Benzylphenyl cyclohexane derivatives and methods of use

A compound of Formula I:

• wherein
• A is selected from the group consisting of oxygen;
• NH;
• methylene;
• and a single bond;
• Q is selected from the group consisting of formulae Q1 to Q4;
• Z is selected from the group consisting of oxygen;
• sulfur;
• SO;
• SO2;
• 1,1-cyclopropylene;
• carbonyl;
• and methylene optionally substituted with one to two substituents independently selected from halo, hydroxy, C1-C6 alkyl, C1-C6 alkoxy, C3-C6 cycloalkyl and C3-C6 cycloalkyloxy;
• R1, R2 and R3 are each independently selected from the group consisting of hydrogen, halo, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C1-C6 alkyloxy, C3-C10 cycloalkyloxy, cyano, amino and nitro, wherein alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by identical or different substituents selected from the group consisting of chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and in cycloalkyl and cycloalkenyl groups or portions one or two methylene groups are optionally replaced independently of one another by NRa, O, S, CO, SO or SO2, and one or two methyne groups are optionally replaced by N, or in the event that R1 and R2 are bound to two adjacent C atoms of the phenyl ring, R1 and R2 are optionally joined together to form a C3-C5 alkylene, C3-C5 alkenylene or butadienylene bridge, which is optionally partly or completely fluorinated and is optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and wherein one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO2 or NRa, and wherein one or two methyne groups optionally may be replaced by N;
• R4 is a member selected from the group consisting of hydrogen, halo, cyano, nitro, amino, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C5-C10 cycloalkenyl, C1-C6 alkyloxy, C3-C10 cycloalkyloxy, (C1-C6 alkyloxy)C1-C6 alkyloxy, C5-C7 cycloalkenyloxy, aryl, heteroaryl, aryloxy, heteroaryloxy, (C2-C4 alkenyl)C1-C3 alkyloxy, (C2-C4 alkynyl)C1-C3 alkyloxy, (aryl)C1-C3 alkyloxy, (heteroaryl)C1-C3 alkyloxy, (C3-C10 cycloalkyl)C1-C3 alkyl, (C3-C10 cycloalkyl)C1-C3 alkyloxy, (C5-C10 cycloalkenyl)C1-C3 alkyl, (C5-C10 cycloalkenyl)C1-C3 alkyloxy, (C1-C4 alkyloxy)C1-C3 alkyl, (C3-C7 cycloalkyloxy)C1-C3 alkyl, (C3-C7 cycloalkyloxy)C2-C4 alkenyl, (C3-C7 cycloalkyloxy)C2-C4 alkynyl, (C3-C7 cycloalkyloxy)C1-C3 alkyloxy, (C1-C4 alkylamino)C1-C3 alkyl, di-(C1-C3 alkylamino)C1-C3 alkyl, tri-(C1-C4 alkyl)silyl-C1-C6 alkyl, tri-(C1-C4 alkyl)silyl-C2-C6 alkenyl, tri-(C1-C4 alkyl)silyl-C2-C6 alkynyl, tri-(C1-C4 alkyl)silyl-C1-C6 alkyloxy, (C3-C7 cycloalkyl)C2-C5 alkenyl, (C3-C7 cycloalkyl)C3-C5 alkenyloxy, (C3-C7 cycloalkyl)C3-C5 alkynyloxy, (C5-C8 cycloalkenyl)C3-C5 alkenyloxy, (C5-C8 cycloalkenyl)C3-C5 alkynyloxy, C3-C6 cycloalkylidenmethyl, (C1-C4 alkyl)carbonyl, arylcarbonyl, heteroarylcarbonyl, aminocarbonyl, (C1-C4 alkyl)aminocarbonyl, di-(C1-C3 alkyl)aminocarbonyl, hydroxycarbonyl, (C1-C4 alkyloxy)carbonyl, C1-C4 alkylamino, di-(C1-C3 alkyl)amino, (C1-C4 alkyl)carbonylamino, arylcarbonylamino, heteroarylcarbonylamino, C1-C4 