CA2597896A1 - 1h-imidazole derivatives as cannabinoid cb2 receptor modulators - Google Patents
1h-imidazole derivatives as cannabinoid cb2 receptor modulators Download PDFInfo
- Publication number
- CA2597896A1 CA2597896A1 CA002597896A CA2597896A CA2597896A1 CA 2597896 A1 CA2597896 A1 CA 2597896A1 CA 002597896 A CA002597896 A CA 002597896A CA 2597896 A CA2597896 A CA 2597896A CA 2597896 A1 CA2597896 A1 CA 2597896A1
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- Canada
- Prior art keywords
- group
- substituted
- alkyl group
- substituents
- hydroxy
- 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
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- 229930003827 cannabinoid Natural products 0.000 title claims abstract description 15
- 239000003557 cannabinoid Substances 0.000 title claims abstract description 15
- RAXXELZNTBOGNW-MQIHXRCWSA-N 1h-imidazole Chemical class C1=C[15NH]C=[15N]1 RAXXELZNTBOGNW-MQIHXRCWSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 201
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 29
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 26
- 102000009135 CB2 Cannabinoid Receptor Human genes 0.000 claims abstract description 23
- 108010073376 CB2 Cannabinoid Receptor Proteins 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 208000035475 disorder Diseases 0.000 claims abstract description 5
- 239000004480 active ingredient Substances 0.000 claims abstract 2
- -1 cyano, methylsulfonyl Chemical group 0.000 claims description 154
- 125000001424 substituent group Chemical group 0.000 claims description 142
- 125000001153 fluoro group Chemical group F* 0.000 claims description 99
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- 125000001072 heteroaryl group Chemical group 0.000 claims description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- 125000000623 heterocyclic group Chemical group 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 40
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
- 125000002950 monocyclic group Chemical group 0.000 claims description 37
- 125000002619 bicyclic group Chemical group 0.000 claims description 34
- 229920006395 saturated elastomer Polymers 0.000 claims description 32
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
- 125000005843 halogen group Chemical group 0.000 claims description 28
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 21
- 125000003277 amino group Chemical group 0.000 claims description 19
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 19
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 125000002837 carbocyclic group Chemical group 0.000 claims description 14
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 13
- 125000001246 bromo group Chemical group Br* 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 12
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 11
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 11
- 150000001204 N-oxides Chemical class 0.000 claims description 10
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 9
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 9
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 9
- 125000006413 ring segment Chemical group 0.000 claims description 8
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims description 7
- 125000003725 azepanyl group Chemical group 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 6
- 102000005962 receptors Human genes 0.000 claims description 6
- 108020003175 receptors Proteins 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 229910052736 halogen Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 230000005062 synaptic transmission Effects 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 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 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- 208000023105 Huntington disease Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 230000007815 allergy Effects 0.000 claims description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 208000026278 immune system disease Diseases 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 208000004296 neuralgia Diseases 0.000 claims description 2
- 208000021722 neuropathic pain Diseases 0.000 claims description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 230000036407 pain Effects 0.000 claims description 2
- 239000012453 solvate Substances 0.000 claims description 2
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 36
