MXPA06002035A - Composicion farmaceutica para la prevencion y el tratamiento de adicciones en mamiferos. - Google Patents
Composicion farmaceutica para la prevencion y el tratamiento de adicciones en mamiferos.Info
- Publication number
- MXPA06002035A MXPA06002035A MXPA06002035A MXPA06002035A MXPA06002035A MX PA06002035 A MXPA06002035 A MX PA06002035A MX PA06002035 A MXPA06002035 A MX PA06002035A MX PA06002035 A MXPA06002035 A MX PA06002035A MX PA06002035 A MXPA06002035 A MX PA06002035A
- Authority
- MX
- Mexico
- Prior art keywords
- chlorophenyl
- methyl
- aza
- hydroxy
- bicyclo
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 25
- 206010012335 Dependence Diseases 0.000 title claims abstract description 18
- 241000124008 Mammalia Species 0.000 title claims description 8
- 230000002265 prevention Effects 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229940123257 Opioid receptor antagonist Drugs 0.000 claims abstract description 25
- 239000003401 opiate antagonist Substances 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 18
- 229940123158 Cannabinoid CB1 receptor antagonist Drugs 0.000 claims abstract description 17
- 239000003555 cannabinoid 1 receptor antagonist Substances 0.000 claims abstract description 17
- 208000011117 substance-related disease Diseases 0.000 claims abstract description 16
- 201000009032 substance abuse Diseases 0.000 claims abstract description 14
- 231100000736 substance abuse Toxicity 0.000 claims abstract description 13
- 230000003542 behavioural effect Effects 0.000 claims abstract description 11
- 208000007848 Alcoholism Diseases 0.000 claims abstract description 10
- 208000001613 Gambling Diseases 0.000 claims abstract description 6
- 239000003937 drug carrier Substances 0.000 claims abstract description 6
- 230000009467 reduction Effects 0.000 claims abstract description 6
- 208000024891 symptom Diseases 0.000 claims abstract description 6
- 208000029650 alcohol withdrawal Diseases 0.000 claims abstract description 5
- 208000025569 Tobacco Use disease Diseases 0.000 claims abstract description 4
- 206010013663 drug dependence Diseases 0.000 claims abstract description 3
- 208000022497 Cocaine-Related disease Diseases 0.000 claims abstract 2
- 201000006145 cocaine dependence Diseases 0.000 claims abstract 2
- -1 1- [9- (4-chlorophenyl) -8- (2-chlorophenyl) -9H-purin-6-yl] -3-isopropyl-amino-azetidine-3-carboxylic acid amide Chemical compound 0.000 claims description 152
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 80
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 73
- 150000003839 salts Chemical class 0.000 claims description 45
- KBPHGUKTJKPERJ-UHFFFAOYSA-N 2-methoxyethanesulfonic acid Chemical compound COCCS(O)(=O)=O KBPHGUKTJKPERJ-UHFFFAOYSA-N 0.000 claims description 25
- 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 claims description 24
- 239000000126 substance Substances 0.000 claims description 18
- 239000012453 solvate Substances 0.000 claims description 16
- CYAYCOCJAVHQSD-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxylic acid Chemical compound CC=1C(C(O)=O)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 CYAYCOCJAVHQSD-UHFFFAOYSA-N 0.000 claims description 12
- 229960003920 cocaine Drugs 0.000 claims description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 12
- 239000000203 mixture Substances 0.000 claims description 11
- XYSDEMQLXPUMBO-UHFFFAOYSA-N [3-[6-ethyl-3-[(2-hydroxy-3,4-dihydro-1h-naphthalen-2-yl)methyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CC3(O)CC4=CC=CC=C4CC3)CC2C1(CC)C1=CC=CC(CS(N)(=O)=O)=C1 XYSDEMQLXPUMBO-UHFFFAOYSA-N 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- KJJLEOOLZLWLSS-UHFFFAOYSA-N 3-[6-ethyl-3-[(1-hydroxy-3-phenylcyclobutyl)methyl]-3-azabicyclo[3.1.0]hexan-6-yl]benzamide Chemical compound C1C2C(CC)(C=3C=C(C=CC=3)C(N)=O)C2CN1CC(C1)(O)CC1C1=CC=CC=C1 KJJLEOOLZLWLSS-UHFFFAOYSA-N 0.000 claims description 7
- RZRVHGLZBLICCS-UHFFFAOYSA-N COC1(C2CN(CCCC3(CCCCC3)O)CC1CC2)C(C=CC=C1)=C1C(N)=O Chemical compound COC1(C2CN(CCCC3(CCCCC3)O)CC1CC2)C(C=CC=C1)=C1C(N)=O RZRVHGLZBLICCS-UHFFFAOYSA-N 0.000 claims description 7
- 150000001408 amides Chemical class 0.000 claims description 7
- VLJHXPKDNBNFPN-UHFFFAOYSA-N 3-[1-[(2-hydroxy-1,3-dihydroinden-2-yl)methyl]-3,4-dimethylpiperidin-4-yl]benzamide Chemical compound CC1CN(CC2(O)CC3=CC=CC=C3C2)CCC1(C)C1=CC=CC(C(N)=O)=C1 VLJHXPKDNBNFPN-UHFFFAOYSA-N 0.000 claims description 6
- SCNSHBHEDUUZDM-UHFFFAOYSA-N 3-[6-ethyl-3-[(2-hydroxy-1,3-dihydroinden-2-yl)methyl]-3-azabicyclo[3.1.0]hexan-6-yl]benzamide Chemical compound C12CN(CC3(O)CC4=CC=CC=C4C3)CC2C1(CC)C1=CC=CC(C(N)=O)=C1 SCNSHBHEDUUZDM-UHFFFAOYSA-N 0.000 claims description 6
- BVBIKNOVWWMBBP-UHFFFAOYSA-N C1N(CC2(O)CC3=CC=CC=C3C2)CC2CCC1C2(OC)C1=CC=CC(CS(N)(=O)=O)=C1 Chemical compound C1N(CC2(O)CC3=CC=CC=C3C2)CC2CCC1C2(OC)C1=CC=CC(CS(N)(=O)=O)=C1 BVBIKNOVWWMBBP-UHFFFAOYSA-N 0.000 claims description 6
- UUIGGJWRCKHZBN-UHFFFAOYSA-N COCC(C1=CC(C2(CCC3)CC3N(CC3(CC4=CC=CC=C4CC3)O)CC2)=CC=C1)S(N)(=O)=O Chemical compound COCC(C1=CC(C2(CCC3)CC3N(CC3(CC4=CC=CC=C4CC3)O)CC2)=CC=C1)S(N)(=O)=O UUIGGJWRCKHZBN-UHFFFAOYSA-N 0.000 claims description 6
- 235000002637 Nicotiana tabacum Nutrition 0.000 claims description 6
- 206010034158 Pathological gambling Diseases 0.000 claims description 6
- CFEHQSDWANWIDE-UHFFFAOYSA-N [3-[2-[(1-hydroxy-3-phenylcyclobutyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]phenyl]methanesulfonamide Chemical compound NS(=O)(=O)CC1=CC=CC(C23CC(CCC2)N(CC2(O)CC(C2)C=2C=CC=CC=2)CC3)=C1 CFEHQSDWANWIDE-UHFFFAOYSA-N 0.000 claims description 6
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 5
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 5
- CMXNJCYHOYIGPE-UHFFFAOYSA-N 3-[1-[(1-hydroxy-3-phenylcyclobutyl)methyl]-3,4-dimethylpiperidin-4-yl]benzamide Chemical compound C1CC(C=2C=C(C=CC=2)C(N)=O)(C)C(C)CN1CC(C1)(O)CC1C1=CC=CC=C1 CMXNJCYHOYIGPE-UHFFFAOYSA-N 0.000 claims description 5
- ZCDWSEYWBPLIPE-UHFFFAOYSA-N 3-[2-[(2-hydroxy-3,4-dihydro-1h-naphthalen-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CC4=CC=CC=C4CC2)CC3)=C1 ZCDWSEYWBPLIPE-UHFFFAOYSA-N 0.000 claims description 5
