NO332143B1 - Imidazolderivater, fremgangsmate for fremstilling av slike, medikament inneholdende slike, slike forbindelser for anvendelse til behandling av sykdom samt anvendelse av slike for fremstilling av medikamenter for behandling av sykdom - Google Patents

Imidazolderivater, fremgangsmate for fremstilling av slike, medikament inneholdende slike, slike forbindelser for anvendelse til behandling av sykdom samt anvendelse av slike for fremstilling av medikamenter for behandling av sykdom Download PDF

Info

Publication number: NO332143B1
Authority: NO; Norway
Prior art keywords: formula; methyl; compound; chloro; ylethynyl
Prior art date: 2003-06-05

Application number

NO20055465A

Other languages

English (en)

Norwegian (no)

Other versions

NO20055465L (no

Inventor

Sabine Kolczewski

Bernd Buettelmann

Georg Jaeschke

Eric Vieira

Simona Maria Ceccarelli

Richard Hugh Phillip Porter

Original Assignee

Hoffmann La Roche

Priority date (The priority date 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 date listed.)

2003-06-05

Filing date

2005-11-18

Publication date

2012-07-02

2005-11-18 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2005-11-18 Publication of NO20055465L publication Critical patent/NO20055465L/no

2012-07-02 Publication of NO332143B1 publication Critical patent/NO332143B1/no

Links

239000003814 drug Substances 0.000 title claims abstract description 12
229940079593 drug Drugs 0.000 title claims abstract description 9
150000001875 compounds Chemical class 0.000 title claims description 173
238000000034 method Methods 0.000 title claims description 27
238000002360 preparation method Methods 0.000 title claims description 11
230000008569 process Effects 0.000 title claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 7
150000002460 imidazoles Chemical class 0.000 title abstract description 4
229940079865 intestinal antiinfectives imidazole derivative Drugs 0.000 title abstract description 4
201000010099 disease Diseases 0.000 title description 3
230000001684 chronic effect Effects 0.000 claims abstract description 14
230000001154 acute effect Effects 0.000 claims abstract description 10
208000012902 Nervous system disease Diseases 0.000 claims abstract description 8
208000025966 Neurological disease Diseases 0.000 claims abstract description 8
230000002265 prevention Effects 0.000 claims abstract description 8
150000003839 salts Chemical class 0.000 claims description 28
229910052736 halogen Inorganic materials 0.000 claims description 27
150000002367 halogens Chemical class 0.000 claims description 27
208000002193 Pain Diseases 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
208000019901 Anxiety disease Diseases 0.000 claims description 9
230000036506 anxiety Effects 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
208000000094 Chronic Pain Diseases 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
239000011737 fluorine Substances 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
125000003373 pyrazinyl group Chemical group 0.000 claims description 7
125000004076 pyridyl group Chemical group 0.000 claims description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
208000005298 acute pain Diseases 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
229910052739 hydrogen Inorganic materials 0.000 claims description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
HVPDVQJRUVMRKM-UHFFFAOYSA-N 2-chloro-4-[2-[1-(4-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(F)C=C1 HVPDVQJRUVMRKM-UHFFFAOYSA-N 0.000 claims description 4
206010046543 Urinary incontinence Diseases 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 4
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 4
WAQFQJHGDDKMQZ-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-4-(trifluoromethyl)pyrimidine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=NC=CC(C(F)(F)F)=N1 WAQFQJHGDDKMQZ-UHFFFAOYSA-N 0.000 claims description 3
VNTBEOOUSIHCDG-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]pyrazine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CN=CC=N1 VNTBEOOUSIHCDG-UHFFFAOYSA-N 0.000 claims description 3
SUXATGYKFSJNDF-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3,5-difluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC(F)=CC(F)=C1 SUXATGYKFSJNDF-UHFFFAOYSA-N 0.000 claims description 3
URCAGOXDMQYRHD-UHFFFAOYSA-N 2-chloro-4-[2-[2-methyl-1-[6-(trifluoromethyl)pyridin-2-yl]imidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=CC(C(F)(F)F)=N1 URCAGOXDMQYRHD-UHFFFAOYSA-N 0.000 claims description 3
UEELPGSDBDHZCZ-UHFFFAOYSA-N 2-fluoro-4-[2-[1-(4-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(F)N=CC=2)=CN1C1=CC=C(F)C=C1 UEELPGSDBDHZCZ-UHFFFAOYSA-N 0.000 claims description 3
239000000654 additive Substances 0.000 claims description 3
UPZWINBEAHDTLA-UHFFFAOYSA-N basimglurant Chemical compound CC=1N(C=2C=CC(F)=CC=2)C(C)=NC=1C#CC1=CC=NC(Cl)=C1 UPZWINBEAHDTLA-UHFFFAOYSA-N 0.000 claims description 3
ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-UHFFFAOYSA-N 0.000 claims description 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
UENGBOCGGKLVJJ-UHFFFAOYSA-N 2-chloro-1-(2,4-difluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CCl)C(F)=C1 UENGBOCGGKLVJJ-UHFFFAOYSA-N 0.000 claims description 2
DDDPMHSOPQMYHR-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3,5-difluorophenyl)-2,5-dimethylimidazol-4-yl]ethynyl]pyridine Chemical compound CC=1N(C=2C=C(F)C=C(F)C=2)C(C)=NC=1C#CC1=CC=NC(Cl)=C1 DDDPMHSOPQMYHR-UHFFFAOYSA-N 0.000 claims description 2