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 23
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 2
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 229910052717 sulfur Inorganic materials 0.000 claims 2
- 229910003870 O—Li Inorganic materials 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- RAXXELZNTBOGNW-UHFFFAOYSA-N 1H-imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 abstract description 8
- 150000002460 imidazoles Chemical class 0.000 abstract description 8
- 229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 107
- 238000002844 melting Methods 0.000 description 77
- 230000008018 melting Effects 0.000 description 77
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 51
- 239000000243 solution Substances 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
- 238000005160 1H NMR spectroscopy Methods 0.000 description 31
- 239000000203 mixture Substances 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 238000010168 coupling process Methods 0.000 description 17
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 15
- 230000008878 coupling Effects 0.000 description 15
- 238000005859 coupling reaction Methods 0.000 description 15
- 230000014759 maintenance of location Effects 0.000 description 15
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- SYJBFPCQIJQYNV-CIUDSAMLSA-N [(1s,4r,5s)-6,6-dimethyl-4-bicyclo[3.1.1]heptanyl]methanamine Chemical compound C1[C@@H]2C(C)(C)[C@H]1CC[C@H]2CN SYJBFPCQIJQYNV-CIUDSAMLSA-N 0.000 description 11
- 229940125904 compound 1 Drugs 0.000 description 11
- 229960004132 diethyl ether Drugs 0.000 description 11
- 201000010099 disease Diseases 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000000113 differential scanning calorimetry Methods 0.000 description 9
- 239000003208 petroleum Substances 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical group O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 5
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 5
- QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 229940125846 compound 25 Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000002883 imidazolyl group Chemical group 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 4
- KYWMCFOWDYFYLV-UHFFFAOYSA-N 1h-imidazole-2-carboxylic acid Chemical class OC(=O)C1=NC=CN1 KYWMCFOWDYFYLV-UHFFFAOYSA-N 0.000 description 4
- NMRZPULCVWCLQH-UHFFFAOYSA-N 2,5-dimethyl-1-phenylimidazole-4-carboxylic acid Chemical compound CC1=NC(C(O)=O)=C(C)N1C1=CC=CC=C1 NMRZPULCVWCLQH-UHFFFAOYSA-N 0.000 description 4
- YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 4
- 102000009132 CB1 Cannabinoid Receptor Human genes 0.000 description 4
- 108010073366 CB1 Cannabinoid Receptor Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 4
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- 239000003480 eluent Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- VLDUBDZWWNLZCU-UHFFFAOYSA-N ethyl 5-methyl-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1NC=NC=1C VLDUBDZWWNLZCU-UHFFFAOYSA-N 0.000 description 4
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- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 4
- OKXALXBKIMGQOO-UHFFFAOYSA-N methyl 2-acetamido-3-oxobutanoate Chemical compound COC(=O)C(C(C)=O)NC(C)=O OKXALXBKIMGQOO-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 238000003260 vortexing Methods 0.000 description 4
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- A—HUMAN NECESSITIES
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A61P37/00—Drugs for immunological or allergic disorders
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- 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
-
- 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
- C07D233/66—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US65309105P | 2005-02-16 | 2005-02-16 | |
| EP05101171.6 | 2005-02-16 | ||
| EP05101171 | 2005-02-16 | ||
| US60/653,091 | 2005-02-16 | ||
| PCT/EP2006/060009 WO2006087355A1 (en) | 2005-02-16 | 2006-02-16 | 1h-imidiazole derivatives as cannabinoid cb2 receptor modulators |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2597896A1 true CA2597896A1 (en) | 2006-08-24 |
Family
ID=36216936
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002597896A Abandoned CA2597896A1 (en) | 2005-02-16 | 2006-02-16 | 1h-imidazole derivatives as cannabinoid cb2 receptor modulators |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1874734A1 (ru) |