- CQMGDWUBLFGSDQ-UHFFFAOYSA-N 3-[3-[(1-hydroxy-3-phenylcyclobutyl)methyl]-8-methoxy-3-azabicyclo[3.2.1]octan-8-yl]benzamide Chemical compound C=1C=CC(C(N)=O)=CC=1C1(OC)C(C2)CCC1CN2CC(C1)(O)CC1C1=CC=CC=C1 CQMGDWUBLFGSDQ-UHFFFAOYSA-N 0.000 claims description 5
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 claims description 5
- JVUOJEOSXJAJGS-UHFFFAOYSA-N CC(CN(CCCC1(CCCCC1)O)CC1)C1(C)C(C=CC=C1)=C1C(N)=O Chemical compound CC(CN(CCCC1(CCCCC1)O)CC1)C1(C)C(C=CC=C1)=C1C(N)=O JVUOJEOSXJAJGS-UHFFFAOYSA-N 0.000 claims description 5
- RYBMKDVAGXFMHB-UHFFFAOYSA-N CCC1(C2C1CN(CC1(CC3=CC=CC=C3CC1)O)C2)C1=CC=CC(C(COC)S(N)(=O)=O)=C1 Chemical compound CCC1(C2C1CN(CC1(CC3=CC=CC=C3CC1)O)C2)C1=CC=CC(C(COC)S(N)(=O)=O)=C1 RYBMKDVAGXFMHB-UHFFFAOYSA-N 0.000 claims description 5
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 5
- 229960002715 nicotine Drugs 0.000 claims description 5
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 5
- UNAZAADNBYXMIV-UHFFFAOYSA-N otenabant Chemical compound C1CC(NCC)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)Cl)N2C1=CC=C(Cl)C=C1 UNAZAADNBYXMIV-UHFFFAOYSA-N 0.000 claims description 5
- SQSZXZKMVHUPRD-UHFFFAOYSA-N 1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-(propan-2-ylamino)piperidine-4-carboxamide Chemical compound C1CC(NC(C)C)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)Cl)N2C1=CC=C(Cl)C=C1 SQSZXZKMVHUPRD-UHFFFAOYSA-N 0.000 claims description 4
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 claims description 4
- YZMRJTFTIRSULG-UHFFFAOYSA-N 3-[2-[(1-hydroxy-3-phenylcyclobutyl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CC(C2)C=2C=CC=CC=2)CC3)=C1 YZMRJTFTIRSULG-UHFFFAOYSA-N 0.000 claims description 4
- PNUIAAYEYHRGJI-UHFFFAOYSA-N 3-[3-[(2-hydroxy-1,3-dihydroinden-2-yl)methyl]-8-methoxy-3-azabicyclo[3.2.1]octan-8-yl]benzamide Chemical compound C1N(CC2(O)CC3=CC=CC=C3C2)CC2CCC1C2(OC)C1=CC=CC(C(N)=O)=C1 PNUIAAYEYHRGJI-UHFFFAOYSA-N 0.000 claims description 4
- YBQGLTGAHBCMME-UHFFFAOYSA-N 4-amino-1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidine-4-carboxamide Chemical compound C1CC(C(=O)N)(N)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)Cl)N2C1=CC=C(Cl)C=C1 YBQGLTGAHBCMME-UHFFFAOYSA-N 0.000 claims description 4
- YJDQIHXWBXWGGO-UHFFFAOYSA-N C(C)C1(C2CN(CC12)CCCC1(CCCCC1)O)C1=C(C(=O)N)C=CC=C1 Chemical compound C(C)C1(C2CN(CC12)CCCC1(CCCCC1)O)C1=C(C(=O)N)C=CC=C1 YJDQIHXWBXWGGO-UHFFFAOYSA-N 0.000 claims description 4
- FDRLWIIAPQXTMO-UHFFFAOYSA-N COCC(C1=CC(C2(CCC3)CC3N(CC(C3)(CC3C3=CC=CC=C3)O)CC2)=CC=C1)S(N)(=O)=O Chemical compound COCC(C1=CC(C2(CCC3)CC3N(CC(C3)(CC3C3=CC=CC=C3)O)CC2)=CC=C1)S(N)(=O)=O FDRLWIIAPQXTMO-UHFFFAOYSA-N 0.000 claims description 4
- IKMIFKMETPRUBK-UHFFFAOYSA-N COCC(C1=CC(C2(CCC3)CC3N(CC3(CC4=CC=CC=C4C3)O)CC2)=CC=C1)S(N)(=O)=O Chemical compound COCC(C1=CC(C2(CCC3)CC3N(CC3(CC4=CC=CC=C4C3)O)CC2)=CC=C1)S(N)(=O)=O IKMIFKMETPRUBK-UHFFFAOYSA-N 0.000 claims description 4
- OPXPEHGRRFTOHD-UHFFFAOYSA-N NC(C1=C(C2(CCC3)CC3N(CCCC3(CCCCC3)O)CC2)C=CC=C1)=O Chemical compound NC(C1=C(C2(CCC3)CC3N(CCCC3(CCCCC3)O)CC2)C=CC=C1)=O OPXPEHGRRFTOHD-UHFFFAOYSA-N 0.000 claims description 4
- HJUAYCORBOWWGO-UHFFFAOYSA-N [3-[6-ethyl-3-[(2-hydroxy-1,3-dihydroinden-2-yl)methyl]-3-azabicyclo[3.1.0]hexan-6-yl]phenyl]methanesulfonamide Chemical compound C12CN(CC3(O)CC4=CC=CC=C4C3)CC2C1(CC)C1=CC=CC(CS(N)(=O)=O)=C1 HJUAYCORBOWWGO-UHFFFAOYSA-N 0.000 claims description 4
- JIHQDMXYYFUGFV-UHFFFAOYSA-N 1,3,5-triazine Chemical compound C1=NC=NC=N1 JIHQDMXYYFUGFV-UHFFFAOYSA-N 0.000 claims description 3
- BMVXCPBXGZKUPN-UHFFFAOYSA-N 1-hexanamine Chemical compound CCCCCCN BMVXCPBXGZKUPN-UHFFFAOYSA-N 0.000 claims description 3
- XWJBBHRGYQANKK-UHFFFAOYSA-N 3-[2-[(2-hydroxy-1,3-dihydroinden-2-yl)methyl]-2-azabicyclo[3.3.1]nonan-5-yl]benzamide Chemical compound NC(=O)C1=CC=CC(C23CC(CCC2)N(CC2(O)CC4=CC=CC=C4C2)CC3)=C1 XWJBBHRGYQANKK-UHFFFAOYSA-N 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- MGXWXNOHTWTTFC-UHFFFAOYSA-N 8-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-1-propan-2-yl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound CC(C)N1CNC(=O)C11CCN(C=2C=3N=C(N(C=3N=CN=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CC1 MGXWXNOHTWTTFC-UHFFFAOYSA-N 0.000 claims description 3
- NVEWRUMMUBKWLP-UHFFFAOYSA-N 9-(4-chlorophenyl)-6-(1-cyclohexylazetidin-3-yl)oxy-8-(2,4-dichlorophenyl)purine Chemical compound C1=CC(Cl)=CC=C1N1C2=NC=NC(OC3CN(C3)C3CCCCC3)=C2N=C1C1=CC=C(Cl)C=C1Cl NVEWRUMMUBKWLP-UHFFFAOYSA-N 0.000 claims description 3
- 206010057852 Nicotine dependence Diseases 0.000 claims description 3
- 239000013543 active substance Substances 0.000 claims description 3
- NUJGJRNETVAIRJ-UHFFFAOYSA-N octanal Chemical compound CCCCCCCC=O NUJGJRNETVAIRJ-UHFFFAOYSA-N 0.000 claims description 3
- RSHRLSNTSNPHBI-UHFFFAOYSA-N 1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-3-[1-(1-phenylethyl)imidazol-4-yl]pyrazole Chemical compound C1=NC(C=2C(=C(N(N=2)C=2C(=CC=CC=2)Cl)C=2C=CC(Cl)=CC=2)C)=CN1C(C)C1=CC=CC=C1 RSHRLSNTSNPHBI-UHFFFAOYSA-N 0.000 claims description 2
- CTSFSQZYEGEKNJ-UHFFFAOYSA-N 1-(oxazepan-4-yl)ethanone Chemical compound O1NCC(CCC1)C(C)=O CTSFSQZYEGEKNJ-UHFFFAOYSA-N 0.000 claims description 2
- KGJHVABFBBJFIG-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-(3,3-dimethylpiperidin-1-yl)ethanol Chemical compound CC=1C(C(O)CN2CC(C)(C)CCC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 KGJHVABFBBJFIG-UHFFFAOYSA-N 0.000 claims description 2
- MJKOCBMDVCJJOQ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-[4-(1-methylpyrrole-2-carbonyl)piperazin-1-yl]ethanone Chemical compound CC=1C(C(=O)CN2CCN(CC2)C(=O)C=2N(C=CC=2)C)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 MJKOCBMDVCJJOQ-UHFFFAOYSA-N 0.000 claims description 2
- JBCFDMJWDPFMLH-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-morpholin-4-ylethanone Chemical compound CC=1C(C(=O)CN2CCOCC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JBCFDMJWDPFMLH-UHFFFAOYSA-N 0.000 claims description 2
- LBBWUMREEVVZRO-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylimidazol-4-yl]-2-morpholin-4-ylethanone Chemical compound C=1C=C(Cl)C=CC=1N1C(C)=C(C(=O)CN2CCOCC2)N=C1C1=CC=C(Cl)C=C1Cl LBBWUMREEVVZRO-UHFFFAOYSA-N 0.000 claims description 2
