Fused bicyclic aromatic compounds that are useful in treating sexual dysfunction
OwnerMarlon D. Cowartinventor
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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.
Claims202
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)
- 499
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is selected from the group consisting
- 500
- X is selected from the group consisting of CRX and N;
- Y is selected from the group consisting of NRY, O, and S;
- V is selected from the group consisting of CRV and N;
- P is selected from the group consisting of CRP and N;
- Q is selected from the group consisting of CRQ and N;
- S is selected from the group consisting of CRS and N;
- T is selected from the group consisting of CRT and N;
- provided that 0, 1, or 2 of P, Q, S, and T are N;
- provided that when P is CRP, Q is CRQ, S is CRS, T is CRT, and Y is N, then X is CRX;
- RP, RQ, RS, RT, RV, and RX are 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)carbonyl, and (NZ3Z4)sulfonyl;
- RY is selected from the group consisting of hydrogen, alkenyl, alkoxycarbonyl, alkyl, arylalkyl, and (NZ3Z4)carbonyl;
- 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;
- L is alkylene;
- D is selected from the group consisting of
- 501
- wherein the left end is attached to L and the right end is attached to B1;
- RA is selected from the group consisting of hydrogen and alkyl;
- Z is selected from the group consisting of N, C and CH;
- — is a bond when Z is C and — is absent when Z is N or CH;
- B1 is selected from the group consisting of
- 502
- 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)carbonyl, and (NZ3Z4)sulfonyl;
- X1 is selected from the group consisting of N(R6), O and S;
- Y1 is selected from the group consisting of C(R7) and N;
- R6 is selected from the group consisting of hydrogen and alkyl;
- R7 is selected from the group consisting of hydrogen and alkyl;
- and
- provided that the compound of formula (I) is other than 5-fluoro-2-{[4-(2-pyridinyl)-1-piperazinyl]methyl}-1H-indole.
The method according to claim 1 wherein
- A is
- 536
- D is
- 537
- and
- B1 is
- 538
- 156. The method according to claim 155 wherein
- RY is selected from the group consisting of hydrogen and alkyl;
- Z is N;
- — is absent;
- and
- R1, R2, R3, R4, and R5 are independently selected from the group consisting of hydrogen, alkoxy, alkyl, alkylthio, cyano, halogen, and hydroxy.
The method according to claim 156 wherein the compound of formula (I) is selected from the group consisting of
- 2-{[4-(2-fluorophenyl)-1-piperazinyl]methyl}-1H-thieno[3,4-d]imidazole;
- 2-{[4-(2-methoxyphenyl)-1-piperazinyl]methyl}-1H-thieno[3,4-d]imidazole;
- 4-[4-(1H-thieno[3,4-d]imidazol-2-ylmethyl)-1-piperazinyl]phenol;
- and
- 2-({4-[2-(methylthio)phenyl]-1-piperazinyl}methyl)-1H-thieno[3,4-d]imidazole.
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 dopamiine 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)
- 542
- or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, wherein
- A is selected from the group consisting
- 543
- X is selected from the group consisting of CRX and N;
- Y is selected from the group consisting of O, and S;
- V is selected from the group consisting of CRV and N;
- P is selected from the group consisting of CRP and N;
- Q is selected from the group consisting of CRQ and N;
- S is selected from the group consisting of CRS and N;
- T is selected from the group consisting of CRT and N;
- provided that 1, or 2 of P, Q, S, and T are N;
- RP, RQ, RS, RT, RV, and RX are 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)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;
- L is alkylene;
- D is selected from the group consisting of
- 544
- wherein the left end is attached to L and the right end is attached to B1;
- RA is selected from the group consisting of hydrogen and alkyl;
- Z is selected from the group consisting of N, C and CH;
- — is a bond when Z is C and— is absent when Z is N or CH;
- B1 is selected from the group consisting of
- 545
- 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)carbonyl, and (NZ3Z4)sulfonyl;
- X1 is selected from the group consisting of N(R6), O and S;
- Y1 is selected from the group consisting of C(R7) 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.
Dependencies are inferred from the claim text.