SEULXXCCZBUNKA-UHFFFAOYSA-N 2-chloro-4-[2-[1-(5-fluoropyridin-3-yl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CN=CC(F)=C1 SEULXXCCZBUNKA-UHFFFAOYSA-N 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
230000006806 disease prevention Effects 0.000 claims 1
150000002431 hydrogen Chemical class 0.000 claims 1
102000005962 receptors Human genes 0.000 abstract description 6
108020003175 receptors Proteins 0.000 abstract description 6
230000001404 mediated effect Effects 0.000 abstract description 4
239000002464 receptor antagonist Substances 0.000 abstract description 2
229940044551 receptor antagonist Drugs 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 78
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
239000011541 reaction mixture Substances 0.000 description 45
238000007429 general method Methods 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
239000000243 solution Substances 0.000 description 34
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 31
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
LNBMKQUSQRZVMB-UHFFFAOYSA-N 2-chloro-4-[2-(2-methyl-1h-imidazol-5-yl)ethynyl]pyridine Chemical compound N1C(C)=NC(C#CC=2C=C(Cl)N=CC=2)=C1 LNBMKQUSQRZVMB-UHFFFAOYSA-N 0.000 description 25
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
239000002904 solvent Substances 0.000 description 20
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
239000012043 crude product Substances 0.000 description 15
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
239000000203 mixture Substances 0.000 description 13
239000001301 oxygen Chemical group 0.000 description 13
229910052760 oxygen Inorganic materials 0.000 description 13
239000007787 solid Substances 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
239000000284 extract Substances 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 10
229910052943 magnesium sulfate Inorganic materials 0.000 description 10
235000019341 magnesium sulphate Nutrition 0.000 description 10
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 10
238000004587 chromatography analysis Methods 0.000 description 9
239000000047 product Substances 0.000 description 9
229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 8
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 8
238000003786 synthesis reaction Methods 0.000 description 8
108010010914 Metabotropic glutamate receptors Proteins 0.000 description 7
102000016193 Metabotropic glutamate receptors Human genes 0.000 description 7
229910052786 argon Inorganic materials 0.000 description 7
125000003118 aryl group Chemical group 0.000 description 7
238000002474 experimental method Methods 0.000 description 7
GUFPUCBBPLNIIN-UHFFFAOYSA-N 2-(2-chloropyridin-4-yl)ethynyl-trimethylsilane Chemical compound C[Si](C)(C)C#CC1=CC=NC(Cl)=C1 GUFPUCBBPLNIIN-UHFFFAOYSA-N 0.000 description 6
FCBLZWOMGVJISE-UHFFFAOYSA-N 4-ethynyl-1-(4-fluorophenyl)-2-methylimidazole Chemical compound CC1=NC(C#C)=CN1C1=CC=C(F)C=C1 FCBLZWOMGVJISE-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
239000000969 carrier Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
238000010992 reflux Methods 0.000 description 6
XMVISPJKNLGHIG-UHFFFAOYSA-N 4-[2-(2-methyl-1h-imidazol-5-yl)ethynyl]pyridine-2-carbonitrile Chemical compound N1C(C)=NC(C#CC=2C=C(N=CC=2)C#N)=C1 XMVISPJKNLGHIG-UHFFFAOYSA-N 0.000 description 5
SEDSLMWYUQACGR-UHFFFAOYSA-N 5-iodo-2-methyl-1h-imidazole Chemical compound CC1=NC=C(I)N1 SEDSLMWYUQACGR-UHFFFAOYSA-N 0.000 description 5
208000024827 Alzheimer disease Diseases 0.000 description 5
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
108010065028 Metabotropic Glutamate 5 Receptor Proteins 0.000 description 5
102100038357 Metabotropic glutamate receptor 5 Human genes 0.000 description 5
239000007903 gelatin capsule Substances 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
239000000825 pharmaceutical preparation Substances 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 5
PNWBKDCEDBHBDD-UHFFFAOYSA-N 1-(4-fluorophenyl)-2-methylimidazole-4-carbaldehyde Chemical compound CC1=NC(C=O)=CN1C1=CC=C(F)C=C1 PNWBKDCEDBHBDD-UHFFFAOYSA-N 0.000 description 4
SOGAKFHVIAQANZ-UHFFFAOYSA-N 1-(4-fluorophenyl)imidazole-4-carboxylic acid Chemical compound C1=NC(C(=O)O)=CN1C1=CC=C(F)C=C1 SOGAKFHVIAQANZ-UHFFFAOYSA-N 0.000 description 4
KJKIPRQNFDUULB-UHFFFAOYSA-N 2-chloro-4-iodopyridine Chemical compound ClC1=CC(I)=CC=N1 KJKIPRQNFDUULB-UHFFFAOYSA-N 0.000 description 4
NEWKHUASLBMWRE-UHFFFAOYSA-N 2-methyl-6-(phenylethynyl)pyridine Chemical compound CC1=CC=CC(C#CC=2C=CC=CC=2)=N1 NEWKHUASLBMWRE-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
208000027089 Parkinsonian disease Diseases 0.000 description 4
206010034010 Parkinsonism Diseases 0.000 description 4
206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
210000003169 central nervous system Anatomy 0.000 description 4
239000010949 copper Substances 0.000 description 4
229930195712 glutamate Natural products 0.000 description 4
NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
238000000746 purification Methods 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 4
SQHSJJGGWYIFCD-UHFFFAOYSA-N (e)-1-diazonio-1-dimethoxyphosphorylprop-1-en-2-olate Chemical compound COP(=O)(OC)C(\[N+]#N)=C(\C)[O-] SQHSJJGGWYIFCD-UHFFFAOYSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
208000023105 Huntington disease Diseases 0.000 description 3
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
208000019695 Migraine disease Diseases 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
LTYHTAAUPRMLFO-UHFFFAOYSA-N [1-(4-fluorophenyl)-2-methylimidazol-4-yl]methanol Chemical compound CC1=NC(CO)=CN1C1=CC=C(F)C=C1 LTYHTAAUPRMLFO-UHFFFAOYSA-N 0.000 description 3
