4-ethynyl pyrazole derivative compounds and methods for treatment of HCV

A compound of the formula I:

• or a pharmaceutically acceptable salt thereof, wherein:
• ring A is selected from a 5- or 6-membered aromatic rings which may optionally contain 0 to 3 ring heteroatoms;
• each R1 is independently selected from alkyl, alkenyl, alkynyl, aralkyl, —(CH2)a—O—R11, —(CH2)a—N(R12)(R13), —(CH2)a—N(R11)—(CH2)bC(O)R14, —(CH2)a—N(R11)SO2R11, —(CH2)a—SR11, —(CH2)a—C(O)R14—(CH2)a—C(O)—(CH2)bOR11, —(CH2)a—C(O)—(CH2)bN(R12)(R13), —(CH2)aO—(CH2)b—C(O)R14, —(CH2)a—OC(O)—(CH2)bN(R12)(R13), CN, CF3, NO2, SO2, —SOR11, —SO3R11, —SO2N(R12)(R13), cycloalkyl, cycloalkenyl, halo, phosphate, phosphonate, aryl and a heterocyclic group;
• additionally or alternatively two R1 substituents on adjacent ring atoms may be combined to form a fused 5 or 6-membered ring, wherein the fused 5- or 6-membered ring may contain from 0 to 3 ring heteroatoms and may be further substituted with one or more substituents selected from R11;
• each R11 is independently selected from H, alkyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• each R12 and R13 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, aralkyl, aryl and a heterocyclic group;
• or R12 and R13 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom and may be optionally substituted with up to three substituents selected from halo, CN, NO2, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, and a heterocyclic group;
• each R14 is independently selected from H, alkyl, —OH, —O-alkyl, —O-aryl, —O-aralkyl, -alkyl-O-alkyl, -alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• a is 0 to 6;
• b is 0 to 6;
• R3 is selected from H, alkyl, alkenyl, alkynyl, aralkyl, —(CH2)z—O—R31, —(CH2)z—N(R32)(R33), —(CH2)w—C(O)R34, —(CH2)wC(O)—N(R32)(R33), —(CH2)w—SO2—R31, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• R31 is selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• R32 and R33 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• or R32 and R33 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• R34 is selected from H, alkyl, —OH, —O-alkyl, —O-aryl, —O-aralkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• w is 0 to 6;
• z is 1 to 6;
• R4 is independently selected from H, CN, CF3, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• ring B is selected from a 5- or 6-membered aromatic rings which may optionally contain 0 to 3 ring heteroatoms;
• R5 is independently selected from H, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• X1 is selected from CH2, O, S, SO2, and —N(R101)—;
• R101 is selected from H, alkyl, alkenyl, alkynyl, aralkyl, —C(═O)—R102, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• R102 is selected from H, alkyl, alkenyl, alkynyl, aralkyl, —N(R103)(R104), cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• R103 and R104 are independently selected from H, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group, or R103 and R104 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom;
• X2 is selected from —CH2—, —CH2CH2—, —C(═O)CH2—, and —C(═O)—;
• Z is selected from H, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, cycloalkenyl, —(CH2)c—O—R15, —(CH2)c—N(R16)(R17), —(CH2)c—N(R15)—(CH2)eC(O)R18, —(CH2)c—SR15, —(CH2)d—C(O)R18, —(CH2)d—C(O)—(CH2)cOR15, —(CH2)d—C(O)—(CH2)eN(R16)(R17), —(CH2)cO—(CH2)e—C(O)R18, —(CH2)cOC(O)—(CH2)eN(R16)(R17), —SO2R15, —SO3R15, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• each R15 is independently selected from H, alkyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• each R16 and R17 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkyl-O-alkyl, alkyl-O-aryl, alkenyl, alkynyl, aralkyl, aryl and a heterocyclic group;
• or R16 and R17 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom and may be optionally substituted with up to three substituents selected from halo, CN, NO2, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, and a heterocyclic group;
• each R18 is independently selected from H, alkyl, —OH, —O-alkyl, —O-aryl, —O-aralkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• c is 1 to 6;
• d is 0 to 6;
• e is 0 to 6;
• or Z is a group having the formula -A-B—C—R8, wherein
• A is selected from —C(═O)—, and —SO2—;
• B is selected from —(CH2)x—CH(R6)—(CH2)y—, and
• x is 0 to 4;
• y is 0 to 4;
• R6 is independently selected from H, alkyl, alkenyl, alkynyl, aralkyl, —(CH2)f—Y—(CH2)g—R61, —(CH2)f—N(R62)(R63), —(CH2)f—N(R61)—(CH2)gC(O)R64,—(CH2)f—N(R61)SO2R61, —(CH2)f—SR61, —(CH2)f—C(O)R64, —(CH2)f—C(O)—(CH2)gOR61, —(CH2)f—C(O)—(CH2)gN(R62)(R63), —(CH2)f—Y—(CH2)g—C(O)R64, —(CH2)f—Y—C(O)—(CH2)gN(R62)(R63), —(CH2)f—Y—(CH2)g—C(═NOR61)—R61, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• each R61 is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• each R62 and R63 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and a heterocyclic group;
• or R62 and R63 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom and may be optionally substituted with up to three substituents selected from halo, CN, NO2, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, and a heterocyclic group;
• each R64 is independently selected from H, alkyl, —OH, —O-alkyl, —O-aryl, —O-aralkyl, -alkyl-O-alkyl, -alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• Y is selected from a chemical bond, —O—, and aryl;
• f is 1 to 6;
• g is 0 to 6;
• C is selected from —N(R7)—C(═O)—, —N(R7)—S(═O)2—, and —CH2—;
• R7 is independently selected from H, alkyl, alkenyl, alkynyl, aralkyl, cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• R8 is independently selected from H, alkyl, alkenyl, alkynyl, aralkyl, —(CH2)r—O—(CH2)—R81, —(CH2)r—N(R82)(R83), —(CH2)r—N(R81)—(CH2)sC(O)R84, —(CH2)r—N(R81)SO2R81, —(CH2)r—SR81, —(CH2)r—C(O)R84, —(CH2)r—C(O)—(CH2)sOR81, —(CH2)r—R81, —(CH2)r—C(O)(CH2)sN(R82)(R83), —(CH2)rO—(CH2)s—C(O)R84, —(CH2)rOC(O)—(CH2)sN(R82)(R83), cycloalkyl, cycloalkenyl, aryl and a heterocyclic group;
• each R81 is independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• each R82 and R83 are independently selected from H, alkyl, cycloalkyl, cycloalkenyl, alkenyl, alkynyl, aralkyl, aryl and a heterocyclic group;
• or R82 and R83 may be taken together with the nitrogen to which they are attached form a 5- to 7-membered ring which may optionally contain a further heteroatom and may be optionally substituted with up to three substituents selected from halo, CN, NO2, oxo, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, aryl, and a heterocyclic group;
• each R84 is independently selected from H, alkyl, —OH, —O-alkyl, —O-aryl, —O-aralkyl, -alkyl-O-alkyl, -alkyl-O-aryl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aryl and a heterocyclic group;
• r is 0 to 6;
• s is 0 to 6;
• and
• n is 0 to 5.