- HUKVRWGDXWJBMB-UHFFFAOYSA-N 1-[1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylimidazol-4-yl]-2-piperidin-1-ylethanone Chemical compound C=1C=C(Cl)C=CC=1N1C(C)=C(C(=O)CN2CCCCC2)N=C1C1=CC=C(Cl)C=C1Cl HUKVRWGDXWJBMB-UHFFFAOYSA-N 0.000 claims description 2
- HVXLAPMGPSSUAP-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-(methylamino)azetidine-3-carboxamide Chemical compound C1C(NC)(C(N)=O)CN1C1=CC=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 HVXLAPMGPSSUAP-UHFFFAOYSA-N 0.000 claims description 2
- IKIJBYVYJILIOG-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-(propan-2-ylamino)azetidine-3-carboxamide Chemical compound C1C(NC(C)C)(C(N)=O)CN1C1=CC=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 IKIJBYVYJILIOG-UHFFFAOYSA-N 0.000 claims description 2
- ZNNPDKATJWCFJB-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-4-(ethylamino)piperidine-4-carboxamide Chemical compound C1CC(NCC)(C(N)=O)CCN1C1=CC=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 ZNNPDKATJWCFJB-UHFFFAOYSA-N 0.000 claims description 2
- GWYHSUUKVUYTOI-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-1-(2-fluorophenyl)-4-methylpyrazol-3-yl]-2-piperidin-1-ylethanone Chemical compound CC=1C(C(=O)CN2CCCCC2)=NN(C=2C(=CC=CC=2)F)C=1C1=CC=C(Cl)C=C1 GWYHSUUKVUYTOI-UHFFFAOYSA-N 0.000 claims description 2
- GVPQEAGKQZOLCM-UHFFFAOYSA-N 1-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-4-(ethylamino)piperidine-4-carboxylic acid Chemical compound CCNC1(CCN(CC1)C2=NC(=NC3=C(C(=NN32)C4=CC=CC=C4Cl)C5=CC=C(C=C5)Cl)C)C(=O)O GVPQEAGKQZOLCM-UHFFFAOYSA-N 0.000 claims description 2
- RSSDYHXNXTWNJY-UHFFFAOYSA-N 1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-(propylamino)piperidine-4-carboxamide Chemical compound C1CC(NCCC)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)Cl)N2C1=CC=C(Cl)C=C1 RSSDYHXNXTWNJY-UHFFFAOYSA-N 0.000 claims description 2
- SKJBKOGUSSCGFF-UHFFFAOYSA-N 1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-phenylpiperidin-4-ol Chemical compound C1CC(O)(C=2C=CC=CC=2)CCN1C(C=1N=2)=NC=NC=1N(C=1C=CC(Cl)=CC=1)C=2C1=CC=CC=C1Cl SKJBKOGUSSCGFF-UHFFFAOYSA-N 0.000 claims description 2
- XGMUXVHFGMMZJM-UHFFFAOYSA-N 1-[9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)purin-6-yl]-4-(propylamino)piperidine-4-carboxamide Chemical compound C1CC(NCCC)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC(Cl)=CC=1)Cl)N2C1=CC=C(Cl)C=C1 XGMUXVHFGMMZJM-UHFFFAOYSA-N 0.000 claims description 2
- LGRHTFQDJMGCCC-UHFFFAOYSA-N 1-[9-(4-chlorophenyl)-8-(2-fluorophenyl)-2-methylpurin-6-yl]-4-(propan-2-ylamino)piperidine-4-carboxamide Chemical compound C1CC(NC(C)C)(C(N)=O)CCN1C1=NC(C)=NC2=C1N=C(C=1C(=CC=CC=1)F)N2C1=CC=C(Cl)C=C1 LGRHTFQDJMGCCC-UHFFFAOYSA-N 0.000 claims description 2
- RLCOBFXHEJIMNV-UHFFFAOYSA-N 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(4-pyrimidin-2-ylpiperazin-1-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=CC(Cl)=CC=C1C1=C2N=CC=C(N3CCN(CC3)C=3N=CC=CN=3)N2N=C1C1=CC=CC=C1Cl RLCOBFXHEJIMNV-UHFFFAOYSA-N 0.000 claims description 2
- VXODHBBNQFCLHC-UHFFFAOYSA-N 2-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-2,5,7-triazaspiro[3.4]octan-8-one Chemical compound C1=CC(Cl)=CC=C1C1=C2N=CC=C(N3CC4(C3)C(NCN4)=O)N2N=C1C1=CC=CC=C1Cl VXODHBBNQFCLHC-UHFFFAOYSA-N 0.000 claims description 2
- UJXKCJMVVWMQAC-UHFFFAOYSA-N 2-[benzyl(propan-2-yl)amino]-1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]ethanol Chemical compound C=1C=CC=CC=1CN(C(C)C)CC(O)C(C=1C)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 UJXKCJMVVWMQAC-UHFFFAOYSA-N 0.000 claims description 2
- OEOZSLHGXZGCMK-UHFFFAOYSA-N 4-(1-benzylpyrrolidin-3-yl)oxy-7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazine Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1OC(C1)CCN1CC1=CC=CC=C1 OEOZSLHGXZGCMK-UHFFFAOYSA-N 0.000 claims description 2
- KPDICBIFKOBCOP-UHFFFAOYSA-N 4-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]morpholine Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1N1CCOCC1 KPDICBIFKOBCOP-UHFFFAOYSA-N 0.000 claims description 2
- DNPSMAHBGIQJNC-UHFFFAOYSA-N 4-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-n-methylpiperazine-2-carboxamide Chemical compound C1CNC(C(=O)NC)CN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)Cl)N2C1=CC=C(Cl)C=C1 DNPSMAHBGIQJNC-UHFFFAOYSA-N 0.000 claims description 2
- CQGPFLMUTINLFP-UHFFFAOYSA-N 4-benzyl-1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]piperidin-4-ol Chemical compound C1CN(C=2N3N=C(C(=C3N=CC=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CCC1(O)CC1=CC=CC=C1 CQGPFLMUTINLFP-UHFFFAOYSA-N 0.000 claims description 2
- HUZIHJMYKVLBGE-UHFFFAOYSA-N 4-benzyl-1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]piperidin-4-ol Chemical compound C1CN(C=2C=3N=C(N(C=3N=CN=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CCC1(O)CC1=CC=CC=C1 HUZIHJMYKVLBGE-UHFFFAOYSA-N 0.000 claims description 2
- IHUJIWXYFXDLJI-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-[1-(2-phenylpropan-2-yl)imidazol-4-yl]pyrazole Chemical compound CC=1C(C=2N=CN(C=2)C(C)(C)C=2C=CC=CC=2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 IHUJIWXYFXDLJI-UHFFFAOYSA-N 0.000 claims description 2
- DQCGCILDBMFEOE-UHFFFAOYSA-N 5-(4-chlorophenyl)-1-(2-fluorophenyl)-4-methyl-3-[1-(2-phenylpropan-2-yl)imidazol-4-yl]pyrazole Chemical compound CC=1C(C=2N=CN(C=2)C(C)(C)C=2C=CC=CC=2)=NN(C=2C(=CC=CC=2)F)C=1C1=CC=C(Cl)C=C1 DQCGCILDBMFEOE-UHFFFAOYSA-N 0.000 claims description 2
- MAOZBIOYMACLOW-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-(5-cyclohexyl-1H-imidazol-2-yl)-1-(2,4-dichlorophenyl)-4-methylpyrazole Chemical compound CC=1C(C=2NC(=CN=2)C2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 MAOZBIOYMACLOW-UHFFFAOYSA-N 0.000 claims description 2
- MPCZFCKCHMXKSZ-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methyl-4-(4-propan-2-ylsulfonylpiperazin-1-yl)pyrazolo[1,5-a][1,3,5]triazine Chemical compound C1CN(S(=O)(=O)C(C)C)CCN1C1=NC(C)=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 MPCZFCKCHMXKSZ-UHFFFAOYSA-N 0.000 claims description 2
- YBOFFNOTZAHZGG-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methyl-4-[(2-methylpropan-2-yl)oxy]pyrazolo[1,5-a][1,3,5]triazine Chemical compound C=12N=C(C)N=C(OC(C)(C)C)N2N=C(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 YBOFFNOTZAHZGG-UHFFFAOYSA-N 0.000 claims description 2
