Tetra-aryl cyclobutane inhibitors of androgen receptor action for the treatment of hormone refractory cancer

A compound having the formula:

• wherein
• each R1 and R2 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) a 7 to 10-membered saturated, unsaturated, or aromatic fused bicyclic carbocyle, (m) a 3 to 10-membered saturated, unsaturated, or aromatic heterocycle or fused bicyclic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, (n) —OR3, (o) —NR3R3, (p) —CN, (q) —N3, (r) —SR3, (s) —SOR3, (t) —SO2R3, (u) —COOR3, (v) —COR3, (w) —CONR3R3, (x) —NR3COR3—, (y) —NR3CONR3R3, (z) —(C1-C8 alkyl)OR3, (aa) —(C1-C8 alkyl)NR3R3, (bb) —(C1-C8 alkyl)SR3, (cc) —(C1-C8 alkyl)SOR3, (dd) —(C1-C8 alkyl)SO2R3, (ee) —(C1-C8 alkyl)COOR3, (ff) —(C1-C8 alkyl)COR3, (gg) —(C1-C8 alkyl)CONR3R3, (hh) —(C1-C8 alkyl)NR3COR3, and (ii) —(C1-C8 alkyl)NR3CONR3R3,
• wherein each of (e) through (j) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), or —N(C1-C8 alkyl)2 and
• wherein each of (k) through (l) immediately recited above is optionally substituted with one or more R4 or R5;
• each R3 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (k) immediately recited above is optionally substituted with one or more R5;
• each R4 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, and (j) —C8 cycloalkynyl, wherein each of (e) through (j) immediately recited above is optionally substituted with one or more R5;
• each R5 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2,
• each Ar is independently selected from (a) phenyl, (b) naphthyl, (c) a 5 or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, and (d) a 7 to 10-membered heteroaromatic ring or fused bicyclic heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof,
• wherein each of (a) through (d) immediately recited above is optionally substituted with one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) —OR6, (m) —NR6R6, (n) —CN, (o) —N3, -(p) —SR6, (q) —SOR6, (r) —SO2R6, (s) —COOR6, (t) —COR6, (u) —CONR6R6, (v) —NR6COR6—, and (w) —NR6CONR6R6,
• wherein each of (e) through (k) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), and —N(C1-C8 alkyl)2;
• each R6 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (i) immediately recited above is optionally substituted with one or more R7;
• and
• each R7 is independently selected from one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2;
• or an enantiomer, diastereomer, or tautomer of said compound, or a pharmaceutically acceptable, salt of said compound, of said enantiomer of said compound, of said diastereomer of said compound, or of said tautomer of said compound.

A compound having the formula:

• wherein
• each R1 and R2 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) a 7 to 10-membered saturated, unsaturated, or aromatic fused bicyclic carbocyle, (m) a 3 to 10-membered saturated, unsaturated, or aromatic heterocycle or fused bicyclic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, (n) —OR3, (o) —NR3R3, (p) —CN, (q) —N3, (r) —SR3, (s) —SOR3, (t) —SO2R3, (u) —COOR3, (v) —COR3, (w) —CONR3R3, (x) —NR3COR3—, (y) —NR3CONR3R3, (z) —(C1-C8 alkyl)OR3, (aa) —(C1-C8 alkyl)NR3R3, (bb) —(C1-C8 alkyl)SR3, (cc) —(C1-C8 alkyl)SOR3, (dd) —(C1-C8 alkyl)SO2R3, (ee) —(C1-C8 alkyl)COOR3, (ft) —(C1-C8 alkyl)COR3, (gg) —(C1-C8 alkyl)CONR3R3, (hh) —(C1-C8 alkyl)NR3COR3, and (ii) —(C1-C8 alkyl)NR3CONR3R3,
• wherein each of (e) through (j) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), or —N(C1-C8 alkyl)2 and wherein each of (k) through (l) immediately recited above is optionally substituted with one or more R4 or R5;
• each R3 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (k) immediately recited above is optionally substituted with one or more R5;
• each R4 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, and (j) —C8 cycloalkynyl, wherein each of (e) through (j) immediately recited above is optionally substituted with one or more R5;
• each R5 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2,
• each Ar is independently selected from (a) phenyl, (b) naphthyl, (c) a 5 or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, and (d) a 7 to 10-membered heteroaromatic ring or fused bicyclic heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof,
• wherein each of (a) through (d) immediately recited above is optionally substituted with one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) —OR6, (m) —NR6R6, (n) —CN, (o) —N3, -(p) —SR6, (q) —SOR6, (r) —SO2R6, (s) —COOR6, (t) —COR6, (u) —CONR6R6, (v) —NR6COR6—, and (w) —NR6CONR6R6,
• wherein each of (e) through (k) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), and —N(C1-C8 alkyl)2;
• each R6 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (i) immediately recited above is optionally substituted with one or more R7;
• and
• each R7 is independently selected from one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2;
• and
• or an enantiomer, diastereomer, or tautomer of said compound, or a pharmaceutically acceptable, salt of said compound, of said enantiomer of said compound, of said diastereomer of said compound, or of said tautomer of said compound.

