Acetamides and benzamides that are useful in treating sexual dysfunction
AssigneeAbbott Laboratories
InventorsPramila A. Bhatia, Jerome F. Daanen, Ahmed A. Hakeem, Teodozyj Kolasa, Mark A. Matulenko, Kathleen H. Mortell, Meena V. Patel, Andrew O. Stewart, Xueqing Wang, Zhiren Xia, Henry Q. Zhang
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Abstract
The present invention relates to the use of compounds of formula (I) 1 for the treatment of sexual dysfunction and to compositions containing compounds of formula (I) for the treatment of sexual dysfunction.
Claims165
A method of treating sexual dysfunction in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (I)
- 280
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is selected from the group consisting of aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heterocycle, and heterocyclealkyl;
- L is selected from the group consisting of —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— wherein the left end of said —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, or —C(S)N(R7)— is attached to A and the right end is attached to D;
- D is selected from the group consisting of alkylene, fluoroalkylene, and hydroxyalkylene;
- Z is selected from the group consisting of N, C and CRB;
- RA is selected from the group consisting of hydrogen and alkyl;
- RB is selected from the group consisting of hydrogen, alkyl, and halogen;
- — is a bond when Z is C and — is absent when Z is N or CRB;
- B is selected from the group consisting of
- 281
- R1, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkoxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxy, cyano, formyl, halogen, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, mercapto, nitro, —NZ1Z2, (NZ3Z4)alkyl, (NZ3Z4)carbonyl, and (NZ3Z4)sulfonyl;
- Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylalkylsulfonyl, arylsulfonyl, and formyl;
- Z3 and Z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and arylalkyl;
- X is selected from the group consisting of N(R6), O and S;
- Y is selected from the group consisting of C(R4) and N;
- R6 is selected from the group consisting of hydrogen and alkyl;
- and
- R7 is selected from the group consisting of hydrogen and alkyl.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with a pharmaceutically acceptable carrier.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with a phosphodiesterase 5 inhibitor.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with an adrenergic receptor antagonist.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with a dopamine agonist.
A method of treating male erectile dysfunction in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
A method of treating female sexual dysfunction in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
A method of treating a disorder selected from the group consisting of cardiovascular disorders, inflammatory disorders, attention deficit hyperactivity disorder, Alzheimer's disease, drug abuse, Parkinson's disease, schizophrenia, anxiety, mood disorders and depression in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
A compound of formula (II)
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- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is selected from the group consisting of aryl, arylalkyl, cycloalkyl, and cycloalkylalkyl;
- L is selected from the group consisting of —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— wherein the left end of the —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— is attached to A and the right end is attached to D;
- D is selected from the group consisting of alkylene, fluoroalkylene, and hydroxyalkylene;
- Z is selected from the group consisting of N, C and CRB;
- RA is selected from the group consisting of hydrogen and alkyl;
- RB is selected from the group consisting of hydrogen, alkyl, and halogen;
- — is a bond when Z is C and — is absent when Z is N or CRB;
- B is selected from the group consisting of
- 346
- R1, R2, R3, and R4 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkoxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxy, cyano, formyl, halogen, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, mercapto, nitro, —NZ1Z2, (NZ3Z4)alkyl, (NZ3Z4)carbonyl, and (NZ3Z4)sulfonyl;
- Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylalkylsulfonyl, arylsulfonyl, and formyl;
- Z3 and Z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and arylalkyl;
- X is selected from the group consisting of N(R6), O and S;
- Y is selected from the group consisting of C(R4) and N;
- R6 is selected from the group consisting of hydrogen and alkyl;
- and
- R7 is selected from the group consisting of hydrogen and alkyl.
