OA11564A - Tetrahydroquinoline derivatives as glycine antagonists. - Google Patents

Tetrahydroquinoline derivatives as glycine antagonists. Download PDF

Info

Publication number: OA11564A
Authority: OA; OAPI
Prior art keywords: phenyl; group; chloro; solution; tetrahydro
Prior art date: 1998-06-10

Application number

OA1200000335A

Other languages

English (en)

Inventor

Fabio Romano Di

Original Assignee

Glaxo Wellcome Spa

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.)

1998-06-10

Filing date

1999-06-08

Publication date

2004-05-24

1998-06-10 Priority claimed from GBGB9812408.4A external-priority patent/GB9812408D0/en

1998-06-10 Priority claimed from GBGB9812410.0A external-priority patent/GB9812410D0/en

1999-06-08 Application filed by Glaxo Wellcome Spa filed Critical Glaxo Wellcome Spa

2004-05-24 Publication of OA11564A publication Critical patent/OA11564A/en

Links

229940127337 Glycine Antagonists Drugs 0.000 title abstract description 3
125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 150
-1 hydroxy, amino Chemical group 0.000 claims abstract description 57
239000001257 hydrogen Substances 0.000 claims abstract description 33
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
150000002148 esters Chemical class 0.000 claims abstract description 29
238000000034 method Methods 0.000 claims abstract description 29
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 22
229910052757 nitrogen Chemical group 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 19
229910052799 carbon Inorganic materials 0.000 claims abstract description 18
231100000252 nontoxic Toxicity 0.000 claims abstract description 12
230000003000 nontoxic effect Effects 0.000 claims abstract description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 8
239000005864 Sulphur Chemical group 0.000 claims abstract description 8
125000005843 halogen group Chemical group 0.000 claims abstract description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
239000001301 oxygen Substances 0.000 claims abstract description 7
125000006163 5-membered heteroaryl group Chemical group 0.000 claims abstract description 4
125000005842 heteroatom Chemical group 0.000 claims abstract description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 3
238000006243 chemical reaction Methods 0.000 claims description 35
125000000217 alkyl group Chemical group 0.000 claims description 23
229920006395 saturated elastomer Polymers 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 14
150000002431 hydrogen Chemical group 0.000 claims description 14
OSJVTYVKQNOXPP-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CCC2=C1 OSJVTYVKQNOXPP-UHFFFAOYSA-N 0.000 claims description 13
150000001721 carbon Chemical group 0.000 claims description 13
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 13
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 12
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 claims description 12
125000006239 protecting group Chemical group 0.000 claims description 12
239000011734 sodium Substances 0.000 claims description 12
229910052708 sodium Inorganic materials 0.000 claims description 12
102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 10
108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 10
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 7
230000000694 effects Effects 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
230000002461 excitatory amino acid Effects 0.000 claims description 6
239000003257 excitatory amino acid Substances 0.000 claims description 6
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
229910052794 bromium Inorganic materials 0.000 claims description 5
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
229910052740 iodine Inorganic materials 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
DGJFOKSXPJLLMX-UHFFFAOYSA-N 7-chloro-4-(2,5-dioxo-1-phenylimidazolidin-4-ylidene)-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound C12=CC=C(Cl)C=C2NC(C(=O)O)CC1=C(C1=O)NC(=O)N1C1=CC=CC=C1 DGJFOKSXPJLLMX-UHFFFAOYSA-N 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
101100295741 Gallus gallus COR4 gene Proteins 0.000 claims description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
125000001072 heteroaryl group Chemical group 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
NEUYJSROPOLVLU-UHFFFAOYSA-N 7-chloro-4-(2-oxo-1-phenylpiperidin-3-ylidene)-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound C12=CC=C(Cl)C=C2NC(C(=O)O)CC1=C(C1=O)CCCN1C1=CC=CC=C1 NEUYJSROPOLVLU-UHFFFAOYSA-N 0.000 claims description 2
125000002947 alkylene group Chemical group 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
159000000000 sodium salts Chemical class 0.000 claims description 2
FCMZVVRKJTVTQK-UHFFFAOYSA-N 5,7-dichloro-4-(2-oxo-1-phenylpyrrolidin-3-ylidene)-2,3-dihydro-1h-quinoline-2-carboxylic acid Chemical compound C12=C(Cl)C=C(Cl)C=C2NC(C(=O)O)CC1=C(C1=O)CCN1C1=CC=CC=C1 FCMZVVRKJTVTQK-UHFFFAOYSA-N 0.000 claims 1
241000124008 Mammalia Species 0.000 claims 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
239000000969 carrier Substances 0.000 claims 1
238000002955 isolation Methods 0.000 claims 1
229940124597 therapeutic agent Drugs 0.000 claims 1
230000001225 therapeutic effect Effects 0.000 claims 1
125000004432 carbon atom Chemical group C* 0.000 abstract description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
125000006164 6-membered heteroaryl group Chemical group 0.000 abstract 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
239000000243 solution Substances 0.000 description 134
