AU2018323459A1 - Spirocycle compounds and methods of making and using same - Google Patents
Spirocycle compounds and methods of making and using same Download PDFInfo
- Publication number
- AU2018323459A1 AU2018323459A1 AU2018323459A AU2018323459A AU2018323459A1 AU 2018323459 A1 AU2018323459 A1 AU 2018323459A1 AU 2018323459 A AU2018323459 A AU 2018323459A AU 2018323459 A AU2018323459 A AU 2018323459A AU 2018323459 A1 AU2018323459 A1 AU 2018323459A1
- Authority
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- Australia
- Prior art keywords
- compound
- solvate
- tautomer
- hydrate
- stereoisomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 1041
- 238000000034 method Methods 0.000 title claims description 101
- 208000002193 Pain Diseases 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims description 937
- 239000012453 solvate Substances 0.000 claims description 890
- 150000001204 N-oxides Chemical class 0.000 claims description 755
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 213
- 229910052736 halogen Inorganic materials 0.000 claims description 211
- 150000002367 halogens Chemical class 0.000 claims description 211
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 157
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 112
- -1 substituted Chemical class 0.000 claims description 111
- 125000001072 heteroaryl group Chemical group 0.000 claims description 102
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 93
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 48
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 47
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 44
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 34
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 239000008194 pharmaceutical composition Substances 0.000 claims description 33
- 201000010099 disease Diseases 0.000 claims description 31
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 29
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 24
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 24
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 22
- 125000002883 imidazolyl group Chemical group 0.000 claims description 22
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- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 12
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical group C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 claims description 12
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 claims description 12
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 12
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 12
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 12
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- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 12
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 208000004296 neuralgia Diseases 0.000 claims description 4
- 208000021722 neuropathic pain Diseases 0.000 claims description 4
- 239000000203 mixture Substances 0.000 abstract description 61
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
- 125000004093 cyano group Chemical group *C#N 0.000 description 60
- 125000000217 alkyl group Chemical group 0.000 description 42
- 238000003786 synthesis reaction Methods 0.000 description 36
- 239000000243 solution Substances 0.000 description 34
- 125000004432 carbon atom Chemical group C* 0.000 description 33
- 230000015572 biosynthetic process Effects 0.000 description 32
- 150000003254 radicals Chemical class 0.000 description 31
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 30
- 229910002092 carbon dioxide Inorganic materials 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 125000003118 aryl group Chemical group 0.000 description 28
- 239000003814 drug Substances 0.000 description 28
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 26
- 150000001413 amino acids Chemical class 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
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- 102000005398 Monoacylglycerol Lipase Human genes 0.000 description 20
- 108020002334 Monoacylglycerol lipase Proteins 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
