ZA200605383B - Pyrrole and pyrazole daao inhibitors - Google Patents
Pyrrole and pyrazole daao inhibitors Download PDFInfo
- Publication number
- ZA200605383B ZA200605383B ZA200605383A ZA200605383A ZA200605383B ZA 200605383 B ZA200605383 B ZA 200605383B ZA 200605383 A ZA200605383 A ZA 200605383A ZA 200605383 A ZA200605383 A ZA 200605383A ZA 200605383 B ZA200605383 B ZA 200605383B
- Authority
- ZA
- South Africa
- Prior art keywords
- hydrogen
- compound
- alkyl
- formula
- xyr
- Prior art date
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- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 19
- 239000003112 inhibitor Substances 0.000 title description 12
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 115
- 229910052739 hydrogen Inorganic materials 0.000 claims description 87
- 239000001257 hydrogen Substances 0.000 claims description 87
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- 238000000034 method Methods 0.000 claims description 60
- 229910052760 oxygen Inorganic materials 0.000 claims description 54
- 150000003839 salts Chemical class 0.000 claims description 45
- 239000000203 mixture Chemical group 0.000 claims description 44
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims description 41
- 230000015654 memory Effects 0.000 claims description 40
- 125000001072 heteroaryl group Chemical group 0.000 claims description 38
- 229930195711 D-Serine Natural products 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 35
- 239000012453 solvate Substances 0.000 claims description 35
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 33
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
- 108010003989 D-amino-acid oxidase Proteins 0.000 claims description 31
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 31
- 239000011734 sodium Chemical group 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 230000013016 learning Effects 0.000 claims description 28
- 239000003814 drug Substances 0.000 claims description 27
- 201000000980 schizophrenia Diseases 0.000 claims description 26
- 230000019771 cognition Effects 0.000 claims description 25
- 208000024827 Alzheimer disease Diseases 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- 229910052717 sulfur Inorganic materials 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000003107 substituted aryl group Chemical group 0.000 claims description 19
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 17
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 16
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 16
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 16
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 16
- 125000002252 acyl group Chemical group 0.000 claims description 16
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 16
- 229910052782 aluminium Inorganic materials 0.000 claims description 16
- 239000011575 calcium Chemical group 0.000 claims description 16
- 229910052791 calcium Inorganic materials 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 229910052744 lithium Inorganic materials 0.000 claims description 16
- 239000011777 magnesium Chemical group 0.000 claims description 16
- 229910052749 magnesium Inorganic materials 0.000 claims description 16
- 230000004770 neurodegeneration Effects 0.000 claims description 16
- 239000011591 potassium Chemical group 0.000 claims description 16
- 229910052700 potassium Inorganic materials 0.000 claims description 16
- 208000000044 Amnesia Diseases 0.000 claims description 15
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 15
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical group [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 15
- 229910052708 sodium Inorganic materials 0.000 claims description 15
- 239000011701 zinc Chemical group 0.000 claims description 15
- 229910052725 zinc Inorganic materials 0.000 claims description 15
- 125000002837 carbocyclic group Chemical group 0.000 claims description 14
- 230000001965 increasing effect Effects 0.000 claims description 12
- 206010003591 Ataxia Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 208000004296 neuralgia Diseases 0.000 claims description 10
