ES2553829T3 - Compuestos para el tratamiento de la adicción - Google Patents
Compuestos para el tratamiento de la adicción Download PDFInfo
- Publication number
- ES2553829T3 ES2553829T3 ES12735394.4T ES12735394T ES2553829T3 ES 2553829 T3 ES2553829 T3 ES 2553829T3 ES 12735394 T ES12735394 T ES 12735394T ES 2553829 T3 ES2553829 T3 ES 2553829T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- optionally substituted
- hydrogen
- compound
- oxo
- 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.)
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 245
- 238000011282 treatment Methods 0.000 title claims description 59
- 206010012335 Dependence Diseases 0.000 title claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 115
- 239000001257 hydrogen Substances 0.000 claims abstract description 115
- 239000000203 mixture Substances 0.000 claims abstract description 74
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 71
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 68
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 50
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 42
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 37
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 37
- 150000002148 esters Chemical class 0.000 claims abstract description 33
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 30
- 125000000547 substituted alkyl group Chemical group 0.000 claims abstract description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 27
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 21
- 125000002252 acyl group Chemical group 0.000 claims abstract description 20
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 20
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims abstract description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 19
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 15
- 125000005415 substituted alkoxy group Chemical group 0.000 claims abstract description 14
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 9
- 125000004475 heteroaralkyl group Chemical group 0.000 claims abstract description 8
- 150000001768 cations Chemical class 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical group 0.000 claims abstract 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 88
- 125000000217 alkyl group Chemical group 0.000 claims description 82
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 38
- 229960002715 nicotine Drugs 0.000 claims description 38
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 38
- 239000003981 vehicle Substances 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 31
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 30
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 30
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 239000011737 fluorine Chemical group 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 239000000460 chlorine Chemical group 0.000 claims description 19
- 229910052801 chlorine Chemical group 0.000 claims description 18
- LHRZBKAEDZUYNC-UHFFFAOYSA-N 2,6-dichloro-4-(2-methoxyethoxy)-n-[[4-(2-oxo-1h-pyridin-4-yl)phenyl]methyl]benzamide Chemical compound ClC1=CC(OCCOC)=CC(Cl)=C1C(=O)NCC1=CC=C(C2=CC(=O)NC=C2)C=C1 LHRZBKAEDZUYNC-UHFFFAOYSA-N 0.000 claims description 17
- CDCUWQFSGRLNTF-UHFFFAOYSA-N 2,6-dichloro-n-[[3-methyl-4-(2-oxo-1h-pyridin-4-yl)phenyl]methyl]benzamide Chemical compound C=1C=C(C2=CC(=O)NC=C2)C(C)=CC=1CNC(=O)C1=C(Cl)C=CC=C1Cl CDCUWQFSGRLNTF-UHFFFAOYSA-N 0.000 claims description 16
- 229960003638 dopamine Drugs 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- SFVKNPJMMRPOCO-UHFFFAOYSA-N 2-chloro-3,6-difluoro-n-[[4-(2-oxo-1h-pyridin-4-yl)phenyl]methyl]benzamide Chemical compound FC1=CC=C(F)C(C(=O)NCC=2C=CC(=CC=2)C2=CC(=O)NC=C2)=C1Cl SFVKNPJMMRPOCO-UHFFFAOYSA-N 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 9
- 230000002829 reductive effect Effects 0.000 claims description 9
- 208000011117 substance-related disease Diseases 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- LWYWZWJVXJWUFS-UHFFFAOYSA-N 2,6-dichloro-n-[[4-(2-methyl-6-oxo-1h-pyridin-4-yl)phenyl]methyl]benzamide Chemical compound O=C1NC(C)=CC(C=2C=CC(CNC(=O)C=3C(=CC=CC=3Cl)Cl)=CC=2)=C1 LWYWZWJVXJWUFS-UHFFFAOYSA-N 0.000 claims description 7