- BACFLWLVLGFHMI-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-4-(1-cyclohexylazetidin-3-yl)oxy-2-methylpyrazolo[1,5-a][1,3,5]triazine Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1OC(C1)CN1C1CCCCC1 BACFLWLVLGFHMI-UHFFFAOYSA-N 0.000 claims description 2
- VTWNGPAUTNLCPN-UHFFFAOYSA-N 8-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-6-methylpyrazolo[1,5-a]pyrimidin-7-yl]-1-propan-2-yl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound CC(C)N1CNC(=O)C11CCN(C=2N3N=C(C(=C3N=CC=2C)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CC1 VTWNGPAUTNLCPN-UHFFFAOYSA-N 0.000 claims description 2
- FMQLEHWCAMNBAG-UHFFFAOYSA-N 8-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-1-propan-2-yl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound CC(C)N1CNC(=O)C11CCN(C=2N3N=C(C(=C3N=C(C)N=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CC1 FMQLEHWCAMNBAG-UHFFFAOYSA-N 0.000 claims description 2
- MOMMTIGOEFZQSC-UHFFFAOYSA-N 9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-6-propan-2-yloxypurine Chemical compound N=1C=2C(OC(C)C)=NC=NC=2N(C=2C=CC(Cl)=CC=2)C=1C1=CC=C(Cl)C=C1Cl MOMMTIGOEFZQSC-UHFFFAOYSA-N 0.000 claims description 2
- QMTNIILDNUELGY-UHFFFAOYSA-N 9-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-1-methyl-4-oxa-1,9-diazaspiro[5.5]undecan-2-one Chemical compound CN1C(=O)COCC11CCN(C=2C=3N=C(N(C=3N=CN=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CC1 QMTNIILDNUELGY-UHFFFAOYSA-N 0.000 claims description 2
- OKOPJSMEUVGYMZ-UHFFFAOYSA-N CC(C)(C1=CC=CC=C1)N1C=NC(C(C(C)=C2C3=CC=CN=C3OC)=NN2C(C=CC(Cl)=C2)=C2Cl)=C1 Chemical compound CC(C)(C1=CC=CC=C1)N1C=NC(C(C(C)=C2C3=CC=CN=C3OC)=NN2C(C=CC(Cl)=C2)=C2Cl)=C1 OKOPJSMEUVGYMZ-UHFFFAOYSA-N 0.000 claims description 2
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims 2
- INMZIBQWBSNYED-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-4-(propan-2-ylamino)piperidine-4-carboxamide Chemical compound C1CC(NC(C)C)(C(N)=O)CCN1C1=CC=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 INMZIBQWBSNYED-UHFFFAOYSA-N 0.000 claims 2
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 claims 2
- 241000208125 Nicotiana Species 0.000 claims 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 2
- NBBLBZXXTIHYGR-UHFFFAOYSA-N 1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[1-(2,2-dimethyloxan-4-yl)imidazol-4-yl]-4-methylpyrazole Chemical compound CC=1C(C=2N=CN(C=2)C2CC(C)(C)OCC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 NBBLBZXXTIHYGR-UHFFFAOYSA-N 0.000 claims 1
- UENAMXBDXIFSQC-UHFFFAOYSA-N 1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methyl-3-[1-(2-phenylpropan-2-yl)imidazol-4-yl]pyrazole Chemical compound CC=1C(C=2N=CN(C=2)C(C)(C)C=2C=CC=CC=2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 UENAMXBDXIFSQC-UHFFFAOYSA-N 0.000 claims 1
- GGFYTGKHBSYTHX-UHFFFAOYSA-N 1-(ethylamino)piperidine-4-carboxylic acid Chemical compound CCNN1CCC(C(O)=O)CC1 GGFYTGKHBSYTHX-UHFFFAOYSA-N 0.000 claims 1
- KIJMGJWYLBFNAV-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-(1-oxa-8-azaspiro[4.5]decan-8-yl)ethanone Chemical compound CC=1C(C(=O)CN2CCC3(OCCC3)CC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 KIJMGJWYLBFNAV-UHFFFAOYSA-N 0.000 claims 1
- CSIFSTSKGZGCOA-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-[4-(1-methylcyclopropanecarbonyl)piperazin-1-yl]ethanone Chemical compound CC=1C(C(=O)CN2CCN(CC2)C(=O)C2(C)CC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 CSIFSTSKGZGCOA-UHFFFAOYSA-N 0.000 claims 1
- ICQCQBMJTILLBT-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-7-yl]-3-(ethylamino)azetidine-3-carboxamide Chemical compound C1C(NCC)(C(N)=O)CN1C1=CC(C)=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 ICQCQBMJTILLBT-UHFFFAOYSA-N 0.000 claims 1
- KVAARXBFBPNASW-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)-6-methylpyrazolo[1,5-a]pyrimidin-7-yl]-3-(ethylamino)azetidine-3-carboxamide Chemical compound C1C(NCC)(C(N)=O)CN1C1=C(C)C=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 KVAARXBFBPNASW-UHFFFAOYSA-N 0.000 claims 1
- LRZAPFUQVRSILO-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-4-(4-fluorophenyl)piperidin-4-ol Chemical compound C1CC(O)(C=2C=CC(F)=CC=2)CCN1C(N1N=2)=CC=NC1=C(C=1C=CC(Cl)=CC=1)C=2C1=CC=CC=C1Cl LRZAPFUQVRSILO-UHFFFAOYSA-N 0.000 claims 1
- DLMCOYGNJWEDLT-UHFFFAOYSA-N 1-[2-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-hydroxyethyl]-4-(propan-2-ylamino)piperidine-4-carboxylic acid Chemical compound ClC1=C(C=CC=C1)N1N=C(C(=C1C1=CC=C(C=C1)Cl)C)C(CN1CCC(CC1)(C(=O)O)NC(C)C)O DLMCOYGNJWEDLT-UHFFFAOYSA-N 0.000 claims 1
- RSLSHEPQFIRFMG-UHFFFAOYSA-N 1-[2-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]morpholin-4-yl]-2-methylpropan-1-one Chemical compound C1N(C(=O)C(C)C)CCOC1C1=NN(C=2C(=CC=CC=2)Cl)C(C=2C=CC(Cl)=CC=2)=C1C RSLSHEPQFIRFMG-UHFFFAOYSA-N 0.000 claims 1
- KXERESOFXDHWKC-UHFFFAOYSA-N 1-[5-(4-chlorophenyl)-1-(2-fluorophenyl)-4-methylpyrazol-3-yl]-2-morpholin-4-ylethanone Chemical compound CC=1C(C(=O)CN2CCOCC2)=NN(C=2C(=CC=CC=2)F)C=1C1=CC=C(Cl)C=C1 KXERESOFXDHWKC-UHFFFAOYSA-N 0.000 claims 1
- NNASPPQLXBWTJY-UHFFFAOYSA-N 1-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-3-(propan-2-ylamino)azetidine-3-carboxylic acid Chemical compound C1C(NC(C)C)(C(O)=O)CN1C1=NC(C)=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 NNASPPQLXBWTJY-UHFFFAOYSA-N 0.000 claims 1
- RPDYFJQLDFRNNV-UHFFFAOYSA-N 1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-(4-fluorophenyl)piperidin-4-ol Chemical compound C1CC(O)(C=2C=CC(F)=CC=2)CCN1C(C=1N=2)=NC=NC=1N(C=1C=CC(Cl)=CC=1)C=2C1=CC=CC=C1Cl RPDYFJQLDFRNNV-UHFFFAOYSA-N 0.000 claims 1
- CGAZBXQGGFUKJS-UHFFFAOYSA-N 1-[9-(4-chlorophenyl)-8-(2-fluorophenyl)purin-6-yl]-4-(propan-2-ylamino)piperidine-4-carboxamide Chemical compound C1CC(NC(C)C)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)F)N2C1=CC=C(Cl)C=C1 CGAZBXQGGFUKJS-UHFFFAOYSA-N 0.000 claims 1
- KPQBABKRCICYCP-UHFFFAOYSA-N 5-(4-chlorophenyl)-3-(2-cyclohexyl-1H-imidazol-5-yl)-1-(2,4-dichlorophenyl)-4-methylpyrazole Chemical compound CC=1C(C=2NC(=NC=2)C2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 KPQBABKRCICYCP-UHFFFAOYSA-N 0.000 claims 1
