| 主权项 |
1. A method of treating or lessening the severity of acute pain, chronic pain, neuropathic pain, inflammatory pain, visceral pain, osteoarthritis pain, radicular pain, sciatica, back pain, head pain, neck pain, severe pain, intractable pain, nociceptive pain, breakthrough pain, postsurgical pain, or pain associated with cancer in a subject, comprising administering to said subject an effective amount of a compound of formula I: or a pharmaceutically acceptable salt thereof, wherein, independently for each occurrence: R1 is H, C1-C8 alkyl, C3-C8 cycloalkyl, halo, CN, NR8SO2R8, SO2R8, SR8, SOR8, NR8COR8, NR8CO2R8, CON(R8)2, SO2N(R8)2, CF3, heterocycloalkyl, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2 or NR8, or two R1 taken together form an oxo group; R2 is H, C1-C8 alkyl, halo, C1-C8 haloalkyl, CN, OH, SO2R8, SR8, SOR8, COR8, CO2R8, CON(R8)2, SO2N(R8)2, CF3, CHF2, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2, CF2, or NR8; R3 is H, C1-C8 alkyl, C3-C8 cycloalkyl, CO2R8, COR8, COH, CON(R8)2, CF3, CH2CF3, CH2CHF2, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2 or NR8; R4 is H, C1-C8 alkyl, halo, C3-C8 cycloalkyl, wherein up to two CH2 units may be replaced by O, CO, S, SO, SO2, or NR8, or 2 R4 taken together form a fused 3 to 7 membered cycloalkyl ring; R8 is H, C1-C8 alkyl, CF3, C3-C8 cycloalkyl, fluoroalkyl, aryl, heteroaryl, or a straight chain, branched, or cyclic (C3-C8)-R9 wherein up to two CH2 units may be replaced with O, CO, S, SO, SO2 or NR, or 2 R8 taken together with the atoms to which they are attached form a ring; R9 is H, CF3, CO2R, OH, aryl, heteroaryl, C3-C8 cycloalkyl, heterocycloalkyl, N(R)2, NRCOR, CON(R)2, CN, halo, or SO2R; R is H, C1-C8 alkyl, aryl, heteroaryl, C3-C8 cycloalkyl, or heterocycloalkyl; A is an aryl optionally substituted with one or more of C1-C8 alkyl, C3-C8 cycloalkyl, C1-C8 alkoxy, C3-C8 cycloalkoxy, halo, CN, OH, OR8, N(R8)2, NR8SO2R8, OSO2R8, SO2R8, SOR8, SR8, CO2R8, NR8COR8, NR8CO2R8, CON(R8)2, SO2N(R8)2, CHF2, CF3, OCF3, OCHF2, R9, heterocycloalkyl, heterocycloalkoxy, aryl, heteroaryl, or a straight chain, branched, or cyclic (C3-C8)-(R9)p wherein p is 1 or 2 and wherein up to three CH2 units may be replaced with O, CO, S, SO, SO2, or NR8; or wherein two adjacent substituents on A together with the carbons to which they are attached form a ring comprising up to 2 heteroatoms; m is 0, 1, 2, 3, or 4; n is 0, 1, 2, or 3; and o is 0, 1, 2, 3, or 4. |