239000002585 base Substances 0.000 description 3
230000027455 binding Effects 0.000 description 3
210000004556 brain Anatomy 0.000 description 3
239000011575 calcium Substances 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
ZVCREOKHHSQOHK-UHFFFAOYSA-N ethyl 1-(4-fluorophenyl)imidazole-4-carboxylate Chemical compound C1=NC(C(=O)OCC)=CN1C1=CC=C(F)C=C1 ZVCREOKHHSQOHK-UHFFFAOYSA-N 0.000 description 3
FTKASJMIPSSXBP-UHFFFAOYSA-N ethyl 2-nitroacetate Chemical compound CCOC(=O)C[N+]([O-])=O FTKASJMIPSSXBP-UHFFFAOYSA-N 0.000 description 3
230000006870 function Effects 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000012528 membrane Substances 0.000 description 3
-1 methoxy, ethoxy Chemical group 0.000 description 3
206010027599 migraine Diseases 0.000 description 3
208000004296 neuralgia Diseases 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000002287 radioligand Substances 0.000 description 3
201000000980 schizophrenia Diseases 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
FQLWHSKVVYKLNR-UHFFFAOYSA-N tert-butyl-[2-[1-(4-fluorophenyl)-2-methylimidazol-4-yl]propan-2-yloxy]silane Chemical compound C(C)(C)(C)[SiH2]OC(C=1N=C(N(C1)C1=CC=C(C=C1)F)C)(C)C FQLWHSKVVYKLNR-UHFFFAOYSA-N 0.000 description 3
SPHALRNWZRAPCT-UHFFFAOYSA-N tert-butyl-[2-[1-(4-fluorophenyl)imidazol-4-yl]propan-2-yloxy]silane Chemical compound C(C)(C)(C)[SiH2]OC(C=1N=CN(C1)C1=CC=C(C=C1)F)(C)C SPHALRNWZRAPCT-UHFFFAOYSA-N 0.000 description 3
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 3
RMGYQBHKEWWTOY-UHFFFAOYSA-N (3,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(F)=C1 RMGYQBHKEWWTOY-UHFFFAOYSA-N 0.000 description 2
IMEPMEDDZNANPY-UHFFFAOYSA-N (4-chloropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CN=CC=C1Cl IMEPMEDDZNANPY-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
QEPWGTIIQGAICJ-UHFFFAOYSA-N 2-(4-iodo-2-methylimidazol-1-yl)-6-methyl-4-(trifluoromethyl)pyridine Chemical compound CC1=NC(I)=CN1C1=CC(C(F)(F)F)=CC(C)=N1 QEPWGTIIQGAICJ-UHFFFAOYSA-N 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
FZRBTBCCMVNZBD-UHFFFAOYSA-N 2-chloro-4-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=CC=NC(Cl)=N1 FZRBTBCCMVNZBD-UHFFFAOYSA-N 0.000 description 2
YTZDAJHYOPWBSR-UHFFFAOYSA-N 2-chloro-4-[2-[2-methyl-1-(5-methylpyridin-2-yl)imidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(C)C=N1 YTZDAJHYOPWBSR-UHFFFAOYSA-N 0.000 description 2
GAAYXNBGNMXZHS-UHFFFAOYSA-N 4-(2-trimethylsilylethynyl)pyridine-2-carbonitrile Chemical compound C[Si](C)(C)C#CC1=CC=NC(C#N)=C1 GAAYXNBGNMXZHS-UHFFFAOYSA-N 0.000 description 2
OVEGSCLVOXWLIV-UHFFFAOYSA-N 4-chloro-2-(trifluoromethyl)pyrimidine Chemical compound FC(F)(F)C1=NC=CC(Cl)=N1 OVEGSCLVOXWLIV-UHFFFAOYSA-N 0.000 description 2
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 2
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 2
BECHBBMVXWYRDE-UHFFFAOYSA-N 5-iodo-2-propan-2-yl-1h-imidazole Chemical compound CC(C)C1=NC=C(I)N1 BECHBBMVXWYRDE-UHFFFAOYSA-N 0.000 description 2
208000030507 AIDS Diseases 0.000 description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
206010012289 Dementia Diseases 0.000 description 2
208000012661 Dyskinesia Diseases 0.000 description 2
206010019196 Head injury Diseases 0.000 description 2
208000010496 Heart Arrest Diseases 0.000 description 2
208000013016 Hypoglycemia Diseases 0.000 description 2
206010021143 Hypoxia Diseases 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
208000007101 Muscle Cramp Diseases 0.000 description 2
206010057852 Nicotine dependence Diseases 0.000 description 2
208000026251 Opioid-Related disease Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
208000028017 Psychotic disease Diseases 0.000 description 2
208000017442 Retinal disease Diseases 0.000 description 2
206010038923 Retinopathy Diseases 0.000 description 2
206010039966 Senile dementia Diseases 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
208000005392 Spasm Diseases 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
208000025569 Tobacco Use disease Diseases 0.000 description 2
206010047700 Vomiting Diseases 0.000 description 2
FABWXZZOQFOZHF-UHFFFAOYSA-N [1-(4-fluorophenyl)imidazol-4-yl]methanol Chemical compound C1=NC(CO)=CN1C1=CC=C(F)C=C1 FABWXZZOQFOZHF-UHFFFAOYSA-N 0.000 description 2
239000013543 active substance Substances 0.000 description 2
239000000556 agonist Substances 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
238000006254 arylation reaction Methods 0.000 description 2
230000036770 blood supply Effects 0.000 description 2
UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 2
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
230000003925 brain function Effects 0.000 description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
229910052794 bromium Inorganic materials 0.000 description 2
239000000872 buffer Substances 0.000 description 2
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
229910000024 caesium carbonate Inorganic materials 0.000 description 2
125000002837 carbocyclic group Chemical group 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
239000003610 charcoal Substances 0.000 description 2
208000010877 cognitive disease Diseases 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
230000036461 convulsion Effects 0.000 description 2
229910052802 copper Inorganic materials 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
230000003412 degenerative effect Effects 0.000 description 2
YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 2
239000008298 dragée Substances 0.000 description 2
