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US 2017/0283392 A1Published application
Dibenzazepine derivatives and use thereof
AssigneePurdue Pharma L.P.
InventorsStephen M. Lynch, Laykea Tafesse
Life of this patent
Estimating the term…
Abstract
The present disclosure provides dibenzazepine derivatives having Formula I or I(A): and the pharmaceutically acceptable salts and solvates thereof, wherein R3a, R3b, R6, V1, V2, Z1, Z2, Z3, and G are defined as set forth in the specification. The present disclosure is also directed to the use of the compounds of Formula I or I(A), and the pharmaceutically acceptable salts or solvates thereof, to treat a disorder responsive to the blockade of one or more sodium channels. In one embodiment, the compounds of the present disclosure are useful for treating pain.
Claims29
A compound having Formula I:
- or a pharmaceutically acceptable salt thereof,
- wherein:
- Z1, Z2, and Z3 are each independently selected from the group consisting of N and CR11;
- with the proviso that at least one of Z1, Z2, and Z3 is N;
- G is selected from the group consisting of hydrogen, dihydroxyalkyl, and —(CHR1a)m—C(═O)E;
- m is 0, 1, or 2;
- each R1a is independently selected from the group consisting of hydrogen and hydroxy;
- E is selected from the group consisting of hydroxy, alkoxy, hydroxyalkyl, and —NR1R2;
- R1 is selected from the group consisting of hydrogen, alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (carboxamido)alkyl, (cyano)alkyl, alkoxyalkyl, hydroxyalkyl, and heteroalkyl;
- R2 is selected from the group consisting of hydrogen and alkyl;
- or
- R1 and R2 taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
- V1 is —O—
- V2 is selected from the group consisting of —W1—C(H)R4d— and —CH2—W2—CH2—;
- W1 is selected from the group consisting of —O—, —NR4b—, —C(═O)—, and —CH(R4c)—;
- W2 is selected from the group consisting of —O— and NR4b;
- R3a is selected from the group consisting of hydrogen, halogen, alkyl, cyano, haloalkyl, hydroxy, alkoxy, and haloalkoxy;
- R3b is selected from the group consisting of hydrogen, halogen, alkyl, cyano, haloalkyl, hydroxy, alkoxy, and haloalkoxy;
- R4b is selected from the group consisting of hydrogen, alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (carboxamido)alkyl, (cyano)alkyl, alkoxyalkyl, hydroxyalkyl, heteroalkyl, and —COR5b;
- R4c is selected from the group consisting of hydrogen and hydroxy;
- R4d is hydrogen;
- or
- R4c and R4d taken together with the carbon atoms to which they are attached form a double bond;
- R5b is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl;
- R6 is selected from the group consisting of hydrogen, halo, hydroxy, alkyl, hydroxyalkyl, cyano, sulfonamido, heterocyclo, and —X—R7;
- X is selected from the group consisting of —O—, —NR8a—, and —(CH2)t—Y—;
- Y is selected from the group consisting of —O— and —NR8b—;
- t is 1 or 2;
- R7 is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl,
- R8a is selected from the group consisting of hydrogen and alkyl;
- R8b is selected from the group consisting of hydrogen and alkyl;
- or
- R8b and R7 taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
- R9 is selected from the group consisting of hydrogen, alkyl, and hydroxyalkyl;
- R10a and R10b are independently selected from the group consisting of hydrogen and alkyl;
- or
- R10a and R10b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
- and
- R11 is selected from the group consisting of hydrogen, halogen, alkyl, cyano, haloalkyl, hydroxy, alkoxy, carboxamido, (carboxamido)alkyl, and haloalkoxy.
36 more elements
A compound having Formula I (A):
- or a pharmaceutically acceptable salt thereof,
- wherein:
- Z1, Z2, and Z3 are each independently selected from the group consisting of N and CR11;
- with the proviso that at least one of Z1, Z2, and Z3 is N;
- G is selected from the group consisting of hydrogen, dihydroxyalkyl, and —(CHR1a)m—C(═O)E;
- m is 0, 1, or 2;
- each R1a is independently selected from the group consisting of hydrogen and hydroxy;
- E is selected from the group consisting of hydroxy, alkoxy, hydroxyalkyl, and —NR1R2;
- R1 is selected from the group consisting of hydrogen, alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (carboxamido)alkyl, (cyano)alkyl, alkoxyalkyl, hydroxyalkyl, and heteroalkyl;
- R2 is selected from the group consisting of hydrogen and alkyl;
- or
- R1 and R2, taken together with the nitrogen atom to which they are attached, form a 3- to 8-membered optionally substituted heterocyclo;
- V1 is —O—;
- V2 is selected from the group consisting of —W2—, —W1—C(H)R4d— and —CH2—W2—CH2—;
- W1 is selected from the group consisting of —O—, —NR4b—, —C(═O)—, and —CH(R4c)—;
- W2 is selected from the group consisting of —O— and NR4b;
- R3a is selected from the group consisting of hydrogen, halogen, alkyl, cyano, haloalkyl, hydroxy, alkoxy, and haloalkoxy;
- R3b is selected from the group consisting of hydrogen, halogen, alkyl, cyano, haloalkyl, hydroxy, alkoxy, and haloalkoxy;
- R4b is selected from the group consisting of hydrogen, alkyl, aralkyl, (heterocyclo)alkyl, (heteroaryl)alkyl, (amino)alkyl, (alkylamino)alkyl, (dialkylamino)alkyl, (carboxamido)alkyl, (cyano)alkyl, alkoxyalkyl, hydroxyalkyl, heteroalkyl, and —COR5b;
- R4c is selected from the group consisting of hydrogen and hydroxy;
- R4d is hydrogen;
- or
- R4c and R4d taken together with the carbon atoms to which they are attached form a double bond;
- R5b is selected from the group consisting of alkyl, cycloalkyl, aryl, and heteroaryl;
- R6 is selected from the group consisting of hydrogen, halo, hydroxy, alkyl, hydroxyalkyl, cyano, sulfonamido, heterocyclo, and —X—R7;
- X is selected from the group consisting of —O—, —NR8a—, and —(CH2)t—Y—;
- Y is selected from the group consisting of —O— and —NR8b—;
- t is 1 or 2;
- R7 is selected from the group consisting of hydrogen, alkyl, hydroxyalkyl,
- R8a is selected from the group consisting of hydrogen and alkyl;
- R8b is selected from the group consisting of hydrogen and alkyl;
- or
- R8b and R7 taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
- R9 is selected from the group consisting of hydrogen, alkyl, and hydroxyalkyl;
- R10a and R10b are independently selected from the group consisting of hydrogen and alkyl;
- or
- R10a and R10b taken together with the nitrogen atom to which they are attached form a 3- to 8-membered optionally substituted heterocyclo;
- and
- R11 is selected from the group consisting of hydrogen, halogen, alkyl, cyano, haloalkyl, hydroxy, alkoxy, carboxamido, (carboxamido)alkyl, and haloalkoxy.
36 more elements
11-13. (canceled)
16-17. (canceled)
(canceled)
21-30. (canceled)
(canceled)
34-37. (canceled)
39-40. (canceled)
43-45. (canceled)
(canceled)
Dependencies are inferred from the claim text.