- 125000003710 aryl alkyl group Chemical group 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- 125000002947 alkylene group Chemical group 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 229940124597 therapeutic agent Drugs 0.000 description 18
- 125000001188 haloalkyl group Chemical group 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 125000004450 alkenylene group Chemical group 0.000 description 11
- 238000002360 preparation method Methods 0.000 description 11
- 239000000651 prodrug Substances 0.000 description 11
- 229940002612 prodrug Drugs 0.000 description 11
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 229910052799 carbon Inorganic materials 0.000 description 10
- 125000004122 cyclic group Chemical group 0.000 description 10
- 239000003937 drug carrier Substances 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 10
- 125000000842 isoxazolyl group Chemical group 0.000 description 10
- 125000002971 oxazolyl group Chemical group 0.000 description 10
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 10
- 125000003226 pyrazolyl group Chemical group 0.000 description 10
- 125000000714 pyrimidinyl group Chemical group 0.000 description 10
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 10
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
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- 230000008901 benefit Effects 0.000 description 9
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- 125000005843 halogen group Chemical group 0.000 description 9
- 150000002431 hydrogen Chemical group 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 8
- 239000004480 active ingredient Substances 0.000 description 8
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- 239000002775 capsule Substances 0.000 description 8
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- NCAIGTHBQTXTLR-UHFFFAOYSA-N phentermine hydrochloride Chemical compound [Cl-].CC(C)([NH3+])CC1=CC=CC=C1 NCAIGTHBQTXTLR-UHFFFAOYSA-N 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
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- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
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- 229960000894 sulindac Drugs 0.000 description 1
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- AGYJKDRKBSJWLJ-UHFFFAOYSA-N tert-butyl 1,8-diazaspiro[4.5]decane-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCC11CCNCC1 AGYJKDRKBSJWLJ-UHFFFAOYSA-N 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- IGIPXGHCLUEPRO-UHFFFAOYSA-N tert-butyl 2-[(3-phenyl-1-propan-2-ylpyrazol-4-yl)methyl]-2,8-diazaspiro[4.5]decane-8-carboxylate Chemical compound C(C)(C)N1N=C(C(=C1)CN1CC2(CC1)CCN(CC2)C(=O)OC(C)(C)C)C1=CC=CC=C1 IGIPXGHCLUEPRO-UHFFFAOYSA-N 0.000 description 1
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- 230000000699 topical effect Effects 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
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- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 125000005455 trithianyl group Chemical group 0.000 description 1
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- 229940093612 zein Drugs 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762551721P | 2017-08-29 | 2017-08-29 | |
| US62/551,721 | 2017-08-29 | ||
| PCT/US2018/048372 WO2019046318A1 (en) | 2017-08-29 | 2018-08-28 | SPIROCYCLIC COMPOUNDS AND METHODS OF PREPARATION AND USE THEREOF |
Publications (1)
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| AU2018323459A1 true AU2018323459A1 (en) | 2020-02-20 |
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| GE (1) | GEP20217327B (enExample) |
| IL (1) | IL272580B (enExample) |
| JO (1) | JOP20200023A1 (enExample) |
| MA (1) | MA50041A (enExample) |
| MX (1) | MX2020002251A (enExample) |
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| PH (1) | PH12020500372A1 (enExample) |
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| NZ627750A (en) | 2012-01-06 | 2016-11-25 | Abide Therapeutics Inc | Carbamate compounds and of making and using same |
| CN109496213B (zh) | 2016-05-12 | 2022-03-04 | H.隆德贝克有限公司 | 螺环化合物及其制备和使用方法 |
| JOP20190107A1 (ar) | 2016-11-16 | 2019-05-09 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
| BR112020003946A2 (pt) | 2017-08-29 | 2020-09-08 | Lundbeck La Jolla Research Center, Inc. | compostos de espirociclo e métodos para produzir e usar os mesmos |