- 208000021722 neuropathic pain Diseases 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 230000002708 enhancing effect Effects 0.000 claims description 9
- 230000003647 oxidation Effects 0.000 claims description 9
- 238000007254 oxidation reaction Methods 0.000 claims description 9
- 231100000863 loss of memory Toxicity 0.000 claims description 8
- 230000003955 neuronal function Effects 0.000 claims description 8
- 231100000331 toxic Toxicity 0.000 claims description 8
- 230000002588 toxic effect Effects 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 6
- DYDCUQKUCUHJBH-UWTATZPHSA-N D-Cycloserine Chemical compound N[C@@H]1CONC1=O DYDCUQKUCUHJBH-UWTATZPHSA-N 0.000 claims description 4
- DYDCUQKUCUHJBH-UHFFFAOYSA-N D-Cycloserine Natural products NC1CONC1=O DYDCUQKUCUHJBH-UHFFFAOYSA-N 0.000 claims description 4
- 229960003077 cycloserine Drugs 0.000 claims description 4
- 229940021746 d- serine Drugs 0.000 claims description 4
- HHEBXMNODWRUEV-UHFFFAOYSA-N 5-(2-phenylethyl)-1h-pyrazole-3-carboxylic acid Chemical compound N1N=C(C(=O)O)C=C1CCC1=CC=CC=C1 HHEBXMNODWRUEV-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 33
- 125000001475 halogen functional group Chemical group 0.000 claims 23
- 102100026908 D-amino-acid oxidase Human genes 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 2
- KSHPUQQHKKJVIO-UHFFFAOYSA-N [Na].[Zn] Chemical group [Na].[Zn] KSHPUQQHKKJVIO-UHFFFAOYSA-N 0.000 claims 1
- NALBLJLOBICXRH-UHFFFAOYSA-N dinitrogen monohydride Chemical compound N=[N] NALBLJLOBICXRH-UHFFFAOYSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 198
- 238000004128 high performance liquid chromatography Methods 0.000 description 128
- 238000003756 stirring Methods 0.000 description 110
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 107
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 106
- 230000015572 biosynthetic process Effects 0.000 description 98
- 238000003786 synthesis reaction Methods 0.000 description 97
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 92
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 86
- 239000000243 solution Substances 0.000 description 78
- 239000007787 solid Substances 0.000 description 61
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 58
- 235000019439 ethyl acetate Nutrition 0.000 description 46
- 238000010992 reflux Methods 0.000 description 39
- 241001465754 Metazoa Species 0.000 description 34
- 239000000047 product Substances 0.000 description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 29
- 102000004674 D-amino-acid oxidase Human genes 0.000 description 28
- 238000012360 testing method Methods 0.000 description 27
- 238000010898 silica gel chromatography Methods 0.000 description 26
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 24
- 208000035475 disorder Diseases 0.000 description 22
- 230000000694 effects Effects 0.000 description 20
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 20
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 20
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 18
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 18
- 239000012535 impurity Substances 0.000 description 18
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 17
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
- 230000014759 maintenance of location Effects 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 238000011282 treatment Methods 0.000 description 17
- 238000009472 formulation Methods 0.000 description 16
- 230000036961 partial effect Effects 0.000 description 16
- -1 4-substituted pyrrole-2-carboxylic acids Chemical class 0.000 description 15
- 239000012267 brine Substances 0.000 description 15
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- 238000007792 addition Methods 0.000 description 14
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- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 10
- 206010012289 Dementia Diseases 0.000 description 10
- PAEYAKGINDQUCT-UHFFFAOYSA-N Ethyl 2-pyrrolecarboxylate Chemical compound CCOC(=O)C1=CC=CN1 PAEYAKGINDQUCT-UHFFFAOYSA-N 0.000 description 10
