Radiolabeled monoacylglycerol lipase occupancy probe
AssigneeLundbeck La Jolla Research Center, Inc.
InventorsCheryl A. Grice, Todd K. Jones, Justin S. Cisar, Iain Peter Fraser
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Abstract
Provided herein are monoacylglycerol lipase (MGLL) occupancy probes comprising a MGLL inhibitor containing a positron emission tomography (PET) tracer radionuclide. Also provided are methods of assessing MGLL enzyme occupancy of a MGLL inhibitor using the radiolabeled occupancy probes described herein.
Claims10
A radiolabeled monoacylglycerol lipase (MGLL) occupancy probe comprising an MGLL inhibitor containing a positron emission tomography (PET) tracer radionuclide, wherein the MGLL inhibitor has the structure of Formula (Ib):
- wherein
- L3 is —CH2—;
- R7 is phenyl;
- wherein R7 is substituted by one, two, or three moieties independently selected from Rh;
- Ra and Rb, together with the nitrogen to which they are attached, form a 4-6 membered saturated heterocyclic ring, which may have an additional heteroatom selected from O, S, and N, wherein the 4-6 membered saturated heterocyclic ring is substituted by C1-6haloalkyl;
- and
- Rh is selected from the group consisting of:
- halogen, C1-6alkyl (optionally substituted by one, two, or three halogens), and RaRbN—, wherein at least one Rh is RaRbN—;
- or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof.
A compound having the structure of Formula (V):
- wherein
- p is 0, 1, or 2;
- Rd is H or C1-6alkyl;
- L3 is a bond, —CH2—, —S(O)2—, or —C(O)—;
- R7 is phenyl substituted by RaRbN— and a moiety selected from the group consisting of:
- halogen and C1-6alkyl (optionally substituted by one, two, or three halogens);
- Ra and Rb, together with the nitrogen to which they are attached, form a 4-6 membered heterocyclic ring or a 9-10 membered bicyclic heterocycle or spirocyclic ring, which may have an additional heteroatom selected from O, S, and N;
- wherein the 4-6 membered heterocyclic ring or 9-10 membered bicyclic heterocycle or spirocycle is substituted by C1-6haloalkyl;
- or a solvate, hydrate, tautomer, stereoisomer, or pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.