- GPSKJJNUXWWNBR-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methyl-4-piperidin-1-ylpyrazolo[1,5-a][1,3,5]triazine Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1N1CCCCC1 GPSKJJNUXWWNBR-UHFFFAOYSA-N 0.000 claims 1
- WKMDUNKYIDESRF-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methyl-4-propan-2-yloxypyrazolo[1,5-a][1,3,5]triazine Chemical compound N=1N2C(OC(C)C)=NC(C)=NC2=C(C=2C=CC(Cl)=CC=2)C=1C1=CC=CC=C1Cl WKMDUNKYIDESRF-UHFFFAOYSA-N 0.000 claims 1
- HDPLEFUIDWOLLX-UHFFFAOYSA-N 9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-6-(4-pyridin-2-ylpiperazin-1-yl)purine Chemical compound C1=CC(Cl)=CC=C1N1C2=NC=NC(N3CCN(CC3)C=3N=CC=CC=3)=C2N=C1C1=CC=C(Cl)C=C1Cl HDPLEFUIDWOLLX-UHFFFAOYSA-N 0.000 claims 1
- VNOGOEOTNFURPS-UHFFFAOYSA-N 9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-6-(4-pyrimidin-2-ylpiperazin-1-yl)purine Chemical compound C1=CC(Cl)=CC=C1N1C2=NC=NC(N3CCN(CC3)C=3N=CC=CN=3)=C2N=C1C1=CC=C(Cl)C=C1Cl VNOGOEOTNFURPS-UHFFFAOYSA-N 0.000 claims 1
- WYFYQRWEWOFVOP-UHFFFAOYSA-N C1N(CC2(O)CC3=CC=CC=C3C2)CC2CCC1C2(OC)C1=CC=CC(N)=C1 Chemical compound C1N(CC2(O)CC3=CC=CC=C3C2)CC2CCC1C2(OC)C1=CC=CC(N)=C1 WYFYQRWEWOFVOP-UHFFFAOYSA-N 0.000 claims 1
- XZAIMUJFXZCSFU-UHFFFAOYSA-N ClC1=C(C=CC=C1)C1=NN2C(N=C(N=C2N2CC(C2)(C(=O)O)NC)C)=C1C1=CC=C(C=C1)Cl Chemical compound ClC1=C(C=CC=C1)C1=NN2C(N=C(N=C2N2CC(C2)(C(=O)O)NC)C)=C1C1=CC=C(C=C1)Cl XZAIMUJFXZCSFU-UHFFFAOYSA-N 0.000 claims 1
- 241001067945 Pyritis Species 0.000 claims 1
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 1
- PBWOAHPCJMFKNX-UHFFFAOYSA-N spiro[4.5]decan-4-one Chemical compound O=C1CCCC11CCCCC1.O=C1CCCC11CCCCC1 PBWOAHPCJMFKNX-UHFFFAOYSA-N 0.000 claims 1
- 201000007930 alcohol dependence Diseases 0.000 abstract description 4
- 230000000694 effects Effects 0.000 description 19
- 239000000556 agonist Substances 0.000 description 17
- 239000003446 ligand Substances 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 238000003556 assay Methods 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 229940044551 receptor antagonist Drugs 0.000 description 13
- 239000002464 receptor antagonist Substances 0.000 description 13
- 239000000872 buffer Substances 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 11
- 210000004027 cell Anatomy 0.000 description 10
- YNZFFALZMRAPHQ-SYYKKAFVSA-N 2-[(1r,2r,5r)-5-hydroxy-2-(3-hydroxypropyl)cyclohexyl]-5-(2-methyloctan-2-yl)phenol Chemical compound OC1=CC(C(C)(C)CCCCCC)=CC=C1[C@H]1[C@H](CCCO)CC[C@@H](O)C1 YNZFFALZMRAPHQ-SYYKKAFVSA-N 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- 239000012528 membrane Substances 0.000 description 8
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
- 102000003840 Opioid Receptors Human genes 0.000 description 7
- 108090000137 Opioid Receptors Proteins 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 125000003277 amino group Chemical group 0.000 description 6
- 229930003827 cannabinoid Natural products 0.000 description 6
- 239000003557 cannabinoid Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 101100244562 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) oprD gene Proteins 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 108700023159 delta Opioid Receptors Proteins 0.000 description 5
- 102000048124 delta Opioid Receptors Human genes 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 102000051367 mu Opioid Receptors Human genes 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- 108020001612 μ-opioid receptors Proteins 0.000 description 5
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 4
- 108050007331 Cannabinoid receptor Proteins 0.000 description 4
- 102100036214 Cannabinoid receptor 2 Human genes 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- PDLGRNGUKAFAAH-UHFFFAOYSA-N NS(=O)(=O)CC1=CC=CC(C23CC(CCC2)N(CC2(O)CC4=CC=CC=C4C2)CC3)=C1 Chemical compound NS(=O)(=O)CC1=CC=CC(C23CC(CCC2)N(CC2(O)CC4=CC=CC=C4C2)CC3)=C1 PDLGRNGUKAFAAH-UHFFFAOYSA-N 0.000 description 4
- 244000061176 Nicotiana tabacum Species 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000002299 complementary DNA Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000001990 intravenous administration Methods 0.000 description 4
- 102000048260 kappa Opioid Receptors Human genes 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 3
- FWCROVAYGPDGPT-UHFFFAOYSA-N CCC1(C2C1CN(CC1(CC3=CC=CC=C3C1)O)C2)C1=CC=CC(C(COC)S(N)(=O)=O)=C1 Chemical compound CCC1(C2C1CN(CC1(CC3=CC=CC=C3C1)O)C2)C1=CC=CC(C(COC)S(N)(=O)=O)=C1 FWCROVAYGPDGPT-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 206010029260 Neuroblastoma Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000012736 aqueous medium Substances 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000005013 brain tissue Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 238000002731 protein assay Methods 0.000 description 3
- 238000001525 receptor binding assay Methods 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 108020001588 κ-opioid receptors Proteins 0.000 description 3
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 2
- ZFMTXYPTAWEVCX-UHFFFAOYSA-N 3-[6-ethyl-3-[(2-hydroxy-3,4-dihydro-1h-naphthalen-2-yl)methyl]-3-azabicyclo[3.1.0]hexan-6-yl]benzamide Chemical compound C12CN(CC3(O)CC4=CC=CC=C4CC3)CC2C1(CC)C1=CC=CC(C(N)=O)=C1 ZFMTXYPTAWEVCX-UHFFFAOYSA-N 0.000 description 2
- QVYSNUZRPPOOSX-UHFFFAOYSA-N 8-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-1-propan-2-yl-1,3,8-triazaspiro[4.5]decan-4-one Chemical compound CC(C)N1CNC(=O)C11CCN(C=2N3N=C(C(=C3N=CC=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)CC1 QVYSNUZRPPOOSX-UHFFFAOYSA-N 0.000 description 2
- 238000000035 BCA protein assay Methods 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 229940124802 CB1 antagonist Drugs 0.000 description 2
- VTFDAGFCEXDLCK-UHFFFAOYSA-N COCC(C1=CC(C2(C3CN(CC4(CC5=CC=CC=C5C4)O)CC2CC3)OC)=CC=C1)S(N)(=O)=O Chemical compound COCC(C1=CC(C2(C3CN(CC4(CC5=CC=CC=C5C4)O)CC2CC3)OC)=CC=C1)S(N)(=O)=O VTFDAGFCEXDLCK-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 208000009132 Catalepsy Diseases 0.000 description 2
- 208000030814 Eating disease Diseases 0.000 description 2
- OHCQJHSOBUTRHG-KGGHGJDLSA-N FORSKOLIN Chemical compound O=C([C@@]12O)C[C@](C)(C=C)O[C@]1(C)[C@@H](OC(=O)C)[C@@H](O)[C@@H]1[C@]2(C)[C@@H](O)CCC1(C)C OHCQJHSOBUTRHG-KGGHGJDLSA-N 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- 208000032612 Glial tumor Diseases 0.000 description 2
