Inhibitors of fatty acid amide hydrolase

A method of treating an FAAH-mediated disorder comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula I:

• or a pharmaceutically acceptable salt, solvate or prodrug thereof, or mixture thereof, wherein:
• is selected from a single bond and a double bond;
• m is 1 when is a single bond;
• m is 0 when is a double bond;
• X1 is selected from NR5 and CR6R7;
• X2 is selected from NR8 and CR9R10;
• X3 is selected from NR11 and CR12R13;
• n is 0 or 1;
• provided that at least one of X1, X2 and X3 is selected from NR5, NR8 or NR11;
• Z1 is selected from —OR14 and C1-6 alkyl;
• Z2 is selected from —OR15 and C1-6 alkyl;
• or alternatively, Z1 and Z2, together with the boron atom to which they are bound, form a 5- to 8-membered ring having at least one O atom directly attached to the boron atom, wherein the ring is comprised of carbon atoms and optionally one or more additional heteroatoms independently selected from the group consisting of N, S, and O, and wherein the ring is optionally substituted with 1-4 substituents selected from halogen, C1-6 alkyl, C7-12 aralkyl, and oxo, and wherein the ring is optionally fused to a phenyl ring;
• R1, R2, R3, R4, R6, R7, R9, R10, R12 and R13 each independently is selected from hydrogen, halogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 perhaloalkyl, —CN, —OR16, —NR17R18, —C(O)R19, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R5, R8 and R11 each independently is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(O)R20, —C(O)OR21, —C(O)NR22R23, —S(O)2R24, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)p—R25;
• R14 and R15, at each occurrence, each independently is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R16, at each occurrence, each independently is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R17 and R18, at each occurrence, each independently is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(O)R26, —C(O)OR27, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R19, at each occurrence, each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R20 and R21 each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)q—R28;
• R22 and R23 each independently is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)r—R29;
• R24 is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, 5-10 membered heteroaryl, and —(CH2)t—R30;
• R25 is selected from C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R26 and R27 each independently is selected from C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R28, R29, and R30, at each occurrence, each independently is selected from —OR31, —NR32R33, C3-10 carbocyclyl, C6-10 aryl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• R31, R32 and R33, at each occurrence, each independently is selected from hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 carbocyclyl, C6-10 aryl, C7-12 aralkyl, 3-10 membered cycloheteroalkyl, and 5-10 membered heteroaryl;
• and
• p, q, r, and t, at each occurrence, each independently is selected from 1, 2, 3, 4, 5 and 6;
• wherein the FAAH-mediated disorder is a pain disorder or an inflammatory disorder.