230000000694 effects Effects 0.000 description 2
206010015037 epilepsy Diseases 0.000 description 2
231100000040 eye damage Toxicity 0.000 description 2
239000003925 fat Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000001530 fumaric acid Substances 0.000 description 2
239000003825 glutamate receptor antagonist Substances 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000007954 hypoxia Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000003446 ligand Substances 0.000 description 2
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
239000000463 material Substances 0.000 description 2
238000005259 measurement Methods 0.000 description 2
238000010907 mechanical stirring Methods 0.000 description 2
206010027175 memory impairment Diseases 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
201000006417 multiple sclerosis Diseases 0.000 description 2
210000000653 nervous system Anatomy 0.000 description 2
208000021722 neuropathic pain Diseases 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
201000005040 opiate dependence Diseases 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
230000035935 pregnancy Effects 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000011343 solid material Substances 0.000 description 2
208000020431 spinal cord injury Diseases 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
238000012360 testing method Methods 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
230000000472 traumatic effect Effects 0.000 description 2
235000015112 vegetable and seed oil Nutrition 0.000 description 2
239000008158 vegetable oil Substances 0.000 description 2
230000008673 vomiting Effects 0.000 description 2
239000001993 wax Substances 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
QQLRSCZSKQTFGY-UHFFFAOYSA-N (2,4-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C=C1F QQLRSCZSKQTFGY-UHFFFAOYSA-N 0.000 description 1
JKIGHOARKAIPJI-UHFFFAOYSA-N (3,4-dichlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C(Cl)=C1 JKIGHOARKAIPJI-UHFFFAOYSA-N 0.000 description 1
QWQBQRYFWNIDOC-UHFFFAOYSA-N (3,5-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC(F)=CC(F)=C1 QWQBQRYFWNIDOC-UHFFFAOYSA-N 0.000 description 1
WJDZZXIDQYKVDG-UHFFFAOYSA-N (3-chloro-4-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(F)C(Cl)=C1 WJDZZXIDQYKVDG-UHFFFAOYSA-N 0.000 description 1
XDBHWPLGGBLUHH-UHFFFAOYSA-N (3-cyanophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(C#N)=C1 XDBHWPLGGBLUHH-UHFFFAOYSA-N 0.000 description 1
WPVBHUUZDFUIJA-UHFFFAOYSA-N (3-fluoro-4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1F WPVBHUUZDFUIJA-UHFFFAOYSA-N 0.000 description 1
KNXQDJCZSVHEIW-UHFFFAOYSA-N (3-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1 KNXQDJCZSVHEIW-UHFFFAOYSA-N 0.000 description 1
NLLGFYPSWCMUIV-UHFFFAOYSA-N (3-methoxyphenyl)boronic acid Chemical compound COC1=CC=CC(B(O)O)=C1 NLLGFYPSWCMUIV-UHFFFAOYSA-N 0.000 description 1
CAYQIZIAYYNFCS-UHFFFAOYSA-N (4-chlorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1 CAYQIZIAYYNFCS-UHFFFAOYSA-N 0.000 description 1
JCIJCHSRVPSOML-UHFFFAOYSA-N (4-fluoro-3-methylphenyl)boronic acid Chemical compound CC1=CC(B(O)O)=CC=C1F JCIJCHSRVPSOML-UHFFFAOYSA-N 0.000 description 1
VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
BIWQNIMLAISTBV-UHFFFAOYSA-N (4-methylphenyl)boronic acid Chemical compound CC1=CC=C(B(O)O)C=C1 BIWQNIMLAISTBV-UHFFFAOYSA-N 0.000 description 1
WPAPNCXMYWRTTL-UHFFFAOYSA-N (6-chloropyridin-3-yl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)N=C1 WPAPNCXMYWRTTL-UHFFFAOYSA-N 0.000 description 1
VWVIKOQAMUIBPB-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-chloro-4-[2-[1-(4-fluorophenyl)-2-propan-2-ylimidazol-4-yl]ethynyl]pyridine Chemical compound OC(=O)\C=C\C(O)=O.CC(C)C1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(F)C=C1 VWVIKOQAMUIBPB-WLHGVMLRSA-N 0.000 description 1
OJQOSIAJFHGHIZ-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-iodo-2-propan-2-ylimidazole Chemical compound CC(C)C1=NC(I)=CN1C1=CC=C(F)C=C1 OJQOSIAJFHGHIZ-UHFFFAOYSA-N 0.000 description 1
LTPVMWIPLWJIJG-UHFFFAOYSA-N 2-[1-(6-chloropyridin-3-yl)-2-methylimidazol-4-yl]ethynyl-trimethylsilane Chemical compound CC1=NC(C#C[Si](C)(C)C)=CN1C1=CC=C(Cl)N=C1 LTPVMWIPLWJIJG-UHFFFAOYSA-N 0.000 description 1
YMYKMIOPVXMQAB-UHFFFAOYSA-N 2-[1-(6-cyclopropylpyridin-3-yl)-2-methylimidazol-4-yl]ethynyl-trimethylsilane Chemical compound CC1=NC(C#C[Si](C)(C)C)=CN1C1=CC=C(C2CC2)N=C1 YMYKMIOPVXMQAB-UHFFFAOYSA-N 0.000 description 1
ZZCVLIWIIQDBIL-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-4-methoxypyrimidine Chemical compound COC1=CC=NC(N2C(=NC(=C2)C#CC=2C=C(Cl)N=CC=2)C)=N1 ZZCVLIWIIQDBIL-UHFFFAOYSA-N 0.000 description 1
HEHVYORCRMHLOK-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-4-methylpyrimidine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=NC=CC(C)=N1 HEHVYORCRMHLOK-UHFFFAOYSA-N 0.000 description 1
RAISWYFIWGNLGN-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-5-fluoropyrimidine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=NC=C(F)C=N1 RAISWYFIWGNLGN-UHFFFAOYSA-N 0.000 description 1
UUDYTQQGFFKWSU-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-6-methyl-4-(trifluoromethyl)pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC(C(F)(F)F)=CC(C)=N1 UUDYTQQGFFKWSU-UHFFFAOYSA-N 0.000 description 1
COAJDNYWAOGKGV-UHFFFAOYSA-N 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]pyrimidine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=NC=CC=N1 COAJDNYWAOGKGV-UHFFFAOYSA-N 0.000 description 1