- 206010018338 Glioma Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 2
- 239000008896 Opium Substances 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 206010047853 Waxy flexibility Diseases 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- 238000007792 addition Methods 0.000 description 2
- 206010001584 alcohol abuse Diseases 0.000 description 2
- 208000025746 alcohol use disease Diseases 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 229940025084 amphetamine Drugs 0.000 description 2
- 230000036592 analgesia Effects 0.000 description 2
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 2
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 2
- 239000012131 assay buffer Substances 0.000 description 2
- GFZWHAAOIVMHOI-UHFFFAOYSA-N azetidine-3-carboxylic acid Chemical compound OC(=O)C1CNC1 GFZWHAAOIVMHOI-UHFFFAOYSA-N 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960002069 diamorphine Drugs 0.000 description 2
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 2
- 235000014632 disordered eating Nutrition 0.000 description 2
- 230000009429 distress Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000011539 homogenization buffer Substances 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 230000002631 hypothermal effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 230000006742 locomotor activity Effects 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 229960001027 opium Drugs 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 2
- 229960003081 probenecid Drugs 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000004129 prosencephalon Anatomy 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- ZIKXMOOJNIZFNL-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-morpholin-4-ylethanol Chemical compound CC=1C(C(O)CN2CCOCC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 ZIKXMOOJNIZFNL-UHFFFAOYSA-N 0.000 description 1
- WFUGOPUQRHLVDJ-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-piperidin-1-ylethanol Chemical compound CC=1C(C(O)CN2CCCCC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 WFUGOPUQRHLVDJ-UHFFFAOYSA-N 0.000 description 1
- KEKFWCUOYHQBHF-UHFFFAOYSA-N 1-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-4-methylpyrazol-3-yl]-2-piperidin-1-ylethanone Chemical compound CC=1C(C(=O)CN2CCCCC2)=NN(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 KEKFWCUOYHQBHF-UHFFFAOYSA-N 0.000 description 1
- CZLBJIOKKYHVOG-UHFFFAOYSA-N 1-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-3-(ethylamino)azetidine-3-carboxamide Chemical compound C1C(NCC)(C(N)=O)CN1C1=CC=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 CZLBJIOKKYHVOG-UHFFFAOYSA-N 0.000 description 1
- IDIMMDMPSGJFFS-UHFFFAOYSA-N 1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)purin-6-yl]-4-pyrrolidin-1-ylpiperidine-4-carboxamide Chemical compound C1CC(C(=O)N)(N2CCCC2)CCN1C(C=1N=2)=NC=NC=1N(C=1C=CC(Cl)=CC=1)C=2C1=CC=CC=C1Cl IDIMMDMPSGJFFS-UHFFFAOYSA-N 0.000 description 1
- VZRIQXJDFHMUGK-UHFFFAOYSA-N 1-[9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)purin-6-yl]-4-(methylamino)piperidine-4-carboxamide Chemical compound C1CC(NC)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC(Cl)=CC=1)Cl)N2C1=CC=C(Cl)C=C1 VZRIQXJDFHMUGK-UHFFFAOYSA-N 0.000 description 1
- WNKABPFCNZDXLQ-UHFFFAOYSA-N 1-[9-(4-chlorophenyl)-8-(2-fluorophenyl)purin-6-yl]-4-(propylamino)piperidine-4-carboxamide Chemical compound C1CC(NCCC)(C(N)=O)CCN1C1=NC=NC2=C1N=C(C=1C(=CC=CC=1)F)N2C1=CC=C(Cl)C=C1 WNKABPFCNZDXLQ-UHFFFAOYSA-N 0.000 description 1
- HYLCYCOHOQLTGX-UHFFFAOYSA-N 1-phenylnonane-1-sulfonamide Chemical compound C(CCCCCCC)C(C1=CC=CC=C1)S(=O)(=O)N HYLCYCOHOQLTGX-UHFFFAOYSA-N 0.000 description 1
- FPEJMPNMDFPDIC-UHFFFAOYSA-N 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(1-cyclohexylazetidin-3-yl)oxypyrazolo[1,5-a]pyrimidine Chemical compound C1=CC(Cl)=CC=C1C1=C2N=CC=C(OC3CN(C3)C3CCCCC3)N2N=C1C1=CC=CC=C1Cl FPEJMPNMDFPDIC-UHFFFAOYSA-N 0.000 description 1
- RZXDBUXHRVUUCT-UHFFFAOYSA-N 2-(2-chlorophenyl)-3-(4-chlorophenyl)-7-(4-methylpiperazin-1-yl)pyrazolo[1,5-a]pyrimidine Chemical compound C1CN(C)CCN1C1=CC=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 RZXDBUXHRVUUCT-UHFFFAOYSA-N 0.000 description 1
- QPQIOJLYMHFFPR-UHFFFAOYSA-N 2-[2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidin-7-yl]-5-methyl-2,5,7-triazaspiro[3.4]octan-8-one Chemical compound CN1CNC(=O)C11CN(C=2N3N=C(C(=C3N=CC=2)C=2C=CC(Cl)=CC=2)C=2C(=CC=CC=2)Cl)C1 QPQIOJLYMHFFPR-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- IUPOIIZOBOILLK-UHFFFAOYSA-N 2-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]-6,6-dimethyl-2,5,7-triazaspiro[3.4]octan-8-one Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1N(C1)CC21NC(C)(C)NC2=O IUPOIIZOBOILLK-UHFFFAOYSA-N 0.000 description 1
- GQFWAZJYQMABLO-UHFFFAOYSA-N 3-amino-1-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]azetidine-3-carboxylic acid Chemical compound NC1(CN(C1)C1=NC(=NC=2N1N=C(C2C2=CC=C(C=C2)Cl)C2=C(C=CC=C2)Cl)C)C(=O)O GQFWAZJYQMABLO-UHFFFAOYSA-N 0.000 description 1
- GMGGPYJLMYPQCD-UHFFFAOYSA-N 4-benzyl-1-[7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazin-4-yl]piperidin-4-ol Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1N(CC1)CCC1(O)CC1=CC=CC=C1 GMGGPYJLMYPQCD-UHFFFAOYSA-N 0.000 description 1
- MZRPLPNMEBKVMW-UHFFFAOYSA-N 6-(1-benzylpyrrolidin-3-yl)oxy-9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)purine Chemical compound C1=CC(Cl)=CC=C1N1C2=NC=NC(OC3CN(CC=4C=CC=CC=4)CC3)=C2N=C1C1=CC=C(Cl)C=C1Cl MZRPLPNMEBKVMW-UHFFFAOYSA-N 0.000 description 1
- CYZRHEQQZJGZRH-UHFFFAOYSA-N 7-(1-benzylpyrrolidin-3-yl)oxy-2-(2-chlorophenyl)-3-(4-chlorophenyl)pyrazolo[1,5-a]pyrimidine Chemical compound C1=CC(Cl)=CC=C1C1=C2N=CC=C(OC3CN(CC=4C=CC=CC=4)CC3)N2N=C1C1=CC=CC=C1Cl CYZRHEQQZJGZRH-UHFFFAOYSA-N 0.000 description 1
- GTEQPYBNPXBWBT-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methyl-4-(4-methylpiperazin-1-yl)pyrazolo[1,5-a][1,3,5]triazine Chemical compound C1CN(C)CCN1C1=NC(C)=NC2=C(C=3C=CC(Cl)=CC=3)C(C=3C(=CC=CC=3)Cl)=NN12 GTEQPYBNPXBWBT-UHFFFAOYSA-N 0.000 description 1
