Pyrazolopyrrolidine Compounds

A compound of formula (I) or a salt thereof,

• wherein
• A is selected from
• B is selected from
• R1 is selected from chloro, fluoro and methyl;
• R2 is selected from chloro, fluoro, trifluoromethyl, methyl and cyano;
• R3 is selected from isopropyl, cyclopropyl, isobutyl, tert-butyl, cyclobutyl, cyclopentyl, or R3 is:
• wherein R14 is selected from OH, methoxy, NH2, NMe2, NHMe, NHCOMe and NHCOH;
• R4 is selected from
• H,
• —(C0-C4)alkyl-phenyl, said phenyl being optionally substituted with 1, 2 or 3 substituents independently selected from:
• (C1-C4)alkyl, optionally substituted by NR9(R10) or —O—(C1-C4)alkyl or by 1, 2 or 3 halo substituents,
• —O—(C1-C4)alkyl, optionally substituted by NR9(R10), phenyl or —O—(C1-C4)alkyl, or by 1, 2 or 3 halo substituents,
• —C(O)NR9(R12),
• cyano,
• halo,
• —(CH2)m—S(O)vNR9(R10),
• —C(O)OH,
• —C(O)O—(C1-C4)alkyl,
• —(CH2)p—NR9(R12),
• heterocyclyl1, and
• phenyl
• and wherein —(C0-C4)alkyl of said —(C0-C4)alkyl-phenyl, when present, is optionally substituted by 1 or 2OH,
• —(C0-C4)alkyl-C(O)-phenyl, said phenyl being optionally substituted with 1, 2 or 3 substituents independently selected from:
• (C1-C4)alkyl, optionally substituted with from 1 to 3 halo,
• —O—(C1-C4)alkyl,
• cyano, and
• halo,
• naphthyl,
• —(C0-C4)alkyl-(C3-C6)cycloalkyl, said (C3-C6)cycloalkyl being optionally substituted with 1, 2 or 3 substituents independently selected from OH, —C(O)NR9(R10), —O—C(O)—(C1-C4)alkyl, halo, —(CH2)m—NR9(R10) and —C(O)—O(C1-C4)alkyl,
• —(C0-C4)alkyl-heteroaryl1, the heteroaryl1 of said —(C0-C4)alkyl-heteroaryl1 being optionally substituted by 1, 2, 3 or 4 substituents independently selected from —O—(C1-C4)alkyl, ═O, OH, cyano, (C1-C4)alkyl, halo and —NR9(R10),
• —(C0-C4)alkyl-C(O)NR9(R13),
• —(C0-C4)alkyl-NR9(R12), wherein —(C0-C4)alkyl of said —(C0-C4)alkyl-NR9(R12), when present, is optionally substituted with 1 or 2OH,
• —(C0-C4)alkyl-heterocyclyl4, said heterocyclyl4 being optionally substituted by 1, 2, 3 or 4 substituents independently selected from
• —C(O)NR9(R12),
• OH,
• —O—C(O)(C1-C4)alkyl, optionally substituted by (C1-C4)alkoxy,
• —C(O)—O(C1-C4)alkyl, optionally substituted by (C1-C4)alkoxy,
• ═O,
• halo,
• —C(O)— heteroaryl2, and
• (C1-C4)alkyl, optionally substituted by phenyl,
• and wherein the —(C0-C4)alkyl of —(C0-C4)alkyl-heterocyclyl4, when present, is optionally substituted with 1 or 2OH,
• (C1-C8)alkyl, said (C1-C8)alkyl being optionally substituted by 1, 2 or 3 substituents independently selected from OH, halo, —O—(C1-C4)alkyl, —C(O)(C1-C4)alkyl, —C(O)O—(C1-C4)alkyl, —C(O)OH, cyano and NR9(R10),
• (C1-C8)alkenyl, said (C1-C8)alkenyl being optionally substituted by 1, 2 or 3 substituents independently selected from OH, halo and —O—(C1-C4)alkyl;
• R5 is selected from:
• H,
• heterocyclyl1-C(O)—(CH2)n—,
• —(C1-C4)alkyl-, said (C1-C4)alkyl- being optionally substituted with 1 or 2 substituents independently selected from OH, ═O,
• heterocyclyl1-(C1-C4)alkyl-, wherein said alkyl of heterocyclyl1-(C1-C4)alkyl- is optionally substituted by 1 or 2OH, and said heterocyclyl1 can be optionally substituted by methyl or ethyl,
• (C1-C4)alkyl-O—C(O)—(CH2)m— and
• cyano;
• R6 is selected from
• H,
• (C1-C4)alkyl-, optionally substituted with (C1-C4)alkoxy,
• (C1-C4)alkoxy, optionally substituted with (C1-C4)alkoxy,
• (C1-C4)alkoxy(C1-C4)alkoxy(C1-C4)alkyl-,
• halo,
• R9(R10)N—C(O)—(CH2)m—,
• cyano
• R9(R10)N—(CH2)m—,
• R9(R10)N—(CH2)n—O—(CH2)m—,
• (C1-C4)alkyl-C(O)—(R10)N—(CH2)m—, and
