TWI503316B - 類大麻酚受體調節劑 - Google Patents
類大麻酚受體調節劑 Download PDFInfo
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- TWI503316B TWI503316B TW099128986A TW99128986A TWI503316B TW I503316 B TWI503316 B TW I503316B TW 099128986 A TW099128986 A TW 099128986A TW 99128986 A TW99128986 A TW 99128986A TW I503316 B TWI503316 B TW I503316B
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- Taiwan
- Prior art keywords
- pyridin
- group
- methyl
- ethyl
- hydroxy
- Prior art date
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- 239000003520 cannabinoid receptor affecting agent Substances 0.000 title 1
- -1 alkyl carbamide Chemical compound 0.000 claims description 3806
- 150000001875 compounds Chemical class 0.000 claims description 253
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 194
- 125000001072 heteroaryl group Chemical group 0.000 claims description 167
- 125000000623 heterocyclic group Chemical group 0.000 claims description 165
- 125000003118 aryl group Chemical group 0.000 claims description 162
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 133
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 126
- 125000001424 substituent group Chemical group 0.000 claims description 123
- 238000000034 method Methods 0.000 claims description 112
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 110
- 125000004076 pyridyl group Chemical group 0.000 claims description 81
- 229910052757 nitrogen Inorganic materials 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 71
- 239000012453 solvate Substances 0.000 claims description 69
- 229910052799 carbon Inorganic materials 0.000 claims description 67
- 229910052739 hydrogen Inorganic materials 0.000 claims description 67
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 64
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 61
- 150000001204 N-oxides Chemical class 0.000 claims description 61
- 150000004677 hydrates Chemical class 0.000 claims description 59
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- 150000002367 halogens Chemical class 0.000 claims description 58
- 239000003814 drug Substances 0.000 claims description 56
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 53
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 52
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 51
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 51
- 238000004519 manufacturing process Methods 0.000 claims description 50
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 47
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 43
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 41
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 39
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 38
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 36
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 35
- 150000001412 amines Chemical class 0.000 claims description 35
- 125000004104 aryloxy group Chemical group 0.000 claims description 33
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- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 28
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 28
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- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 25
- 125000001769 aryl amino group Chemical group 0.000 claims description 25
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 25
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 25
- 125000003277 amino group Chemical group 0.000 claims description 24
- 206010020751 Hypersensitivity Diseases 0.000 claims description 23
- 125000005605 benzo group Chemical group 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 22
- 125000006413 ring segment Chemical group 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 22
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 21
- 102000005962 receptors Human genes 0.000 claims description 20
- 108020003175 receptors Proteins 0.000 claims description 20
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 19
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- 208000024891 symptom Diseases 0.000 claims description 19
- 125000003554 tetrahydropyrrolyl group Chemical group 0.000 claims description 19
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 18
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 18
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- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 18
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 17
- 206010061218 Inflammation Diseases 0.000 claims description 17
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 17
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 17
- 230000004054 inflammatory process Effects 0.000 claims description 17
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 17
- 201000008482 osteoarthritis Diseases 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 15
- 125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 claims description 15