- VUTLQAOPBPMEKF-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methyl-4-(4-pyrimidin-2-ylpiperazin-1-yl)pyrazolo[1,5-a][1,3,5]triazine Chemical compound N12N=C(C=3C(=CC=CC=3)Cl)C(C=3C=CC(Cl)=CC=3)=C2N=C(C)N=C1N(CC1)CCN1C1=NC=CC=N1 VUTLQAOPBPMEKF-UHFFFAOYSA-N 0.000 description 1
- OYIVUEVJQOAMGP-UHFFFAOYSA-N 7-(2-chlorophenyl)-8-(4-chlorophenyl)-2-methylpyrazolo[1,5-a][1,3,5]triazine Chemical compound C=12N=C(C)N=CN2N=C(C=2C(=CC=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 OYIVUEVJQOAMGP-UHFFFAOYSA-N 0.000 description 1
- PPNKCVSOPVJBPB-UHFFFAOYSA-N 9-(4-chlorophenyl)-8-(2,4-dichlorophenyl)-6-[(2-methylpropan-2-yl)oxy]purine Chemical compound N=1C=2C(OC(C)(C)C)=NC=NC=2N(C=2C=CC(Cl)=CC=2)C=1C1=CC=C(Cl)C=C1Cl PPNKCVSOPVJBPB-UHFFFAOYSA-N 0.000 description 1
- BUZAJRPLUGXRAB-UHFFFAOYSA-N AM-251 Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(I)C=C1 BUZAJRPLUGXRAB-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 1
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 description 1
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- SUZLHDUTVMZSEV-UHFFFAOYSA-N Deoxycoleonol Natural products C12C(=O)CC(C)(C=C)OC2(C)C(OC(=O)C)C(O)C2C1(C)C(O)CCC2(C)C SUZLHDUTVMZSEV-UHFFFAOYSA-N 0.000 description 1
- 206010012434 Dermatitis allergic Diseases 0.000 description 1
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010019196 Head injury Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000030990 Impulse-control disease Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 208000012488 Opiate Overdose Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000023146 Pre-existing disease Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 208000020339 Spinal injury Diseases 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 206010043903 Tobacco abuse Diseases 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 102000030621 adenylate cyclase Human genes 0.000 description 1
- 108060000200 adenylate cyclase Proteins 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- PXXJHWLDUBFPOL-UHFFFAOYSA-N benzamidine Chemical compound NC(=N)C1=CC=CC=C1 PXXJHWLDUBFPOL-UHFFFAOYSA-N 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 238000013262 cAMP assay Methods 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 229940065144 cannabinoids Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 239000012501 chromatography medium Substances 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- OHCQJHSOBUTRHG-UHFFFAOYSA-N colforsin Natural products OC12C(=O)CC(C)(C=C)OC1(C)C(OC(=O)C)C(O)C1C2(C)C(O)CCC1(C)C OHCQJHSOBUTRHG-UHFFFAOYSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 239000001177 diphosphate Substances 0.000 description 1
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
- 235000011180 diphosphates Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 229960004242 dronabinol Drugs 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000002650 habitual effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 210000004754 hybrid cell Anatomy 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000003068 molecular probe Substances 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 230000001962 neuropharmacologic effect Effects 0.000 description 1
- 238000010899 nucleation Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000001823 pruritic effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000004017 serum-free culture medium Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 201000006152 substance dependence Diseases 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 229940055764 triaz Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940072690 valium Drugs 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- 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
- A61K31/41—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
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- 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
- A61K31/41—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
- A61K31/4164—1,3-Diazoles
- A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
-
- 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
- A61K31/435—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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- 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
- A61K31/53—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Addiction (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US49680303P | 2003-08-21 | 2003-08-21 | |
| PCT/IB2004/002596 WO2005018645A1 (en) | 2003-08-21 | 2004-08-09 | A pharmaceutical composition for the prevention and treatment of addiction in a mammal |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA06002035A true MXPA06002035A (es) | 2006-05-17 |
Family
ID=34216038
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA06002035A MXPA06002035A (es) | 2003-08-21 | 2004-08-09 | Composicion farmaceutica para la prevencion y el tratamiento de adicciones en mamiferos. |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20050043327A1 (https=) |
| EP (1) | EP1658082A1 (https=) |
| JP (1) | JP2007502808A (https=) |
| BR (1) | BRPI0413693A (https=) |
| CA (1) | CA2536280A1 (https=) |
| MX (1) | MXPA06002035A (https=) |
| WO (1) | WO2005018645A1 (https=) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA006708B1 (ru) * | 2001-10-22 | 2006-02-24 | Пфайзер Продактс Инк. | Производные 3-азабицикло (3.1.0) гексана в качестве антагонистов опиоидного рецептора |
| EP1551402A4 (en) * | 2002-09-23 | 2009-05-27 | Verion Inc | PHARMACEUTICAL COMPOSITIONS NOT INDUCING ABUSE |
| US7129239B2 (en) * | 2002-10-28 | 2006-10-31 | Pfizer Inc. | Purine compounds and uses thereof |
| MXPA05007485A (es) | 2003-01-14 | 2006-01-30 | Arena Pharm Inc | Derivados de arilo y heteroarilo 1,2,3-trisubstituidos como moduladores del metabolismo y la profilaxis y tratamiento de trastornos relacionados con ello tales como diabetes e hiperglicemia. |
| RS20060018A (sr) * | 2003-07-14 | 2007-12-31 | Arena Pharmaceuticals Inc., | Derivati spojenih arila i heteroarila kao modulatori metabolizma u profilaksi i lečenju sa njima povezanih stanja |