| ES2952332T3 (es) | 2017-08-29 | 2023-10-30 | H Lundbeck As | Compuestos espirocíclicos y sus métodos de preparación y uso |
| KR20220034104A (ko) * | 2019-07-09 | 2022-03-17 | 에프. 호프만-라 로슈 아게 | 신규 헤테로고리 화합물 |
| JP7785755B2 (ja) * | 2020-08-26 | 2025-12-15 | エフ． ホフマン－ラ ロシュ アーゲー | Ｍａｇｌ阻害剤として有用な複素環化合物 |
| US11434222B2 (en) * | 2020-11-13 | 2022-09-06 | H. Lundbeck A/S | MAGL inhibitors |
| US20250084065A1 (en) | 2021-12-29 | 2025-03-13 | Psy Therapeutics, Inc. | Inhibiting monoacylglycerol lipase (magl) |
| CN119137114A (zh) | 2022-05-04 | 2024-12-13 | H.隆德贝克有限公司 | 作为单酰基甘油脂肪酶抑制剂的(s)-1-(哒嗪-3-基氨基甲酰基)-6-氮杂螺[2.5]辛烷-6-甲酸1,1,1,3,3,3-六氟丙-2-酯的结晶形式 |
| WO2024168426A1 (en) | 2023-02-13 | 2024-08-22 | Apogee Pharmaceuticals, Inc. | Small molecules as monoacylglycerol lipase (magl) inhibitors, compositions and use thereof |
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| EP2065369A4 (en) | 2006-08-23 | 2011-12-28 | Astellas Pharma Inc | UREA CONNECTION OR SALT THEREOF |
| AU2009221860A1 (en) | 2008-03-05 | 2009-09-11 | Targacept, Inc. | Nicotinic acetylcholine receptor sub-type selective amides of diazabicycloal kanes |
| FR2941696B1 (fr) | 2009-02-05 | 2011-04-15 | Sanofi Aventis | Derives d'azaspiranyl-alkylcarbamates d'heterocycles a 5 chainons, leur preparation et leur application en therapeutique |
| US20120083476A1 (en) | 2009-06-05 | 2012-04-05 | Janssen Pharmaceutica Nv | Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase |
| CA2775703C (en) | 2009-09-29 | 2014-07-08 | Polyone Corporation | Polyester articles having simulated metallic or pearlescent appearance |
| HUE043962T2 (hu) | 2009-10-23 | 2019-09-30 | Janssen Pharmaceutica Nv | Diszubsztituált oktahidro-pirrolo[3,4-C]pirrolok mint orexin receptor modulátorok |
| CA2791672A1 (en) | 2010-03-04 | 2011-09-09 | Merck Sharp & Dohme Corp. | Positive allosteric modulators of mglur2 |
| FR2960875B1 (fr) * | 2010-06-04 | 2012-12-28 | Sanofi Aventis | Derives de carbamates d'hexafluoroisopropyle, leur preparation et leur application en therapeutique |
| EP2444084A1 (en) | 2010-10-21 | 2012-04-25 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Use of PI3K inibitors for the treatment of obesity |
| NZ627750A (en) * | 2012-01-06 | 2016-11-25 | Abide Therapeutics Inc | Carbamate compounds and of making and using same |
| HRP20191937T1 (hr) | 2012-09-25 | 2020-01-10 | F. Hoffmann - La Roche Ag | Derivati heksahidropirolo [3,4-c]pirola i srodni spojevi kao inhibitori autotaksina (atx) i kao inhibitori proizvodnje lizofosfatidne kiseline (lpa) za liječenje npr. bubrežnih bolesti |
| US9828379B2 (en) | 2013-07-03 | 2017-11-28 | Abide Therapeutics, Inc. | Pyrrolo-pyrrole carbamate and related organic compounds, pharmaceutical compositions, and medical uses thereof |
| US10093630B2 (en) * | 2014-05-21 | 2018-10-09 | Abide Therapeutics, Inc. | Pyrazole compounds and methods of making and using same |
| WO2016149401A2 (en) | 2015-03-18 | 2016-09-22 | Abide Therapeutics, Inc. | Piperazine carbamates and methods of making and using same |
| WO2017021805A1 (en) | 2015-07-31 | 2017-02-09 | Pfizer Inc. | 1,1,1-trifluoro-3-hydroxypropan-2-yl carbamate derivatives and 1,1,1-trifluoro-4-hydroxybutan-2-yl carbamate derivatives as magl inhibitors |
| US10385057B2 (en) | 2015-11-20 | 2019-08-20 | Lundbeck La Jolla Research Center, Inc. | Pyrazole compounds and methods of making and using same |
| TWI738753B (zh) | 2016-03-31 | 2021-09-11 | 日商武田藥品工業股份有限公司 | 雜環化合物 |
| CN109496213B (zh) | 2016-05-12 | 2022-03-04 | H.隆德贝克有限公司 | 螺环化合物及其制备和使用方法 |
| JOP20190049A1 (ar) | 2016-09-23 | 2019-03-20 | Bial Portela & C? S A | مثبطات دوبامين-b-هيدروكسيلاز |
| JOP20190105A1 (ar) | 2016-11-16 | 2019-05-09 | Lundbeck La Jolla Research Center Inc | مثبطات أحادي أسيل جليسرول ليباز (magl) |
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| HUE064559T2 (hu) | 2016-11-16 | 2024-03-28 | H Lundbeck As | MAGL inhibitor kristályos formája |
| ES2952332T3 (es) | 2017-08-29 | 2023-10-30 | H Lundbeck As | Compuestos espirocíclicos y sus métodos de preparación y uso |
| BR112020003946A2 (pt) | 2017-08-29 | 2020-09-08 | Lundbeck La Jolla Research Center, Inc. | compostos de espirociclo e métodos para produzir e usar os mesmos |
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