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 15
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 208000024827 Alzheimer disease Diseases 0.000 claims description 14
- 125000005363 dialkylsulfonamide group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims description 14
- 208000006011 Stroke Diseases 0.000 claims description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 12
- 206010012289 Dementia Diseases 0.000 claims description 12
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 12
- 230000002757 inflammatory effect Effects 0.000 claims description 12
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 12
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 12
- 241000725303 Human immunodeficiency virus Species 0.000 claims description 11
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 11
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 11
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 11
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 11
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- 241001465754 Metazoa Species 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 8
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
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- 125000004190 benzothiazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)SC2=C1[H] 0.000 claims description 7
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- 125000004122 cyclic group Chemical group 0.000 claims description 7
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- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000005919 1,2,2-trimethylpropyl group Chemical group 0.000 claims description 6
- 125000001617 2,3-dimethoxy phenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 6
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
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Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
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- 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
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- 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]
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- 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
- C07D401/14—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 three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
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- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pyrane Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| EP2678330A1 (en) | 2011-02-25 | 2014-01-01 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of condensed azacycles ( cannabinoid receptor modulators) |
| ITMI20122221A1 (it) | 2012-12-21 | 2014-06-22 | C4T S C A R L | Nuovi composti del 2,3-diidro-4h-1,3-benzossazin-4-one, metodo per prepararli e forma farmaceutica che li comprende |
| EP2803668A1 (en) | 2013-05-17 | 2014-11-19 | Boehringer Ingelheim International Gmbh | Novel (cyano-dimethyl-methyl)-isoxazoles and -[1,3,4]thiadiazoles |
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| WO2015095953A1 (en) | 2013-12-27 | 2015-07-02 | The Centre For Drug Research And Development | Sulfonamide-containing linkage systems for drug conjugates |
| ES2905569T3 (es) | 2014-09-17 | 2022-04-11 | Zymeworks Inc | Compuestos citotóxicos y antimitóticos y métodos para utilizarlos |
| WO2016085941A1 (en) * | 2014-11-25 | 2016-06-02 | Arena Pharmaceuticals, Inc. | Processes for the preparation of cannabinoid receptor modulators |
| US10172786B2 (en) | 2014-12-16 | 2019-01-08 | Axim Biotechnologies, Inc. | Oral care composition comprising cannabinoids |
| AU2017249211A1 (en) * | 2016-04-10 | 2018-11-22 | Arena Pharmaceuticals, Inc. | Methods of treatment with selective CB2 receptor agonists |
| CN109689045A (zh) | 2016-05-04 | 2019-04-26 | 因美制药公司 | 大麻素的局部制剂在治疗大疱性表皮松解症和相关结缔组织病症中的用途 |
| WO2018208847A1 (en) | 2017-05-08 | 2018-11-15 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of pain from inflammatory bowel disease |
| US20200078358A1 (en) | 2017-05-08 | 2020-03-12 | Arena Pharmaceuticals, Inc. | Compounds and Methods for Treatment of Visceral Pain |
| WO2019043635A1 (en) | 2017-09-01 | 2019-03-07 | Richter Gedeon Nyrt. | COMPOUNDS INHIBITING THE ACTIVITY OF D-AMINO ACID OXIDASE |
| US12357604B2 (en) | 2017-09-22 | 2025-07-15 | Inmed Pharmaceuticals Inc. | Topical formulations of cannabinoids and use thereof in the treatment of pain |
| EP3886845B1 (en) | 2018-11-28 | 2024-09-04 | Merck Sharp & Dohme LLC | Novel substituted piperazine amide compounds as indoleamine 2, 3-dioxygenase (ido) inhibitors |
| WO2021047583A1 (zh) * | 2019-09-12 | 2021-03-18 | 四川海思科制药有限公司 | 一种三环吡唑衍生物及其制备 |
| WO2021047581A1 (zh) * | 2019-09-12 | 2021-03-18 | 四川海思科制药有限公司 | 一种六氢化苯并吡唑衍生物及其制备 |
| JP7620024B2 (ja) | 2020-09-24 | 2025-01-22 | 富士フイルム株式会社 | 複合パターンの製造方法、樹脂組成物、積層体の製造方法、及び、半導体デバイスの製造方法 |
| CN115536648B (zh) * | 2021-06-29 | 2024-09-17 | 深圳开悦生命科技有限公司 | 一类抑制rna解旋酶dhx33的多环化合物及其应用 |
