Cyclothiocarbamate derivatives as progesterone receptor modulators

A compound of the formula:

• wherein:
• R1 and R2 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, and NRBCORA;
• or R1 and R2 are fused to form a spirocyclic ring selected from the group consisting of (i), (ii), ahd (iii), said spirocyclic ring being optionally substituted by from 1 to 3 substituents selected from the group consisting of H and C1 to C3 alkyl;
• (i) a carbon-based saturated 3 to 8 membered spirocyclic ring;
• (ii) a carbon-based 3 to 8 membered spirocyclic ring having one or more carbon-carbon double bonds in said ring;
• or
• (iii) a 3 to 8 membered spirocyclic ring containing in its backbone one to three heteroatoms selected from the group consisting of O, S and N;
• RA is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, amino, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, substituted alkynyl, or CORC;
• RC is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• R4 is selected from the group consisting of H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, and substituted C1 to C6 aminoalkyl;
• R5 is selected from the group consisting of a) and b):
• a) a substituted benzene ring having the substituents X, Y and Z as shown below:
• X is selected firom the group consisting of H, halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, Cl to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, CORD, OCORD, and NRECORD;
• RD is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RE is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C3 alkyl, and C1 to C3 thioalkoxy;
• and
• b) a five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, S(O), S(O2), and NR6 and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, C1 to C3 perfluoroalkyl, 5 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, C1 to C3 thioalkoxy, CORF, and NRGCORF;
• RF is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RG is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R6 is H or C1 to C3 alkyl;
• Q1 is S, NR7, or CR8R9;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, SO2CF3, OR11 and NR11R12;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR8R9 comprise a six membered ring as shown by the structure below:
• R11 and R12 are independently selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, and sulfonyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 and R2 are C1 to C6 alkyl;
• R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, substituted alkynyl, or CORC;
• RC is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• R4 is selected from the group consisting of H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, and substituted C1 to C6 aminoalkyl;
• R5 is selected from the group consisting of a) and b):
• a) a substituted benzene ring having the substituents X, Y and Z as shown below:
• X is selected from the group consisting of H, halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, CORD, OCORD, and NRECORD;
• RD is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RE is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C3 alkyl, and C1 to C3 thioalkoxy;
• wherein not all of X, Y, and Z are H;
• and
• b) a five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, S(O), S(O2), and NR6 and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, C1 to C3 perfluoroalkyl, 5 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, C1 to C3 thioalkoxy, CORF, and NRGCORF;
• RF is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RG is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R6 is H or C1 to C3 alkyl;
• Q1 is S, NR7, or CR8R9;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, SO2CF3, OR11 and NR11R12;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR8R9 comprise a six membered ring as shown by the structure below:
• R11 and R12 are independently selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, and sulfonyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 and R2 are CH3;
• R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, or substituted alkynyl, or CORC;
• RC is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• R4 is selected from the group consisting of H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, and substituted C1 to C6 aminoalkyl;
• R5 is selected from the group consisting of a) and b):
• a) a substituted benzene ring having the substituents X, Y and Z as shown below:
• wherein:
• X is selected from the group consisting of H, halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, CORD, OCORD, and NRECORD;
• RD is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RE is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• Y and Z are independent substituents is selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C3 alkyl, and C1 to C3 thioalkoxy;
• wherein not all of X, Y, and Z are H;
• and
• b) a five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, S(O), S(O2), and NR6 and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, C1 to C3 perfluoroalkyl, 5 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, C1 to C3 thioalkoxy, CORF, and NRGCORF;
• RF is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RG is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R6 is H or C1 to C3 alkyl;
• Q1 is S, NR7, or CR8R9;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, SO2CF3, OR11 and NR11R12;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR8R9 comprise a six membered ring as shown by the structure below:
• R11 and R12 are independently selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, and sulfonyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 and R2 are C1 to C3 alkyl, or R1 and R2 are fused to form a carbon-based 3 to 6 membered saturated spirocyclic ring;
• R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, or CORC;
• RC is selected from the group consisting of H, C1 to C4 alkyl, and C1 to C4 alkoxy;
• R4 is selected from the group consisting of H, halogen, NO2, C1 to C3 alkyl, and substituted C1 to C3 alkyl;
• R5 is selected from the group consisting of a), b), and c):
• a) a substituted benzene ring of the structure:
• wherein:
• X is selected from the group consisting of halogen, CN, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 thioalkoxy, NO2, C1 to C3 perfluoroalkyl, and 5 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms;
• Y is selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C4 alkyl, and C1 to C3 thioalkoxy;
• b) a five membered heterocyclic ring of the structure:
• wherein:
• X′ is halogen, CN, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 perfluoroalkyl, 5 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, or C1 to C3 thioalkoxy;
• Y′ is H or C1 to C4 alkyl;
• U is O, S, or NR6;
• R6 is H, C1 to C3 alkyl, or C1 to C4 CO2 alkyl;
• and
• c) a six-membered ring of the structure:
• wherein:
• X1 is N or CX2;
• X2 is halogen, CN, or NO2;
