ZA200603124B - 1H-imidazole derivatives as cannabinoid receptor modulators - Google Patents
1H-imidazole derivatives as cannabinoid receptor modulators Download PDFInfo
- Publication number
- ZA200603124B ZA200603124B ZA200603124A ZA200603124A ZA200603124B ZA 200603124 B ZA200603124 B ZA 200603124B ZA 200603124 A ZA200603124 A ZA 200603124A ZA 200603124 A ZA200603124 A ZA 200603124A ZA 200603124 B ZA200603124 B ZA 200603124B
- Authority
- ZA
- South Africa
- Prior art keywords
- group
- disorders
- obesity
- composition
- substance
- Prior art date
Links
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title description 9
- 239000003520 cannabinoid receptor affecting agent Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 89
- 208000008589 Obesity Diseases 0.000 claims description 30
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 235000020824 obesity Nutrition 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- -1 methoxy, ethoxy, hydroxy, hydroxymethyl Chemical group 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 21
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 19
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 239000000126 substance Substances 0.000 claims description 18
- 238000003786 synthesis reaction Methods 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 230000015572 biosynthetic process Effects 0.000 claims description 13
- 208000035475 disorder Diseases 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000005842 heteroatom Chemical group 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 229930003827 cannabinoid Natural products 0.000 claims description 11
- 239000003557 cannabinoid Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 230000000366 juvenile effect Effects 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 9
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 229940002612 prodrug Drugs 0.000 claims description 7
- 239000000651 prodrug Substances 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 206010015037 epilepsy Diseases 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 230000005062 synaptic transmission Effects 0.000 claims description 5
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 4
- 208000012902 Nervous system disease Diseases 0.000 claims description 4
- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 208000027520 Somatoform disease Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000001246 bromo group Chemical group Br* 0.000 claims description 4
- 230000002490 cerebral effect Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 208000027753 pain disease Diseases 0.000 claims description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 208000027559 Appetite disease Diseases 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 206010008120 Cerebral ischaemia Diseases 0.000 claims description 3
- 206010008190 Cerebrovascular accident Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 206010012335 Dependence Diseases 0.000 claims description 3
- 206010012735 Diarrhoea Diseases 0.000 claims description 3
- 208000014094 Dystonic disease Diseases 0.000 claims description 3
- 206010014612 Encephalitis viral Diseases 0.000 claims description 3
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- 208000023105 Huntington disease Diseases 0.000 claims description 3
- SIKWOTFNWURSAY-UHFFFAOYSA-N Lipstatin Natural products CCCCCCC1C(CC(CC=CCC=CCCCCC)C(=O)OC(CC(C)C)NC=O)OC1=O SIKWOTFNWURSAY-UHFFFAOYSA-N 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 208000008238 Muscle Spasticity Diseases 0.000 claims description 3
- 206010028813 Nausea Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 3
- 208000018737 Parkinson disease Diseases 0.000 claims description 3
- 208000028017 Psychotic disease Diseases 0.000 claims description 3
- 208000034189 Sclerosis Diseases 0.000 claims description 3
- 206010040070 Septic Shock Diseases 0.000 claims description 3
- 208000007107 Stomach Ulcer Diseases 0.000 claims description 3
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 3
- 208000016620 Tourette disease Diseases 0.000 claims description 3
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 3
- 206010044565 Tremor Diseases 0.000 claims description 3
- 206010047700 Vomiting Diseases 0.000 claims description 3
- 230000036506 anxiety Effects 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 3
- 208000010877 cognitive disease Diseases 0.000 claims description 3