A compound having the formula:

• wherein
• each R1 and R2 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) a 7 to 10-membered saturated, unsaturated, or aromatic fused bicyclic carbocyle, (m) a 3 to 10-membered saturated, unsaturated, or aromatic heterocycle or fused bicyclic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, (n) —OR3, (o) —NR3R3, (p) —CN, (q) —N3, (r) —SR3, (s) —SOR3, (t) —SO2R3, (u) —COOR3, (v) —COR3, (w) —CONR3R3, (x) —NR3COR3—, (y) —NR3CONR3R3, (z) —(C1-C8 alkyl)OR3, (aa) —(C1-C8 alkyl)NR3R3, (bb) —(C1-C8 alkyl)SR3, (cc) —(C1-C8 alkyl)SOR3, (dd) —(C1-C8 alkyl)SO2R3, (ee) —(C1-C8 alkyl)COOR3, (ff) —(C1-C8 alkyl)COR3, (gg) —(C1-C8 alkyl)CONR3R3, (hh) —(C1-C8 alkyl)NR3COR3, and (ii) —(C1-C8 alkyl)NR3CONR3R3,
• wherein each of (e) through (j) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), or —N(C1-C8 alkyl)2 and
• wherein each of (k) through (l) immediately recited above is optionally substituted with one or more R4 or R5;
• each R3 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (k) immediately recited above is optionally substituted with one or more R5;
• each R4 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, and (j) —C8 cycloalkynyl, wherein each of (e) through (j) immediately recited above is optionally substituted with one or more R5;
• each R5 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2,
• each Ar is independently selected from (a) phenyl, (b) naphthyl, (c) a 5 or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, and (d) a 7 to 10-membered heteroaromatic ring or fused bicyclic heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof,
• wherein each of (a) through (d) immediately recited above is optionally substituted with one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) —OR6, (m) —NR6R6, (n) —CN, (o) —N3, -(p) —SR6, (q) —SOR6, (r) —SO2R6, (s) —COOR6, (t) —COR6, (u) —CONR6R6, (v) —NR6COR6—, and (w) —NR6CONR6R6,
• wherein each of (e) through (k) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), and —N(C1-C8 alkyl)2;
• each R6 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (i) immediately recited above is optionally substituted with one or more R7;
• and
• each R7 is independently selected from one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2;
• or an enantiomer, diastereomer, or tautomer of said compound, or a pharmaceutically acceptable, salt of said compound, of said enantiomer of said compound, of said diastereomer of said compound, or of said tautomer of said compound.

A compound having the formula:

• wherein
• each R1 and R2 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) a 7 to 10-membered saturated, unsaturated, or aromatic fused bicyclic carbocyle, (m) a 3 to 10-membered saturated, unsaturated, or aromatic heterocycle or fused bicyclic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, (n) —OR3, (o) —NR3R3, (p) —CN, (q) —N3, (r) —SR3, (s) —SOR3, (t) —SO2R3, (u) —COOR3, (v) —COR3, (w) —CONR3R3, (x) —NR3COR3—, (y) —NR3CONR3R3, (z) —(C1-C8 alkyl)OR3, (aa) —(C1-C8 alkyl)NR3R3, (bb) —(C1-C8 alkyl)SR3, (cc) —(C1-C8 alkyl)SOR3, (dd) —(C1-C8 alkyl)SO2R3, (ee) —(C1-C8 alkyl)COOR3, (ff) —(C1-C8 alkyl)COR3, (gg) —(C1-C8 alkyl)CONR3R3, (hh) —(C1-C8 alkyl)NR3COR3, and (ii) —(C1-C8 alkyl)NR3CONR3R3,
• wherein each of (e) through (j) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), or —N(C1-C8 alkyl)2 and
• wherein each of (k) through (l) immediately recited above is optionally substituted with one or more R4 or R5;
• each R3 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (k) immediately recited above is optionally substituted with one or more R5;
• each R4 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, and (j) —C8 cycloalkynyl, wherein each of (e) through (j) immediately recited above is optionally substituted with one or more R5;
• each R5 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2,
• each Ar is independently selected from (a) phenyl, (b) naphthyl, (c) a 5 or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, and (d) a 7 to 10-membered heteroaromatic ring or fused bicyclic heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof,
• wherein each of (a) through (d) immediately recited above is optionally substituted with one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) —OR6, (m) —NR6R6, (n) —CN, (o) —N3, -(p) —SR6, (q) —SOR6, (r) —SO2R6, (s) —COOR6, (t) —COR6, (u) —CONR6R6, (v) —NR6COR6—, and (w) —NR6CONR6R6,
• wherein each of (e) through (k) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), and —N(C1-C8 alkyl)2;
• each R6 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (i) immediately recited above is optionally substituted with one or more R7;
• and
• each R7 is independently selected from one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2;
• or an enantiomer, diastereomer, or tautomer of said compound, or a pharmaceutically acceptable, salt of said compound, of said enantiomer of said compound, of said diastereomer of said compound, or of said tautomer of said compound.

