MXPA03000906A - Derivados de piperazina. - Google Patents
Derivados de piperazina.Info
- Publication number
- MXPA03000906A MXPA03000906A MXPA03000906A MXPA03000906A MXPA03000906A MX PA03000906 A MXPA03000906 A MX PA03000906A MX PA03000906 A MXPA03000906 A MX PA03000906A MX PA03000906 A MXPA03000906 A MX PA03000906A MX PA03000906 A MXPA03000906 A MX PA03000906A
- Authority
- MX
- Mexico
- Prior art keywords
- indole
- pyrazino
- methyl
- hexahydro
- compound
- Prior art date
Links
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 3
- 150000004885 piperazines Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 401
- 238000011282 treatment Methods 0.000 claims abstract description 30
- 150000002148 esters Chemical class 0.000 claims abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 208000008589 Obesity Diseases 0.000 claims abstract description 23
- 235000020824 obesity Nutrition 0.000 claims abstract description 22
- 208000035475 disorder Diseases 0.000 claims abstract description 20
- 210000003169 central nervous system Anatomy 0.000 claims abstract description 12
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 7
- 208000018522 Gastrointestinal disease Diseases 0.000 claims abstract description 6
- 239000012453 solvate Substances 0.000 claims abstract description 6
- 230000002265 prevention Effects 0.000 claims abstract description 5
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims abstract description 3
- 201000010064 diabetes insipidus Diseases 0.000 claims abstract description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 164
- 239000000203 mixture Substances 0.000 claims description 158
- -1 hydroxy, carboxy Chemical group 0.000 claims description 135
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 82
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 82
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- 238000006243 chemical reaction Methods 0.000 claims description 58
- 238000000034 method Methods 0.000 claims description 58
- 239000001257 hydrogen Substances 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 46
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 125000006239 protecting group Chemical group 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 22
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical group CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 claims description 19
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 18
- 229960001243 orlistat Drugs 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 239000003638 chemical reducing agent Substances 0.000 claims description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 230000009467 reduction Effects 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 8
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 5
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 208000020016 psychiatric disease Diseases 0.000 claims description 5
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
- 230000004064 dysfunction Effects 0.000 claims description 4
- 231100000331 toxic Toxicity 0.000 claims description 4
- 230000002588 toxic effect Effects 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- 208000032841 Bulimia Diseases 0.000 claims description 3
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
- 208000027691 Conduct disease Diseases 0.000 claims description 3
- 206010012289 Dementia Diseases 0.000 claims description 3
- 206010019233 Headaches Diseases 0.000 claims description 3
- 206010022773 Intracranial pressure increased Diseases 0.000 claims description 3
- 208000026139 Memory disease Diseases 0.000 claims description 3
- 201000009906 Meningitis Diseases 0.000 claims description 3
- 208000019695 Migraine disease Diseases 0.000 claims description 3
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 claims description 3
- 206010036618 Premenstrual syndrome Diseases 0.000 claims description 3
- 208000028017 Psychotic disease Diseases 0.000 claims description 3
- 206010041250 Social phobia Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 208000008784 apnea Diseases 0.000 claims description 3
- 208000025748 atypical depressive disease Diseases 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 231100000869 headache Toxicity 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- 208000022821 personality disease Diseases 0.000 claims description 3
- 201000000484 premenstrual tension Diseases 0.000 claims description 3
- GCZDLZHMAMLSJF-UHFFFAOYSA-N pyrazino[1,2-a]indole Chemical compound C1=CN=CC2=CC3=CC=CC=C3N21 GCZDLZHMAMLSJF-UHFFFAOYSA-N 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 230000001225 therapeutic effect Effects 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- SZSZDBFJCQKTRG-UHFFFAOYSA-N 1h-indole-6-carbonitrile Chemical compound N#CC1=CC=C2C=CNC2=C1 SZSZDBFJCQKTRG-UHFFFAOYSA-N 0.000 claims description 2
- 206010051290 Central nervous system lesion Diseases 0.000 claims description 2
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 230000010933 acylation Effects 0.000 claims description 2
- 238000005917 acylation reaction Methods 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 206010061428 decreased appetite Diseases 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims description 2
- 206010013663 drug dependence Diseases 0.000 claims description 2
- 230000005176 gastrointestinal motility Effects 0.000 claims description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 2
- 230000004770 neurodegeneration Effects 0.000 claims description 2
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 2
- 230000000422 nocturnal effect Effects 0.000 claims description 2
