Highly active pyrazolo-piperidine substituted indole-2-carboxamides active against the hepatitis B virus (HBV)

Compound of Formula Ia

• in which
• Z is H, D, C(═O)N(R5)(R6), C(═O)N(R5)O(R6), C(═O)N(R5)N(R6)(R7), N(R5)(R6), N(R5)SO2(R6), C(═O)O(R5), CH2—N(R5)(R6), C(R5)=NO(R6), O—R5, SO2N(R5)(R6), SO2—R5, alkyl, cycloalkyl, heterocycloalkyl, heteroaryl, or heteroaryl substituted with C2-C6 alkenyl, wherein cycloalkyl is optionally substituted with carboxy, carboxyl ester, halo, C1-C6 alkyl, C1-C6-haloalkyl or NH2
• R1 is H, D, F, Cl, Br or NH2
• R2a, R2b, R2c and R2d are for each position independently selected from the group comprising H, CF2H, CF3, CF2CH3, F, Cl, Br, CH3, Et, i-Pr, c-Pr, D, CH2OH, CH(CH3)OH, CH2F, C(F)CH3, I, C═C, C≡C, C≡N, C(CH3)2OH, Si(CH3)3, SMe, OH, with the proviso that when Z is H, R2b is not F and R2c is not Cl or CH3
• R3, R4, R8 and R9 are for each position independently selected from the group comprising H, methyl and ethyl
• R3 and R4 are optionally connected to form a C3-C5-cycloalkyl ring
• R3 and R8 are optionally connected to form a bridged heterobicyclic ring
• R5, R6 and R7 are independently selected from the group comprising H, D, C1-C6-alkyl, C3-C6-cycloalkyl, C1-C4-carboxyalkyl, C1-C4-acylsulfonamido-alkyl, C1-C4-carboxamidoalkyl, C4-C7-heterocycloalkyl, C2-C6-aminoalkyl, C2-C6-hydroxyalkyl, and C2-C6-alkynyl, optionally substituted with 1, 2, or 3 groups each independently selected from OH, halo, C≡N, amino, acyl, SO2Me, SO3H, carboxy, carboxyl ester, carbamoyl, substituted carbamoyl, C6-aryl, heteroaryl, C1-C6-alkyl, C3-C6-cycloalkyl, C3-C7-heterocycloalkyl, C1-C4-carboxamidoalkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-alkyl-O-C1-C6-alkyl, C1-C6-hydroxyalkyl, and C1-C6 alkenyloxy, wherein C1-C6-alkyl, C6-aryl and heteroaryl are optionally substituted with acyloxy, carboxy, carboxyl ester, C6-aryl, C2-C6-alkynyloxy, C1-C6-alkyl, C1-C6-haloalkyl, S-C1-C6-alkyl, SO2-C1-C6-alkyl, or C≡N
• R5 and R6 are optionally connected to form a C4-C7-heterocyclic ring containing 1 or 2 nitrogen, sulfur or oxygen atoms, or hetero-spirocyclic system consisting of 2 or 3 C3-C7 rings and containing 1 or 2 nitrogen, sulfur or oxygen atoms, optionally substituted with 1, 2, or 3 groups each independently selected from OH, halo, amino, acyl, SO2Me, SO3H, carboxy, carboxyl ester, carbamoyl, substituted carbamoyl, C6-aryl, heteroaryl, C1-C6-alkyl, C3-C6-cycloalkyl, C3-C7-heterocycloalkyl, C1-C6-haloalkyl, C1-C6-alkoxy, C1-C6-hydroxyalkyl, and C1-C6 alkenyloxy
• n is 1 or 2
• m is 0 or 1
• or a pharmaceutically acceptable salt thereof or a solvate or a hydrate of a compound of Formula Ia or the pharmaceutically acceptable salt thereof or a prodrug of a compound of Formula Ia or a pharmaceutically acceptable salt or a solvate or a hydrate thereof.