Pharmaceutical compositions for hepatitis C viral protease inhibitors

A pharmaceutical composition comprising:

• (a) a compound of formula (I):
• 135
• wherein:
• ------ designates an optional bond forming a double bond between positions 13 and 14;
• R1 is H, halo, C1-6 alkyl, C3-6 cycloalkyl, C6 haloalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, hydroxy, or N(R5)2, wherein each R5 is independently H, C1-6 alkyl or C3-6 cycloalkyl;
• R2 is H, halo, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, C1-6 thioalky, C1-6 alkoxy, C3-6 cycloalkoxy, C2-7 alkoxyalkyl, C6 or 10 aryl or Het, wherein Het is a five-, six-, or seven-membered saturated or unsaturated heterocycle containing from one to four ring heteroatoms selected from nitrogen, oxygen and sulfur;
• said cycloalkyl, aryl or Het being optionally substituted with R6,
• wherein R6 is H, halo, C1-6 alkyl, C3-6 cycloalkyl, C1-6 alkoxy, C3-6 cycloalkoxy, NO2, N(R7)2, NH—C(O)—R7;
• or NH—C(O)—NH—R7, wherein each R7 is independently:
• H, C1-6 alkyl or C3-6 cycloalkyl;
• or R6 is NH—C(O)—OR8 wherein R8 is C1-6 alkyl or C3-6 cycloalkyl;
• R3 is R9O— or R9NH—, wherein R9 is C1-6alkyl or C3-6cycloalkyl;
• R4is H or from one to three substituents on any available carbon atom at positions 8, 9, 10, 11, 12, 13 or 14, said substituent independently selected from the group consisting of:
• C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, hydroxy, halo, amino, oxo, thio or C1-6 thioalkyl;
• or a tautomer thereof;
• (b) about 0.1 to 10% by weight of a pharmaceutically acceptable amine or a mixture of pharmaceutically acceptable amines;
• and
• (c) one or more pharmaceutically acceptable oils, carriers or hydrophilic solvents;
• and when (c) is one or more pharmaceutically acceptable oils, the pharmaceutical composition further comprises:
• (d) optionally one or more pharmaceutically acceptable hydrophilic solvents;
• (e) optionally one or more pharmaceutically acceptable polymers;
• and
• (f) optionally one or more pharmaceutically acceptable surfactants;
• and when (c) is one or more pharmaceutically acceptable carriers, the pharmaceutical composition further comprises:
• (d) optionally one or more pharmaceutically acceptable surfactants.