- 230000006735 deficit Effects 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 208000010118 dystonia Diseases 0.000 claims description 3
- 125000004404 heteroalkyl group Chemical group 0.000 claims description 3
- OQMAKWGYQLJJIA-CUOOPAIESA-N lipstatin Chemical compound CCCCCC[C@H]1[C@H](C[C@H](C\C=C/C\C=C/CCCCC)OC(=O)[C@H](CC(C)C)NC=O)OC1=O OQMAKWGYQLJJIA-CUOOPAIESA-N 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 230000008693 nausea Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 3
- 229960001243 orlistat Drugs 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 3
- 208000015891 sexual disease Diseases 0.000 claims description 3
- 208000020431 spinal cord injury Diseases 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 230000009529 traumatic brain injury Effects 0.000 claims description 3
- 125000004306 triazinyl group Chemical group 0.000 claims description 3
- 201000002498 viral encephalitis Diseases 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 2
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 208000030814 Eating disease Diseases 0.000 claims 6
- 235000014632 disordered eating Nutrition 0.000 claims 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 3
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 206010019196 Head injury Diseases 0.000 claims 2
- 208000004296 neuralgia Diseases 0.000 claims 2
- 208000021722 neuropathic pain Diseases 0.000 claims 2
- 102000005962 receptors Human genes 0.000 description 17
- 108020003175 receptors Proteins 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 8
- 108050007331 Cannabinoid receptor Proteins 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- 230000008485 antagonism Effects 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 239000011550 stock solution Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000699802 Cricetulus griseus Species 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 230000001270 agonistic effect Effects 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 229940114079 arachidonic acid Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- 150000002460 imidazoles Chemical class 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 210000001672 ovary Anatomy 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 244000141218 Alpinia officinarum Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- 229940127470 Lipase Inhibitors Drugs 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- HQVHOQAKMCMIIM-HXUWFJFHSA-N WIN 55212-2 Chemical compound C([C@@H]1COC=2C=CC=C3C(C(=O)C=4C5=CC=CC=C5C=CC=4)=C(N1C3=2)C)N1CCOCC1 HQVHOQAKMCMIIM-HXUWFJFHSA-N 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- FFBGKIOSTPTUEO-UHFFFAOYSA-N ethyl 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(pyrrolidin-1-ylmethyl)imidazole-4-carboxylate Chemical compound C=1C=C(Cl)C=CC=1N1C(CN2CCCC2)=C(C(=O)OCC)N=C1C1=CC=C(Cl)C=C1Cl FFBGKIOSTPTUEO-UHFFFAOYSA-N 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000005567 liquid scintillation counting Methods 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002287 radioligand Substances 0.000 description 2
- 239000000018 receptor agonist Substances 0.000 description 2
- 229940044601 receptor agonist Drugs 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- LHYUTHUWHYHROB-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-[[ethyl(methyl)amino]methyl]-n-piperidin-1-ylimidazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N1C(CN(C)CC)=C(C(=O)NN2CCCCC2)N=C1C1=CC=C(Cl)C=C1Cl LHYUTHUWHYHROB-UHFFFAOYSA-N 0.000 description 1
- SUKLGYYHKWBPAB-UHFFFAOYSA-N 1-(4-chlorophenyl)-n-cyclohexyl-2-(2,4-dichlorophenyl)-5-[(dimethylamino)methyl]imidazole-4-carboxamide Chemical compound C=1C=C(Cl)C=CC=1N1C(CN(C)C)=C(C(=O)NC2CCCCC2)N=C1C1=CC=C(Cl)C=C1Cl SUKLGYYHKWBPAB-UHFFFAOYSA-N 0.000 description 1
- YCVHHBIJYZETRR-UHFFFAOYSA-N 1-(4-chlorophenyl)-n-cyclohexyl-2-(2,4-dichlorophenyl)imidazole-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1N1C(C=2C(=CC(Cl)=CC=2)Cl)=NC(C(=O)NC2CCCCC2)=C1 YCVHHBIJYZETRR-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
- 206010002091 Anaesthesia Diseases 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
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- UNBMQQNYLCPCHS-UHFFFAOYSA-N Ebelactone B Natural products CCC(C)C(O)C(C)C(=O)C(C)C=C(C)CC(C)C1OC(=O)C1CC UNBMQQNYLCPCHS-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- LYISDADPVOHJBJ-UHFFFAOYSA-N Galangin 3-methyl ether Natural products O1C2=CC(O)=CC(O)=C2C(=O)C(OC)=C1C1=CC=CC=C1 LYISDADPVOHJBJ-UHFFFAOYSA-N 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 241000958270 Kitasatospora aburaviensis Species 0.000 description 1
- 239000004367 Lipase Substances 0.000 description 1
- 102000004882 Lipase Human genes 0.000 description 1
- 108090001060 Lipase Proteins 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- 241000946767 Streptomyces toxytricini Species 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000001774 alpinia officinarum Substances 0.000 description 1
- 238000007112 amidation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003579 anti-obesity Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 230000003375 cannabimimetic effect Effects 0.000 description 1
- 229940065144 cannabinoids Drugs 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 210000004978 chinese hamster ovary cell Anatomy 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 125000004188 dichlorophenyl group Chemical group 0.000 description 1
- UNBMQQNYLCPCHS-VYNDPHDASA-N ebelactone b Chemical compound CC[C@@H](C)[C@@H](O)[C@H](C)C(=O)[C@H](C)\C=C(/C)C[C@H](C)[C@@H]1OC(=O)[C@H]1CC UNBMQQNYLCPCHS-VYNDPHDASA-N 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000001435 haemodynamic effect Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229940040461 lipase Drugs 0.000 description 1
- 235000019421 lipase Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000541 pulsatile effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP03103867 | 2003-10-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200603124B true ZA200603124B (en) | 2007-09-26 |
Family
ID=34924117
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200603124A ZA200603124B (en) | 2003-10-20 | 2006-04-19 | 1H-imidazole derivatives as cannabinoid receptor modulators |
Country Status (7)
| Country | Link |
|---|---|
| CN (1) | CN100556894C (zh) |
| AR (1) | AR046182A1 (zh) |
| HK (1) | HK1091823A1 (zh) |
| SA (1) | SA04250339B1 (zh) |
| TW (1) | TW200524908A (zh) |
| UA (1) | UA82908C2 (zh) |
| ZA (1) | ZA200603124B (zh) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101302200B (zh) * | 2007-05-09 | 2011-04-20 | 上海医药工业研究院 | 制备n-哌啶子基-5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基吡唑-3-甲酰胺的方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI231757B (en) * | 2001-09-21 | 2005-05-01 | Solvay Pharm Bv | 1H-Imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity |
| WO2003063781A2 (en) * | 2002-01-29 | 2003-08-07 | Merck & Co., Inc. | Substituted imidazoles as cannabinoid receptor modulators |
-
2004
- 2004-10-15 TW TW93131338A patent/TW200524908A/zh unknown
- 2004-10-15 AR ARP040103749 patent/AR046182A1/es not_active Application Discontinuation
- 2004-10-17 SA SA4250339A patent/SA04250339B1/ar unknown
- 2004-10-19 UA UAA200605398A patent/UA82908C2/uk unknown
- 2004-10-19 CN CNB2004800243493A patent/CN100556894C/zh not_active Expired - Fee Related
-
2006
- 2006-04-19 ZA ZA200603124A patent/ZA200603124B/en unknown
- 2006-11-09 HK HK06112346.0A patent/HK1091823A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| TW200524908A (en) | 2005-08-01 |
| CN1842520A (zh) | 2006-10-04 |
| CN100556894C (zh) | 2009-11-04 |
| UA82908C2 (en) | 2008-05-26 |
| HK1091823A1 (en) | 2007-01-26 |
| SA04250339B1 (ar) | 2008-07-19 |
| AR046182A1 (es) | 2005-11-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP1713475B1 (en) | 1,3,5-trisubstituted 4,5-dihydro-1h-pyrazole derivatives having cb1-antagonistic activity | |
| US7109216B2 (en) | 1H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity | |
| AU2005214084B2 (en) | Imidazoline derivatives having CB1-antagonistic activity | |
| US7745476B2 (en) | 1,3,5-trisubstituted 4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity | |
| IL173436A (en) | 1h-imidazole derivatives, intermediates thereof, pharmaceutical compositions comprising them and their use as cannabinoid receptor modulators | |
| US7498348B2 (en) | 1 H-imidazole derivatives as cannabinoid receptor modulators | |
| US7524867B2 (en) | Tetrasubstituted imidazole derivatives as cannabinoid CB1 receptor modulators with a high CB1/CB2 receptor subtype selectivity | |
| EP1756066B1 (en) | Tetrasubstituted imidazole derivatives as cannabinoid cb1 receptor modulators with a high cb1/cb2 receptor subtype selectivity | |
| ZA200603124B (en) | 1H-imidazole derivatives as cannabinoid receptor modulators | |
| US7173044B2 (en) | Imidazoline derivatives having CB1-antagonistic activity | |
| TW200528442A (en) | 1,3,5-trisubstituted 4,5-dihydro-1h-pyrazole derivatives having CB1-antagonistic activity |