CA2445294A1 - Bisarylimidazolyl fatty acid amide hydrolase inhibitors - Google Patents
Bisarylimidazolyl fatty acid amide hydrolase inhibitors Download PDFInfo
- Publication number
- CA2445294A1 CA2445294A1 CA002445294A CA2445294A CA2445294A1 CA 2445294 A1 CA2445294 A1 CA 2445294A1 CA 002445294 A CA002445294 A CA 002445294A CA 2445294 A CA2445294 A CA 2445294A CA 2445294 A1 CA2445294 A1 CA 2445294A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- imidazol
- biphenyl
- carbamic acid
- phenyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003940 fatty acid amidase inhibitor Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 116
- 208000002193 Pain Diseases 0.000 claims abstract description 26
- 230000036407 pain Effects 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 4
- 208000010412 Glaucoma Diseases 0.000 claims abstract description 4
- 206010061218 Inflammation Diseases 0.000 claims abstract description 4
- 230000004054 inflammatory process Effects 0.000 claims abstract description 4
- 206010001513 AIDS related complex Diseases 0.000 claims abstract description 3
- 208000030814 Eating disease Diseases 0.000 claims abstract description 3
- 208000019454 Feeding and Eating disease Diseases 0.000 claims abstract description 3
- 206010020772 Hypertension Diseases 0.000 claims abstract description 3
- 206010028813 Nausea Diseases 0.000 claims abstract description 3
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 3
- 208000029808 Psychomotor disease Diseases 0.000 claims abstract description 3
- 235000014632 disordered eating Nutrition 0.000 claims abstract description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims abstract description 3
- 230000008693 nausea Effects 0.000 claims abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 49
- 150000002923 oximes Chemical class 0.000 claims description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 49
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 48
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 19
- -1 N-pyridyl Chemical group 0.000 claims description 17
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 208000004296 neuralgia Diseases 0.000 claims description 11
- 208000021722 neuropathic pain Diseases 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 10
- FROPPAHABGJTLA-UHFFFAOYSA-N (2-fluorophenyl) n-[6-[4,5-bis(4-fluorophenyl)-2-methylimidazol-1-yl]hexyl]carbamate Chemical compound C=1C=CC=C(F)C=1OC(=O)NCCCCCCN1C(C)=NC(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 FROPPAHABGJTLA-UHFFFAOYSA-N 0.000 claims description 7
- ZETIVVHRRQLWFW-UHFFFAOYSA-N 3-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC(C=O)=C1 ZETIVVHRRQLWFW-UHFFFAOYSA-N 0.000 claims description 7
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 claims description 7
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 claims description 7
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 7
- QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 claims description 7
- FTFMPYWXZDLNAM-UHFFFAOYSA-N (2,6-difluorophenyl) n-[6-[4,5-bis(4-fluorophenyl)-2-methylimidazol-1-yl]hexyl]carbamate Chemical compound FC=1C=CC=C(F)C=1OC(=O)NCCCCCCN1C(C)=NC(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 FTFMPYWXZDLNAM-UHFFFAOYSA-N 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 208000005298 acute pain Diseases 0.000 claims description 5
- 125000001153 fluoro group Chemical group F* 0.000 claims description 5
- 208000000094 Chronic Pain Diseases 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 15
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 3
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 102100027297 Fatty acid 2-hydroxylase Human genes 0.000 claims 1
- 101000937693 Homo sapiens Fatty acid 2-hydroxylase Proteins 0.000 claims 1
- 101000918494 Homo sapiens Fatty-acid amide hydrolase 1 Proteins 0.000 claims 1
- 108010046094 fatty-acid amide hydrolase Proteins 0.000 abstract description 16
- 102100029111 Fatty-acid amide hydrolase 1 Human genes 0.000 abstract description 15