239000000203 mixture Substances 0.000 description 93
239000000543 intermediate Substances 0.000 description 83
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 65
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 62
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 61
229940093499 ethyl acetate Drugs 0.000 description 58
235000019439 ethyl acetate Nutrition 0.000 description 58
239000007787 solid Substances 0.000 description 57
238000005481 NMR spectroscopy Methods 0.000 description 55
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 43
229910001868 water Inorganic materials 0.000 description 41
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
239000012267 brine Substances 0.000 description 38
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 35
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
239000012074 organic phase Substances 0.000 description 26
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 24
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 22
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
239000003921 oil Substances 0.000 description 19
235000019198 oils Nutrition 0.000 description 19
238000003756 stirring Methods 0.000 description 19
238000004440 column chromatography Methods 0.000 description 18
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 16
238000003818 flash chromatography Methods 0.000 description 15
235000011121 sodium hydroxide Nutrition 0.000 description 15
239000002904 solvent Substances 0.000 description 15
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
229960004132 diethyl ether Drugs 0.000 description 14
239000000047 product Substances 0.000 description 14
239000012047 saturated solution Substances 0.000 description 14
238000005160 1H NMR spectroscopy Methods 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 13
239000012043 crude product Substances 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
239000012045 crude solution Substances 0.000 description 12
235000019441 ethanol Nutrition 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
238000000746 purification Methods 0.000 description 12
239000000725 suspension Substances 0.000 description 12
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 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
108090001060 Lipase Proteins 0.000 description 10
102000004882 Lipase Human genes 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
239000004367 Lipase Substances 0.000 description 9
208000002193 Pain Diseases 0.000 description 9
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
235000019421 lipase Nutrition 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
239000004471 Glycine Substances 0.000 description 8
239000000843 powder Substances 0.000 description 8
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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 7
239000007864 aqueous solution Substances 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
239000003513 alkali Substances 0.000 description 6
239000006260 foam Substances 0.000 description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 6
239000007924 injection Substances 0.000 description 6
238000002347 injection Methods 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 6
239000012071 phase Substances 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 5
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BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
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CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 4
239000000010 aprotic solvent Substances 0.000 description 4
239000002585 base Substances 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
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238000001727 in vivo Methods 0.000 description 4
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239000011591 potassium Substances 0.000 description 3
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
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IXXMVXXFAJGOQO-RXMQYKEDSA-N tert-butyl (2r)-2-hydroxypropanoate Chemical compound C[C@@H](O)C(=O)OC(C)(C)C IXXMVXXFAJGOQO-RXMQYKEDSA-N 0.000 description 3
238000012360 testing method Methods 0.000 description 3
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QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
RWWYLEGWBNMMLJ-YSOARWBDSA-N remdesivir Chemical compound NC1=NC=NN2C1=CC=C2[C@]1([C@@H]([C@@H]([C@H](O1)CO[P@](=O)(OC1=CC=CC=C1)N[C@H](C(=O)OCC(CC)CC)C)O)O)C#N RWWYLEGWBNMMLJ-YSOARWBDSA-N 0.000 description 1
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CJIIUHXNKIOWLT-UHFFFAOYSA-N tert-butyl n-[4-(2,4-dibromobutanoylamino)phenyl]carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(NC(=O)C(Br)CCBr)C=C1 CJIIUHXNKIOWLT-UHFFFAOYSA-N 0.000 description 1
238000010998 test method Methods 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
150000003530 tetrahydroquinolines Chemical class 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
MPVGERFLOBRUPY-UHFFFAOYSA-M tributyl-(2-oxo-1-pyridin-3-ylpyrrolidin-3-yl)phosphanium;bromide Chemical compound [Br-].O=C1C([P+](CCCC)(CCCC)CCCC)CCN1C1=CC=CN=C1 MPVGERFLOBRUPY-UHFFFAOYSA-M 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
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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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- 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
- A61P25/04—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
- A61P25/28—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)