| CN114736173B (zh) * | 2022-05-24 | 2024-06-11 | 无锡捷化医药科技有限公司 | 一种3-（二氟甲基）氧杂环丁烷-3-胺盐酸盐的制备方法 |
| WO2025090133A1 (en) | 2023-10-23 | 2025-05-01 | Inmed Pharmaceuticals Inc. | Compositions and methods for use of cannabinol compounds in neuroprotection |
| WO2025090587A1 (en) | 2023-10-23 | 2025-05-01 | Inmed Pharmaceuticals Inc. | Cannabinoids compounds and their use in the treatment of neuronal disorders |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006129178A1 (en) * | 2005-06-02 | 2006-12-07 | Glenmark Pharmaceuticals S.A. | Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3964478B2 (ja) | 1995-06-30 | 2007-08-22 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | ヘテロ環含有カルボン酸誘導体及びそれを含有する医薬 |
| YU72201A (sh) | 1999-04-28 | 2005-07-19 | Aventis Pharma Deutschland Gmbh. | Derivati di-aril kiseline kao ppar receptorski ligandi |
| EP1461027A4 (en) | 2001-12-07 | 2005-09-07 | Univ Virginia Commonwealth | TREATMENT OF NEOPLASIA |
| SE0300010D0 (sv) | 2003-01-07 | 2003-01-07 | Astrazeneca Ab | Novel Compounds |
| ITMI20041033A1 (it) * | 2004-05-24 | 2004-08-24 | Neuroscienze S C A R L | Composti farmaceutici |
| EP2343302A1 (en) | 2004-07-12 | 2011-07-13 | Cadila Healthcare Limited | Tricyclic pyrazole derivatives as cannabinoid receptor modulators |
| WO2006010379A1 (en) * | 2004-07-29 | 2006-02-02 | Actelion Pharmaceuticals Ltd. | Novel thiophene derivatives as immunosuppressive agents |
| FR2875230A1 (fr) * | 2004-09-13 | 2006-03-17 | Sanofi Aventis Sa | Derives de pyrazole condense, leur preparation et leur application en therapeutique |
| DE102004054666A1 (de) | 2004-11-12 | 2006-05-18 | Bayer Cropscience Gmbh | Substituierte Pyrazol-3-carboxamide, Verfahren zur Herstellung und Verwendung als Herbizide und Pflanzenwachstumsregulatoren |
| PE20060949A1 (es) * | 2004-12-23 | 2006-10-11 | Arena Pharm Inc | Derivados fusionados de pirazol como agonistas del receptor de niacina |
| ATE459352T1 (de) | 2006-07-04 | 2010-03-15 | Janssen Pharmaceutica Nv | Benzimidazol-cannabinoid-agonisten mit einer substituierten heterocyclischen gruppe |
| US7928123B2 (en) | 2006-09-25 | 2011-04-19 | Boehringer Ingelheim International Gmbh | Compounds which modulate the CB2 receptor |
| US8481574B2 (en) | 2006-10-12 | 2013-07-09 | Abbott Laboratories | Compounds as cannabinoid receptor ligands |
| WO2008048914A1 (en) | 2006-10-17 | 2008-04-24 | Boehringer Ingelheim International Gmbh | Polycyclic compounds which modulate the cb2 receptor |
| EP2091921A2 (en) | 2006-11-03 | 2009-08-26 | Glenmark Pharmaceuticals S.A. | Bridged bicyclic indazoles as cannabinoid receptor ligands |
| US8173638B2 (en) | 2006-11-21 | 2012-05-08 | Boehringer Ingelheim International Gmbh | Compounds which modulate the CB2 receptor |
| US20080161340A1 (en) | 2006-12-20 | 2008-07-03 | Cara Therapeutics, Inc. | Tetrahydroquinilinones, tetrahydronaphthyridones and derivatives thereof |
| WO2008085302A1 (en) | 2006-12-20 | 2008-07-17 | Merck & Co., Inc. | Imidazopyridine analogs as cb2 receptor modulators, useful in the treatment of pain, respiratory and non-respiratory diseases |
| US20080214537A1 (en) | 2007-03-02 | 2008-09-04 | Cara Therapeutics, Inc. | Bridged phenanthridines |
| US8193369B2 (en) | 2007-03-30 | 2012-06-05 | Janssen Pharmaceutica Nv | Benzimidazole cannabinoid agonists |
| WO2008157500A1 (en) | 2007-06-17 | 2008-12-24 | Kalypsys, Inc. | Aminoquinazoline cannabinoid receptor modulators for treatment of disease |
| CN101686989B (zh) | 2007-06-21 | 2016-10-19 | 卡拉治疗学股份有限公司 | 取代的咪唑并杂环 |
| US8338623B2 (en) | 2007-07-09 | 2012-12-25 | Abbvie Inc. | Compounds as cannabinoid receptor ligands |
| US7943658B2 (en) | 2007-07-23 | 2011-05-17 | Bristol-Myers Squibb Company | Indole indane amide compounds useful as CB2 agonists and method |
| EP2203171A2 (en) | 2007-08-21 | 2010-07-07 | Merck Sharp & Dohme Corp. | Cb2 receptor ligands for the treatment of pain |
| UA104010C2 (en) | 2008-12-18 | 2013-12-25 | Эли Лилли Энд Компани | Purine compounds |
| US7741350B1 (en) | 2009-01-28 | 2010-06-22 | Cara Therapeutics, Inc. | Bicyclic pyrazolo-heterocycles |
| WO2010088050A2 (en) | 2009-01-28 | 2010-08-05 | Cara Therapeutics, Inc. | Bicyclic pyrazolo-heterocycles |
| IN2012DN02474A (https=) | 2009-08-28 | 2015-08-21 | Arena Pharm Inc | |
| AU2012222149B2 (en) * | 2011-02-25 | 2017-06-29 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| US9597340B2 (en) * | 2011-02-25 | 2017-03-21 | Arena Pharmaceuticals, Inc. | Cannabinoid receptor modulators |
| EP2678330A1 (en) * | 2011-02-25 | 2014-01-01 | Arena Pharmaceuticals, Inc. | Crystalline forms and processes for the preparation of condensed azacycles ( cannabinoid receptor modulators) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006129178A1 (en) * | 2005-06-02 | 2006-12-07 | Glenmark Pharmaceuticals S.A. | Novel cannabinoid receptor ligands, pharmaceutical compositions containing them, and process for their preparation |
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