- 230000002401 inhibitory effect Effects 0.000 abstract description 3
- 238000004949 mass spectrometry Methods 0.000 description 92
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 66
- 238000004128 high performance liquid chromatography Methods 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 31
- 239000000543 intermediate Substances 0.000 description 31
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 19
- 229910001868 water Inorganic materials 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- 239000000203 mixture Substances 0.000 description 15
- 239000007858 starting material Substances 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000012071 phase Substances 0.000 description 10
- 239000002621 endocannabinoid Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000001914 filtration Methods 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 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 7
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 7
- 229930003827 cannabinoid Natural products 0.000 description 7
- 239000003557 cannabinoid Substances 0.000 description 7
- 229910052681 coesite Inorganic materials 0.000 description 7
- 229910052906 cristobalite Inorganic materials 0.000 description 7
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 7
- 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 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- 229910052682 stishovite Inorganic materials 0.000 description 7
- 229910052905 tridymite Inorganic materials 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 239000012044 organic layer Substances 0.000 description 6
- 208000004454 Hyperalgesia Diseases 0.000 description 5
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- 239000003981 vehicle Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 102000018208 Cannabinoid Receptor Human genes 0.000 description 4
- 108050007331 Cannabinoid receptor Proteins 0.000 description 4
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 4
- 208000035154 Hyperesthesia Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 230000001154 acute effect Effects 0.000 description 4
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- 239000013058 crude material Substances 0.000 description 4
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- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 4
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- WBDSXISQIHMTGL-UHFFFAOYSA-N 2-methyl-4,5-diphenyl-1h-imidazole Chemical compound N1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 WBDSXISQIHMTGL-UHFFFAOYSA-N 0.000 description 3
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 3
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- JIZHOPJSMAYQIB-UHFFFAOYSA-N ethyl 2-methyl-7-(2-methyl-4,5-diphenylimidazol-1-yl)heptanoate Chemical compound CCOC(=O)C(C)CCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 JIZHOPJSMAYQIB-UHFFFAOYSA-N 0.000 description 1
- PQXMPJGYWQAWPW-UHFFFAOYSA-N ethyl 4-[3-(2-methyl-4,5-diphenylimidazol-1-yl)propoxy]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1OCCCN1C(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N=C1C PQXMPJGYWQAWPW-UHFFFAOYSA-N 0.000 description 1
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- ALGSAAUKYXPCAA-UHFFFAOYSA-N ethyl 7-(2-methyl-4,5-diphenylimidazol-1-yl)-2-propan-2-ylheptanoate Chemical compound CCOC(=O)C(C(C)C)CCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 ALGSAAUKYXPCAA-UHFFFAOYSA-N 0.000 description 1
- BZNKOJZOSNRABX-UHFFFAOYSA-N ethyl 7-[4,5-bis(4-fluorophenyl)-2-methylimidazol-1-yl]heptanoate Chemical compound CCOC(=O)CCCCCCN1C(C)=NC(C=2C=CC(F)=CC=2)=C1C1=CC=C(F)C=C1 BZNKOJZOSNRABX-UHFFFAOYSA-N 0.000 description 1
- OOBFNDGMAGSNKA-UHFFFAOYSA-N ethyl 7-bromoheptanoate Chemical compound CCOC(=O)CCCCCCBr OOBFNDGMAGSNKA-UHFFFAOYSA-N 0.000 description 1
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- 125000004494 ethyl ester group Chemical group 0.000 description 1