VOEQLPFXAQLNSJ-UHFFFAOYSA-N 2-chloro-4-[2-(2-methyl-1H-imidazol-5-yl)ethynyl]pyridine 2-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-4-(trifluoromethyl)pyrimidine Chemical compound ClC1=NC=CC(=C1)C#CC=1N=C(NC1)C.ClC1=NC=CC(=C1)C#CC=1N=C(N(C1)C1=NC=CC(=N1)C(F)(F)F)C VOEQLPFXAQLNSJ-UHFFFAOYSA-N 0.000 description 1
SDRAFRVZLASHCU-UHFFFAOYSA-N 2-chloro-4-[2-[1-(2,4-difluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(F)C=C1F SDRAFRVZLASHCU-UHFFFAOYSA-N 0.000 description 1
AISZTMSTDMCYGD-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3,4-dichlorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(Cl)C(Cl)=C1 AISZTMSTDMCYGD-UHFFFAOYSA-N 0.000 description 1
SQPGUYGAYFBXLA-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3,4-difluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(F)C(F)=C1 SQPGUYGAYFBXLA-UHFFFAOYSA-N 0.000 description 1
WKANHNSWSOMISO-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3-chloro-4-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(F)C(Cl)=C1 WKANHNSWSOMISO-UHFFFAOYSA-N 0.000 description 1
NWRKWFGXUPJQEM-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3-fluoro-4-methylphenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(C)C(F)=C1 NWRKWFGXUPJQEM-UHFFFAOYSA-N 0.000 description 1
DBIHPTUQXRWMIV-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=CC(F)=C1 DBIHPTUQXRWMIV-UHFFFAOYSA-N 0.000 description 1
ACDLCLSBUKTPCA-UHFFFAOYSA-N 2-chloro-4-[2-[1-(3-methoxyphenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound COC1=CC=CC(N2C(=NC(=C2)C#CC=2C=C(Cl)N=CC=2)C)=C1 ACDLCLSBUKTPCA-UHFFFAOYSA-N 0.000 description 1
TZSQKSDQFFUKKC-UHFFFAOYSA-N 2-chloro-4-[2-[1-(4-chlorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine 2-chloro-4-[2-(2-methyl-1H-imidazol-5-yl)ethynyl]pyridine Chemical compound ClC1=NC=CC(=C1)C#CC=1N=C(NC1)C.ClC1=NC=CC(=C1)C#CC=1N=C(N(C1)C1=CC=C(C=C1)Cl)C TZSQKSDQFFUKKC-UHFFFAOYSA-N 0.000 description 1
KWQOUOLNDOTCMA-UHFFFAOYSA-N 2-chloro-4-[2-[1-(4-fluoro-3-methylphenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(F)C(C)=C1 KWQOUOLNDOTCMA-UHFFFAOYSA-N 0.000 description 1
HPIXPSVDVOKVOT-UHFFFAOYSA-N 2-chloro-4-[2-[1-(4-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine 2-chloro-4-iodopyridine Chemical compound ClC1=NC=CC(=C1)I.ClC1=NC=CC(=C1)C#CC=1N=C(N(C1)C1=CC=C(C=C1)F)C HPIXPSVDVOKVOT-UHFFFAOYSA-N 0.000 description 1
VDLRPBLWORNTJU-UHFFFAOYSA-N 2-chloro-4-[2-[1-(4-methoxyphenyl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound C1=CC(OC)=CC=C1N1C(C)=NC(C#CC=2C=C(Cl)N=CC=2)=C1 VDLRPBLWORNTJU-UHFFFAOYSA-N 0.000 description 1
MZHGPULYDKUHJN-UHFFFAOYSA-N 2-chloro-4-[2-[1-(6-chloropyridin-3-yl)-2-propan-2-ylimidazol-4-yl]ethynyl]pyridine Chemical compound CC(C)C1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(Cl)N=C1 MZHGPULYDKUHJN-UHFFFAOYSA-N 0.000 description 1
DJKXIZOPODBQSP-UHFFFAOYSA-N 2-chloro-4-[2-[1-(6-cyclopropylpyridin-3-yl)-2-methylimidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C(C=N1)=CC=C1C1CC1 DJKXIZOPODBQSP-UHFFFAOYSA-N 0.000 description 1
RMIXLTWEGHVDSR-UHFFFAOYSA-N 2-chloro-4-[2-[2-methyl-1-(4-methylphenyl)imidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=C(C)C=C1 RMIXLTWEGHVDSR-UHFFFAOYSA-N 0.000 description 1
FCLUDVNGQZXBCS-UHFFFAOYSA-N 2-chloro-4-[2-[2-methyl-1-(6-methylpyridin-2-yl)imidazol-4-yl]ethynyl]pyridine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=CC(C)=N1 FCLUDVNGQZXBCS-UHFFFAOYSA-N 0.000 description 1
BDXYNMVQMBCTDB-UHFFFAOYSA-N 2-chloro-4-methoxypyrimidine Chemical compound COC1=CC=NC(Cl)=N1 BDXYNMVQMBCTDB-UHFFFAOYSA-N 0.000 description 1
BHAKRVSCGILCEW-UHFFFAOYSA-N 2-chloro-4-methylpyrimidine Chemical compound CC1=CC=NC(Cl)=N1 BHAKRVSCGILCEW-UHFFFAOYSA-N 0.000 description 1
UBSJWIRWCJSODT-UHFFFAOYSA-N 2-chloro-5-(4-iodo-2-methylimidazol-1-yl)pyridine Chemical compound CC1=NC(I)=CN1C1=CC=C(Cl)N=C1 UBSJWIRWCJSODT-UHFFFAOYSA-N 0.000 description 1
HSTZWCJKIABDFE-UHFFFAOYSA-N 2-chloro-5-(4-iodo-2-propan-2-ylimidazol-1-yl)pyridine Chemical compound CC(C)C1=NC(I)=CN1C1=CC=C(Cl)N=C1 HSTZWCJKIABDFE-UHFFFAOYSA-N 0.000 description 1
AGYUQBNABXVWMS-UHFFFAOYSA-N 2-chloro-5-fluoropyrimidine Chemical compound FC1=CN=C(Cl)N=C1 AGYUQBNABXVWMS-UHFFFAOYSA-N 0.000 description 1
SXLBWNSGCIEART-UHFFFAOYSA-N 2-chloro-6-methyl-4-(trifluoromethyl)pyridine Chemical compound CC1=CC(C(F)(F)F)=CC(Cl)=N1 SXLBWNSGCIEART-UHFFFAOYSA-N 0.000 description 1
GELVZYOEQVJIRR-UHFFFAOYSA-N 2-chloropyrazine Chemical compound ClC1=CN=CC=N1 GELVZYOEQVJIRR-UHFFFAOYSA-N 0.000 description 1
UNCQVRBWJWWJBF-UHFFFAOYSA-N 2-chloropyrimidine Chemical compound ClC1=NC=CC=N1 UNCQVRBWJWWJBF-UHFFFAOYSA-N 0.000 description 1
ADPRIAVYIGHFSO-UHFFFAOYSA-N 2-fluoro-4-iodopyridine Chemical compound FC1=CC(I)=CC=N1 ADPRIAVYIGHFSO-UHFFFAOYSA-N 0.000 description 1
IZOIOCQPMHHDHN-UHFFFAOYSA-N 2-fluoro-6-(trifluoromethyl)pyridine Chemical compound FC1=CC=CC(C(F)(F)F)=N1 IZOIOCQPMHHDHN-UHFFFAOYSA-N 0.000 description 1
UDMNVTJFUISBFD-UHFFFAOYSA-N 2-fluoro-6-methylpyridine Chemical compound CC1=CC=CC(F)=N1 UDMNVTJFUISBFD-UHFFFAOYSA-N 0.000 description 1
WRXAZPPGFLETFR-UHFFFAOYSA-N 3,5-difluoropyridine Chemical compound FC1=CN=CC(F)=C1 WRXAZPPGFLETFR-UHFFFAOYSA-N 0.000 description 1
IEVPBJJUHYCBIO-UHFFFAOYSA-N 3-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]benzonitrile Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=CC(C#N)=C1 IEVPBJJUHYCBIO-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
HRSHTGZDQSKMTC-UHFFFAOYSA-N 4-[2-[1-(3,4-difluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine-2-carbonitrile Chemical compound CC1=NC(C#CC=2C=C(N=CC=2)C#N)=CN1C1=CC=C(F)C(F)=C1 HRSHTGZDQSKMTC-UHFFFAOYSA-N 0.000 description 1
