Amides that inhibit vanilloid receptor subtype 1 (VR1)
The present invention relates to compounds of formula (I) that are novel VR1 antagonists useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence, or bladder overactivity.
1. A method of treating pain wherein the pain is ameliorated by inhibiting vanilloid receptor subtype 1 (VR1) receptor in a mammal, comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof
A is aryl or heteroaryl;
X is CH or N;
Y is CH or N;
L is —C(O)N(R 3 )— or —N(R 3 )C(O)—;
R 1 and R 2 are independently hydrogen, alkoxy, alkyl, aryloxy, haloalkoxy, haloalkyl, halogen, or heterocycle; and
R 3 is hydrogen or alkyl.
2. A method of treating urinary incontinence wherein the urinary incontinence is ameliorated by inhibiting vanilloid receptor subtype 1 (VR1) receptor in a mammal, comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof
A is aryl or heteroaryl;
X is CH or N;
X is CH or N;
L is —C(O)N(R 3 )— or —N(R 3 )C(O)—;
R 1 and R 2 are independently hydrogen, alkoxy, alkyl, aryloxy, haloalkoxy, haloalkyl, halogen, or heterocycle; and
R 3 is hydrogen or alkyl.
3. A method of treating bladder overactivity wherein the bladder overactivity is ameliorated by inhibiting vanilloid receptor subtype 1 (VR1) receptor in a mammal, comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof
A is aryl or heteroaryl;
X is CH or N;
Y is CH or N;
L is —C(O)N(R 3 )— or —N(R 3 )C(O)—;
R 1 and R 2 are independently hydrogen, alkoxy, alkyl, aryloxy, haloalkoxy, haloalkyl, halogen, or heterocycle; and
R 3 is hydrogen or alkyl.
4. A method of treating inflammatory hyperalgesia wherein the inflammatory hyperalgesia is ameliorated by inhibiting vanilloid receptor subtype 1 (VR1) receptor in a mammal, comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof
A is aryl or heteroaryl;
X is CH or N;
Y is CH or N;
L is —C(O)N(R 3 )— or —N(R 3 )C(O)—;
R 1 and R 2 are independently hydrogen, alkoxy, alkyl, aryloxy, haloalkoxy, haloalkyl, halogen, or heterocycle; and
R 3 is hydrogen or alkyl.