- WIHGSFJBAYXSNS-UHFFFAOYSA-N ethyl n-[4-[2-(2-methyl-4,5-diphenylimidazol-1-yl)ethoxy]phenyl]carbamate Chemical compound C1=CC(NC(=O)OCC)=CC=C1OCCN1C(C=2C=CC=CC=2)=C(C=2C=CC=CC=2)N=C1C WIHGSFJBAYXSNS-UHFFFAOYSA-N 0.000 description 1
- VZSXUVQCPYUMAW-UHFFFAOYSA-N ethyl n-[5-(2-methyl-4,5-diphenylimidazol-1-yl)pentyl]carbamate Chemical compound CCOC(=O)NCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 VZSXUVQCPYUMAW-UHFFFAOYSA-N 0.000 description 1
- GSVJWQNGCOHAMM-UHFFFAOYSA-N ethyl n-[6-(2-methyl-4,5-diphenylimidazol-1-yl)hexyl]carbamate Chemical compound CCOC(=O)NCCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 GSVJWQNGCOHAMM-UHFFFAOYSA-N 0.000 description 1
- VJHMAYPKFOEEMF-UHFFFAOYSA-N ethyl n-[7-(2-methyl-4,5-diphenylimidazol-1-yl)heptyl]carbamate Chemical compound CCOC(=O)NCCCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 VJHMAYPKFOEEMF-UHFFFAOYSA-N 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
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- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 1
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- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- CRYHRFPPPYGXLU-UHFFFAOYSA-N methyl n-[6-(2-methyl-4,5-diphenylimidazol-1-yl)hexyl]carbamate Chemical compound COC(=O)NCCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 CRYHRFPPPYGXLU-UHFFFAOYSA-N 0.000 description 1
- OFSWZLPOOKDXDP-UHFFFAOYSA-N methyl n-[7-(2-methyl-4,5-diphenylimidazol-1-yl)heptyl]carbamate Chemical compound COC(=O)NCCCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFSWZLPOOKDXDP-UHFFFAOYSA-N 0.000 description 1
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- 229960005489 paracetamol Drugs 0.000 description 1
- RNYLSGGTAIRFDR-UHFFFAOYSA-N phenyl n-[4-[2-(2-methyl-4,5-diphenylimidazol-1-yl)ethoxy]phenyl]carbamate Chemical compound C=1C=C(NC(=O)OC=2C=CC=CC=2)C=CC=1OCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 RNYLSGGTAIRFDR-UHFFFAOYSA-N 0.000 description 1
- VNIZFYRBACXAQP-UHFFFAOYSA-N phenyl n-[5-(2-methyl-4,5-diphenylimidazol-1-yl)pentyl]carbamate Chemical compound C=1C=CC=CC=1OC(=O)NCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 VNIZFYRBACXAQP-UHFFFAOYSA-N 0.000 description 1
- UWKODOYNVJUKMA-UHFFFAOYSA-N phenyl n-[7-(2-methyl-4,5-diphenylimidazol-1-yl)heptyl]carbamate Chemical compound C=1C=CC=CC=1OC(=O)NCCCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 UWKODOYNVJUKMA-UHFFFAOYSA-N 0.000 description 1
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- 229920001155 polypropylene Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
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- DWNVRDYRAQCINB-UHFFFAOYSA-N propan-2-yl n-[6-(2-methyl-4,5-diphenylimidazol-1-yl)hexyl]carbamate Chemical compound CC(C)OC(=O)NCCCCCCN1C(C)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 DWNVRDYRAQCINB-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
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- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
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- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000000392 somatic effect Effects 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
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- VLTNNAFYFSVVGS-UHFFFAOYSA-N tert-butyl n-[6-(2-ethyl-4,5-diphenylimidazol-1-yl)hexyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCCCCN1C(CC)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 VLTNNAFYFSVVGS-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
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- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 230000009278 visceral effect Effects 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/14—Prodigestives, e.g. acids, enzymes, appetite stimulants, antidyspeptics, tonics, antiflatulents
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- A—HUMAN NECESSITIES
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- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/00—Drugs for disorders of the nervous system
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- A61P25/12—Antiepileptics; Anticonvulsants for grand-mal
