| 主权项 |
1. A method of treating neuropathic pain, nociceptive pain, and inflammatory pain in a mammal in need of such treatment comprising administering to the mammal a therapeutically effective amount of a compound of formula (I)or a pharmaceutically acceptable salt, prodrug, salt of a prodrug, or a combination thereof, wherein
A is ORb, CN, NRcRd, NRc′C(O)Rd′, NRc′C(S)Rd′, C(O)ORw1, or C(O)Rw2; R1 is C2-C10 alkyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclyalkyl, Rg1Rh1N—C(O)—, Rg1Rh1N—C(O)-alkyl, alkenyl, alkoxycarbonylalkyl, alkylcarbonylalkyl, alkylsulfinylalkyl, alkylsulfonylalkyl, alkynyl, carboxyalkyl, cyanoalkyl, Rn1O—N═CRz—, Rn1O—N═CRz-alkyl-, Ro1Rp1N—N═CRz—, Ro1Rp1N—N═CRz-alkyl-, alkoxyalkyl, alkylthioalkyl, aryloxyalkyl, arylalkoxyalkyl, alkoxyalkoxyalkyl, haloalkyl, haloalkoxyalkyl, heteroaryloxyalkyl, heterocycleoxyalkyl, hydroxyalkyl, Re1Rf1N-alkyl, Rj1Rk1N—C(O)—NRm1-alkyl, RzC(O)—O—C2-C6 alkyl-, Rz1SO2NRz2-alkyl-, Rz1C(O)NRz2-alkyl-, Rj1Rk1N—SO2—NRm1-alkyl-, or Rg1Rh1NSO2-alkyl-; R2 and R3 are each independently hydrogen, alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkynyl, alkylcarbonyl, alkylsulfinyl, alkylsulfonyl, alkylthio, aryl, arylalkyl, arylalkenyl, azidoalkyl, cyano, cycloalkyl, formyl, halo, haloalkyl, heteroaryl, heterocycle, hydroxyalkyl, Re2Rf2N—, Re2Rf2Nalkyl-, Rg2Rh2N—C(O)—, Rj2Rk2N—C(O)—NRm2—, Rn2O—N═CRz-alkyl-, Rn2O—N═CRz—, or Ro2Rp2N—N═CRz-alkyl-; or R2 and R3, taken together with the carbon atoms to which they are attached, optionally form a 4-, 5-, 6-, or 7-membered monocyclic ring, said monocyclic ring contains zero or one additional double bond, zero or one oxygen atom, and zero or one nitrogen atom as ring atoms; two non-adjacent atoms of said monocyclic ring can be optionally linked by an alkenylene bridge of 2, 3, or 4 carbon atoms, or optionally linked by an alkylene bridge of 1, 2, 3, or 4 carbon atoms, said monocyclic ring is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents independently selected from the group consisting of oxo, alkyl, halo, hydroxy, alkoxy, and haloalkyl; two substituents on the same carbon atom of said monocyclic ring, together with the carbon atom to which they are attached, optionally form a 3-, 4-, 5-, or 6-membered monocyclic cycloalkyl ring, wherein the monocyclic cycloalkyl ring is optionally substituted with 1, 2, 3, 4, 5, or 6 substituents independently selected from the group consisting of alkyl and haloalkyl; or R2 and R3, taken together with the carbon atoms to which they are attached, optionally form a 6-membered monocyclic ring, said monocyclic ring contains two additional double bonds, zero or one nitrogen atom as ring atoms; said monocyclic ring is independently unsubstituted or substituted with 1, 2, 3 or 4 substituents independently selected from the group consisting of alkyl, halo, cyano, hydroxy, alkoxy, and haloalkyl; R4 is alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, heteroaryl, heterocycle, arylalkyl, cycloalkylalkyl, cycloalkenylalkyl, heteroarylalkyl, or heterocyclealkyl; L2 is a bond or —NRm1—; Rb is alkyl, alkenyl, alkoxyalkyl, or arylalkyl; Rc and Rd are each independently alkyl, arylalkyl, or heteroarylalkyl, or Rc and Rd taken together with the nitrogen atom to which they are attached form a 5-7 membered heterocyclic ring; Rc′, at each occurrence, is independently hydrogen or alkyl; Rd′, at each occurrence, is independently alkyl, alkoxy, amino, alkylamino, dialkylamino, arylamino, heteroarylamino, cycloalkylamino, heterocycleamino, or heterocycle; Re1 and Rf1 are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, alkoxycarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycle, or heterocyclealkyl; Rg1 and Rh1 are each independently hydrogen, alkyl, alkenyl, alkoxycarbonyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocyclalkyl, hydroxyalkyl, nitroalkyl, cycloalkyl, or haloalkoxyalkyl; or Rg1 and Rh1 together with the nitrogen atom to which they are attached form a 5-7 membered heterocyclic ring; Rj1 and Rk1, at each occurrence, are each independently hydrogen, alkyl, alkenyl, alkoxycarbonyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocyclalkyl; cycloalkyl, or haloalkoxyalkyl; or Rj1 and Rk1 together with the nitrogen atom to which they are attached form a 5-7 membered heterocyclic ring; Rm1, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, haloalkyl, alkoxyalkyl, or haloalkoxyalkyl; Rn1, at each occurrence, is independently hydrogen, alkyl, alkenyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, heteroarylalkyl, heterocyclalkyl, haloalkyl, hydroxyalkyl, or nitroalkyl; Ro1 and Rp1, at each occurrence, are each independently hydrogen, alkyl, alkenyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocyclalkyl, hydroxyalkyl, or nitroalkyl; or Ro1 and Rp1 together with the nitrogen atom to which they are attached form a 5-7 membered heterocyclic ring; Re2 and Rf2, at each occurrence, are each independently hydrogen, alkyl, alkylcarbonyl, alkylsulfonyl, alkoxycarbonyl, aryl, arylalkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocycle, or heterocyclealkyl; Rg2 and Rh2 are each independently hydrogen, alkyl, alkenyl, alkoxycarbonyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocyclalkyl, hydroxyalkyl, or nitroalkyl; or Rg2 and Rh2 together with the nitrogen atom to which they are attached form a 5-7 membered heterocyclic ring; Rj2 and Rk2 are each independently hydrogen, alkyl, alkenyl, alkoxycarbonyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, or heterocyclalkyl; Rm2 is hydrogen or alkyl; Rn2, at each occurrence, is independently hydrogen, alkyl, alkenyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, heteroarylalkyl, heterocyclalkyl, haloalkyl, hydroxyalkyl, or nitroalkyl; Ro2 and Rp2, at each occurrence, are each independently hydrogen, alkyl, alkenyl, alkoxyalkyl, alkynyl, arylalkyl, cyanoalkyl, cycloalkylalkyl, haloalkyl, heteroarylalkyl, heterocyclalkyl, hydroxyalkyl, or nitroalkyl; or Ro2 and Rp2 together with the nitrogen atom to which they are attached form a 5-7 membered heterocyclic ring; Rz is hydrogen or alkyl; Rz1, at each occurrence, is independently alkyl, cycloalkyl, cycloalkylalkyl, alkoxyalkyl, haloalkyl, or cyanoalkyl; Rz2, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, haloalkyl, alkoxyalkyl, or haloalkoxyalkyl; and Rw1 and Rw2 are each independently alkyl, haloalkyl, aryl, cycloalkyl, or alkoxyalkyl. |