UGEGKQSGYKYNSV-UHFFFAOYSA-N 4-[2-[1-(3,5-difluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine-2-carbonitrile Chemical compound CC1=NC(C#CC=2C=C(N=CC=2)C#N)=CN1C1=CC(F)=CC(F)=C1 UGEGKQSGYKYNSV-UHFFFAOYSA-N 0.000 description 1
BUFRBQOWKOARSF-UHFFFAOYSA-N 4-[2-[1-(4-fluorophenyl)-2-methylimidazol-4-yl]ethynyl]pyridine-2-carbonitrile Chemical compound CC1=NC(C#CC=2C=C(N=CC=2)C#N)=CN1C1=CC=C(F)C=C1 BUFRBQOWKOARSF-UHFFFAOYSA-N 0.000 description 1
HPQXKUHRANOKCK-UHFFFAOYSA-N 4-[2-[1-(6-chloropyridin-3-yl)-2-methylimidazol-4-yl]ethynyl]pyridine-2-carbonitrile Chemical compound CC1=NC(C#CC=2C=C(N=CC=2)C#N)=CN1C1=CC=C(Cl)N=C1 HPQXKUHRANOKCK-UHFFFAOYSA-N 0.000 description 1
KWJCJWRBBDCDSF-UHFFFAOYSA-N 4-[4-[2-(2-chloropyridin-4-yl)ethynyl]-2-methylimidazol-1-yl]-2-(trifluoromethyl)pyrimidine Chemical compound CC1=NC(C#CC=2C=C(Cl)N=CC=2)=CN1C1=CC=NC(C(F)(F)F)=N1 KWJCJWRBBDCDSF-UHFFFAOYSA-N 0.000 description 1
CZXDCTUSFIKLIJ-UHFFFAOYSA-N 4-bromopyridine-2-carbonitrile Chemical compound BrC1=CC=NC(C#N)=C1 CZXDCTUSFIKLIJ-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
206010004663 Biliary colic Diseases 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
208000001387 Causalgia Diseases 0.000 description 1
208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
206010012335 Dependence Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
201000005569 Gout Diseases 0.000 description 1
208000004454 Hyperalgesia Diseases 0.000 description 1
208000035154 Hyperesthesia Diseases 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
206010065390 Inflammatory pain Diseases 0.000 description 1
102000004310 Ion Channels Human genes 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
102100036837 Metabotropic glutamate receptor 2 Human genes 0.000 description 1
102100038352 Metabotropic glutamate receptor 3 Human genes 0.000 description 1
102100038354 Metabotropic glutamate receptor 4 Human genes 0.000 description 1
102100038300 Metabotropic glutamate receptor 6 Human genes 0.000 description 1
102100038294 Metabotropic glutamate receptor 7 Human genes 0.000 description 1
102100037636 Metabotropic glutamate receptor 8 Human genes 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
208000018737 Parkinson disease Diseases 0.000 description 1
208000004550 Postoperative Pain Diseases 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
206010038419 Renal colic Diseases 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
238000003477 Sonogashira cross-coupling reaction Methods 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
206010047115 Vasculitis Diseases 0.000 description 1
QOMNQGZXFYNBNG-UHFFFAOYSA-N acetyloxymethyl 2-[2-[2-[5-[3-(acetyloxymethoxy)-2,7-difluoro-6-oxoxanthen-9-yl]-2-[bis[2-(acetyloxymethoxy)-2-oxoethyl]amino]phenoxy]ethoxy]-n-[2-(acetyloxymethoxy)-2-oxoethyl]-4-methylanilino]acetate Chemical compound CC(=O)OCOC(=O)CN(CC(=O)OCOC(C)=O)C1=CC=C(C)C=C1OCCOC1=CC(C2=C3C=C(F)C(=O)C=C3OC3=CC(OCOC(C)=O)=C(F)C=C32)=CC=C1N(CC(=O)OCOC(C)=O)CC(=O)OCOC(C)=O QOMNQGZXFYNBNG-UHFFFAOYSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
230000000996 additive effect Effects 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
239000012148 binding buffer Substances 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
235000011148 calcium chloride Nutrition 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000002775 capsule Substances 0.000 description 1
210000000170 cell membrane Anatomy 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
BYIHXUHOYZDNTR-UHFFFAOYSA-M chlorozinc(1+);cyclopropane Chemical compound [Cl-].[Zn+2].C1C[CH-]1 BYIHXUHOYZDNTR-UHFFFAOYSA-M 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
238000012937 correction Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
230000002964 excitative effect Effects 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
238000003384 imaging method Methods 0.000 description 1
230000003993 interaction Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
229960004903 invert sugar Drugs 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
230000001057 ionotropic effect Effects 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
230000000873 masking effect Effects 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
230000005906 menstruation Effects 0.000 description 1
108010038421 metabotropic glutamate receptor 2 Proteins 0.000 description 1
108010038445 metabotropic glutamate receptor 3 Proteins 0.000 description 1
108010038422 metabotropic glutamate receptor 4 Proteins 0.000 description 1
108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
108010038448 metabotropic glutamate receptor 8 Proteins 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000002569 neuron Anatomy 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
208000020016 psychiatric disease Diseases 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
210000002265 sensory receptor cell Anatomy 0.000 description 1
230000019491 signal transduction Effects 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
229910052717 sulfur Chemical group 0.000 description 1
239000011593 sulfur Chemical group 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
POWXEZFICWTNCC-UHFFFAOYSA-N tert-butyl-[2-[1-(4-fluorophenyl)imidazol-4-yl]propan-2-yloxy]silane [1-(4-fluorophenyl)imidazol-4-yl]methanol Chemical compound C1=NC(CO)=CN1C1=CC=C(F)C=C1.C1=NC(C(C)(C)O[SiH2]C(C)(C)C)=CN1C1=CC=C(F)C=C1 POWXEZFICWTNCC-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000007306 turnover Effects 0.000 description 1
239000011534 wash buffer Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000002023 wood Substances 0.000 description 1