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
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- Neurosurgery (AREA)
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- Immunology (AREA)
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- Pain & Pain Management (AREA)
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- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Dermatology (AREA)
- Nutrition Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28682701P | 2001-04-27 | 2001-04-27 | |
| US60/286,827 | 2001-04-27 | ||
| PCT/US2002/012853 WO2002087569A1 (en) | 2001-04-27 | 2002-04-23 | Bisarylimidazolyl fatty acid amide hydrolase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2445294A1 true CA2445294A1 (en) | 2002-11-07 |
Family
ID=23100337
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002445294A Abandoned CA2445294A1 (en) | 2001-04-27 | 2002-04-23 | Bisarylimidazolyl fatty acid amide hydrolase inhibitors |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US6562846B2 (enExample) |
| EP (1) | EP1389107A4 (enExample) |
| JP (1) | JP2004532229A (enExample) |
| CA (1) | CA2445294A1 (enExample) |
| IL (1) | IL158300A0 (enExample) |
| MX (1) | MXPA03009850A (enExample) |
| WO (1) | WO2002087569A1 (enExample) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CA2442330A1 (en) * | 2001-03-29 | 2002-10-10 | Emory University | Acute pharmacologic augmentation of psychotherapy with enhancers of learning or conditioning |
| PL373970A1 (en) * | 2002-02-08 | 2005-09-19 | Bristol-Myers Squibb Company | (oxime)carbamoyl fatty acid amide hydrolase inhibitors |
| MXPA05003715A (es) | 2002-10-07 | 2005-09-30 | Univ California | Modulacion de ansiedad a traves de bloqueo de hidrolisis de anandamida. |
| FR2850377B1 (fr) * | 2003-01-23 | 2009-02-20 | Sanofi Synthelabo | Derives d'arylalkylcarbamates, leur preparation et leur application en therapeutique |
| FR2865205B1 (fr) | 2004-01-16 | 2006-02-24 | Sanofi Synthelabo | Derives de type aryloxyalkylcarbamates, leur preparation et leur application en therapeutique |
| FR2866885B1 (fr) | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives de piperidinylalkylcarbamates, leur prepation et leur application en therapeutique |
| FR2866884B1 (fr) * | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-piperidinecarboxylates, leur preparation et leur application en therapeutique |
| FR2866886B1 (fr) | 2004-02-26 | 2007-08-31 | Sanofi Synthelabo | Derives d'aryl-et d'heteroaryl-akylcarbamates, leur preparation et leur application en therapeutique |
| US20080103209A1 (en) * | 2004-04-23 | 2008-05-01 | The Regents Of The University Of California | Compounds And Methods For Treating Non-Inflammatory Pain Using Ppar Alpha Agonists |
| WO2006044617A1 (en) | 2004-10-15 | 2006-04-27 | The Scripps Research Institute | Oxadiazole ketone inhibitors of fatty acid amide hydrolase |
| US20060084659A1 (en) * | 2004-10-19 | 2006-04-20 | Michael Davis | Augmentation of psychotherapy with cannabinoid reuptake inhibitors |
| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| EP2937341B1 (en) | 2004-12-30 | 2017-07-05 | Janssen Pharmaceutica N.V. | 4-(benzyl)-piperazine-1-carboxylic acid phenylamide derivatives and related compounds as modulators of fatty acid amide hydrolase (faah) for the treatment of anxiety, pain and other conditions |
| CN101247853B (zh) * | 2005-04-13 | 2014-11-12 | 轴突公司 | 具有nos抑制活性的取代的吲哚化合物 |
| WO2006116773A2 (en) * | 2005-04-28 | 2006-11-02 | The Regents Of The University Of California | Methods, compositions, and compounds for modulation of monoacylglycerol lipase, pain, and stress-related disorders |
| US7915270B2 (en) | 2006-02-17 | 2011-03-29 | The Scripps Research Institute | Oxazole ketones as modulators of fatty acid amide hydrolase |
| KR100753240B1 (ko) | 2006-03-10 | 2007-08-30 | 한국지질자원연구원 | 합금 나노분말의 제조방법 |
| WO2009051666A1 (en) | 2007-10-12 | 2009-04-23 | The Government Of The U.S.A. As Represented By The Secretary Of The Dept. Of Health& Human Services | Therapeutic applications of fatty acid amide hydrolase inhibitors |