OA1200000335A 1998-06-10 1999-06-08 Tetrahydroquinoline derivatives as glycine antagonists. OA11564A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB9812408.4A GB9812408D0 (en)	1998-06-10	1998-06-10	Heterocyclic compounds
GBGB9812410.0A GB9812410D0 (en)	1998-06-10	1998-06-10	Heterocyclic derivatives

Publications (1)

Publication Number	Publication Date
OA11564A true OA11564A (en)	2004-05-24

Family

ID=26313826

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200000335A OA11564A (en)	1998-06-10	1999-06-08	Tetrahydroquinoline derivatives as glycine antagonists.

Country Status (33)

Country	Link
US (3)	US6362199B1 (pl)
EP (1)	EP1086093B1 (pl)
JP (1)	JP2002517492A (pl)
KR (1)	KR100586762B1 (pl)
CN (1)	CN1173970C (pl)
AP (1)	AP2000002008A0 (pl)
AR (1)	AR018632A1 (pl)
AT (1)	ATE301650T1 (pl)
AU (1)	AU753867B2 (pl)
BG (1)	BG105123A (pl)
BR (1)	BR9911145A (pl)
CA (1)	CA2334727C (pl)
CO (1)	CO5080785A1 (pl)
CZ (1)	CZ293605B6 (pl)
DE (1)	DE69926632T2 (pl)
DK (1)	DK1086093T3 (pl)
EA (1)	EA003276B1 (pl)
EE (1)	EE200000733A (pl)
ES (1)	ES2249010T3 (pl)
HR (1)	HRP20000845A2 (pl)
HU (1)	HUP0102767A3 (pl)
ID (1)	ID27845A (pl)
IL (2)	IL140062A0 (pl)
IS (1)	IS5746A (pl)
MY (1)	MY125037A (pl)
NO (1)	NO321904B1 (pl)
NZ (1)	NZ508638A (pl)
OA (1)	OA11564A (pl)
PE (1)	PE20000724A1 (pl)
PL (1)	PL197160B1 (pl)
TR (1)	TR200003652T2 (pl)
TW (1)	TWI229079B (pl)
WO (1)	WO1999064411A1 (pl)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MY125037A (en) *	1998-06-10	2006-07-31	Glaxo Wellcome Spa	1,2,3,4 tetrahydroquinoline derivatives
US6455734B1 (en) *	2000-08-09	2002-09-24	Magnesium Diagnostics, Inc.	Antagonists of the magnesium binding defect as therapeutic agents and methods for treatment of abnormal physiological states
GB9929037D0 (en) *	1999-12-08	2000-02-02	Glaxo Wellcome Spa	Heterocyclic derivatives
DE10000311A1 (de)	2000-01-05	2001-07-12	Gruenenthal Gmbh	Aminomethyl-Phonyl-Cyclohexanonderivate
DE10005302A1 (de) *	2000-02-07	2002-01-17	Gruenenthal Gmbh	Substituierte 1,2,3,4-Tetrahydrochinolin-2-carbonsäurederivate
DE10137488A1 (de) *	2001-08-03	2003-02-20	Gruenenthal Gmbh	Salze substituierter 1,2,3,4-Tetrahydrochinolin-2-carbonsäurederivate
DE10137487A1 (de)	2001-08-03	2003-03-27	Gruenenthal Gmbh	Substituierte 5,6,6a,11b-Tetrahydro-7-oxa-6-aza- benzo[c]fluoren-6-carbonsäurederivate
PL376156A1 (pl) *	2002-10-04	2005-12-27	Millennium Pharmaceuticals, Inc.	Antagoniści receptora PGD2 do leczenia chorób zapalnych
US20090181966A1 (en) *	2002-10-04	2009-07-16	Millennium Pharmaceuticals, Inc.	PGD2 receptor antagonists for the treatment of inflammatory diseases
US7504508B2 (en) *	2002-10-04	2009-03-17	Millennium Pharmaceuticals, Inc.	PGD2 receptor antagonists for the treatment of inflammatory diseases
GB0327912D0 (en) *	2003-12-02	2004-01-07	Glaxo Group Ltd	Medicament
BRPI0608553A2 (pt) *	2005-02-24	2010-01-12	Millennium Pharm Inc	antagonistas de receptor de pgd2 para o tratamento de doenças inflamatórias