• Q1 is S, NR7, or CR8R9;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, or SO2CF3;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR8R9 comprise a six membered ring as shown by the structure below:
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 and R2 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C2 to C6 alkenyl, substituted C2 to C6 alkenyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic. substituted heterocyclic, CORA, and NRBCORA;
• or R1 and R2 are fused to form a spirocyclic ring selected from the group consisting of (i), (ii), and (iii), said spirocyclic ring being optionally substituted by from 1 to 3 substituents selected from the group consisting of H and C1 to C3 alkyl:
• (i) a carbon-based saturated 3 to 8 membered spirocyclic ring;
• (ii) a carbon-based 3 to 8 membered spirocyclic ring having one or more carbon-carbon double bonds in said ring;
• or
• (iii) a 3 to 8 membered spirocyclic ring containing in its backbone one to three heteroatoms selected from the group consisting of O, S and N;
• RA is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, amino, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, substituted alkynyl, or CORC;
• RC is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• R4 is selected from the group consisting of H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, and substituted C1 to C6 aminoalkyl;
• R5 is selected from the group consisting of a) and b):
• a) a substituted benzene ring containing the substituents X, Y and Z as shown below:
• X is selected from the group consisting of H, halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, CORD, OCORD, and NRECORD;
• RD is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RE is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C3 alkyl, and C1 to C3 thioalkoxy;
• wherein not all of X, Y, and Z are H;
• and
• b) a five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, S(O), S(O2), and NR6 and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkyl, C1 to C3 alkoxy, C1 to C3 aminoalkyl, C1 to C3 perfluoroalkyl, 5 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms, C1 to C3 thioalkoxy, CORF, and NRGCORF;
• RF is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RG is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R6 is H or C1 to C3 alkyl;
• Q1 is NR7 or CR8R9;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, SO2CF3, OR11 and NR11R12;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR8R9 comprise a six membered ring as shown by the structure below:
• R11 and R12 are independently selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, and sulfonyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 is an independent substituent selected from the group consisting of H, C1 to C6 alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, and NRBCORA;
• R2 is an independent substituent selected from the group consisting of H, C1 to C6 alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, CORA, and NRBCORA;
• or R1 and R2 are fused to form a spirocyclic ring selected from the group consisting of (i), (ii), and (iii), said spirocyclic ring being optionally substituted by from 1 to 3 substituents selected from the group consisting of H and C1 to C3 alkyl:
• (i) a carbon-based saturated 3 to 8 membered spirocyclic ring;
• (ii) a carbon-based 3 to 8 membered spirocyclic ring having one or more carbon-carbon double bonds in said ring;
• or
• (iii) a 3 to 8 membered spirocyclic ring containing in its backbone one to three heteroatoms selected from the group consisting of O, S and N;
• RA is selected from the group consisting of H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, and substituted C1 to C3 aminoalkyl;
• RB is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• R3 is H, OH, NH2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C6 alkenyl, substituted C1 to C6 alkenyl, alkynyl, substituted alkynyl, or CORC;
• RC is selected from the group consisting of H, C1 to C4 alkyl, substituted C1 to C4 alkyl, aryl, substituted aryl, C1 to C4 alkoxy, substituted C1 to C4 alkoxy, C1 to C4 aminoalkyl, and substituted C1 to C4 aminoalkyl;
• R4 is selected from the group consisting of H, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, C1 to C6 aminoalkyl, and substituted C1 to C6 aminoalkyl;
• R5 is selected from the group consisting of a) and b):
• a) a substituted benzene ring having the substituents X, Y and Z as shown below:
• X is selected from the group consisting of halogen, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, 5 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms, CORD, OCORD, and NRECORD;
• RD is H, C1 to C3 alkyl, substituted C1 to C3 alkyl, aryl, substituted aryl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
• RE is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
• Y and Z are independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkoxy, C1 to C4 alkyl, and C1 to C3 thioalkoxy;
• wherein not all of X, Y, and Z are H;
• and
• b) a five or six membered heterocyclic ring having in its backbone 1, 2, or 3 heteroatoms selected from the group consisting of O, S, S(O), S(O2), and NR6 and containing one or two independent substituents selected from the group consisting of H, halogen, CN, NO2, C1 to C3 alkyl, and C1 to C3 alkoxy;
• R6 is H or C1 to C3 alkyl;
• Q1 is S, NR7, or CR8R9;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, SO2CF3, OR11 and NR11R12;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR8R9 comprise a six membered ring as shown by the structure below:
• R11 and R12 are independently selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, acyl, and sulfonyl;
• or a pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 and R2 are C1 alkyl or R1 and R2 are fused to form a carbon-based 3 to 6 membered spirocyclic ring;
• R3 is H, OH, NH2, C1 alkyl, substituted C1 alkyl, or CORC;
• RC is selected from the group consisting of H, C1 to C3 alkyl, and C1 to C4 alkoxy;
• R4 is selected from the group consisting of H, halogen, and C1 to C3 alkyl;
• R5 is selected from the group consisting of a) and b):
• a) a substituted benzene ring of the structure:
• wherein:
• X is selected from the group consisting of halogen, C1 alkoxy, NO2, and 2-thiazole;
• Y is H or F;
• b) a five membered heterocyclic ring of the structure:
• wherein:
• X′ is halogen, CN, or NO2;
• Y′ is H and C1 to C4 alkyl;
• U is O, S, or NH;
• R7 is selected from the group consisting of CN, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C6 cycloalkyl, aryl, substituted aryl, heterocyclic, and SO2CF3;
• R8 and R9 are independent substituents selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C3 to C8 cycloalkyl, substituted C3 to C8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, and CO2R10;
• R10 is C1 to C3 alkyl;
• or CR1 R1 comprise a six membered ring as shown by the structure below:
• or a pharmaceutically acceptable salt thereof.