| EP2062578A1 (en) * | 2007-11-12 | 2009-05-27 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Novel use of chemical compounds for the treatment of AIDS |
| JP2011503120A (ja) | 2007-11-16 | 2011-01-27 | ニューラクソン，インコーポレーテッド | 内臓痛を治療するためのインドール化合物および方法 |
| CA2714743C (en) | 2008-02-19 | 2017-01-17 | Janssen Pharmaceutica N.V. | Aryl-hydroxyethylamino-pyrimidines and triazines as modulators of fatty acid amide hydrolase |
| US8207226B1 (en) | 2008-06-03 | 2012-06-26 | Alcon Research, Ltd. | Use of FAAH antagonists for treating dry eye and ocular pain |
| US8461159B2 (en) | 2008-11-25 | 2013-06-11 | Jannsen Pharmaceutica BV | Heteroaryl-substituted urea modulators of fatty acid amide hydrolase |
| WO2010068452A1 (en) | 2008-11-25 | 2010-06-17 | Janssen Pharmaceutica Nv | Heteroaryl-substituted urea modulators of fatty acid amide hydrolase |
| US20120083476A1 (en) | 2009-06-05 | 2012-04-05 | Janssen Pharmaceutica Nv | Heteroaryl-substituted spirocyclic diamine urea modulators of fatty acid amide hydrolase |
| WO2010141809A1 (en) | 2009-06-05 | 2010-12-09 | Janssen Pharmaceutica Nv | Aryl-substituted heterocyclic urea modulators of fatty acid amide hydrolase |
| US8906914B2 (en) | 2009-08-18 | 2014-12-09 | Janssen Pharmaceutica Nv | Ethylene diamine modulators of fatty acid hydrolase |
| US8735406B2 (en) | 2009-09-09 | 2014-05-27 | Dainippon Sumitomo Pharma Co., Ltd. | 8-oxodihydropurine derivative |
| US20120225097A1 (en) | 2009-11-12 | 2012-09-06 | Hawryluk Natalie A | Piperazinecarboxamide derivative useful as a modulator of fatty acid amide hydrolase (faah) |
| UA108233C2 (uk) | 2010-05-03 | 2015-04-10 | Модулятори активності гідролази амідів жирних кислот | |
| DE102012018115A1 (de) | 2012-09-13 | 2014-03-13 | Matthias Lehr | Aryl-N-(arylalkyl)carbamate als Hemmstoffe der Fatty Acid Amide Hydrolase |
| US9737562B2 (en) | 2012-12-11 | 2017-08-22 | The Mclean Hospital Corporation | Xenon and/or argon treatment as an adjunct to psychotherapy for psychiatric disorders |
| DE102013016573A1 (de) | 2013-10-04 | 2015-04-09 | Matthias Lehr | 1-Tetrazolylpropan-2-one als Inhibitoren von cytosolischer Phospholipase A2 und Fatty Acid Amide Hydrolase, insbesondere geeignet zur topischen Anwendung |
| US10414721B1 (en) | 2018-06-04 | 2019-09-17 | University Of Bern | Inhibitor of endocannabinoid cellular reuptake |
| CN111269083B (zh) * | 2020-02-24 | 2023-08-25 | 珠海市柏瑞医药科技有限公司 | 一种格尔伯特酸的合成方法 |
| US11999703B1 (en) | 2023-10-25 | 2024-06-04 | King Faisal University | 5-(2,4,5-tris(4-chlorophenyl)-1H-imidazol-1-yl)pentanoic acid as an antimicrobial compound |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8902441A (nl) * | 1988-10-03 | 1990-05-01 | Glaxo Group Ltd | Chemische verbinding. |
| PT626969E (pt) * | 1992-02-11 | 2000-11-30 | Smithkline Beecham Corp | Inibidores de co.a-it e de p.a.f. |
| US5700826A (en) * | 1995-06-07 | 1997-12-23 | Ontogen Corporation | 1,2,4,5-tetra substituted imidazoles as modulators of multi-drug resistance |
-
2002
- 2002-04-23 JP JP2002584915A patent/JP2004532229A/ja active Pending
- 2002-04-23 WO PCT/US2002/012853 patent/WO2002087569A1/en not_active Ceased
- 2002-04-23 MX MXPA03009850A patent/MXPA03009850A/es active IP Right Grant
- 2002-04-23 IL IL15830002A patent/IL158300A0/xx unknown
- 2002-04-23 US US10/128,480 patent/US6562846B2/en not_active Ceased
- 2002-04-23 EP EP02728952A patent/EP1389107A4/en not_active Withdrawn
- 2002-04-23 CA CA002445294A patent/CA2445294A1/en not_active Abandoned
-
2004
- 2004-07-01 US US10/883,195 patent/USRE39634E1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002087569A1 (en) | 2002-11-07 |
| IL158300A0 (en) | 2004-05-12 |
| EP1389107A1 (en) | 2004-02-18 |
| EP1389107A4 (en) | 2005-10-12 |
| MXPA03009850A (es) | 2004-02-12 |
| JP2004532229A (ja) | 2004-10-21 |
| US6562846B2 (en) | 2003-05-13 |
| US20020188009A1 (en) | 2002-12-12 |
| USRE39634E1 (en) | 2007-05-15 |
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