A method for contraception comprising administering to a female of child-bearing age a progesterone receptor modulator having the formula:
- wherein:
- R1 is H, OH, C1 to C3 alkyl, substituted C1 to C3 alkyl, C1 to C3 perfluoroalkyl, or COR6;
- R6 is H, C1 to C4 alkyl, substituted C1 to C4 alkyl, aryl, substituted aryl, C1 to C4 alkoxy, substituted C1 to C4 alkoxy, C1 to C3 aminoalkyl, or substituted C1 to C3 aminoalkyl;
- R2 and R3 are independently selected from the group consisting of H, C1 to C6 alkyl, substituted C1 to C6 alkyl, C1 to C6 perfluoroalkyl, C2 to C6 alkenyl, substituted C2 to C6 alkenyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C3 to C6 cycloalkyl, substituted C3 to C6 cycloalkyl, aryl, substituted aryl, heterocyclic, and substituted heterocyclic;
- or R2 and R3 are fused to form:
- (i) 3 to 8 membered saturated spirocyclic ring;
- (ii) 3 to 8 membered spirocyclic ring having in its backbone one or more carbon-carbon double bonds;
- or
- (iii) 3 to 8 membered saturated spirocyclic ring having in its backbone one to three heteroatoms selected from the group consisting of O, S, and N;
- R4 is NHR7, OR7, NHSO2R7, OSO2R7, NCH3R7 or NCH3SO2R7;
- R7 is selected from the group consisting of (a) and (b):
- (a) an aryl ring which is optionally substituted with one to three independent substituents selected from the group consisting of H, halogen, OH, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C2 to C3 alkenyl, substituted C2 to C3 alkenyl, C2 to C3 alkynyl, substituted C2 to C3 alkynyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C5 to C8 aryloxy, substituted C5 to C8 aryloxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, amino, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, CORB, CRB═NORC, OCORB, NRCCORB, 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms selected from the group consisting of N, O, and S;
- and
- (b) a 5 or 6 membered heterocyclic ring containing in its backbone 1 to 3 heteroatoms selected from the group consisting of O, S, SO, SO2 and N and optionally substituted with one to three independent substituents selected from the group consisting of H, halogen, OH, CN, C1 to C3 alkyl, substituted C1 to C3 alkyl, C2 to C3 alkenyl, substituted C2 to C3 alkenyl, C2 to C3 alkynyl, substituted C2 to C3 alkynyl, C1 to C3 alkoxy, substituted C1 to C3 alkoxy, C1 to C3 thioalkoxy, substituted C1 to C3 thioalkoxy, amino, C1 to C3 aminoalkyl, substituted C1 to C3 aminoalkyl, NO2, C1 to C3 perfluoroalkyl, CORB, CRB═NORC, OCORB, NRCCORB, and 5 or 6 membered heterocyclic ring having in its backbone 1 to 3 heteroatoms selected from the group consisting of N, O, and S;
- RB 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;
- RC is H, C1 to C3 alkyl, or substituted C1 to C3 alkyl;
- R5 is H, OH, halogen, CN, NO2, C1 to C6 alkyl, substituted C1 to C6 alkyl, C2 to C6 alkynyl, substituted C2 to C6 alkynyl, C1 to C6 alkoxy, substituted C1 to C6 alkoxy, amino, C1 to C6 aminoalkyl, or substituted C1 to C6 aminoalkyl;
- Q is O, S, NR8, or CR9R10;
- R8 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;
- R9 and R10 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 CO2R11;
- or CR9R10 is 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, heterocyclic, substituted heterocyclic, acyl, and sulfonyl;
- X is O;
- or a pharmaceutically acceptable salt, or tautomer thereof;
- wherein:
- said substituted alkyl, substituted alkenyl, and substituted alkynyl is an alkyl, alkenyl, and alkynyl, respectively, comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyche, aryl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, amino, and arylthio;
- said substituted aryl is an aryl comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and aryithio;
- said substituted cycloalkyl is a cycloalkyl comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, aryl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, amino, and aryithio;
- said substituted alkoxy is an alkoxy comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, aryl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, amino, and arylthio;
- said substituted aminoalkyl is an aminoalkyl comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, aryl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, amino, and arylthio;
- said substituted heterocyclic is a heterocycle comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
- said substituted aryloxy is an aryloxy comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, aryl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, amino, and arylthio;
- said substituted thioalkoxy is a thioalkoxy comprising one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, aryl, alkoxy, aryloxy, alkyloxy, alkylcarbonyl, alkylcarboxy, amino, and arylthio.