alkylsulfonylamino, arylsulfonylamino, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C3-C10 cycloalkylsulfanyl, C3-C10 cycloalkylsulfinyl, C3-C10 cycloalkylsulfonyl, C5-C10 cycloalkenylsulfanyl, C5-C10 cycloalkenylsulfinyl, C5-C10 cycloalkenylsulfonyl, arylsulfanyl, arylsulfinyl and arylsulfonyl, wherein alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and in cycloalkyl and cycloalkenyl groups or portions one or two methylene groups are optionally replaced independently of one another by NRa, O, S, CO, SO or SO2, and one or two methyne groups are optionally replaced by N;
• R5 and R6 each independently selected from the group consisting of hydrogen, halo, cyano, nitro, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C3 alkyloxy and C3-C10 cycloalkyloxy, wherein alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and in cycloalkyl and cycloalkenyl groups or portions one or two methylene groups are optionally replaced independently of one another by NRa, O, S, CO, SO or SO2, and one or two methyne groups are optionally replaced by N, or
• if R5 and R6 are bound to two adjacent C atoms of the phenyl ring, R5 and R6 are optionally joined together to form a C3-C5 alkylene, C3-C5 alkenylene or butadienylene bridge, which is optionally partly or completely fluorinated and mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and wherein one or two methylene groups are optionally replaced independently of one another by O, S, CO, SO, SO2 or NRa, and wherein one or two methyne groups are optionally replaced by N;
• R7, R8, R9 and R10 are each independently selected from the group consisting of hydroxy, (C1-C18 alkyl)carbonyloxy, (C1-C18 alkyl)oxycarbonyloxy, arylcarbonyloxy, aryl-(C1-C3 alkyl)carbonyloxy, (C3-C10 cycloalkyl)carbonyloxy, hydrogen, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C3-C10 cycloalkyl)C1-C3 alkyl, (C5-C7 cycloalkenyl)C1-C3 alkyl, (aryl)C1-C3 alkyl, (heteroaryl)C1-C3 alkyl, C1-C6 alkyloxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy, C3-C7 cycloalkyloxy, C5-C7 cycloalkenyloxy, aryloxy, heteroaryloxy, (C3-C7 cycloalkyl)C1-C3 alkyloxy, (C5-C7 cycloalkenyl)C1-C3 alkyloxy, (aryl)C1-C3 alkyloxy, (heteroaryl)C1-C3 alkyloxy, aminocarbonyl, hydroxycarbonyl, (C1-C4 alkyl)aminocarbonyl, di-(C1-C3 alkyl)aminocarbonyl, (C1-C4 alkyloxy)carbonyl, (aminocarbonyl)C1-C3 alkyl, (C1-C4 alkyl)aminocarbonyl-(C1-C3)alkyl, di-(C1-C3 alkyl)aminocarbonyl-(C1-C3)alkyl, (hydroxycarbonyl)C1-C3 alkyl, (C1-C4 alkyloxy)carbonyl-(C1-C3)alkyl, (C3-C7 cycloalkyloxy)C1-C3 alkyl, (C5-C7 cycloalkenyloxy)C1-C3 alkyl, (aryloxy)C1-C3 alkyl, (heteroaryloxy)C1-C3 alkyl, C1-C4 alkylsulfonyloxy, arylsulfonyloxy, (aryl)C1-C3 alkylsulfonyloxy, trimethylsilyloxy, t-butyldimethylsilyloxy, and cyano;
• wherein alkyl, alkenyl, alkynyl, cycloalkyl and cycloalkenyl groups or portions are optionally partly or completely fluorinated and are optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and in cycloalkyl and cycloalkenyl groups or portions one or two methylene groups are optionally replaced independently of one another by NRa, O, S, CO, SO or SO2;
