoxy.