N-HYDROXY BICYCLIC HYDANTOIN CARBAMATES AS TOOLS FOR INDETIFICATION OF SERINE HYDROLASE TARGETS

Provided herein are N-hydroxy bicyclic hydantoin carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of serine hydrolases. Furthermore, the subject compounds and compositions are useful for the treatment of one or more of cancer, pain, diabetes, obesity/metabolic syndrome, epilepsy, traumatic brain injury, and inflammation. 2. The compound of claim 1 , or a stereoisomer or a pharmaceutically acceptable salt thereof claim 1 , wherein each m is 1.3. The compound of or claim 1 , or a stereoisomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H claim 1 , halo claim 1 , —OH claim 1 , cyano claim 1 , amino claim 1 , (C-C)alkyl claim 1 , (C-C)alkoxy claim 1 , (C-C)aryl claim 1 , or (C-C)aryl(C-C)alkyl.4. The compound of any one of - claim 1 , or a stereoisomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.6. The compound of any one of - claim 1 , or a stereoisomer or a pharmaceutically acceptable salt thereof claim 1 , wherein:{'sup': '2', 'Ris H; and'}{'sup': '3', 'sub': 6', '10', '6', '10', '1', '8, 'Ris substituted or unsubstituted (C-C)aryl or substituted or unsubstituted (C-C)aryl(C-C)alkyl.'}7. The compound of any one of - claim 1 , or a stereoisomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris substituted or unsubstituted phenyl claim 1 , substituted or unsubstituted benzyl claim 1 , or substituted or unsubstituted phenethyl.8. The compound of any one of - claim 1 , or a stereoisomer or a pharmaceutically acceptable salt thereof claim 1 , wherein Ris phenyl claim 1 , benzyl claim 1 , or phenethyl claim 1 , and Ris substituted with one or more substituents selected from the group consisting of halo claim 1 , (C-C)alkyl claim 1 , (C-C)alkoxy claim 1 , (C-C)alkenyl claim 1 , (C-C)alkynyl claim 1 , (C-C)alkenyloxy claim 1 , and (C-C)alkynyloxy.9. The compound of any one of - claim 1 , or a stereoisomer or a ...

PIPERAZINE CARBAMATES AND METHODS OF MAKING AND USING SAME

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —NRR.3. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein Rand R claim 2 , together with the nitrogen to which they are attached claim 2 , form a monocyclic heterocycle claim 2 , a fused bicyclic heterocycle claim 2 , or a spirocycle claim 2 , wherein:{'sup': 7', '12', '13', '9', '9', '10', '8', '9', '8', '9', '8', '9', '10, 'sub': '2', 'the monocyclic heterocycle, the fused bicyclic heterocycle, or the spirocycle is substituted with one or more substituents independently selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle, optionally substituted cycloalkyl, haloalkyl, —OR, —NRR, —C(O)OR, —C(O)NRR, —NRSOR, —NRC(O)OR, and —NRC(O)NRR; and'}the monocyclic heterocycle, the fused bicyclic heterocycle, or the spirocycle optionally contains an additional O, N, or S.4. The compound of claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein Rand R claim 3 , together with the nitrogen to which they are attached claim 3 , form a monocyclic heterocycle wherein:{'sup': 7', '12', '13', '9', '9', '10', '8', '9', '8', '9', '8', '9', '10, 'sub': '2', 'the monocyclic heterocycle is substituted with one or more substituents independently selected from optionally substituted aryl, optionally substituted ...

Dual magl and faah inhibitors

CARBAMATE COMPOUNDS AND METHODS OF MAKING AND USING SAME

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition. 28.-. (canceled)9. The compound of claim 1 , wherein:{'sup': '3', 'sub': 2', '2, 'Lis selected from the group consisting of a bond, —CH—, —C(O)—, and —S(O)—.'}10. The compound of claim 9 , wherein Lis —CH—.11. The compound of claim 10 , wherein Ris selected from the group consisting of indazole claim 10 , isoxazole claim 10 , pyridine claim 10 , and pyrazole claim 10 , and Ris optionally substituted by one claim 10 , two claim 10 , or three substituents selected from the group consisting of halogen claim 10 , phenyl (optionally substituted by one claim 10 , two claim 10 , or three substituents selected from the group consisting of: halogen claim 10 , methyl claim 10 , ethyl claim 10 , propyl claim 10 , t-butyl claim 10 , CFor Calkoxy) claim 10 , Calkyl (optionally substituted by one claim 10 , two or three halogens claim 10 , or hydroxyl) claim 10 , Calkoxy (optionally substituted by one claim 10 , two or three halogens) claim 10 , and heteroaryl (optionally substituted by one or two substituents each selected from Calkyl and halogen).14. The compound of claim 13 , wherein{'sup': i', 'j', 'c', 'c, 'sub': 3', '2-6, 'Rand Rare independently selected from the group consisting of: H, halogen, CH, Calkyl (optionally substituted by one, two or three moieties independently selected from R), and phenyl (optionally substituted by one or two moieties independently selected from R);'}{'sup': 'c', 'sub': 1-6', '1-6, 'Ris selected from the group consisting of halogen, Calkyl (optionally ...

PYRAZOLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of one or more of MAGL, ABHD6, and FAAH. Furthermore, the subject compounds and compositions are useful for the treatment of, for example, pain, solid tumors and/or obesity. 4. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris fluoro or chloro.5. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris iodo or bromo.6. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris isopropyl.7. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —COMe.8. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris optionally substituted phenyl.11. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris optionally substituted pyrazolyl claim 1 , optionally substituted pyrimidinyl claim 1 , optionally substituted thiazolyl claim 1 , or optionally substituted pyridinyl.13. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris optionally substituted phenyl.18. The compound of claim 14 , or a solvate claim 14 , hydrate claim 14 , tautomer claim 14 , N-oxide claim 14 , or pharmaceutically ...

METHODS OF TREATING DISEASE WITH MAGL INHIBITORS

Provided herein are methods for the treatment of disease with monoacylglycerol lipase (MAGL) inhibitors. 3. The method of or , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein m is 1 , n is 1 , q is 0 , and p is 2.4. The method of any one of - , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein Y is —CH— and A is C(H).5. The method of any one of - , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein Ris H and Ris H.6. The method of any one of - , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein Ris halogen , —OR , Chaloalkyl , Cheterocycloalkyl , Caryl , or Cheteroaryl , wherein Cheterocycloalkyl , Caryl , or Cheteroaryl are optionally substituted with 1 or 2 R.7. The method of any one of - , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein Ris halogen or Ris Cheterocycloalkyl optionally substituted with 1 or 2 R.8. The method of any one of - , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein Ris H , Ris H , and Ris H , halogen , Calkyl , Chaloalkyl , or Chaloalkoxy.9. The method of any one of - , or a solvate , hydrate , tautomer , N-oxide , stereoisomer , or pharmaceutically acceptable salt thereof , wherein Ris —C(O)ORand Ris H. This application claims benefit of U.S. Provisional Application No. 62/772,554, filed on Nov. 28, 2018, which is herein incorporated by reference in its entirety.Monoacylglycerol lipase (MAGL) is an enzyme responsible for hydrolyzing endocannabinoids such as 2-AG (2-arachidonoylglycerol), an arachidonate based lipid, in the nervous system.This disclosure provides, for example, methods for treating disease with compounds and pharmaceutical compositions ...

CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition. 2. The compound of claim 1 , wherein T is CX.3. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , iso-propyl claim 1 , tert-butyl claim 1 , benzyl and phenyl.43. The compound of anyone of - claims 1 , wherein at least four occurrences of X is halogen.54. The compound of any one of - claims 1 , wherein six occurrences of X is halogen.76. The compound of any one of - claims 1 , wherein Rand Rtaken together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring B having an additional nitrogen.9. The compound of claim 8 , wherein:{'sup': '3', 'sub': 1', '2', 'w', '1', '2', 'w', '1', '2', '1-6, 'Lis selected from the group consisting of a bond, C-Calkylene, —C(O)—, —CH—C(O)—NH, —S(O)—, and C-Calkylene-S(O)—, wherein w is 0, 1, or 2, and wherein C-Calkylene is optionally substituted by a substituent selected from the group consisting of: phenyl, biphenyl, phenyloxyphenyl (each optionally substituted by halogen, Calkyl (optionally substituted by one, two or three halogens, or hydroxyl)), mono or bicyclic heteroaryl having 1, 2 or 3 heteroatoms independently selected from O, S, or N and mono or bicyclic heterocycle having 1, 2 or 3 heteroatoms independently selected from O, S, or N; and'}{'sup': 7', '7', 'a', 'b', 'a', 'b', 'a', 'b', 'a', 'b', 'a, 'sub': 3', '1-6', '1-6', '2', 'w', '1-6', '1-6', '1-6, 'Ris selected from the group consisting of phenyl, biphenyl, phenyloxyphenyl, and mono or bicyclic ...

SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are spirocycle compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 146.-. (canceled)48. The method of claim 47 , or a solvate claim 47 , hydrate claim 47 , tautomer claim 47 , N-oxide claim 47 , stereoisomer claim 47 , or pharmaceutically acceptable salt thereof claim 47 , wherein each Ris independently selected from Calkyl claim 47 , Calkynyl claim 47 , halogen claim 47 , —CN claim 47 , Chaloalkyl claim 47 , heterocycloalkyl claim 47 , —Calkyl(heterocycloalkyl) claim 47 , heteroaryl claim 47 , —SF claim 47 , —NRR claim 47 , —OR claim 47 , —COR claim 47 , and —C(O)NRR.49. The method of claim 47 , or a solvate claim 47 , hydrate claim 47 , tautomer claim 47 , N-oxide claim 47 , stereoisomer claim 47 , or pharmaceutically acceptable salt thereof claim 47 , wherein Rand Rare both H.50. The method of claim 47 , or a solvate claim 47 , hydrate claim 47 , tautomer claim 47 , N-oxide claim 47 , stereoisomer claim 47 , or pharmaceutically acceptable salt thereof claim 47 , wherein Rand Rare both —CH.51. The method of claim 47 , or a solvate claim 47 , hydrate claim 47 , tautomer claim 47 , N-oxide claim 47 , stereoisomer claim 47 , or pharmaceutically acceptable salt thereof claim 47 , wherein each Ris independently selected from Calkyl claim 47 , halogen claim 47 , Chaloalkyl claim 47 , —Calkyl(heterocycloalkyl) claim 47 , —NRR claim 47 , —OR claim 47 , —COR claim 47 , and —C(O)NRR.52. The method of claim 51 , or a solvate claim 51 , hydrate claim 51 , tautomer claim 51 , N-oxide claim 51 , stereoisomer claim 51 , or pharmaceutically acceptable salt thereof claim 51 , wherein each Ris independently selected from halogen claim 51 , Chaloalkyl claim 51 , —NRR claim 51 , and —OR.53. The method of claim 51 , or a solvate claim 51 , hydrate claim 51 , tautomer claim 51 , N ...

Radiolabeled monoacylglycerol lipase occupancy probe

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.

PYRAZOLE MAGL INHIBITORS

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of monoacylglycerol lipase (MAGL). Furthermore, the subject compounds and compositions are useful for the treatment of pain. 4. The compound of claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein A is C(H).5. The compound of claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein A is N.6. The compound of any one of - claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein Ris H.9. The compound of or claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein Z is —S—.10. The compound of or claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein Z is —N(H)—.12. The compound of claim 11 , or a solvate claim 11 , hydrate claim 11 , tautomer claim 11 , N-oxide claim 11 , stereoisomer claim 11 , or pharmaceutically acceptable salt thereof claim 11 , wherein Z is —S—.14. The compound of any one of - claim 11 , or a solvate claim 11 , hydrate claim 11 , tautomer claim 11 , N-oxide claim 11 , stereoisomer claim 11 , or pharmaceutically acceptable salt thereof claim 11 , wherein m is 1 claim 11 , n is 1 claim 11 , q is 1 claim 11 , and p is 1.15. The compound of any one of - claim 11 , or a solvate claim 11 , hydrate claim 11 , tautomer claim 11 , N-oxide claim 11 , stereoisomer claim 11 , or pharmaceutically acceptable salt thereof claim 11 ...

METHODS OF TREATING INFLAMMATION OR NEUROPATHIC PAIN

Provided herein are methods of treating inflammation or neuropathic pain using an effective dose of a monoacylglycerol lipase inhibitor or a composition thereof. 1. (canceled)2. A method of treating Neuromyelitis Optica (NMO) or vasoocclussive painful crises in sickle cell disease in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof.3. The method of claim 2 , wherein the effective dose is from about 1 mg to about 100 mg.4. The method of claim 2 , wherein at least 30% of MGLL in PBMCs from the patient are covalently modified after administration of the effective dose.5. (canceled)6. The method of claim 2 , wherein the steady state plasma AUCof Compound 1 is at least 0.05 μM·hr after administration of the effective dose.729.-. (canceled)30. The method of claim 2 , wherein the effective dose is from about 1 mg to about 50 mg.31. The method of claim 2 , wherein the effective dose is from about 2 mg to about 25 mg.32. (canceled)33. (canceled)34. The method of claim 2 , wherein the effective dose is from about 1 mg to about 15 mg.35. The method of claim 2 , wherein the effective dose is from about 10 mg to about 25 mg.36. The method of claim 2 , wherein Compound 1 is administered orally.37. (canceled)38. (canceled)39. The method of claim 2 , wherein the effective dose is administered to the patient once per day.40. The method of claim 2 , wherein the effective dose is administered to the patient twice per day.4175.-. (canceled) This application is a continuation of U.S. application Ser. No. 15/573,272, filed Nov. 10, 2017, which is a U.S. National Stage Entry of International Application Number PCT/US2016/031668, filed May 10, 2016, which claims the benefit of priority from U.S. Provisional Application No. 62/297,670, filed Feb. 19, 2016, and also ...

CARBAMATE COMPOUNDS AND OF MAKING AND USING SAME

Provided herein are carbamate compounds which may be useful in the treatment of for example, pain, solid tumors and/or obesity. 54. The compound of any one of - claims 1 , wherein Rand Rtaken together with the nitrogen to which they are attached form a 6 membered heterocyclic ring B having an additional nitrogen.7. The compound of claim 6 , wherein:{'sup': 3', 'h', 'h', 'h, 'sub': 1', '2', '2', '2', '2', '1', '2, 'Lis selected from the group consisting of a bond, C-Calkylene, —C(O)—, —CH—C(O)—, and C(O)—CH—, —NHC(O)CH—, wherein C-Calkylene is optionally substituted by a substituent selected from the group consisting of: phenyl (optionally substituted by one, two or three substituents selected independently from R), mono or bicyclic heteroaryl having 1, 2 or 3 heteroatoms independently selected from O, S, or N (optionally substituted by one, two or three substituents selected independently from R) and mono or bicyclic heterocycle having 1, 2 or 3 heteroatoms independently selected from O, S, or N (optionally substituted by one, two or three substituents selected independently from R); and'}{'sup': 7', '7', 'h, 'Ris selected from the group consisting of phenyl, mono or bicyclic heteroaryl and mono or bicyclic heterocycle, wherein the heteroaryl or heterocycle has 1, 2 or 3 heteroatoms independently selected from O, S, or N, and Ris optionally substituted by one, two, three or four substituents each independently selected from R.'}8. The compound of or claim 6 , wherein Ris selected from the group consisting of phenyl claim 6 , naphthyl claim 6 , indanyl claim 6 , benzodioxolyl claim 6 , benzoxazolyl claim 6 , benzoisoxazolyl claim 6 , benzimidazolyl claim 6 , benzotriazolyl claim 6 , oxadiazolyl claim 6 , indazolyl claim 6 , oxazolyl claim 6 , isooxazolyl claim 6 , quinolinyl claim 6 , isoquinolinyl claim 6 , pyridinyl claim 6 , pyrazinyl claim 6 , pyrimidinyl claim 6 , thienyl claim 6 , thiazolyl claim 6 , benzothiopenyl claim 6 , indolyl claim 6 , benzothiadiazolyl ...

MAGL INHIBITORS

Provided herein are spirocyclic and fused bicyclic carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

PYRAZOLE MAGL INHIBITORS

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 3. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein m is 1 claim 2 , n is 1 claim 2 , p is 1 claim 2 , and w is 1.4. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein m is 0 claim 2 , n is 1 claim 2 , p is 1 claim 2 , and w is 2.5. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein m is 1 claim 2 , n is 1 claim 2 , p is 0 claim 2 , and w is 1.6. The compound of any one of - claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein A is C(H).7. The compound of any one of - claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein A is N.9. The compound of claim 8 , or a solvate claim 8 , hydrate claim 8 , tautomer claim 8 , N-oxide claim 8 , stereoisomer claim 8 , or pharmaceutically acceptable salt thereof claim 8 , wherein m is 1 claim 8 , n is 1 claim 8 , q is 1 claim 8 , and p is 1.10. The compound of claim 8 , or a solvate claim 8 , hydrate claim 8 , tautomer claim 8 , N-oxide claim 8 , stereoisomer claim 8 , or pharmaceutically acceptable salt thereof claim 8 , wherein m is 0 claim 8 , n is 1 claim 8 , q is 2 claim 8 , and p is 1.11. The compound of claim 8 , or a ...

METHODS OF TREATING INFLAMMATION OR NEUROPATHIC PAIN

Provided herein are methods of treating inflammation or neuropathic pain using an effective dose of a monoacylglycerol lipase inhibitor or a composition thereof. 1. A method of treating inflammation or neuropathic pain in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3 -hexafluoropropan-2-yl 4-(2 -(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof , wherein the effective dose is from about 1 mg to about 500 mg.2. A method of treating Epilepsy/Seizure Disorder , Multiple Sclerosis , Neuromyelitis Optica (NMO) , Tourette Syndrome , Alzheimer Disease , or abdominal pain associated with Irritable Bowel Syndrome in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof , wherein the effective dose is from about 1 mg to about 100 mg.3. A method of treating acute pain , inflammatory pain , cancer pain , pain caused by peripheral neuropathy , central pain , fibromyalgia , migraine , vasoocclussive painful crises in sickle cell disease , spasticity or pain associated with multiple sclerosis , functional chest pain , rheumatoid arthritis , osteoarthritis , or functional dyspepsia in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof , wherein the effective dose is from about 1 mg to about 100 mg.4. A method of treating inflammation or neuropathic pain in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3- ...

PYRROLO-PYRROLE CARBAMATE AND RELATED ORGANIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, AND MEDICAL USES THEREOF

The invention provides pyrrolo-pyrrole carbamate and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., solid tumor cancer, obesity, Down's syndrome, Alzheimer's disease, or pain, in a patient. The octahydropyrrolo pyrrole carbamates could be derived from hexafluoroisopropanol, N,N-disuccinimide and such. The activity of carbamates in MAGL, FAAH, and ABHD6 assays are also described. 2. The compound of claim 1 , wherein Ais phenylene optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cycloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , and haloalkoxy.3. The compound of claim 1 , wherein Ais phenylene optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , methyl claim 1 , —CF claim 1 , and —O—CF.4. The compound of claim 1 , wherein Ais a 5-membered or 6-membered heteroarylene optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cycloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , and haloalkoxy.5. The compound of claim 1 , wherein Ais a 5-membered heteroarylene optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cycloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , and haloalkoxy6. The compound of claim 1 , wherein Ais pyridinylene or pyrazolylene claim 1 , each of which is optionally substituted with 1 or 2 substituents independently selected from the group consisting of halogen claim 1 , alkyl claim 1 , haloalkyl claim 1 , cycloalkyl claim 1 , hydroxyl claim 1 , alkoxy claim 1 , and haloalkoxy.7. The compound of claim 1 , wherein Ais pyrazolylene optionally substituted with 1 ...

MAGL INHIBITORS

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Ris —OR.3. The compound of claim 2 , or a pharmaceutically acceptable salt or solvate thereof claim 2 , wherein Ris —(CRR)—R.4. The compound of claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein m is 1 claim 3 , 2 claim 3 , or 3.5. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein each Rand Ris each independently selected from H and Calkyl claim 4 , or Rand R claim 4 , together with the carbon to which they are attached claim 4 , form a Ccycloalkyl ring.6. The compound of claim 5 , or a pharmaceutically acceptable salt or solvate thereof claim 5 , wherein Ris —C(O)OR.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris H.8. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris Calkyl.9. The compound of claim 5 , or a pharmaceutically acceptable salt or solvate thereof claim 5 , wherein Ris —C(O)R.10. The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof claim 9 , wherein Ris —NHSOR.11. The compound of claim 10 , or a pharmaceutically acceptable salt or solvate thereof claim 10 , wherein Ris Calkyl.12. The compound of claim 10 , or a pharmaceutically acceptable salt or solvate thereof claim 10 , wherein Ris Ccycloalkyl.13. The compound of claim 7 , or a pharmaceutically acceptable salt or solvate thereof claim 7 , wherein each Ris independently selected from Calkyl claim 7 , halogen claim 7 , and Chaloalkyl.14. The compound of claim 13 , or a pharmaceutically acceptable salt or solvate ...

Magl inhibitors

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Carbamate compounds and of making and using same

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

MAGL INHIBITORS

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein p is 0.3. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein p is 1.4. The compound of claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Rand Rare H.5. The compound of any one of - claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Ris H.6. The compound of any one of - claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Ris Calkyl.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris —CH.8. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris —CH.9. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein each Ris independently selected from Calkyl claim 6 , halogen claim 6 , —CN claim 6 , Chaloalkyl claim 6 , —OR claim 6 , Ccycloalkyl claim 6 , Cheterocycloalkyl claim 6 , and Cheteroaryl claim 6 , wherein Ccycloalkyl claim 6 , Cheterocycloalkyl claim 6 , and Cheteroaryl are optionally substituted with one or two groups independently selected from halogen claim 6 , Calkyl claim 6 , Chaloalkyl claim 6 , and Calkoxy.10. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein each Ris independently selected from Calkyl claim 6 , halogen claim 6 , —CN claim 6 , Chaloalkyl claim 6 , —OR claim 6 , and Ccycloalkyl.11. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein ...

Carbamate compounds and methods of making and using same

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from post-traumatic stress disorder comprising administering a disclosed compound or composition.

MAGL INHIBITORS

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein p is 0.3. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein p is 1.4. The compound of claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Rand Rare H.5. The compound of any one of - claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Ris H.6. The compound of any one of - claim 3 , or a pharmaceutically acceptable salt or solvate thereof claim 3 , wherein Ris Calkyl.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris —CH.8. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris —CH.9. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein each Ris independently selected from Calkyl claim 6 , halogen claim 6 , —CN claim 6 , Chaloalkyl claim 6 , —OR claim 6 , Ccycloalkyl claim 6 , Cheterocycloalkyl claim 6 , and Cheteroaryl claim 6 , wherein Ccycloalkyl claim 6 , Cheterocycloalkyl claim 6 , and Cheteroaryl are optionally substituted with one or two groups independently selected from halogen claim 6 , Calkyl claim 6 , Chaloalkyl claim 6 , and Calkoxy.10. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein each Ris independently selected from Calkyl claim 6 , halogen claim 6 , —CN claim 6 , Chaloalkyl claim 6 , —OR claim 6 , and Ccycloalkyl.11. The compound of any one of - claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein ...

SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —Ccycloalkyl-COH.4. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —C≡C—Calkyl-COH.6. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is —CH—.7. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is —C(O)—.16. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.17. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.18. The compound of of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Rand Rare both H.19. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein each Ris independently selected from halogen and Chaloalkyl.20. The compound of any one of - claim 1 , or a solvate ...

PHARMACEUTICAL FORMLATIONS

Provided herein are pharmaceutical formulations comprising a monoacylglycerol lipase (MAGL) inhibitor, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient. 1. A pharmaceutical formulation in a solid dosage form comprising:(a) about 1 mg to about 60 mg of 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof;(b) about 5 mg to about 425 mg of a polymeric carrier;(c) about 0.2 mg to about 10 mg of a surfactant; and(d) about 0.2 mg to about 10 mg of a glidant.2. The pharmaceutical formulation of claim 1 , comprising about 10 mg to about 150 mg of the polymeric carrier.3. The pharmaceutical formulation of claim 1 , comprising about 14 mg to about 85 mg of the polymeric carrier.4. The pharmaceutical formulation of any one of - claim 1 , wherein the polymeric carrier is selected from polyvinyl pyrrolidone K30 (PVP K30) claim 1 , polyvinyl pyrrolidone K17 (PVP K17) claim 1 , polyvinyl pyrrolidone K12 (PVP K12) claim 1 , polyvinyl pyrrolidone vinyl acetate (PVPVA 64) claim 1 , hydroxypropylmethyl cellulose (HPMC) claim 1 , hydroxypropylmethylcellulose acetylsuccinate (HPMC AS) claim 1 , and methylmethacrylate polymers (Eudragit polymers).5. The pharmaceutical formulation of claim 4 , wherein the polymeric carrier is polyvinyl pyrrolidone K30 (PVP K30).6. The pharmaceutical formulation of claim 4 , wherein the polymeric carrier is polyvinyl pyrrolidone vinyl acetate (PVPVA 64).7. The pharmaceutical formulation of any one of - claim 4 , comprising about 0.2 mg to about 4 mg of a surfactant.8. The pharmaceutical formulation of any one of - claim 4 , comprising about 0.4 mg to about 2 mg of a surfactant.9. The pharmaceutical formulation of any one of - claim 4 , wherein the surfactant is selected from polysorbates claim 4 , polaxomers claim 4 , bile salts claim 4 , glyceryl monostearate claim 4 , sodium lauryl sulfate claim 4 , ...

CRYSTALLINE FORMS OF A MAGL INHIBITOR

Described herein is the MAGL inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, including crystalline forms and pharmaceutically acceptable salts and solvates thereof. 1. A crystalline form of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate , or a pharmaceutically acceptable salt , or solvate thereof.2. The crystalline form of claim 1 , wherein the 1 claim 1 ,1 claim 1 ,1 claim 1 ,3 claim 1 ,3 claim 1 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate is a free base.3. The crystalline form of claim 2 , wherein the crystalline form of 1 claim 2 ,1 claim 2 ,1 claim 2 ,3 claim 2 ,3 claim 2 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate free base has at least one of the following properties:{'figref': {'@idref': 'DRAWINGS', 'FIG. 1'}, '(a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in ;'}(b) an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 7.8° 2-Theta, 12.0° 2-Theta, 18.5° 2-Theta, 19.0° 2-Theta, 19.6° 2-Theta and 21.2° 2-Theta;{'figref': {'@idref': 'DRAWINGS', 'FIG. 2'}, '(c) a thermo-gravimetric analysis (TGA) substantially similar to the one set forth in ;'}{'figref': {'@idref': 'DRAWINGS', 'FIG. 3'}, '(d) a DSC thermogram substantially similar to the one set forth in ;'}(e) a DSC thermogram with an endotherm having an onset at about 80° C.;{'figref': {'@idref': 'DRAWINGS', 'FIG. 6'}, '(f) infrared (IR) spectrum substantially similar to the one set forth in ;'}{'sup': −1', '−1', '−1', '−1', '−1, '(g) infrared (IR) spectrum with peaks at about 1735 cm, 1427 cm, 1102 cm, 982 cm, and 888 cm;'}(h) non-hygroscopicity; or(i) combinations thereof.4. The crystalline form of claim 3 , wherein the crystalline form has an X-ray powder diffraction (XRPD) pattern substantially the same as shown ...

METHODS OF TREATING INFLAMMATION OR NEUROPATHIC PAIN

Provided herein are methods of treating inflammation or neuropathic pain using an effective dose of a monoacylglycerol lipase inhibitor or a composition thereof. 1. A method of treating inflammation or neuropathic pain in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof , wherein the effective dose is from about 1 mg to about 500 mg.2. A method of treating Epilepsy/Seizure Disorder , Multiple Sclerosis , Neuromyelitis Optica (NMO) , Tourette Syndrome , Alzheimer Disease , or abdominal pain associated with Irritable Bowel Syndrome in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof , wherein the effective dose is from about 1 mg to about 100 mg.3. A method of treating acute pain , inflammatory pain , cancer pain , pain caused by peripheral neuropathy , central pain , fibromyalgia , migraine , vasoocclussive painful crises in sickle cell disease , spasticity or pain associated with multiple sclerosis , functional chest pain , rheumatoid arthritis , osteoarthritis , or functional dyspepsia in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate (Compound 1) , or a pharmaceutically acceptable salt thereof , wherein the effective dose is from about 1 mg to about 100 mg.4. A method of treating inflammation or neuropathic pain in a patient in need thereof , comprising administering to the patient in need thereof an effective dose of 1 ,1 ,1 ,3 ,3 ,3- ...

CARBAMATE COMPOUNDS AND METHODS OF MAKING AND USING SAME

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition. 2. The compound of claim 1 , wherein T is CX.3. The compound of claim 1 , wherein Ris selected from the group consisting of methyl claim 1 , ethyl claim 1 , iso-propyl claim 1 , tert-butyl claim 1 , benzyl and phenyl.4. The compound of anyone of - claim 1 , wherein at least four occurrences of X is halogen.5. The compound of any one of - claim 1 , wherein six occurrences of X is halogen.7. The compound of any one of - claim 1 , wherein Rand Rtaken together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring B having an additional nitrogen.9. The compound of claim 8 , wherein:{'sup': '3', 'sub': 1', '2', 'w', '1', '2', 'w', '1', '2', '1-6, 'Lis selected from the group consisting of a bond, C-Calkylene, —C(O)—, —CH—C(O)—NH, —S(O)—, and C-Calkylene-S(O)—, wherein w is 0, 1, or 2, and wherein C-Calkylene is optionally substituted by a substituent selected from the group consisting of: phenyl, biphenyl, phenyloxyphenyl (each optionally substituted by halogen, Calkyl (optionally substituted by one, two or three halogens, or hydroxyl)), mono or bicyclic heteroaryl having 1, 2 or 3 heteroatoms independently selected from O, S, or N and mono or bicyclic heterocycle having 1, 2 or 3 heteroatoms independently selected from O, S, or N; and'}{'sup': 7', '7', 'a', 'b', 'a', 'b', 'a', 'b', 'a', 'b', 'a, 'sub': 3', '1-6', '1-6', '2', 'w', '1-6', '1-6', '1-6, 'Ris selected from the group consisting of phenyl, biphenyl, phenyloxyphenyl, and mono or bicyclic ...

PIPERAZINE CARBAMATES AND METHODS OF MAKING AND USING SAME

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently halogen.3. The compound of claim 2 , or a pharmaceutically acceptable salt or solvate thereof claim 2 , wherein each Ris —Cl.4. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently Chaloalkyl.5. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein each Ris —CF.6. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently Calkyl.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein each Ris —CH.8. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently Calkoxy.9. The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein each Ris —OCH.10. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently Chaloalkoxy.11. The compound of claim 10 , or a pharmaceutically acceptable salt or solvate thereof claim 10 , wherein each Ris —OCF.12. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently Ccycloalkyl.13. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein p is 0 claim 1 , 1 claim 1 , 2 claim 1 , or 3.14. The compound of any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein p is 1 or 2.15. The compound ...

DUAL MAGL AND FAAH INHIBITORS

Provided herein are compounds and pharmaceutical compositions comprising said compounds useful as modulators of MAGL and/or FAAH. The subject compounds and compositions are useful for the treatment of pain and neurological disorders. 2. The compound of claim 1 , or a pharmaceutically acceptable salt claim 1 , solvate claim 1 , or stereoisomer thereof claim 1 , wherein each Ris H.3. (canceled)4. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein p is 0.5. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein p is 1.6. The compound of claim 5 , or a pharmaceutically acceptable salt claim 5 , solvate claim 5 , or stereoisomer thereof claim 5 , wherein Ris —CH.710.-. (canceled)12. (canceled)13. (canceled)14. (canceled)15. (canceled)16. The compound of claim 11 , or a pharmaceutically acceptable salt claim 11 , solvate claim 11 , or stereoisomer thereof claim 11 , wherein m is 1 or 2.17. (canceled)18. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein Ris Chaloalkyl.19. The compound of claim 18 , or a pharmaceutically acceptable salt claim 18 , solvate claim 18 , or stereoisomer thereof claim 18 , wherein Ris —CF.20. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein Ris halogen.21. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein Ris —C(O)NH.22. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein Ris —CN.23. The compound of claim 2 , or a pharmaceutically acceptable salt claim 2 , solvate claim 2 , or stereoisomer thereof claim 2 , wherein q is 0.24. The compound of claim 2 , or a ...

Synthesis of a Monoacylglycerol Lipase Inhibitor

Described herein is the manufacture of MAGL inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate including salts thereof. 1. A process for the manufacture of 1 ,1 ,1 ,3 ,3 ,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate comprising the steps of:a) reacting tert-butyl piperazine-1-carboxylate with hexafluoropropan-2-ol in the presence of an acyl transfer agent to form 1-(tert-butyl) 4-(1,1,1,3,3,3-hexafluoropropan-2-yl) piperazine-1,4-dicarboxylate, wherein step a) is carried out in a first solvent;b) reacting 1-(tert-butyl) 4-(1,1,1,3,3,3-hexafluoropropan-2-yl) piperazine-1,4-dicarboxylate obtained in step a) with a strong acid to form 1,1,1,3,3,3-hexafluoropropan-2-yl piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof, wherein step b) is optionally carried out in a second solvent;c) reacting 1,1,1,3,3,3-hexafluoropropan-2-yl piperazine-1-carboxylate, or a pharmaceutically acceptable salt thereof obtained in step b) with 2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzaldehyde in the presence of a reducing agent and an organic base to form a reaction mixture comprising 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate, wherein the reaction in step c) is carried out in a third solvent.2. The process according to claim 1 , wherein step a) is carried out under pressure of 2 bar to 6 bar.3. The process according to claim 1 , wherein the ingredients in step a) are added in the consecutive order of the acyl transfer agent claim 1 , the first solvent claim 1 , tert-butyl piperazine-1-carboxylate claim 1 , and hexafluoropropan-2-ol as the last ingredient.4. The process according to claim 1 , wherein the strong acid in step b) is HCl; and wherein the step b) is carried out in a second solvent.5. The process according to claim 4 , wherein the second solvent is selected from the group ...

PYRAZOLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of, for example, pain. 13.-. (canceled)6. (canceled)7. The compound of claim 4 , or a solvate claim 4 , hydrate claim 4 , tautomer claim 4 , N-oxide claim 4 , or pharmaceutically acceptable salt thereof claim 4 , wherein Ris optionally substituted heterocycloalkyl and the heterocycloalkyl is a 4-6 membered monocyclic heterocycloalkyl claim 4 , a 8-9 membered bicyclic heterocycloalkyl claim 4 , a 7-8 membered bridged heterocycloalkyl claim 4 , a 5 claim 4 ,5 fused heterocycloalkyl claim 4 , or an 8-11 membered spirocyclic heterocycloalkyl.8. (canceled)9. The compound of claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris optionally substituted with one or two groups selected from halogen claim 7 , hydroxy claim 7 , Calkyl claim 7 , —Calkyl-OH claim 7 , Cfluoroalkyl claim 7 , Ccycloalkyl claim 7 , heteroaryl claim 7 , —COH claim 7 , —Calkyl-COH claim 7 , —C(O)Calkyl claim 7 , —C(O)Calkyl-OH claim 7 , —N(H)C(O)Calkyl claim 7 , —C(O)NH claim 7 , —C(O)N(H)(Calkyl) claim 7 , —C(O)N(Calkyl) claim 7 , —C(O)Cheterocycloalkyl claim 7 , and —S(O)Calkyl.10. (canceled)13. The compound of claim 4 , or a solvate claim 4 , hydrate claim 4 , tautomer claim 4 , N-oxide claim 4 , or pharmaceutically acceptable salt thereof claim 4 , wherein Ris optionally substituted heteroaryl and the heteroaryl is a 5-6 membered heteroaryl ring.14. The compound of claim 13 , or a solvate claim 13 , hydrate claim 13 , tautomer claim 13 , N-oxide claim 13 , or pharmaceutically acceptable salt thereof claim 13 , wherein Ris a 5-6 membered heteroaryl ring heteroaryl optionally substituted with one or two groups selected from halogen claim 13 , ...

SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are compounds and compositions useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is a bond.3. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is a Calkyl.4. The compound of claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein Y is —CH—.5. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is Chaloalkyl.6. The compound of claim 5 , or a solvate claim 5 , hydrate claim 5 , tautomer claim 5 , N-oxide claim 5 , stereoisomer claim 5 , or pharmaceutically acceptable salt thereof claim 5 , wherein Y is —CF—.7. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is Ccycloalkyl.8. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Y is cyclopropyl.10. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris H.11. The compound of any one of - claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt ...

DUAL MAGL AND FAAH INHIBITORS

Provided herein are compounds and pharmaceutical compositions comprising said compounds useful as modulators of MAGL and/or FAAH. The subject compounds and compositions are useful for the treatment of pain and neurological disorders. 2. The method of claim 1 , wherein Ris —CH.4. The method of claim 3 , wherein m is 1 or 2.5. The method of claim 1 , wherein Ris Chaloalkyl.6. The method of claim 5 , wherein Ris —CF.7. The method of claim 1 , wherein Ris halogen.8. The method of claim 1 , wherein Ris —C(O)NH.9. The method of claim 1 , wherein Ris —CN.10. The method of claim 1 , wherein q is 0.11. The method of claim 1 , wherein q is 1.12. The method of claim 1 , wherein each Ris independently selected from halogen claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , and —OR.13. The method of claim 12 , wherein Ris independently selected from Calkyl claim 12 , Chaloalkyl claim 12 , Ccycloalkyl claim 12 , aryl claim 12 , and heteroaryl.14. The method of claim 13 , wherein Ris independently selected from Calkyl and Chaloalkyl.15. The method of claim 1 , wherein each Ris H.18. The method of claim 17 , wherein Ris —CH.20. The method of claim 19 , wherein m is 1 or 2.21. The method of claim 17 , wherein Ris Chaloalkyl.22. The method of claim 21 , wherein Ris —CF.23. The method of claim 17 , wherein Ris halogen.24. The method of claim 17 , wherein Ris —C(O)NH.25. The method of claim 17 , wherein Ris —CN.26. The method of claim 17 , wherein q is 0.27. The method of claim 17 , wherein q is 1.28. The method of claim 17 , wherein each Ris independently selected from halogen claim 17 , Calkyl claim 17 , Chaloalkyl claim 17 , and —OR.29. The method of claim 2 , wherein Ris independently selected from Calkyl claim 2 , Chaloalkyl claim 2 , Ccycloalkyl claim 2 , aryl claim 2 , and heteroaryl.30. The method of claim 29 , wherein Ris independently selected from Calkyl and Chaloalkyl.31. The method of claim 17 , wherein each Ris H. This application claims benefit of U.S. Provisional ...

Carbamate compounds and methods of making and using same

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

LP-PLA2 INHIBITORS

Provided herein are lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitors, pharmaceutical compositions of said inhibitors, and methods of their use for the treatment of disease. 2. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Ris hydrogen or halogen.3. The compound of or claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Ris selected from the group consisting of —N(R)R claim 1 , C-Calkyl claim 1 , and C-Calkoxy.4. The compound any one of - claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Ris —N(R)R.5. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein Rand Rare each hydrogen.6. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein Rand Rare each C-Calkyl.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Rand Rare each —CH.8. The compound of claim 4 , or a pharmaceutically acceptable salt or solvate thereof claim 4 , wherein Rand Rtogether with the nitrogen atom to which they are attached claim 4 , form a 4-6 membered heterocyclic ring optionally substituted by C-Calkyl or —COH.9. The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein Rand Rtogether with the nitrogen atom to which they are attached claim 8 , form an unsubstituted pyrrolidine ring.10. The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein Rand Rtogether with the nitrogen atom to which they are attached claim 8 , form an unsubstituted piperidine ring.11. The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein Rand Rtogether with the nitrogen atom to which they are attached claim 8 , form a piperidine ring substituted by —COH.12. The compound of claim 8 , or a pharmaceutically acceptable ...

DUAL MAGL AND FAAH INHIBITORS

Provided herein are compounds and pharmaceutical compositions comprising said compounds useful as modulators of MAGL and/or FAAH. The subject compounds and compositions are useful for the treatment of pain and neurological disorders. 2. The method of claim 1 , wherein Ris —CH.4. The method of claim 3 , wherein m is 1 or 2.5. The method of claim 1 , wherein Ris Chaloalkyl.6. The method of claim 5 , wherein Ris —CF.7. The method of claim 1 , wherein Ris halogen.8. The method of claim 1 , wherein Ris —C(O)NH.9. The method of claim 1 , wherein Ris —CN.10. The method of claim 1 , wherein q is 0.11. The method of claim 1 , wherein q is 1.12. The method of claim 1 , wherein each Ris independently selected from halogen claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , and —OR.13. The method of claim 12 , wherein Ris independently selected from Calkyl claim 12 , Chaloalkyl claim 12 , Ccycloalkyl claim 12 , aryl claim 12 , and heteroaryl.14. The method of claim 13 , wherein Ris independently selected from Calkyl and Chaloalkyl.15. The method of claim 1 , wherein each Ris H.18. The method of claim 17 , wherein Ris —CH.20. The method of claim 19 , wherein m is 1 or 2.21. The method of claim 17 , wherein Ris Chaloalkyl.22. The method of claim 21 , wherein Ris —CF.23. The method of claim 17 , wherein Ris halogen.24. The method of claim 17 , wherein Ris —C(O)NH.25. The method of claim 17 , wherein Ris —CN.26. The method of claim 17 , wherein q is 0.27. The method of claim 17 , wherein q is 1.28. The method of claim 17 , wherein each Ris independently selected from halogen claim 17 , Calkyl claim 17 , Chaloalkyl claim 17 , and —OR.29. The method of claim 2 , wherein Ris independently selected from Calkyl claim 2 , Chaloalkyl claim 2 , Ccycloalkyl claim 2 , aryl claim 2 , and heteroaryl.30. The method of claim 29 , wherein Ris independently selected from Calkyl and Chaloalkyl.31. The method of claim 17 , wherein each Ris H. This application claims benefit of U.S. Provisional ...

MAGL INHIBITORS

Provided herein are spirocyclic and fused bicyclic carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

SPIROCYCLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are spirocycle compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 1. (canceled)3. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein each Ris independently selected from Calkyl claim 2 , Calkynyl claim 2 , halogen claim 2 , —CN claim 2 , Chaloalkyl claim 2 , heterocycloalkyl claim 2 , —Calkyl(heterocycloalkyl) claim 2 , heteroaryl claim 2 , —SF claim 2 , —NRR claim 2 , —OR claim 2 , —COR claim 2 , and —C(O)NRR.4. (canceled)5. (canceled)6. (canceled)7. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein Rand Rare both H.8. (canceled)9. (canceled)10. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein Rand Rare both —CH.11. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein each Ris independently selected from Calkyl claim 2 , halogen claim 2 , Chaloalkyl claim 2 , —Calkyl(heterocycloalkyl) claim 2 , —NRR claim 2 , —OR claim 2 , —COR claim 2 , and —C(O)NRR.12. The compound of claim 11 , or a solvate claim 11 , hydrate claim 11 , tautomer claim 11 , N-oxide claim 11 , stereoisomer claim 11 , or pharmaceutically acceptable salt thereof claim 11 , wherein each Ris independently selected from halogen claim 11 , Chaloalkyl claim 11 , —NRR claim 11 , and —OR.13. (canceled)14. The compound of claim 11 , or a solvate claim 11 , ...

Pyrazole compounds and methods of making and using same

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or FAAH. Furthermore, the subject compounds and compositions are useful for the treatment of, for example, pain.

PYRAZOLE COMPOUNDS AND METHODS OF MAKING AND USING SAME

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or FAAH. Furthermore, the subject compounds and compositions are useful for the treatment of, for example, pain. 8. The compound of claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris H.9. The compound of claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris Calkyl.10. The compound of claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris —C(O)Calkyl.12. The compound of any one of - claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris optionally substituted heterocycloalkyl.15. The compound of any one of - claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris —OR.17. The compound of any one of - claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris optionally substituted heteroaryl.20. The compound of any one of - claim 7 , or a solvate claim 7 , hydrate claim 7 , tautomer claim 7 , N-oxide claim 7 , or pharmaceutically acceptable salt thereof claim 7 , wherein Ris halogen.21. The compound of claim 20 , or a solvate claim 20 , hydrate claim 20 , tautomer claim 20 , N-oxide claim 20 , or pharmaceutically acceptable salt thereof claim 20 , wherein Ris —Cl.22. The compound of any one of - claim 20 , or a solvate claim 20 , hydrate claim 20 , tautomer claim 20 , N-oxide claim 20 , or pharmaceutically ...

PIPERAZINE CARBAMATES AND METHODS OF MAKING AND USING SAME

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. The compound of claim 1 , or a solvate claim 1 , hydrate claim 1 , tautomer claim 1 , N-oxide claim 1 , stereoisomer claim 1 , or pharmaceutically acceptable salt thereof claim 1 , wherein Ris —NRR.3. The compound of claim 2 , or a solvate claim 2 , hydrate claim 2 , tautomer claim 2 , N-oxide claim 2 , stereoisomer claim 2 , or pharmaceutically acceptable salt thereof claim 2 , wherein Rand R claim 2 , together with the nitrogen to which they are attached claim 2 , form a monocyclic heterocycle claim 2 , a fused bicyclic heterocycle claim 2 , or a spirocycle claim 2 , wherein:{'sup': 7', '12', '13', '9', '9', '10', '8', '9', '8', '9', '8', '9', '10, 'sub': '2', 'the monocyclic heterocycle, the fused bicyclic heterocycle, or the spirocycle is substituted with one or more substituents independently selected from optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle, optionally substituted cycloalkyl, haloalkyl, —OR, —NRR, —C(O)OR, —C(O)NRR, —NRSOR, —NRC(O)OR, and —NRC(O)NRR; and'}the monocyclic heterocycle, the fused bicyclic heterocycle, or the spirocycle optionally contains an additional O, N, or S.4. The compound of claim 3 , or a solvate claim 3 , hydrate claim 3 , tautomer claim 3 , N-oxide claim 3 , stereoisomer claim 3 , or pharmaceutically acceptable salt thereof claim 3 , wherein Rand Rtogether with the nitrogen to which they are attached form a heterocycle optionally containing an additional O claim 3 , N claim 3 , or S; wherein the heterocycle is substituted with one or more substituents independently selected from halogen claim 3 , oxo claim 3 , —OR claim 3 , —CN claim 3 , aryl (optionally substituted by one claim 3 , two claim 3 , or ...

Pyrazole magl inhibitors

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of monoacylglycerol lipase (MAGL). Furthermore, the subject compounds and compositions are useful for the treatment of pain.

MAGL INHIBITORS

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain. 2. (canceled)3. (canceled)4. (canceled)5. (canceled)6. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein Ris Calkyl.7. The compound of claim 6 , or a pharmaceutically acceptable salt or solvate thereof claim 6 , wherein Ris —CHand Ris —CH.8. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof claim 1 , wherein each Ris independently selected from Calkyl claim 1 , halogen claim 1 , —CN claim 1 , Chaloalkyl claim 1 , —OR claim 1 , Ccycloalkyl claim 1 , Cheterocycloalkyl claim 1 , and Cheteroaryl claim 1 , wherein Ccycloalkyl claim 1 , Cheterocycloalkyl claim 1 , and Cheteroaryl are optionally substituted with one or two groups independently selected from halogen claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , and Calkoxy.9. The compound of claim 8 , or a pharmaceutically acceptable salt or solvate thereof claim 8 , wherein each Ris independently selected from Calkyl claim 8 , halogen claim 8 , —CN claim 8 , Chaloalkyl claim 8 , —OR claim 8 , and Ccycloalkyl.10. The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof claim 9 , wherein each Ris independently selected from Calkyl and Chaloalkyl.11. The compound of claim 9 , or a pharmaceutically acceptable salt or solvate thereof claim 9 , wherein each Ris independently selected from Calkyl claim 9 , halogen claim 9 , —CN claim 9 , and Chaloalkyl.12. The compound of claim 11 , or a pharmaceutically acceptable salt or solvate thereof claim 11 , wherein each Ris independently selected from halogen and Chaloalkyl.13. (canceled)14. (canceled)15. (canceled)16. (canceled)17. The compound of claim 1 , or a pharmaceutically acceptable salt or solvate thereof ...

Phenyl and pyridyl lta4h modulators

Leukotrfene A4 hydrolase (LTA4H) inhibitors, compositions containing them, and methods of use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and inflammatory conditions.

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

Use of substituted pyrazoles for the manufacture of a drug for the treatment of allergies

A crystalline form of a magl inhibitor

La présente invention concerne l'inhibiteur magl 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluorométhyl)benzyl)pipérazine-1-carboxylate, y compris des formes cristallines et des sels et solvates pharmaceutiquement acceptables de ceux-ci. The present invention relates to the magl inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4- (2- (pyrrolidin-1-yl) -4- (trifluoromethyl) benzyl) piperazine-1-carboxylate , including crystalline forms and pharmaceutically acceptable salts and solvates thereof.

A CRYSTALLINE FORM OF A MAGL INHIBITOR

Method for treating allergies using substituted pyrazoles

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as lta4h modulators

Leukotriene A4 hydrolase (LTA4H) inhibitors of Formula (I), compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation. Wherein X is selected from the group consisting of NR5' 0, and S, with R5 being on of H and CH3; Y is selected from the group consisting; W is selected from the group consisting of CH2 and CHR, -CH2, with R' being one H and OH, wherein R1-attached carbon member in said CHR'- CH2 is not directly attached; R4 is selected from the group consisting of H, OCH3, Cl, F Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently selected from various groups.

MAGL inhibitors

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as lta4h modulators

Leukotriene A4 hydrolase (LTA4H) inhibitors of Formula (I), compositions containing them, and their use for the inhibition of LTA4H enzyme activity and the treatment, prevention or inhibition of inflammation and/or conditions associated with inflammation. Wherein X is selected from the group consisting of NR5, O, and S, with R5 being on of H and CH3; Y is selected from the group consisting; W is selected from the group consisting Of CH2 and CHR1-CH2,with R1 being one H and OH, wherein R1-attached carbon member in said CHR1-CH2 is not directly attached; R4 is selected from the group consisting of H, OCH3, CI, F Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently selected from various groups.

Methods of treating disease with magl inhibitors

Magl inhibitors

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as lta4h modulators

Pyrrolo-pyrrole carbamate and related organic compounds, pharmaceutical compositions, and medical uses thereof.

La invención proveé compuestos orgánicos pirrolo-pirrol carbamato y relacionados, composiciones que contienen tales compuestos, kits médicos, y métodos para utilizar tales compuestos y composiciones para tratar trastornos médicos, por ejemplo, cáncer de tumor sólido, obesidad, síndrome de Down, enfermedad de Alzheimer, o dolor, en un paciente.

Magl inhibitors

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Heterocyclic compounds

Certain thienopyrrolyl and furanopyrrolyl compounds are disclosed as useful to treat or prevent disorders and conditions mediated by the histamine H 4 receptor, including allergic rhinitis.

Crystalline forms of a magl inhibitor.

Aquí se describe el inhibidor de MAGL. 4-(2-(pirrolidin-1-il)-4-(t rifluorometil)bencil)piperazin-1-carboxilato de 1,1,1,3,3,3-hexafluoropropan-2-ilo, incluyendo formas cristalinas y sales y solvatos farmacéuticamente aceptables del mismo.

Aryl-substituted bridged or fused diamines as modulators of leukotriene a4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

Crystalline forms of a magl inhibitor

Described herein is the MAGL inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluorinethyl)benzyl)piperazine-1-carboxylate mono-hydrochloride salt is Form 2, having an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 8.6° 2-Theta, 15.6° 2-Theta, 19.0° 2-Theta, 19.8° 2-Theta, and 20.7° 2-Theta.

MAGL INHIBITORS

Se proporcionan en este documento carbamatos de piperazina y composiciones farmacéuticas que comprenden dichos compuestos. Los compuestos y composiciones objeto son útiles como moduladores de MAGL. Adicionalmente, los compuestos y composiciones objeto son útiles para el tratamiento del dolor.

A crystalline form of a magl inhibitor

Described herein is the crystalline fumarate salt of the MAGL inhibitor 1,1,1,3,3,3-hexafluoropropan-2-yl 4-(2-(pyrrolidin-1-yl)-4-(trifluoromethyl)benzyl)piperazine-1-carboxylate

Aryl-substituted bridged or fused diamines as modulators of leukotriene a4 hydrolase

Aryl-substituted bridged or fused diamine compounds, pharmaceutical compositions containing them, and methods of using the compounds and the pharmaceutical compositions for leukotriene A4 hydrolase (LTA4H or LTA4H) modulation and for the treatment of disease states, disorders, and conditions mediated by LTA4H activity, such as allergy, asthma, autoimmune diseases, pruritis, inflammatory bowel disease, ulcerative colitis, and cardiovascular disease, including atherosclerosis and prevention of myocardial infarction.

Magl inhibitors

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Bicyclic pyrazole compounds as antibacterial agents

Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.

Benzofuro- and benzothienopyrimidine modulators of the histamine H4 receptor

Benzofuro- and benzothienopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Pharmaceutical formulations

Provided herein are pharmaceutical formulations comprising a monoacylglycerol lipase (MAGL) inhibitor, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

Heterocyclic compounds

A compound of formula (I) wherein: wherein X4 is NR1 or S; _ X1 is CR3; X2 is NRe or O, provided that X2 is NRe where X1 is N; X3 is N; to treat or prevent disorders ans conditions mediated by the histamine H4 receptor.

Bicyclic pyrazole compounds as antibacterial agents

Antibacterial compounds, compositions containing them, and methods of use for the inhibition of bacterial activity and the treatment, prevention or inhibition of bacterial infection.