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 10
- 125000005843 halogen group Chemical group 0.000 description 10
- 239000011347 resin Substances 0.000 description 10
- 229920005989 resin Polymers 0.000 description 10
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 9
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 9
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 239000001301 oxygen Chemical group 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical class OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- UIJZMDMZDGZOOP-UHFFFAOYSA-N 4-methyl-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-3-carboxylic acid Chemical compound N1N=C(C(O)=O)C2=C1CCC2C UIJZMDMZDGZOOP-UHFFFAOYSA-N 0.000 description 7
- 208000026139 Memory disease Diseases 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000013058 crude material Substances 0.000 description 7
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- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 7
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- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical class OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 6
- BNMHOYMKFKJRNG-UHFFFAOYSA-N 4-[2-(2-bromophenyl)ethyl]-1h-pyrrole-2-carboxylic acid Chemical compound N1C(C(=O)O)=CC(CCC=2C(=CC=CC=2)Br)=C1 BNMHOYMKFKJRNG-UHFFFAOYSA-N 0.000 description 6
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical class C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 6
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
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- JUYNTPXARYNBSL-UHFFFAOYSA-N methyl 4-benzyl-1h-pyrrole-2-carboxylate Chemical compound N1C(C(=O)OC)=CC(CC=2C=CC=CC=2)=C1 JUYNTPXARYNBSL-UHFFFAOYSA-N 0.000 description 6
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- 230000001225 therapeutic effect Effects 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- SYOVWIRLZABVDO-VIFPVBQESA-N (4s)-4-phenylpentan-2-one Chemical compound CC(=O)C[C@H](C)C1=CC=CC=C1 SYOVWIRLZABVDO-VIFPVBQESA-N 0.000 description 5
- XBHPGYLNHFKIOB-UHFFFAOYSA-N 5-(2-phenylpropyl)-1h-pyrazole-3-carboxylic acid Chemical compound C=1C=CC=CC=1C(C)CC1=CC(C(O)=O)=NN1 XBHPGYLNHFKIOB-UHFFFAOYSA-N 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
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- JMEDQVJDWBMQPO-UHFFFAOYSA-N ethyl 5-(2-phenylacetyl)-1h-pyrrole-2-carboxylate Chemical compound N1C(C(=O)OCC)=CC=C1C(=O)CC1=CC=CC=C1 JMEDQVJDWBMQPO-UHFFFAOYSA-N 0.000 description 5
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- CZGAFRRLHYXBMG-UHFFFAOYSA-N 3-methyl-2,4,5,6-tetrahydro-1h-cyclopenta[c]pyrazole-3-carboxylic acid Chemical compound C1CCC2=C1C(C)(C(O)=O)NN2 CZGAFRRLHYXBMG-UHFFFAOYSA-N 0.000 description 4
- VQFOFEOCMXJUHQ-UHFFFAOYSA-N 4-(2-phenylethyl)-1h-pyrrole-2-carboxylic acid Chemical compound N1C(C(=O)O)=CC(CCC=2C=CC=CC=2)=C1 VQFOFEOCMXJUHQ-UHFFFAOYSA-N 0.000 description 4
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- AHWHSXHQVPNDRK-UHFFFAOYSA-N 4-(3-phenylpropyl)-1h-pyrrole-2-carboxylic acid Chemical compound N1C(C(=O)O)=CC(CCCC=2C=CC=CC=2)=C1 AHWHSXHQVPNDRK-UHFFFAOYSA-N 0.000 description 4
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- ZBSCFAWMXYYNNB-UHFFFAOYSA-N 5-benzyl-1h-pyrrole-2-carboxylic acid Chemical compound N1C(C(=O)O)=CC=C1CC1=CC=CC=C1 ZBSCFAWMXYYNNB-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
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- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
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- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/16—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
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EP (1) | EP1709004A2 (ru) |
JP (1) | JP2007517056A (ru) |
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CN (1) | CN1922149A (ru) |
AU (1) | AU2004312530A1 (ru) |
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CZ (1) | CZ2006427A3 (ru) |
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RU (3) | RU2361862C2 (ru) |
WO (1) | WO2005066135A2 (ru) |
ZA (1) | ZA200605383B (ru) |