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
RU2024516C1 (ru) *	1989-02-02	1994-12-15	Яманути Фармасьютикал Ко., Лтд.	Способ получения производного тетрагидробензимидазола или его фармацевтически приемлемой соли
US4902695A (en) *	1989-02-13	1990-02-20	Eli Lilly And Company	Excitatory amino acid receptor antagonists
US5231102A (en) *	1989-03-08	1993-07-27	Merck Sharp & Dohme, Ltd.	Tetrahydroquinoline derivatives useful for neurodegenerative disorders
IL93610A0 (en) *	1989-03-08	1990-12-23	Merck Sharp & Dohme	Tetrahydroquinoline derivatives,their preparation and pharmaceutical compositions containing them
US5529999A (en)	1994-03-04	1996-06-25	Eli Lilly And Company	Antitumor compositions and methods of treatment
CZ292379B6 (cs)	1995-09-29	2003-09-17	Glaxo Wellcome Spa	Tetrahydrochinolinové deriváty, způsob jejich výroby a farmaceutický prostředek s jejich obsahem
GB9617305D0 (en) *	1996-08-17	1996-09-25	Glaxo Wellcome Spa	Heterocyclic compounds
MY125037A (en) *	1998-06-10	2006-07-31	Glaxo Wellcome Spa	1,2,3,4 tetrahydroquinoline derivatives

1999
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- 1999-06-08 DK DK99927911T patent/DK1086093T3/da active
- 1999-06-08 JP JP2000553420A patent/JP2002517492A/ja active Pending
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Also Published As

Publication number	Publication date
PL344694A1 (en)	2001-11-19
IL140062A (en)	2007-05-15
HUP0102767A3 (en)	2003-01-28
PL197160B1 (pl)	2008-03-31
HUP0102767A2 (hu)	2001-12-28
ATE301650T1 (de)	2005-08-15
ES2249010T3 (es)	2006-03-16
EE200000733A (et)	2002-06-17
KR100586762B1 (ko)	2006-06-08
CO5080785A1 (es)	2001-09-25
US6413985B1 (en)	2002-07-02
CN1173970C (zh)	2004-11-03
EP1086093B1 (en)	2005-08-10
NZ508638A (en)	2003-08-29
CA2334727A1 (en)	1999-12-16
CA2334727C (en)	2009-08-04
US6362199B1 (en)	2002-03-26
US20020169186A1 (en)	2002-11-14
DK1086093T3 (da)	2005-11-28
ID27845A (id)	2001-04-26
NO20006227L (no)	2001-02-08
NO321904B1 (no)	2006-07-17
HK1034079A1 (en)	2001-10-12
EA003276B1 (ru)	2003-04-24
DE69926632D1 (de)	2005-09-15
BR9911145A (pt)	2001-03-06
IS5746A (is)	2000-11-30
EA200001165A1 (ru)	2001-06-25
IL140062A0 (en)	2002-02-10
TWI229079B (en)	2005-03-11
JP2002517492A (ja)	2002-06-18
BG105123A (en)	2001-11-30
CN1311785A (zh)	2001-09-05
AU753867B2 (en)	2002-10-31
TR200003652T2 (tr)	2001-04-20
AR018632A1 (es)	2001-11-28
AP2000002008A0 (en)	2000-12-31
US6495566B2 (en)	2002-12-17
US20020052391A1 (en)	2002-05-02
KR20010052722A (ko)	2001-06-25
WO1999064411A1 (en)	1999-12-16
AU4509299A (en)	1999-12-30
PE20000724A1 (es)	2000-08-17
MY125037A (en)	2006-07-31
CZ293605B6 (cs)	2004-06-16
DE69926632T2 (de)	2006-01-19
CZ20004587A3 (en)	2001-05-16
EP1086093A1 (en)	2001-03-28
HRP20000845A2 (en)	2001-10-31
NO20006227D0 (no)	2000-12-07

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US20030013875A1 (en)	2003-01-16	3-azabicyclo[3.1.0]hexane derivatives useful in therapy
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CA2090635A1 (en)	1993-09-04	Substituted phenylquinazoline derivatives
ZA200007225B (en)	2002-03-06	Tetrahydroquinoline derivatives as glycine antagonists.
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