• and optionally, R10 and R11 can be combined with the carbon atoms to which each is attached to form a five- to seven-membered fused cycloalkane or cycloalkene ring that is optionally partly or completely fluorinated and may be mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl, and wherein in the cycloalkyl and cycloalkenyl rings one or two methylene groups are optionally replaced independently of one another by NRa, O, S, CO, SO or SO2;
• R11 and R12 are each independently selected from the group consisting of hydrogen, hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkyloxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy or C3-C6 cycloalkyloxy, wherein alkyl, alkenyl, alkynyl and cycloalkyl groups or portions are optionally partly or completely fluorinated, or
• R11 and R12 are optionally joined together with the carbon atom to which they are attached to form a C3-C7 spirocycloalkane ring which is optionally partly or completely fluorinated and is optionally mono- or disubstituted by identical or different substituents selected from chlorine, hydroxy, C1-C3 alkoxy and C1-C3 alkyl;
• wherein
• (i) when Q is Q1 and both R11 and R12 are hydrogen, then at least one of R10 or R14 is halo or R13 is other than hydrogen or R4 is C2-C6 alkynyl, C3-C10 cycloalkyloxy, C5-C7 cycloalkenyloxy, (C3-C10 cycloalkyl)C1-C3 alkyloxy, (C3-C7 cycloalkyl)C3-C5 alkenyloxy, (C3-C7 cycloalkyl)C3-C5 alkynyloxy, (C5-C10 cycloalkenyl)C1-C3 alkyloxy, (C5-C8 cycloalkenyl)C3-C5 alkenyloxy or (C5-C8 cycloalkenyl)C3-C5 alkynyloxy;
• (ii) when Q is Q2 and R11 is hydrogen, then at least R10 is halo or R4 is C2-C6 alkynyl, C3-C10 cycloalkyloxy, C5-C7 cycloalkenyloxy, (C3-C10 cycloalkyl)C1-C3 alkyloxy, (C3-C7 cycloalkyl)C3-C5 alkenyloxy, (C3-C7 cycloalkyl)C3-C5 alkynyloxy, (C5-C10 cycloalkenyl)C1-C3 alkyloxy, (C5-C8 cycloalkenyl)C3-C5 alkenyloxy or (C5-C8 cycloalkenyl)C3-C5 alkynyloxy;
• (iii) when Q is Q4 and R11 is hydrogen, then at least R10 is halo or R13 is other than hydrogen or R4 is C2-C6 alkynyl, C3-C10 cycloalkyloxy, C5-C7 cycloalkenyloxy, (C3-C10 cycloalkyl)C1-C3 alkyloxy, (C3-C7 cycloalkyl)C3-C5 alkenyloxy, (C3-C7 cycloalkyl)C3-C5 alkynyloxy, (C5-C10 cycloalkenyl)C1-C3 alkyloxy, (C5-C8 cycloalkenyl)C3-C5 alkenyloxy or (C5-C8 cycloalkenyl)C3-C5 alkynyloxy;
• R13 and R14 each independently selected from the group consisting of hydrogen, hydroxy, halo, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C10 cycloalkyl, C1-C6 alkyloxy, C2-C6 alkenyloxy, C2-C6 alkynyloxy and C3-C6 cycloalkyloxy, wherein alkyl, alkenyl, alkynyl and cycloalkyl groups or portions are optionally partly or completely fluorinated;
• R15 is selected from the group consisting of oxygen and CRbRc;
• each Ra independently is selected from the group consisting of hydrogen, C1-C4 alkyl and (C1-C4 alkyl)carbonyl, wherein alkyl groups or portions are optionally partly or completely fluorinated;
• and
• Rb and Rc are each independently selected from the group consisting of hydrogen, halo and C1-C4 alkyl, wherein alkyl groups are optionally partly or completely fluorinated;
• and pharmaceutically acceptable salts thereof.