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US 2011/0178065 A1Published application
Novel cyp17 inhibitors
AssigneeBiomarin Pharmaceutical Inc.
InventorsDaniel Chu, Bing Wang, Tao Ye
Life of this patent
Estimating the term…
Abstract
Provided herein are inhibitors of CYP17 enzyme. Also described herein are pharmaceutical compositions that include at least one compound described herein and the use of a compound or pharmaceutical composition described herein to treat androgen-dependent diseases, disorders and conditions.
Claims31
A compound having the structure of Formula (I):
- wherein:
- R is (CH2)p wherein p is an integer from 0 to 1;
- T is (CH2)q wherein q is an integer from 0 to 1;
- W is O, NR1, NCOR1, N—COOR1or null;
- V is CR7, R8, O, NR1, N—COR1or N—COOR1;
- with the proviso that when W is O, NR1, NCOR1 or N—COOR1 and p and q are each 0, or when W is null and one of p and q is 0, V cannot be CR7R8;
- A is a heteroaryl optionally substituted with 1, 2, 3, or 4 R4;
- is a single bond or double bond;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyl, and haloalkoxyalkyl;
- wherein the alkyl, cycloalkyl, alkenyl, alkynyl, alkoxyalkyl, and haloalkoxyalkyl groups are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, alkyl, alkenyl, aryl, heteroaryl, alkoxy, alkoxycarbonyl, hydroxyl, hydroxyalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, nitro, NRARB, and (NRARB)carbonyl;
- RA and RB are independently selected from the group consisting of hydrogen, optionally substituted alkyl, halosubstituted alkyl, optionally substituted alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
- or
- RA and RB taken together with the nitrogen atom form an optionally substituted 4 to 7 membered heterocyclic ring having one or two heteroatoms;
- R2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, cyano, nitro, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted haloalkoxy, optionally substituted haloalkoxyalkyl, hydroxyl, optionally substituted hydroxyalkyl and optionally substituted alkylcarbonyloxy;
- R3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkynyl, cyano, optionally substituted haloalkoxy, optionally substituted haloalkyl, hydroxyl, optionally substituted hydroxyalkyl, nitro, RAcarbonyl, NRARB, and (NRARB)carbonyl;
- and
- R5 and R6 are each independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, and optionally substituted alkoxyalkyl;
- R4 is independently selected from the group consisting of halogen, cyano, hydroxyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, CORA, NRARBcarbonyl, and/Elf NRARB;
- and
- R7 and R8 are each independently selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, and optionally substituted alkoxyalkyl;
- or a single stereoisomer or single tautomer or mixture thereof, or a pharmaceutically acceptable salt or solvate thereof.
18 more elements
-5. (canceled)
A compound having the structure of Formula (II):
- wherein:
- Y is (CH2)m wherein m is an integer from 1 to 3;
- Z is O, S(O)u, NR1, N—COR1or N—COOR1;
- wherein u is an integer from 0 to 2;
- A is a heteroaryl optionally substituted with 1, 2, 3, or 4 R4;
- R1 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, alkoxyalkyl, hydroxyl, and haloalkoxyalkyl;
- wherein the alkyl, cycloalkyl, alkenyl, alkynyl, alkoxyalkyl, and haloalkoxyalkyl groups are optionally substituted with 1, 2, or 3 substituents independently selected from the group consisting of halogen, alkyl, alkenyl, aryl, heteroaryl, alkoxy, alkoxycarbonyl, hydroxyl, hydroxyalkyl, alkynyl, cyano, haloalkoxy, haloalkyl, nitro, NRARB, and (NRARB)carbonyl;
- RA and RB are independently selected from the group consisting of hydrogen, optionally substituted alkyl, halosubstituted alkyl, optionally substituted alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
- or
- RA and RB taken together with the nitrogen atom form an optionally substituted 4 to 7 membered heterocyclic ring having one or two heteroatoms;
- R2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, cyano, nitro, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted haloalkoxy, optionally substituted haloalkoxyalkyl, hydroxyl, optionally substituted hydroxyalkyl and optionally substituted alkylcarbonyloxy;
- R3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkynyl, cyano, optionally substituted haloalkoxy, optionally substituted haloalkyl, hydroxyl, optionally substituted hydroxyalkyl, nitro, RAcarbonyl, NRARB, and (NRARB)carbonyl;
- and
- R4 is independently selected from the group consisting of halogen, cyano, hydroxyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, CORA, NRARBcarbonyl, and NRARB;
- or a single stereoisomer or single tautomer or mixture thereof, or a pharmaceutically acceptable salt or solvate thereof.
12 more elements
A compound having the structure of Formula (III):
- wherein:
- A is a heteroaryl optionally substituted with 1, 2, 3, or 4 R4;
- RA and RB are independently selected from the group consisting of hydrogen, optionally substituted alkyl, halosubstituted alkyl, optionally substituted alkoxyalkyl, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted arylalkyl, optionally substituted heteroaryl, and optionally substituted heteroarylalkyl;
- or
- RA and RB taken together with the nitrogen atom form an optionally substituted 4 to 7 membered heterocyclic ring having one or two heteroatoms;
- R2 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, cyano, nitro, optionally substituted alkoxy, optionally substituted alkoxyalkyl, optionally substituted haloalkoxy, optionally substituted haloalkoxyalkyl, hydroxyl, optionally substituted hydroxyalkyl and optionally substituted alkylcarbonyloxy;
- R3 is selected from the group consisting of hydrogen, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted alkynyl, cyano, optionally substituted haloalkoxy, optionally substituted haloalkyl, hydroxyl, optionally substituted hydroxyalkyl, nitro, RAcarbonyl, NRARB, and (NRARB)carbonyl;
- and
- R4 is independently selected from the group consisting of halogen, cyano, hydroxyl, optionally substituted alkoxy, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocycloalkyl, optionally substituted aryl, optionally substituted heteroaryl, CORA, NRARBcarbonyl, and NRARB;
- or a single stereoisomer or single tautomer or mixture thereof, or a pharmaceutically acceptable salt or solvate thereof.
7 more elements
-47. (canceled)
A compound having a structure selected from the group consisting of:
- or a single stereoisomer or single tautomer or mixture thereof, or a pharmaceutically acceptable salt or solvate thereof.
(canceled)
-56. (canceled)
(canceled)
-61. (canceled)
-68. (canceled)
Dependencies are inferred from the claim text.