Classifications

- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- C07D401/14—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 three or more hetero rings

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Pain & Pain Management (AREA)
Psychiatry (AREA)
Psychology (AREA)
Addiction (AREA)
Hospice & Palliative Care (AREA)
Anesthesiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

NO20055465A 2003-06-05 2005-11-18 Imidazolderivater, fremgangsmate for fremstilling av slike, medikament inneholdende slike, slike forbindelser for anvendelse til behandling av sykdom samt anvendelse av slike for fremstilling av medikamenter for behandling av sykdom NO332143B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP03012200		2003-06-05
PCT/EP2004/005881 WO2004108701A1 (en)	2003-06-05	2004-06-01	Imidazole derivatives as glutmate receptor antagonists

Publications (2)

Publication Number	Publication Date
NO20055465L NO20055465L (no)	2005-11-18
NO332143B1 true NO332143B1 (no)	2012-07-02

Family

ID=33483899

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20055465A NO332143B1 (no)	2003-06-05	2005-11-18	Imidazolderivater, fremgangsmate for fremstilling av slike, medikament inneholdende slike, slike forbindelser for anvendelse til behandling av sykdom samt anvendelse av slike for fremstilling av medikamenter for behandling av sykdom

Country Status (38)

Country	Link
US (3)	US7332510B2 (es)
EP (1)	EP1636206B1 (es)
JP (1)	JP4401384B2 (es)
KR (1)	KR100778948B1 (es)
CN (1)	CN100408572C (es)
AR (1)	AR044478A1 (es)
AT (1)	ATE377008T1 (es)
AU (1)	AU2004245208B2 (es)
BR (1)	BRPI0411095B8 (es)
CA (1)	CA2527315C (es)
CL (1)	CL2004001347A1 (es)
CR (1)	CR8094A (es)
CY (1)	CY1107856T1 (es)
DE (1)	DE602004009796T2 (es)
DK (1)	DK1636206T3 (es)
EA (1)	EA010577B1 (es)
EC (1)	ECSP056202A (es)
ES (1)	ES2294504T3 (es)
GT (1)	GT200400117A (es)
HN (1)	HN2004000208A (es)
HR (1)	HRP20070529T3 (es)
IL (1)	IL171930A (es)
MA (1)	MA27881A1 (es)
MX (1)	MXPA05013149A (es)
MY (2)	MY137272A (es)
NO (1)	NO332143B1 (es)
NZ (1)	NZ543637A (es)
PA (1)	PA8604101A1 (es)
PE (1)	PE20050162A1 (es)
PL (1)	PL1636206T3 (es)
PT (1)	PT1636206E (es)
RS (1)	RS53183B (es)
SI (1)	SI1636206T1 (es)
TN (2)	TNSN05309A1 (es)
TW (1)	TWI338007B (es)
UA (1)	UA80888C2 (es)
WO (1)	WO2004108701A1 (es)
ZA (2)	ZA200509807B (es)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
UA80888C2 (en) *	2003-06-05	2007-11-12	Hoffmann La Roche	Imidazole derivatives as glutmate receptor antagonists
US7531529B2 (en)	2003-06-05	2009-05-12	Roche Palo Alto Llc	Imidazole derivatives
US7452909B2 (en)	2003-09-04	2008-11-18	Hoffman-La Roche Inc.	Imidazole derivatives
KR100907108B1 (ko) *	2004-06-01	2009-07-09	에프. 호프만-라 로슈 아게	Ｍｇｌｕ5 수용체 길항제로서 피리딘-4-일-에틴일-이미다졸및 피라졸
GB0514296D0 (en) *	2005-07-12	2005-08-17	Novartis Ag	Organic compounds
DE102006011574A1 (de)	2006-03-10	2007-10-31	Grünenthal GmbH	Substituierte Imidazo[2,1-b]thiazol-Verbindungen und ihre Verwendung zur Herstellung von Arzneimitteln
ES2577391T3 (es)	2006-12-21	2016-07-14	F. Hoffmann-La Roche Ag	Polimorfos de un antagonista del receptor mglur5
US8334287B2 (en) *	2009-07-17	2012-12-18	Hoffmann-La Roche Inc.	Imidazoles
US20120040008A1 (en) *	2010-08-11	2012-02-16	Ashish Chatterji	Pharmaceutical compositions of metabotropic glutamate 5 receptor (mglu5) antagonists
US20120039999A1 (en) *	2010-08-11	2012-02-16	Ashish Chatterji	Pharmaceutical compositions of metabotropic glutamate 5 receptor (mglu5) antagonists
WO2012127393A1 (en)	2011-03-18	2012-09-27	Novartis Ag	COMBINATIONS OF ALPHA 7 NICOTINIC ACETYLCHOLINE RECEPTOR ACTIVATORS AND mGluR5 ANTAGONISTS FOR USE IN DOPAMINE INDUCED DYSKINESIA IN PARKINSON'S DISEASE
MX2015002823A (es) *	2012-10-18	2015-05-15	Hoffmann La Roche	Derivados de etilinilo como moduladores de la actividad del receptor de glutamato metabotropico 5 (mglur5).
ES2599553T3 (es) *	2012-10-18	2017-02-02	F. Hoffmann-La Roche Ag	Derivados de etinilo como moduladores de la actividad del receptor mGluR5
CN108883104A (zh) *	2016-03-30	2018-11-23	森泰克希斯公司	用于在治疗成熟脑损伤中使用的mGluR5的负性变构调节剂
JP2023504177A (ja) *	2019-12-02	2023-02-01	エフ．ホフマン－ラロシュアーゲー	アルキニル－（ヘテロアリール）－カルボキサミドｈｃｎ１阻害剤
KR20250116184A (ko)	2020-06-05	2025-07-31	노에마 파르마 아게	결절성 경화증 복합증의 치료 방법
WO2022023519A1 (en) *	2020-07-30	2022-02-03	Noema Pharma Ag	Methods of treatment of trigeminal neuralgia
KR20250140536A (ko)	2023-02-02	2025-09-25	노에마 파르마 아게	드라베 증후군의 치료 방법

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4508560A (en)	1981-11-11	1985-04-02	Ciba Geigy Corporation	Certain pyridylacetylene compounds, compositions containing same and herbicidal methods of use
TW544448B (en) *	1997-07-11	2003-08-01	Novartis Ag	Pyridine derivatives
EP1214303A1 (en) *	1999-08-31	2002-06-19	Merck & Co., Inc.	Heterocyclic compounds and methods of use thereof
DK1303495T3 (da) *	2000-07-24	2010-09-20	Krenitsky Pharmaceuticals Inc	Substituerede 5-alkylnylpyrimidiner med neurotrofisk aktivitet
MXPA03004862A (es) *	2000-12-04	2005-02-14	Hoffmann La Roche	Derivados de feniletenilo o feniletinilo como antagonistas del receptor de glutamato.
CA2470612A1 (en) *	2001-12-19	2003-07-03	Merck & Co., Inc.	Heteroaryl substituted imidazole modulators of metabotropic glutamate receptor-5
WO2004038374A2 (en) *	2002-10-24	2004-05-06	Merck & Co., Inc.	Alkyne derivatives as tracers for metabotropic glutamate receptor binding
TWI292318B (en) *	2003-03-10	2008-01-11	Hoffmann La Roche	Imidazol-4-yl-ethynyl-pyridine derivatives
UA80888C2 (en) *	2003-06-05	2007-11-12	Hoffmann La Roche	Imidazole derivatives as glutmate receptor antagonists
US7091222B2 (en) *	2003-07-03	2006-08-15	Hoffmann-La Roche Inc.	Imidazole derivatives