A method of treating prostate cancer in a subject comprising administering to the subject a therapeutically effective amount of a compound having the formula:

• wherein in each ring system,
• each X1 is —C═;
• each of X2, X3, X4, X5, and X6 is independently selected from —CH═, —CR1═, —CR2═, —NH—, —NR1—, —NR2—, —N═, and —CO—;
• such that each ring system (X) contains 1 to 3 nitrogen atoms, each ring system (X) contains no more than 2-CO—, and each ring system (X) contains no more than one of each R1 and each R2;
• each R1 and R2 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) a 7 to 10-membered saturated, unsaturated, or aromatic fused bicyclic carbocyle, (m) a 3 to 10-membered saturated, unsaturated, or aromatic heterocycle or fused bicyclic heterocycle containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, (n) —OR3, (o) —NR3R3, (p) —CN, (q) —N3, (r) —SR3, (s) —SOR3, (t) —SO2R3, (u) —COOR3, (v) —COR3, (w) —CONR3R3, (x) —NR3COR3—, (y) —NR3CONR3R3, (z) —(C1-C8 alkyl)OR3, (aa) —(C1-C8 alkyl)NR3R3, (bb) —(C1-C8 alkyl)SR3, (cc) —(C1-C8 alkyl)SOR3, (dd) —(C1-C8 alkyl)SO2R3, (ee) —(C1-C8 alkyl)COOR3, (ff) —(C1-C8 alkyl)COR3, (gg) —(C1-C8 alkyl)CONR3R3, (hh) —(C1-C8 alkyl)NR3COR3, and (ii) —(C1-C8 alkyl)NR3CONR3R3,
• wherein each of (e) through (j) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), or —N(C1-C8 alkyl)2 and
• wherein each of (k) through (l) immediately recited above is optionally substituted with one or more R4 or R5;
• each R3 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (k) immediately recited above is optionally substituted with one or more R5;
• each R4 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, and (j) —C8 cycloalkynyl, wherein each of (e) through (j) immediately recited above is optionally substituted with one or more R5;
• each R5 is independently selected from (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2,
• each Ar is independently selected from (a) phenyl, (b) naphthyl, (c) a 5 or 6-membered heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof, and (d) a 7 to 10-membered heteroaromatic ring or fused bicyclic heteroaromatic ring containing one or more heteroatoms selected from nitrogen, oxygen, sulfur, and combinations thereof,
• wherein each of (a) through (d) immediately recited above is optionally substituted with one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —C1-C8 alkyl, (f) —C2-C8 alkenyl, (g) —C2-C8 alkynyl, (h) —C3-C8 cycloalkyl, (i) —C3-C8 cycloalkenyl, (j) —C8 cycloalkynyl, (k) phenyl, (l) —OR6, (m) —NR6R6, (n) —CN, (o) —N3, -(p) —SR6, (q) —SOR6, (r) —SO2R6, (s) —COOR6, (t) —COR6, (u) —CONR6R6, (v) —NR6COR6—, and (w) —NR6CONR6R6,
• wherein each of (e) through (k) immediately recited above is optionally substituted with one or more F, Cl, Br, I, —OH, —SH, —NH2, —NH(C1-C8 alkyl), and —N(C1-C8 alkyl)2;
• each R6 is independently selected from (a) H, (b) —C1-C8 alkyl, (c) —C2-C8 alkenyl, (d) —C2-C8 alkynyl, (e) —C3-C8 cycloalkyl, (f) —C3-C8 cycloalkenyl, (g) —C8 cycloalkynyl, (h) phenyl, (i) naphthyl, (j) —C1-C8 alkyl(phenyl), and (k) —C1-C8 alkyl(naphthyl), wherein each of (b) through (i) immediately recited above is optionally substituted with one or more R7;
• and
• each R7 is independently selected from one or more (a) F, (b) Cl, (c) Br, (d) I, (e) —OH, (f) —NH2, (g) —CN, (h) —SH, (i) —COOH, (j) —CHO, (k) —CONH2, (l) —O(—C1-C8 alkyl), (m) —NH(—C1-C8 alkyl), (n) —N(—C1-C8 alkyl)2, (o) —S(—C1-C8 alkyl), (p) —COO(—C1-C8 alkyl), (q) —CO(—C1-C8 alkyl), (r) —CONH(—C1-C8 alkyl), and (s) —CON(—C1-C8 alkyl)2;
• and
• or an enantiomer, diastereomer, or tautomer of said compound, or a pharmaceutically acceptable, salt of said compound, of said enantiomer of said compound, of said diastereomer of said compound, or of said tautomer of said compound, such that the cancer is treated.