A compound of formula (III)
- 395
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- X1 is selected from the group consisting of a bond and CRBRC;
- X2 is selected from the group consisting of a bond and CRDRE;
- provided that when X1 is a bond, then X2 is CRDRE;
- further provided that when X2 is bond, then X1 is CRBRC;
- A is selected from the group consisting of aryl, arylalkyl, cycloalkyl, and cycloalkylalkyl;
- L1 is selected from the group consisting of —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— wherein the left end of the —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— is attached to A and the right end is attached to D;
- L2 is selected from the group consisting of a bond and alkylene;
- D is selected from the group consisting of alkylene, fluoroalkylene, and hydroxyalkylene;
- RA, RB, RC, RD, and RE are independently selected from the group consisting of hydrogen and alkyl;
- B is selected from the group consisting of
- 396
- R1, R2, R3, and R4 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkoxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxy, cyano, formyl, halogen, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, mercapto, nitro, —NZ1Z2, (NZ3Z4)alkyl, (NZ3Z4)carbonyl, and (NZ3Z4)sulfonyl;
- Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylalkylsulfonyl, arylsulfonyl, and formyl;
- Z3 and Z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and arylalkyl;
- X is selected from the group consisting of N(R6), O and S;
- Y is selected from the group consisting of C(R4) and N;
- R6 is selected from the group consisting of hydrogen and alkyl;
- and
- R7 is selected from the group consisting of hydrogen and alkyl.
A method of treating sexual dysfunction in a mammal comprising administering to said mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV)
- 409
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- X1 is selected from the group consisting of a bond and CRBRC;
- X2 is selected from the group consisting of a bond and CRDRE;
- provided that when X1 is a bond, then X2 is CRDRE;
- further provided that when X2 is bond, then X1 is CRBRC;
- A is selected from the group consisting of aryl, arylalkyl, cycloalkyl, and cycloalkylalkyl;
- L1 is selected from the group consisting of —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— wherein the left end of the —N(R7)C(O)—, —C(O)N(R7)—, —N(R7)C(S)—, and —C(S)N(R7)— is attached to A and the right end is attached to D;
- L2 is selected from the group consisting of a bond and alkylene;
- D is selected from the group consisting of alkylene, fluoroalkylene, and hydroxyalkylene;
- RA, RB, RC, RD, and RE are independently selected from the group consisting of hydrogen and alkyl;
- B is selected from the group consisting of
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- R1, R2, R3, and R4 are each independently selected from the group consisting of hydrogen, alkoxy, alkenyl, alkyl, alkylsulfinyl, alkylsulfonyl, alkylthio, alkynyl, alkoxycarbonyl, alkylcarbonyl, alkylcarbonyloxy, carboxy, cyano, formyl, halogen, haloalkoxy, haloalkyl, hydroxy, hydroxyalkyl, mercapto, nitro, —NZ1Z2, (NZ3Z4)alkyl, (NZ3Z4)carbonyl, and (NZ3Z4)sulfonyl;
- Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, aryl, arylalkyl, arylalkylsulfonyl, arylsulfonyl, and formyl;
- Z3 and Z4 are each independently selected from the group consisting of hydrogen, alkyl, aryl, and arylalkyl;
- X is selected from the group consisting of N(R6), O and S;
- Y is selected from the group consisting of C(R4) and N;
- R6 is selected from the group consisting of hydrogen and alkyl;
- and
- R7 is selected from the group consisting of hydrogen and alkyl.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with a pharmaceutically acceptable carrier.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with a phosphodiesterase 5 inhibitor.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with an adrenergic receptor antagonist.
A method of treating sexual dysfunction in a mammal comprising administering to the mammal a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof in combination with a dopamine agonist.
A method of treating male erectile dysfunction in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
A method of treating female sexual dysfunction in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
A method of treating a disorder selected from the group consisting of cardiovascular disorders, inflammatory disorders, attention deficit hyperactivity disorder, Alzheimer's disease, drug abuse, Parkinson's disease, schizophrenia, anxiety, mood disorders and depression in a mammal comprising administering to the mammal in need of such treatment a therapeutically effective amount of a compound of formula (IV) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
Dependencies are inferred from the claim text.