| JP (1) | JP2008530179A (ru) |
| AU (1) | AU2006215567B2 (ru) |
| BR (1) | BRPI0607439A2 (ru) |
| CA (1) | CA2597896A1 (ru) |
| IL (1) | IL184006A0 (ru) |
| NO (1) | NO20074710L (ru) |
| RU (1) | RU2410377C2 (ru) |
| WO (1) | WO2006087355A1 (ru) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8273738B2 (en) * | 2006-09-05 | 2012-09-25 | Kyowa Hakko Kirin Co., Ltd. | Imidazole derivatives |
| FR2908766B1 (fr) * | 2006-11-20 | 2009-01-09 | Sanofi Aventis Sa | Derives de pyrrole,leur preparation et leur utilisation en therapeutique. |
| US20110105567A1 (en) * | 2007-08-22 | 2011-05-05 | Allergan, Inc. | Pyrrole Compounds Having Sphingosine-1-Phosphate Receptor Agonist Or Antagonist Biological Activity |
| WO2009131957A2 (en) | 2008-04-21 | 2009-10-29 | Institute For Oneworld Health | Compounds, compositions and methods comprising oxadiazole derivatives |
| WO2010033626A1 (en) * | 2008-09-19 | 2010-03-25 | Institute For Oneworld Health | Compounds, compositions and methods comprising imidazole and triazole derivatives |
| BR112012018631A8 (pt) | 2010-01-28 | 2017-12-19 | President And Fellows Of Harvard Colege | composições e métodos para intensificação da atividade do proteassoma |
| JP6208122B2 (ja) | 2011-05-12 | 2017-10-04 | プロテオステイシス セラピューティクス，インコーポレイテッド | プロテオスタシス調節因子 |
| IN2014CN02346A (ru) * | 2011-09-28 | 2015-06-19 | Fujifilm Corp | |
| JPWO2013147160A1 (ja) * | 2012-03-29 | 2015-12-14 | 東レ株式会社 | 環状アミン誘導体及びその医薬用途 |
| WO2014116228A1 (en) | 2013-01-25 | 2014-07-31 | President And Fellows Of Harvard College | Usp14 inhibitors for treating or preventing viral infections |
| CA2914997C (en) * | 2013-06-12 | 2021-07-20 | Kaken Pharmaceutical Co., Ltd. | 4-alkynyl imidazole derivative and medicine comprising same as active ingredient |
| WO2015073528A1 (en) | 2013-11-12 | 2015-05-21 | Proteostasis Therapeutics, Inc. | Proteasome activity enhancing compounds |
| EP3312170A4 (en) | 2015-06-22 | 2018-12-12 | Sumitomo Dainippon Pharma Co., Ltd. | 1,4-di-substituted imidazole derivative |
| KR20180030545A (ko) * | 2015-06-22 | 2018-03-23 | 다이닛본 스미토모 세이야꾸 가부시끼가이샤 | 바이사이클릭 헤테로사이클릭 아미드 유도체 |
| WO2017146128A1 (ja) | 2016-02-26 | 2017-08-31 | 大日本住友製薬株式会社 | イミダゾリルアミド誘導体 |
| TW201803869A (zh) | 2016-04-27 | 2018-02-01 | 健生藥品公司 | 作為ＲＯＲγＴ調節劑之６－胺基吡啶－３－基噻唑 |
| CN112334450A (zh) * | 2018-06-18 | 2021-02-05 | 詹森药业有限公司 | 作为RORγt的调节剂的苯基和吡啶基取代的咪唑 |
| CN112292373A (zh) | 2018-06-18 | 2021-01-29 | 詹森药业有限公司 | 作为RORγt的调节剂的吡啶基吡唑类 |
| CA3103929A1 (en) | 2018-06-18 | 2019-12-26 | Janssen Pharmaceutica Nv | Phenyl substituted pyrazoles as modulators of roryt |
| US10975057B2 (en) | 2018-06-18 | 2021-04-13 | Janssen Pharmaceutica Nv | 6-aminopyridin-3-yl pyrazoles as modulators of RORgT |
| RU2725878C1 (ru) * | 2019-12-30 | 2020-07-07 | Федеральное государственное бюджетное учреждение науки Федеральный исследовательский центр "КОМИ научный центр Уральского отделения Российской академии наук" | Хиральные миртанилсульфонамиды |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2399791A1 (en) * | 2000-02-11 | 2001-08-16 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators in treating respiratory and non-respiratory diseases |
| CA2593156C (en) * | 2005-01-10 | 2015-05-05 | Exelixis, Inc. | Heterocyclic carboxamide compounds as steroid nuclear receptors ligands |
-
2006
- 2006-02-16 JP JP2007555612A patent/JP2008530179A/ja not_active Withdrawn
- 2006-02-16 BR BRPI0607439-1A patent/BRPI0607439A2/pt not_active IP Right Cessation
- 2006-02-16 AU AU2006215567A patent/AU2006215567B2/en not_active Expired - Fee Related
- 2006-02-16 EP EP06708303A patent/EP1874734A1/en not_active Withdrawn
- 2006-02-16 WO PCT/EP2006/060009 patent/WO2006087355A1/en active Application Filing
- 2006-02-16 CA CA002597896A patent/CA2597896A1/en not_active Abandoned
- 2006-02-16 RU RU2007134428/04A patent/RU2410377C2/ru not_active IP Right Cessation
-
2007
- 2007-06-18 IL IL184006A patent/IL184006A0/en unknown
- 2007-09-14 NO NO20074710A patent/NO20074710L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| JP2008530179A (ja) | 2008-08-07 |
| RU2007134428A (ru) | 2009-03-27 |
| NO20074710L (no) | 2007-09-14 |
| IL184006A0 (en) | 2007-10-31 |
| RU2410377C2 (ru) | 2011-01-27 |
| AU2006215567B2 (en) | 2011-05-12 |
| EP1874734A1 (en) | 2008-01-09 |
| BRPI0607439A2 (pt) | 2010-04-06 |
| WO2006087355A1 (en) | 2006-08-24 |
| AU2006215567A1 (en) | 2006-08-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130218 |