| AR056876A1 (es) * | 2005-10-21 | 2007-10-31 | Tanabe Seiyaku Co | Compuestos de pirazolo[1-5-a]pirimidina, antagonistas de receptores canabinoides cb1, composiciones farmaceuticas que los contienen y usos en el tratamiento de enfermedades del sistema nervioso central, tales como trastornos psicoticos, neurologicos y similares |
| AR061793A1 (es) | 2006-07-05 | 2008-09-24 | Mitsubishi Tanabe Pharma Corp | Compuesto de pirazolo[1,5-a] pirimidina y composicion farmaceutica |
| WO2008039023A1 (en) * | 2006-09-29 | 2008-04-03 | Green Cross Corporation | Heteroaryl-pyrazole derivatives as cannabinoid cb1 receptor antagonists |
| WO2008044111A1 (en) * | 2006-10-13 | 2008-04-17 | Pfizer Products Inc. | Pharmaceutical formulation tablet |
| JP3145620U (ja) | 2008-07-30 | 2008-10-16 | 公二 平井 | 擬似嗜好物品 |
| US8252791B2 (en) * | 2008-08-13 | 2012-08-28 | Jenrin Discovery, Inc. | Purine compounds as cannabinoid receptor blockers |
| UA104010C2 (en) * | 2008-12-18 | 2013-12-25 | Эли Лилли Энд Компани | Purine compounds |
| GB0908394D0 (en) | 2009-05-15 | 2009-06-24 | Univ Leuven Kath | Novel viral replication inhibitors |
| GB0913636D0 (en) | 2009-08-05 | 2009-09-16 | Univ Leuven Kath | Novel viral replication inhibitors |
| EP3323818A1 (en) | 2010-09-22 | 2018-05-23 | Arena Pharmaceuticals, Inc. | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| KR20140003438A (ko) | 2010-11-15 | 2014-01-09 | 카톨리에케 유니버시테이트 루벤 | 항바이러스성 축합 헤테로사이클릭 화합물 |
| CN105764888B (zh) | 2013-11-20 | 2018-04-06 | 株式会社三和化学研究所 | 一种新的3‑氮杂双环[3.1.0]己烷衍生物以及其医药用途 |
| PL3242666T3 (pl) | 2015-01-06 | 2025-02-17 | Arena Pharmaceuticals, Inc. | Związek do zastosowania w leczeniu dolegliwości związanych z receptorem s1p1 |
| CN107428687B (zh) | 2015-05-20 | 2021-06-11 | 宇部兴产株式会社 | 一种3-氮杂双环[3.1.0]己烷衍生物的盐的晶体以及其医药应用 |
| CA3036382A1 (en) | 2016-12-21 | 2018-06-28 | Research Triangle Institute | Diaryl purine derivatives with improved bioavailability |
| JPWO2018159716A1 (ja) * | 2017-03-02 | 2019-12-26 | 株式会社三和化学研究所 | アルコール使用障害の治療薬 |
| SG11202007422QA (en) * | 2018-02-05 | 2020-09-29 | Alkermes Inc | Compounds for the treatment of pain |
| WO2023064228A1 (en) * | 2021-10-11 | 2023-04-20 | Anebulo Pharmaceuticals, Inc. | Method of treating addiction |
| AU2022362107A1 (en) | 2021-10-11 | 2024-05-02 | Anebulo Pharmaceuticals, Inc. | Crystalline forms of a cannabinoid receptor type 1 (cb1) modulator and methods of use and preparation thereof |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA006708B1 (ru) * | 2001-10-22 | 2006-02-24 | Пфайзер Продактс Инк. | Производные 3-азабицикло (3.1.0) гексана в качестве антагонистов опиоидного рецептора |
| US20040077650A1 (en) * | 2002-10-18 | 2004-04-22 | Pfizer Inc. | Cannabinoid receptor ligands and uses thereof |
| US7129239B2 (en) * | 2002-10-28 | 2006-10-31 | Pfizer Inc. | Purine compounds and uses thereof |
| US7247628B2 (en) * | 2002-12-12 | 2007-07-24 | Pfizer, Inc. | Cannabinoid receptor ligands and uses thereof |
| US7329658B2 (en) * | 2003-02-06 | 2008-02-12 | Pfizer Inc | Cannabinoid receptor ligands and uses thereof |
| US7176210B2 (en) * | 2003-02-10 | 2007-02-13 | Pfizer Inc. | Cannabinoid receptor ligands and uses thereof |
-
2004
- 2004-06-17 US US10/870,209 patent/US20050043327A1/en not_active Abandoned
- 2004-08-09 EP EP04744231A patent/EP1658082A1/en not_active Withdrawn
- 2004-08-09 JP JP2006523697A patent/JP2007502808A/ja active Pending
- 2004-08-09 MX MXPA06002035A patent/MXPA06002035A/es not_active Application Discontinuation
- 2004-08-09 BR BRPI0413693-4A patent/BRPI0413693A/pt not_active IP Right Cessation
- 2004-08-09 CA CA002536280A patent/CA2536280A1/en not_active Abandoned
- 2004-08-09 WO PCT/IB2004/002596 patent/WO2005018645A1/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0413693A (pt) | 2006-10-24 |
| US20050043327A1 (en) | 2005-02-24 |
| WO2005018645A1 (en) | 2005-03-03 |
| CA2536280A1 (en) | 2005-03-03 |
| JP2007502808A (ja) | 2007-02-15 |
| EP1658082A1 (en) | 2006-05-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| MXPA06002035A (es) | Composicion farmaceutica para la prevencion y el tratamiento de adicciones en mamiferos. | |
| AU2003304527B2 (en) | Uses of adenosine A2a receptor antagonists | |
| EP3010503B1 (en) | Novel bicyclic bromodomain inhibitors | |
| EP2155201B1 (en) | Quinoxaline derivatives as inhibitors of the tyrosine kinase activity of janus kinases | |
| CN101175488B (zh) | 治疗眼病的组合物和方法 | |
| CN105492439B (zh) | 作为溴结构域抑制剂的取代的双环化合物 | |
| AU2013203153B2 (en) | Treatment of cancer with TOR kinase inhibitors | |
| US20210322408A1 (en) | Methods of Treating Cancers, Immune and Autoimmune Diseases, and Inflammatory Diseases Based on BTK Occupancy and BTK Resynthesis Rate | |
| JP6604664B2 (ja) | 核内受容体に対して活性な化合物 | |
| US7985745B2 (en) | Method for pain treatment | |
| Mosberg et al. | Opioid peptidomimetics: leads for the design of bioavailable mixed efficacy μ opioid receptor (MOR) agonist/δ opioid receptor (DOR) antagonist ligands | |
| JP2010510224A (ja) | ケモカイン受容体拮抗薬としてのアミノピロリジン類 | |
| US20130296333A1 (en) | Hedgehog pathway modulators | |
| Megens et al. | Pharmacology of JNJ-42314415, a centrally active phosphodiesterase 10A (PDE10A) inhibitor: a comparison of PDE10A inhibitors with D2 receptor blockers as potential antipsychotic drugs | |
| JP2003515602A (ja) | 免疫抑制薬として有用な２，４−ジアミノピリミジン化合物 | |
| CA2772922C (en) | Thiazoles derivatives for treating or preventing anxiety disorders | |
| CN115611856B (zh) | 一种哌啶衍生物及其药物组合物、制备方法和用途 | |
| MXPA04012389A (es) | Composiciones anti-inflamatorias y metodos de uso. | |
| US20040224963A1 (en) | Pharmaceutical composition for the prevention and treatment of nicotine addiction in a mammal | |
| US20040224962A1 (en) | Pharmaceutical composition for the treatment of obesity or to facilitate or promote weight loss | |
| Mostallino et al. | The novel synthesized naltrexone-related MOR antagonist AT-99 counteracts dopamine releasing and behavioral depressant morphine-induced effects | |
| JP2005534665A (ja) | うつ病の治療のためのｐｄｅ−ｖ阻害物質及びｎｋ１拮抗薬の組合せ | |
| HK1171441A (en) | Compositions and methods for treatment of eye disorders | |
| HK1117083B (en) | Compositions and methods for treatment of eye disorders | |
| HK1173143A (en) | Therapeutic agent for anxiety disorders |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FA | Abandonment or withdrawal |