Benzimidazoles that are useful in treating sexual dysfunction
AssigneeAbbott Laboratories
InventorsMarlon D. Cowart, Pramila A. Bhatia, Jerome F. Daanen, Andrew O. Stewart, Meena V. Patel, Teodozyj Kolasa, Jorge D. Brioni, Jeffrey Rohde
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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.
Claims112
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)
- 48
- a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is a selected from the group consisting of
- 49
- X is selected from the group consisting of NH, O and S;
- L is selected from the group consisting of CH, CH2CH2, CH2CH2CH2 and CH2CH2CH2CH2;
- 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, (NZ1Z2)carbonyl and (NZ1Z2)sulfonyl wherein Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl and formyl;
- RA, RB, RC and RD 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 and (NZ1Z2)carbonyl;
- RE is selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocyclecarbonyl and (NZ1Z2)carbonyl;
- RF is selected from the group consisting of hydrogen and alkyl;
- Z is selected from the group consisting of N, C and CH;
- and
- — is a bond when Z is C and — is absent when Z is N or CH.
A method of treating sexual dysfunction in a mammal comprising administering to said 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 said 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 said 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 said 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 male human comprising administering to said male human 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 female human comprising administering to said female human 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 attention deficit hyperactivity disorder, Alzheimer's disease, drug abuse, Parkinson's disease, schizophrenia, anxiety, mood disorders and depression in a mammal comprising administering to said 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 cardiovascular disorders in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
A method of treating inflammatory disorders in a mammal comprising administering to said mammal 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)
- 70
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is a selected from the group consisting of
- 71
- X is selected from the group consisting of NH, O and S;
- L is selected from the group consisting of CH2, CH2CH2, CH2CH2CH2 and CH2CH2CH2CH2;
- 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 and (NZ1Z2)carbonyl wherein Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl and formyl;
- RA, RB, RC and RD 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 and (NZ1Z2)carbonyl;
- RE is selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocyclecarbonyl and (NZ1Z2)carbonyl;
- and
- RF is selected from the group consisting of hydrogen and alkyl;
- provided that when A is
- 72
- and X is S, then R2 or R3 is other than hydrogen.
A compound of formula (III)
- 75
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- R1, R2, R3 and R4 are each independently selected from the group consisting of hydrogen, alkylsulfinyl, alkylsulfonyl, alkylsulfonylamino, alkylthio and hydroxy;
- L is selected from the group consisting of CH2, CH2CH2, CH2CH2CH2 and CH2CH2CH2CH2;
- RA, RB, RC and RD 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 and (NZ1Z2)carbonyl wherein Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl and formyl;
- RE is selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocyclecarbonyl and (NZ1Z2)carbonyl;
- and
- RF is selected from the group consisting of hydrogen and alkyl;
- provided that when RF is hydrogen, than at least one of R1, R2, R3, or R4 is other than hydrogen;
A compound of formula (IV)
- 76
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is a selected from the group consisting of
- 77
- X is selected from the group consisting of NH, 0 and S;
- L is selected from the group consisting of CH2, CH2CH2, CH2CH2CH2 and CH2CH2CH2CH2;
- 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 and (NZ1Z2)carbonyl wherein Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl and formyl;
- RA, RB, RC and RD 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 and (NZ1Z2)carbonyl wherein Z1 and Z2 are each independently selected from the group consisting of hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl and formyl;
- RE is selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, arylcarbonyl, cycloalkylcarbonyl, heterocyclecarbonyl and (NZ1Z2)carbonyl;
- RF is selected from the group consisting of hydrogen and alkyl;
- Z is selected from the group consisting of C and CH;
- and
- — is a bond when Z is C and — is absent when Z is CH.
Dependencies are inferred from the claim text.