- MROYYAOBHCNTQW-UHFFFAOYSA-N 2,6-dichloro-n-[[4-(2-oxo-1h-pyridin-4-yl)phenyl]methyl]benzamide Chemical compound ClC1=CC=CC(Cl)=C1C(=O)NCC1=CC=C(C2=CC(=O)NC=C2)C=C1 MROYYAOBHCNTQW-UHFFFAOYSA-N 0.000 claims description 6
- SPADNYVJQZNTKZ-UHFFFAOYSA-N [4-[4-[[(2,6-dichlorobenzoyl)amino]methyl]phenyl]-2-oxopyridin-1-yl]methyl dihydrogen phosphate Chemical compound O=C1N(COP(O)(=O)O)C=CC(C=2C=CC(CNC(=O)C=3C(=CC=CC=3Cl)Cl)=CC=2)=C1 SPADNYVJQZNTKZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 6
- 206010013663 drug dependence Diseases 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 229940127240 opiate Drugs 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 2
- -1 amphetamines Chemical compound 0.000 description 133
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 84
- 241000700159 Rattus Species 0.000 description 69
- 125000001424 substituent group Chemical group 0.000 description 65
- 125000003118 aryl group Chemical group 0.000 description 57
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 45
- 238000000034 method Methods 0.000 description 41
- 238000002360 preparation method Methods 0.000 description 39
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 33
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- 239000002253 acid Substances 0.000 description 31
- 125000003545 alkoxy group Chemical group 0.000 description 31
- 150000001412 amines Chemical class 0.000 description 28
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- 230000000694 effects Effects 0.000 description 26
- 229910052736 halogen Inorganic materials 0.000 description 26
- 150000002367 halogens Chemical class 0.000 description 26
- 239000003814 drug Substances 0.000 description 25
- 239000003153 chemical reaction reagent Substances 0.000 description 24
- 102000010909 Monoamine Oxidase Human genes 0.000 description 23
- 108010062431 Monoamine oxidase Proteins 0.000 description 23
- 125000003342 alkenyl group Chemical group 0.000 description 23
- 125000000392 cycloalkenyl group Chemical group 0.000 description 23
- 239000000243 solution Substances 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 229940079593 drug Drugs 0.000 description 22
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- 125000005553 heteroaryloxy group Chemical group 0.000 description 21
- 230000004044 response Effects 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 235000019439 ethyl acetate Nutrition 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 239000003826 tablet Substances 0.000 description 20
- 125000000304 alkynyl group Chemical group 0.000 description 19
- 229960003920 cocaine Drugs 0.000 description 19
- 239000004615 ingredient Substances 0.000 description 19
- ZTQCTWHLFXVYGO-UHFFFAOYSA-N 2,6-dimethyl-n-[[4-(2-oxo-1h-pyridin-4-yl)phenyl]methyl]benzamide Chemical compound CC1=CC=CC(C)=C1C(=O)NCC1=CC=C(C2=CC(=O)NC=C2)C=C1 ZTQCTWHLFXVYGO-UHFFFAOYSA-N 0.000 description 18
- 241001465754 Metazoa Species 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 235000013305 food Nutrition 0.000 description 18
- 102000005369 Aldehyde Dehydrogenase Human genes 0.000 description 17
- 108020002663 Aldehyde Dehydrogenase Proteins 0.000 description 17
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 17
- 239000013543 active substance Substances 0.000 description 17
- 238000012360 testing method Methods 0.000 description 17
- 208000007848 Alcoholism Diseases 0.000 description 16
- 230000008033 biological extinction Effects 0.000 description 16
- AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 description 16
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 16
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- 125000004429 atom Chemical group 0.000 description 15
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- ZQSIJRDFPHDXIC-UHFFFAOYSA-N daidzein Chemical compound C1=CC(O)=CC=C1C1=COC2=CC(O)=CC=C2C1=O ZQSIJRDFPHDXIC-UHFFFAOYSA-N 0.000 description 14
- 239000000843 powder Substances 0.000 description 14
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 125000005110 aryl thio group Chemical group 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
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- 238000012549 training Methods 0.000 description 12
- DUUGKQCEGZLZNO-UHFFFAOYSA-N 5-hydroxyindoleacetic acid Chemical compound C1=C(O)C=C2C(CC(=O)O)=CNC2=C1 DUUGKQCEGZLZNO-UHFFFAOYSA-N 0.000 description 11