Methods of treating inflammation or neuropathic pain

Provided herein are methods of treating inflammation or neuropathic pain using an effective dose of a monoacylglycerol lipase inhibitor or a composition thereof.

Thiazolopyridin-2-yloxy-phenyl and thiazolopyrazin-2-yloxy-phenyl amines as modulators of leukotriene a4 hydrolase

Substituted pyrazoles

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases mediated by cathepsin S are described.

SPIROCYCLICAL COMPOUNDS AND THEIR PREPARATION AND USE METHODS

En la presente se proporcionan compuestos y composiciones útiles como moduladores de MAGL. Además, los compuestos y las composiciones en cuestión son útiles para el tratamiento del dolor.

Magl inhibitors.

Se proporcionan en este documento carbamatos de piperazina y composiciones farmacéuticas que comprenden dichos compuestos. Los compuestos y composiciones objeto son útiles como moduladores de MAGL. Adicionalmente, los compuestos y composiciones objeto son útiles para el tratamiento del dolor.

SPIROCYCLICAL COMPOUNDS AND THEIR PREPARATION AND USE METHODS

En la presente se proporcionan compuestos y composiciones útiles como moduladores de MAGL. Además, los compuestos y las composiciones en cuestión son útiles para el tratamiento del dolor.

Method for treating allergies using substituted pyrazoles

A method for treating an allergic condition, including an atopic allergic condition, using substituted pyrazoles of formula (I).

TETRAHYDROISOQUINOLINE COMPOUNDS AS HISTAMINE H3 RECEPTOR MODULATORS

Carbamate compounds and of making and using same

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compounds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

Benzofuro- and benzothienopyrimidine modulators of the histamine H4 receptor

Benzofuro- and benzothienopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Pyrrolo-pyrrole carbamate and related organic compounds, pharmaceutical compositions, and medical uses thereof

The invention provides pyrrolo-pyrrole carbamate and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., solid tumor cancer, obesity, Down's syndrome, Alzheimer's disease, or pain, in a patient. The octahydropyrrolo pyrrole carbamates could be derived from hexafluoroisopropanol, ?,?-disuccinimide and such. The activity of carbamates in MAGL, FAAH, and ABHD6 assays are also described.

Cyclopropylamines with histamine H3 receptor modulators

Pyrazole MAGL inhibitors

Provided herein are pyrazole compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of monoacylglycerol lipase (MAGL). Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Thiazolopyridin-2-yloxy-phenyl and thiazolopyrazin-2-yloxy-phenyl amines as modulators of leukotriene a4 hydrolase

Benzofuro- and benzothienopyrimidine modulators of the histamine H4 receptor

Benzofuro- and benzothienopyrimidine compounds are described, which are useful as H 4 receptor modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by H 4 receptor activity, such as allergy, asthma, autoimmune diseases, and pruritis.

Piperazine carbamates and methods of making and using same

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL and/or ABHD6. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Dual magl and faah inhibitors

Method for treating allergies using substituted pyrazoles

Disclosed is the use of compounds of formula (I) for the manufacture of medicaments for the treatment of allergic conditions, wherein: X is nitrogen or R12C, Y is nitrogen or R13C, Z is nitrogen or R14C, G is optionally substituted alkenediyl or alkanediyl, and the remaining substituents are defined herein.

Carbamate compounds and of making and using same

This disclosure provides compounds and compositions which may be modulators of MAGL and/or ABHD6 and their use as medicinal agents, processes for their preparation, and pharmaceutical compositions that include disclosed compunds as at least one active agent. The disclosure also provides for method of treating a patient in need thereof, where the patient is suffering from indications such as pain, solid tumor cancer and/or obesity comprising administering a disclosed compound or composition.

Heterocyclic compounds

Magl inhibitors

Provided herein are piperazine carbamates and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as modulators of MAGL. Furthermore, the subject compounds and compositions are useful for the treatment of pain.

Use of substituted pyrazoles for the manufacture of a medicament for the treatment of allergies

MODULAR BENZOFIDE AND BENZOTIENOPIRIMIDINE HISTAMINE RECEIVER H4

1.- Una entidad química seleccionada de compuestos de la fórmula (I):en donde R1 y R2 son cada uno independientemente H, CI, F, Br, metilo, etilo, metoxi, NO2, o CF3; R5 es H, metoxi, CI, F, Br, o CF3; A es N o CRa; donde Ra es H o CI; con la condición de que al menos dos de R1, R2, R5, y Ra sean H; X es O o S; -N(R3)R4 es uno de los radicales: donde q es 0 o 1; R3 y R4 se toman en conjunto o separadamente como se define por la estructura de cada uno de dichos radicales; Rb, Rc, y Rd son cada uno independientemente H o alquilo de C1-3, y cada sustituyente Re es metilo o dos sustituyentes Re tomados juntos forman un puente metileno o etileno; R6 es H o metilo; R7 es H; alquilo de C1-4 no sustituido o sustituido con -OH, -SCH3, o -NH2; alilo; o ciclopropilo; y sales farmacéuticamente aceptables de compuestos de fórmula (I), profármacos farmacéuticamente aceptables de compuestos de fórmula (I), y metabolitos farmacéuticamente activos de fórmula (I). 2.- La entidad química de conformidad con la reivindicación 1, caracterizada además porque R1 es H, metoxi, CI, Br, F, o CF3. 3.- La entidad química de conformidad con a reivindicación 1, caracterizada además porque R2 es H. 4.- La entidad química de conformidad con la reivindicación 2, caracterizada además porque R2 es H. 5.- La entidad química de conformidad con la reivindicación 1, caracterizada además porque R5 es H o CF3. 6.- La entidad química de conformidad con la reivindicación 1, caracterizada además porque A es N. 7.- La entidad química de conformidad con la reivindicación 1, caracterizada además porque A es CRa.

Crystalline forms of a MAGL inhibitor

Described herein is new crystalline forms of the MAGL inhibitor 2-(2-((4-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)piperazin-1-yl)methyl)-5-(trifluoromethyl)phenoxy)-2-methylpropanoic acid, or a pharmaceutically acceptable salt thereof.

Pyrazole magl inhibitors.

EN EL PRESENTE DOCUMENTO SE PROPORCIONAN COMPUESTOS DE PIRAZOL Y COMPOSICIONES FARMACÉUTICAS QUE COMPRENDEN DICHOS COMPUESTOS. LOS COMPUESTOS Y LAS COMPOSICIONES OBJETO SON ÚTILES COMO MODULADORES DE MAGL. ADEMÁS, LOS COMPUESTOS Y LAS COMPOSICIONES OBJETO SON ÚTILES PARA EL TRATAMIENTO DEL DOLOR. PIRAZOLE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS INCLUDING SUCH COMPOUNDS ARE PROVIDED HEREIN. THE COMPOUNDS AND SUBJECT COMPOSITIONS ARE USEFUL AS MAGL MODULATORS. IN ADDITION, THE SUBJECT COMPOUNDS AND COMPOSITIONS ARE USEFUL FOR THE TREATMENT OF PAIN.

Tetrahydroisoquinoline compounds as modulators of the histamine h3 receptor

Certain substituted tetrahydroisoquinoline compounds are histamine H3 receptor modulators useful in the treatment of histamine H3 receptor-mediated diseases.

MAGL PYRAZOLIC INHIBITORS

En esta memoria se proporcionan compuestos de pirazol y composiciones farmacéuticas que comprenden dichos compuestos. Los compuestos y las composiciones objeto son útiles como moduladores de monoacilglicerol lipasa (MAGL). Además, los compuestos y las composiciones objeto son útiles para el tratamiento del dolor.

Phenyl and pyridyl LTA4H modulators

Substituted benzyl amine compounds

Certain substituted benzyl amine compounds are histamine H3 receptor and/or serotonin transporter modulators useful in the treatment of histamine H3 receptor- and/or serotonin-mediated diseases.

Substituted pyrazoles

Benzimidazole, benzthiazole and benzoxazole derivatives and their use as LTA4H modulators