2004
- 2004-01-06 UA UAA200512695A patent/UA80888C2/uk unknown
- 2004-06-01 BR BRPI0411095A patent/BRPI0411095B8/pt not_active IP Right Cessation
- 2004-06-01 AU AU2004245208A patent/AU2004245208B2/en not_active Expired
- 2004-06-01 NZ NZ543637A patent/NZ543637A/en not_active IP Right Cessation
- 2004-06-01 EP EP04739484A patent/EP1636206B1/en not_active Expired - Lifetime
- 2004-06-01 PT PT04739484T patent/PT1636206E/pt unknown
- 2004-06-01 PL PL04739484T patent/PL1636206T3/pl unknown
- 2004-06-01 MX MXPA05013149A patent/MXPA05013149A/es active IP Right Grant
- 2004-06-01 DK DK04739484T patent/DK1636206T3/da active
- 2004-06-01 HR HR20070529T patent/HRP20070529T3/xx unknown
- 2004-06-01 RS YU20050892A patent/RS53183B/sr unknown
- 2004-06-01 WO PCT/EP2004/005881 patent/WO2004108701A1/en not_active Ceased
- 2004-06-01 CA CA2527315A patent/CA2527315C/en not_active Expired - Lifetime
- 2004-06-01 JP JP2006508238A patent/JP4401384B2/ja not_active Expired - Lifetime
- 2004-06-01 DE DE602004009796T patent/DE602004009796T2/de not_active Expired - Lifetime
- 2004-06-01 ES ES04739484T patent/ES2294504T3/es not_active Expired - Lifetime
- 2004-06-01 CN CNB2004800156669A patent/CN100408572C/zh not_active Expired - Lifetime
- 2004-06-01 EA EA200501887A patent/EA010577B1/ru not_active IP Right Cessation
- 2004-06-01 KR KR1020057023137A patent/KR100778948B1/ko not_active Expired - Lifetime
- 2004-06-01 SI SI200430525T patent/SI1636206T1/sl unknown
- 2004-06-01 AT AT04739484T patent/ATE377008T1/de active
- 2004-06-02 US US10/858,969 patent/US7332510B2/en not_active Expired - Lifetime
- 2004-06-02 PE PE2004000558A patent/PE20050162A1/es active IP Right Grant
- 2004-06-02 CL CL200401347A patent/CL2004001347A1/es unknown
- 2004-06-02 TW TW093115811A patent/TWI338007B/zh not_active IP Right Cessation
- 2004-06-02 PA PA20048604101A patent/PA8604101A1/es unknown
- 2004-06-03 GT GT200400117A patent/GT200400117A/es unknown
- 2004-06-03 MY MYPI20042150A patent/MY137272A/en unknown
- 2004-06-03 HN HN2004000208A patent/HN2004000208A/es unknown
- 2004-06-03 AR ARP040101908A patent/AR044478A1/es active IP Right Grant
2005
- 2005-05-27 MY MYPI20052424A patent/MY143353A/en unknown
- 2005-11-13 IL IL171930A patent/IL171930A/en active IP Right Grant
- 2005-11-14 CR CR8094A patent/CR8094A/es unknown
- 2005-11-18 NO NO20055465A patent/NO332143B1/no unknown
- 2005-12-01 TN TNP2005000309A patent/TNSN05309A1/fr unknown
- 2005-12-02 ZA ZA200509807A patent/ZA200509807B/en unknown
- 2005-12-02 EC EC2005006202A patent/ECSP056202A/es unknown
- 2005-12-09 MA MA28648A patent/MA27881A1/fr unknown
2006
- 2006-11-21 ZA ZA200609681A patent/ZA200609681B/xx unknown
- 2006-11-27 TN TNP2006000391A patent/TNSN06391A1/fr unknown
2007
- 2007-10-31 US US11/930,258 patent/US8481548B2/en active Active
- 2007-12-13 US US11/955,421 patent/US7973165B2/en not_active Expired - Lifetime
2008
- 2008-01-11 CY CY20081100047T patent/CY1107856T1/el unknown

Also Published As

Publication number	Publication date
US20080119489A1 (en)	2008-05-22
CA2527315C (en)	2010-08-10
HK1093070A1 (zh)	2007-02-23
CN100408572C (zh)	2008-08-06
CR8094A (es)	2006-05-30
AU2004245208A1 (en)	2004-12-16
CY1107856T1 (el)	2013-06-19
MY143353A (en)	2011-04-29
TNSN06391A1 (fr)	2008-02-22
DE602004009796T2 (de)	2008-08-28
KR20060057537A (ko)	2006-05-26
US20080103306A1 (en)	2008-05-01
US20040248888A1 (en)	2004-12-09
CL2004001347A1 (es)	2005-05-06
US7973165B2 (en)	2011-07-05
BRPI0411095A (pt)	2006-07-18
RS53183B (sr)	2014-06-30
PT1636206E (pt)	2008-01-28
MXPA05013149A (es)	2006-03-17
KR100778948B1 (ko)	2007-11-28
NO20055465L (no)	2005-11-18
SI1636206T1 (sl)	2008-02-29
PL1636206T3 (pl)	2008-04-30
DK1636206T3 (da)	2008-02-11
US7332510B2 (en)	2008-02-19
ZA200609681B (en)	2008-06-25
PE20050162A1 (es)	2005-03-22
IL171930A (en)	2010-12-30
BRPI0411095B8 (pt)	2021-05-25
MA27881A1 (fr)	2006-05-02
WO2004108701A1 (en)	2004-12-16
ES2294504T3 (es)	2008-04-01
ECSP056202A (es)	2006-04-19
EP1636206A1 (en)	2006-03-22
MY137272A (en)	2009-01-30
EP1636206B1 (en)	2007-10-31
UA80888C2 (en)	2007-11-12
RS20050892A (sr)	2007-12-31
JP2006526588A (ja)	2006-11-24
EA010577B1 (ru)	2008-10-30
IL171930A0 (en)	2006-04-10
TNSN05309A1 (fr)	2007-07-10
EA200501887A1 (ru)	2006-10-27
TW200509920A (en)	2005-03-16
NZ543637A (en)	2008-04-30
JP4401384B2 (ja)	2010-01-20
HN2004000208A (es)	2009-02-03
GT200400117A (es)	2005-02-07
ZA200509807B (en)	2006-12-27
ATE377008T1 (de)	2007-11-15
AU2004245208B2 (en)	2007-04-26
BRPI0411095B1 (pt)	2018-04-03
CN1802367A (zh)	2006-07-12
DE602004009796D1 (de)	2007-12-13
AR044478A1 (es)	2005-09-14
HRP20070529T3 (hr)	2008-05-31
CA2527315A1 (en)	2004-12-16
PA8604101A1 (es)	2004-12-16
TWI338007B (en)	2011-03-01
US8481548B2 (en)	2013-07-09

Publication	Publication Date	Title
EP1606277B1 (en)	2008-05-14	Imidazol-4-yl-ethynyl-pyridine derivatives
US8481548B2 (en)	2013-07-09	Imidazole derivatives
CA2537826C (en)	2012-04-17	Imidazole derivatives
NO332175B1 (no)	2012-07-16	Heteroarylsubstituerte imidazolderivater, fremstilling av slike forbindelser, medikament inneholdende slike forbindelser, slike forbindelser for anvendelse til behandling av sykdom samt anvendelse av slike forbindelser for fremstilling av medikamenter for behandling av sykdom
CA2531210C (en)	2012-05-29	Imidazole derivatives and their use in the treatment of mglur5 receptor mediated disorders
HK1093070B (en)	2009-01-23	Imidazole derivatives as glutamate receptor antagonists