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- 125000005368 heteroarylthio group Chemical group 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
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- 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 9
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
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Classifications
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- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- 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
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- 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
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
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- Obesity (AREA)
- Diabetes (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| ES2648820T3 (es) | 2011-05-10 | 2018-01-08 | Gilead Sciences, Inc. | Compuestos heterocíclicos condensados como moduladores de los canales de sodio |
| TWI567061B (zh) | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
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| KR20150135332A (ko) | 2013-03-14 | 2015-12-02 | 더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티 | 미토콘드리아 알데히드 탈수소효소-2 조절인자들 및 이들의 사용 방법 |
| JP6463580B2 (ja) * | 2013-12-13 | 2019-02-06 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | ナトリウムチャネルの調節剤として有用なピリドンアミドのプロドラッグ |
| US10077669B2 (en) | 2014-11-26 | 2018-09-18 | United Technologies Corporation | Non-metallic engine case inlet compression seal for a gas turbine engine |
| US10289971B2 (en) | 2015-02-13 | 2019-05-14 | Atlassian Pty Ltd | Issue and trigger rebalancing in a ranked issue management system |
| HRP20221497T1 (hr) * | 2016-08-19 | 2023-02-17 | The University Of Bristol | Derivati citizina za liječenje ovisnosti |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| WO2019079209A1 (en) * | 2017-10-16 | 2019-04-25 | Amygdala Neurosciences, Inc. | POLYTHERAPY FOR THE PREVENTION OF AN ADDICTION |
| WO2019160882A1 (en) | 2018-02-13 | 2019-08-22 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| WO2019204609A1 (en) | 2018-04-19 | 2019-10-24 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| US10703733B2 (en) | 2018-05-14 | 2020-07-07 | Gilead Sciences, Inc. | MCL-1 inhibitors |
| BR112020026746A2 (pt) | 2018-07-13 | 2021-03-30 | Gilead Sciences, Inc. | Composto, composição farmacêutica, métodos para inibir pd-1, pd-l1 e/ou a interação de pd-1/pd-l1 e para tratar câncer, e, kit para tratar ou prevenir câncer ou uma doença ou condição. |
| WO2020023792A1 (en) * | 2018-07-27 | 2020-01-30 | Amygdala Neurosciences, Inc. | Combination therapy for nicotine addiction |
| WO2020076974A1 (en) * | 2018-10-12 | 2020-04-16 | Amygdala Neurosciences, Inc. | Addiction treatment of an alcohol-consuming patient population |
| CN112955435B (zh) | 2018-10-24 | 2024-09-06 | 吉利德科学公司 | Pd-1/pd-l1抑制剂 |
| US12029718B2 (en) | 2021-11-09 | 2024-07-09 | Cct Sciences, Llc | Process for production of essentially pure delta-9-tetrahydrocannabinol |
| WO2023244574A1 (en) | 2022-06-14 | 2023-12-21 | Amygdala Neurosciences, Inc. | Aldh-2 inhibitor compounds and methods of use |
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| US20080207610A1 (en) | 2006-07-27 | 2008-08-28 | Jeff Zablocki | Aldh-2 inhibitors in the treatment of addiction |
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| EP2126574B1 (en) | 2007-03-08 | 2015-12-23 | The Board of Trustees of the Leland Stanford Junior University | Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof |
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| WO2010028175A1 (en) | 2008-09-08 | 2010-03-11 | The Board Of Trustees Of The Leland Stanford Junior University | Modulators of aldehyde dehydrogenase activity and methods of use thereof |
| EP2349279A4 (en) * | 2008-10-28 | 2013-12-25 | Univ Leland Stanford Junior | MODIFIERS OF ALDEHYDE DEHYDROGENASE AND METHODS OF USE THEREOF |
| UY33469A (es) * | 2010-06-29 | 2012-01-31 | Irm Llc Y Novartis Ag | Composiciones y metodos para modular la via de señalizacion de wnt |
| TWI567061B (zh) | 2011-07-01 | 2017-01-21 | 吉李德科學股份有限公司 | 用於治療成癮之化合物 |
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