• —O—(CH2)p-heteroaryl2;
• R7 is selected from
• H,
• halo,
• (C1-C4)alkyl-, optionally substituted with (C1-C4)alkoxy,
• (C1-C4)alkoxy, optionally substituted with (C1-C4)alkoxy,
• (C1-C4)alkoxy(C1-C4)alkoxy(C1-C4)alkyl-,
• R9(R10)N—(CH2)n—O—(CH2)m—, and
• (C1-C4)alkyl-C(O)O—(CH2)n—(R10)N—;
• R8 is selected from
• d H,
• (C1-C4)alkoxy(C1-C4)alkyl-,
• (C1-C4)alkyl-, said (C1-C4)alkyl- being optionally substituted by 1, 2 or 3 substituents independently selected from OH, halo, —O—(C1-C4)alkyl, NR9(R10), and
• (C1-C4)alkyl-C(O)NR9(R10);
• R9 is H, methyl or ethyl;
• R10 is H, methyl or ethyl, wherein said methyl and ethyl can each independently be substituted by 1 or 2 substituents independently selected from methoxy, ethoxy and halo;
• R11 is H, methyl, methoxy or halo;
• R12 is selected from
• H,
• (C1-C4)alkyl-, optionally substituted with heterocyclyl3,
• —C(O)(C1-C4)alkyl,
• —C(O)O(C1-C4)alkyl,
• —C(O)H, and
• —C(O)-phenyl, optionally substituted with 1 or 2 substituents independently selected from (C1-C4)alkyl, —O—(C1-C4)alkyl, cyano, halo, —C(O)OH, —C(O)O—(C1-C4)alkyl and —C(O)—(C1-C4)alkyl;
• R13 is selected from
• —(C0-C3)alkyl-phenyl, said phenyl being optionally substituted with 1 or 2 substituents independently selected from (C1-C4)alkyl, —O—(C1-C4)alkyl, cyano, halo, —C(O)OH, —C(O)O—(C1-C4)alkyl and —C(O)—(C1-C4)alkyl,
• —(C0-C3)alkyl-heterocyclyl4, said heterocyclyl4 being optionally substituted by 1, 2 or 3 substituents independently selected from —O—(C1-C4)alkyl, C(O)(C1-C4)alkyl and C(O)O—(C1-C4)alkyl,
• (C1-C4)alkyl, said (C1-C4)alkyl being optionally substituted with a substituent independently selected from —O—(C1-C4)alkyl, C(O)(C1-C4)alkyl and C(O)O—(C1-C4)alkyl,
• —(C0-C3)alkyl-(C3-C6)cycloalkyl;
• or R9 and R13, together with the nitrogen to which they are attached form heterocyclyl3, said heterocyclyl3 being optionally substituted with 1, 2 or 3 substitutents selected independently from
• ═O,
• (C1-C4)alkyl, said (C1-C4)alkyl being optionally substituted with 1, 2 or 3 substitutents selected independently from halo and OH,
• OH,
• C(O)(C1-C4)alkyl,
• C(O)O—(C1-C4)alkyl and
• C(O)NR9R10;
• m is 0, 1 or 2;
• n is 1, 2 or 3;
• p is 0, 1, 2 or 3;
• v is 0, 1 or 2;
• heterocyclyl1 is a 3, 4, 5 or 6 membered fully saturated or partially unsaturated monocyclic group comprising ring carbon atoms and 1 or 2 ring heteroatoms independently selected from N, O and S;
• heterocyclyl3 is a 4, 5 or 6 membered fully saturated or partially unsaturated monocyclic group comprising ring carbon atoms and 1 or 2 ring heteroatoms independently selected from N, O and S;
• heterocyclyl4 is a 3, 4, 5, 6 or 7 membered fully saturated or partially unsaturated monocyclic group comprising carbon ring atoms and 1 or 2 ring atoms selected independently from N, O and S;
• heteroaryl1 is a 5, 6, 7, 8, 9 or 10 membered, mono or bicyclic, fully unsaturated or partially unsaturated group, comprising carbon ring atoms and 1, 2, 3 or 4 ring heteratoms independently selected from N, O and S, wherein the total number of S atoms does not exceed 1, and the total number of O atoms does not exceed 1;
• heteroaryl2 is 5 or 6 membered fully unsaturated monocyclic group comprising ring carbon atoms and 1, 2, 3 or 4 ring heteroatoms independently selected from N, O and S, wherein the total number of ring S atoms does not exceed 1, and the total number of ring O atoms does not exceed 1;
• and * indicates the point of attachment to the remainder of the molecule.