7-aryl 1,5-dihydro-4,1-benzoxazepin-2(3H)-one derivatives and their use as progesterone receptor modulators

A compound of the formula:

• wherein:
• R1 is H, C1-3 alkyl, or CORA;
• RA is H, C1-4 alkyl, C1-4 alkoxy, or C1-3 aminoalkyl;
• R2 and R3 are each independently H, CF3, or C1-3 alkyl;
• R4 and R5 are each independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CF3, CF2CF3, C3-6 cycloalkyl, aryl, substituted aryl, heterocycle, substituted heterocycle, or together with the carbon atom to which they are attached form a 3 to 6 membered alkylspirocyclic ring or a 3 to 6 membered heterospirocyclic ring containing one to three heteroatoms within the spirocyclic ring, said heteroatoms being O, S, SO, SO2, or N;
• R6 is substituted phenyl containing 1 to 3 substituents, said substituents independently being H, halogen, CN, NO2, OH, amino, C1-3 alkyl, C1-3 alkoxy, C1-3 aminoalkyl, C═NORC, CORD, or NRCCORD;
• or
• R6 is a benzofused heterocyclic ring of the following formula
• where A, B, and D are each independently CH, N, O, or S;
• RC is H, C1-4 alkyl, substituted C1-4 alkyl, or CORD;
• RD is H, C1-3 alkyl, C1-3 alkoxy, or C1-3 aminoalkyl;
• R7 is H, halogen, CN, NO2, OH, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 alkoxy, amino, or C1-3 aminoalkyl;
• Q is O, S, NR8, CR9R10, or R13R14;
• R8 is CN, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, substituted C3-8 cycloalkyl, aryl, substituted aryl, heterocyclic, or substituted heterocyclic, SO2CF3, OR11 or NR11R12;
• R9 and R10 are independently H, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, substituted C3-8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, or CO2R11;
• or CR9R10 is a six membered ring of the structure:
• R11 and R12 are independently each H, C1-6 alkyl, substituted C1-6 alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, alkyl carbonyl or sulfonyl;
• R13 and R14 are each independently H, C1-3 lower alkyl, C1-3 lower perfluoroalkyl, aryl, heterocyclic, a 3 to 6 membered alkylspirocyclic ring is a 3 to 6 membered heterospirocyclic ring containing one to three heteroatoms within the spirocyclic ring, said heteroatoms being O, S, SO, SO2 or N;
• X is S, NRE, or CRERF;
• RE and RF are each independently H or C1-4 alkyl;
• the alkyl group of said substituted alkyl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• the alkenyl group of said substituted alkenyl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• the alkynyl group of said substituted alkynyl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• the aryl group of said substituted aryl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• wherein said heterocycle is a stable 4- to 7-membered monocyclic or a stable multicyclic heterocyclic ring which is saturated, partially unsaturated, or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S atoms;
• the heterocyclic group of said substituted heterocyclic comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, alkyl, substituted alkyl, cycloalkyl, alkenyl, substituted alkenyl, alkynyl, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• or pharmaceutically acceptable salt thereof.

A compound of the formula:

• wherein:
• R1 is H, C1-3 alkyl, or CORA;
• RA is H, C1-4 alkyl, C1-4 alkoxy, or C1-3 aminoalkyl;
• R2 and R3 are each independently H, CF3, or C1-3 alkyl;
• R4 and R5 are each independently H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, CF3, CF2CF3, C3-6 cycloalkyl, aryl, substituted aryl, heterocycle, substituted heterocycle, or together with the carbon atom to which they are attached form a 3 to 6 membered alkylspirocyclic ring or a 3 to 6 membered heterospirocyclic ring containing one to three heteroatoms within the spirocyclic ring, said heteroatoms being O, S, SO, SO2, or N;
• R6 is a 5 or 6 membered heterocyclic ring containing 2 heteroatoms and 1 to 3 substituents, said heteroatoms being O, S, SO, SO2 or N and said substituents independently being H, halogen, CN, NO2, OH, C1-3 alkoxy, C1-3 aminoalkyl,
• C═NORC, CORD, or NRCCORD;
• R7 is H, halogen, CN, NO2, OH, C1-3 alkyl, C2-3 alkenyl, C2-3 alkynyl, C1-3 alkoxy, amino, or C1-3 aminoalkyl;
• Q is O, S, NR8, CR9R10, or R13R14;
• R8 is CN, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, substituted C3-8 cycloalkyl, aryl, substituted aryl, heterocyclic, or substituted heterocyclic, SO2CF3, OR11 or NR11R12;
• R9 and R10 are independently H, C1-6 alkyl, substituted C1-6 alkyl, C3-8 cycloalkyl, substituted C3-8 cycloalkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, NO2, CN, or CO2R11;
• or CR9R10 is a six membered ring of the structure:
• R11 and R12 are independently each H, C1-6 alkyl, substituted C1-6 alkyl, aryl, substituted aryl, heterocyclic, substituted heterocyclic, alkyl carbonyl or sulfonyl;
• R13 and R14 are each independently H, C1-3 lower alkyl, C1-3 lower perfluoroalkyl, aryl, heterocyclic, a 3 to 6 membered alkylspirocyclic ring is a 3 to 6 membered heterospirocyclic ring containing one to three heteroatoms within the spirocyclic ring, said heteroatoms being O, S, SO, SO2 or N;
• X is S, NRE, or CRERF;
• RE and RF are each independently H or C1-4 alkyl;
• provided that when X is NRE, Q is O or S, R6 is a 5 or 6 membered heterocyclic ring, and R4 is cyclopropyl or C1-3 alkyl, then R5 is H, CF3, CF2CF3, C3-6 cycloalkyl, aryl, substituted aryl, heterocycle, or a substituted heterocycle;
• the alkyl group of said substituted alkyl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• the alkenyl group of said substituted alkenyl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• the alkynyl group of said substituted alkynyl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, aryl, heterocyclic, substituted aryl, substituted heterocyclic, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• the aryl group of said substituted aryl comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• wherein said heterocycle is a stable 4- to 7-membered monocyclic or a stable multicyclic heterocyclic ring which is saturated, partially unsaturated, or unsaturated, and which consists of carbon atoms and from one to four heteroatoms selected from the group consisting of N, O, and S atoms;
• the heterocyclic group of said substituted heterocyclic comprises one or more substituents selected from the group consisting of halogen, CN, OH, NO2, amino, alkyl, substituted alkyl, cycloalkyl, alkenyl, substituted alkenyl, alkynyl, alkoxy, aryloxy, substituted alkyloxy, alkylcarbonyl, alkylcarboxy, alkylamino, and arylthio;
• or pharmaceutically acceptable salt thereof.