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DE60327446D1 (de) * | 2002-10-10 | 2009-06-10 | Arena Pharm Inc | 5-substituierte 2h-pyrazon-3-carbonsäure-derivate als antilipolytische mittel zur behandlung von stoffwechselstörungen, wie z.b. dyslipidemie |
EP1633351A1 (en) * | 2003-06-13 | 2006-03-15 | Arena Pharmaceuticals, Inc. | 5-substituted 2h-pyrazole-3-carboxylic acid derivatives as agonists for the nicotinic acid receptor rup25 for the treatment of dyslipidemia and related diseases |
CZ2006427A3 (cs) * | 2003-12-29 | 2006-11-15 | Sepracor Inc. | Pyrrolové a pyrazolové inhibitory DAAO |
CA2957667A1 (en) | 2005-07-06 | 2007-01-11 | Sepracor Inc. | Combinations of eszopiclone and trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-n-methyl-1-napthalenamine or trans 4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1-napthalenamine, and methods of treatment of menopause and mood, anxiety, and cognitive disorders |
AU2007205114B2 (en) | 2006-01-06 | 2012-11-08 | Sunovion Pharmaceuticals Inc. | Cycloalkylamines as monoamine reuptake inhibitors |
AU2006335174B2 (en) * | 2006-01-06 | 2012-09-06 | Sunovion Pharmaceuticals Inc. | Tetralone-based monoamine reuptake inhibitors |
AU2007233041B2 (en) | 2006-03-31 | 2013-05-02 | Sepracor Inc. | Preparation of chiral amides and amines |
US7579370B2 (en) | 2006-06-30 | 2009-08-25 | Sepracor Inc. | Fused heterocycles |
US7884124B2 (en) | 2006-06-30 | 2011-02-08 | Sepracor Inc. | Fluoro-substituted inhibitors of D-amino acid oxidase |
EP2057162A2 (en) * | 2006-06-30 | 2009-05-13 | Sepracor Inc. | Fused heterocyclic inhibitors of d-amino acid oxidase |
US20080082066A1 (en) * | 2006-10-02 | 2008-04-03 | Weyerhaeuser Co. | Crosslinked carboxyalkyl cellulose fibers having non-permanent and temporary crosslinks |
DE102006060598A1 (de) * | 2006-12-21 | 2008-06-26 | Merck Patent Gmbh | Tetrahydrobenzoisoxazole |
US7902252B2 (en) * | 2007-01-18 | 2011-03-08 | Sepracor, Inc. | Inhibitors of D-amino acid oxidase |
KR20090111322A (ko) * | 2007-01-18 | 2009-10-26 | 세프라코 아이엔시. | 디 아미노산 옥시다제의 억제제 |
CN101677555A (zh) * | 2007-03-21 | 2010-03-24 | 詹森药业有限公司 | 治疗cb2受体介导的疼痛的方法 |
EP3296289A3 (en) | 2007-05-31 | 2018-06-20 | Sunovion Pharmaceuticals Inc. | Phenyl substituted cycloalkylamines as monoamine reuptake inhibitors |
SI2308838T1 (sl) * | 2008-07-08 | 2016-09-30 | Daiichi Sankyo Company, Limited | Dušik vsebujoča aromatska heterociklična spojina |
US20100120740A1 (en) * | 2008-08-07 | 2010-05-13 | Sepracor Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
GB0817379D0 (en) * | 2008-09-23 | 2008-10-29 | Merck Sharp & Dohme | New use |
IT1394400B1 (it) * | 2009-02-25 | 2012-06-15 | Neuroscienze Pharmaness S C Ar L | Composizioni farmaceutiche |
IT1393930B1 (it) | 2009-02-25 | 2012-05-17 | Neuroscienze Pharmaness S C A R L | Composti farmaceutici |
WO2011017634A2 (en) * | 2009-08-07 | 2011-02-10 | Sepracore Inc. | Prodrugs of fused heterocyclic inhibitors of d-amino acid oxidase |
JP2013517295A (ja) | 2010-01-19 | 2013-05-16 | セラヴァンス, インコーポレーテッド | 二重に作用するチオフェン、ピロール、チアゾールおよびフラン抗高血圧症薬 |
US10387135B2 (en) * | 2010-11-05 | 2019-08-20 | FedEx Supply Chain Logistics & Electronics, Inc. | System and method for remotely flashing a wireless device |
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KR20060128976A (ko) | 2006-12-14 |
US7488747B2 (en) | 2009-02-10 |
US7615572B2 (en) | 2009-11-10 |
CZ2006427A3 (cs) | 2006-11-15 |
RU2361862C2 (ru) | 2009-07-20 |
CN1922149A (zh) | 2007-02-28 |
JP2007517056A (ja) | 2007-06-28 |
IL200842A0 (en) | 2010-05-17 |
WO2005066135A2 (en) | 2005-07-21 |
AU2004312530A1 (en) | 2005-07-21 |
RU2009110913A (ru) | 2010-09-27 |
RU2006127440A (ru) | 2008-02-10 |
PL380887A1 (pl) | 2007-04-02 |
IL176606A0 (en) | 2006-10-31 |
US20050143443A1 (en) | 2005-06-30 |
US20090170916A1 (en) | 2009-07-02 |
WO2005066135A3 (en) | 2005-10-06 |
NZ548212A (en) | 2010-07-30 |
BRPI0418244A (pt) | 2007-04-17 |
EP1709004A2 (en) | 2006-10-11 |
US20110092559A1 (en) | 2011-04-21 |
CA2551952A1 (en) | 2005-07-21 |
US20100016397A1 (en) | 2010-01-21 |
US7893098B2 (en) | 2011-02-22 |
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