- 208000019116 sleep disease Diseases 0.000 claims description 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 125000004521 1,3,4-thiadiazol-2-yl group Chemical group S1C(=NN=C1)* 0.000 claims 1
- 208000007848 Alcoholism Diseases 0.000 claims 1
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims 1
- 208000022531 anorexia Diseases 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 claims 1
- 230000001568 sexual effect Effects 0.000 claims 1
- 208000011117 substance-related disease Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract description 2
- 201000002859 sleep apnea Diseases 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 206
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 183
- 238000007429 general method Methods 0.000 description 182
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 118
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 112
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 239000000243 solution Substances 0.000 description 100
- 239000007787 solid Substances 0.000 description 87
- 239000002253 acid Substances 0.000 description 77
- 125000004494 ethyl ester group Chemical group 0.000 description 76
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 75
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 75
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 72
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
- 235000019439 ethyl acetate Nutrition 0.000 description 69
- 239000002904 solvent Substances 0.000 description 63
- 239000000741 silica gel Substances 0.000 description 61
- 229910002027 silica gel Inorganic materials 0.000 description 61
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- 239000012074 organic phase Substances 0.000 description 54
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 42
- 238000004587 chromatography analysis Methods 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 39
- 239000012267 brine Substances 0.000 description 38
- 239000000047 product Substances 0.000 description 34
- 239000003921 oil Substances 0.000 description 31
- 235000019198 oils Nutrition 0.000 description 31
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 26
- 235000019341 magnesium sulphate Nutrition 0.000 description 26
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
- 235000019441 ethanol Nutrition 0.000 description 21
- SGNPIGAGPRLGEJ-UHFFFAOYSA-N oxathiazolidine-3-carboxylic acid Chemical compound OC(=O)N1CCOS1 SGNPIGAGPRLGEJ-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000000543 intermediate Substances 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- 238000004885 tandem mass spectrometry Methods 0.000 description 17
- 239000002585 base Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- 238000001704 evaporation Methods 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 230000008020 evaporation Effects 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 239000008346 aqueous phase Substances 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 229910000104 sodium hydride Inorganic materials 0.000 description 12
- 238000003756 stirring Methods 0.000 description 12
- 239000012230 colorless oil Substances 0.000 description 11
- 239000013078 crystal Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 235000011181 potassium carbonates Nutrition 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 10
- 229940117360 ethyl pyruvate Drugs 0.000 description 10
- 239000000706 filtrate Substances 0.000 description 10
- RJTZUHVCZIGJMB-UHFFFAOYSA-N hydron;1h-indole;chloride Chemical compound Cl.C1=CC=C2NC=CC2=C1 RJTZUHVCZIGJMB-UHFFFAOYSA-N 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 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 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 9
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
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- 239000006260 foam Substances 0.000 description 8
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
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- 239000012279 sodium borohydride Substances 0.000 description 8
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- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 6
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- 241001465754 Metazoa Species 0.000 description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 6
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- 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
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- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 6
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- 238000009835 boiling Methods 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 238000004440 column chromatography Methods 0.000 description 5
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 5
- 238000006880 cross-coupling reaction Methods 0.000 description 5
- 239000003925 fat Substances 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 150000007857 hydrazones Chemical class 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 208000011580 syndromic disease Diseases 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 4
- GPZDWQUDHYWQBS-UHFFFAOYSA-N 1h-indole-2,7-dicarboxylic acid Chemical compound C1=CC(C(O)=O)=C2NC(C(=O)O)=CC2=C1 GPZDWQUDHYWQBS-UHFFFAOYSA-N 0.000 description 4
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- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical class OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
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- 235000019260 propionic acid Nutrition 0.000 description 1
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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
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 229910001925 ruthenium oxide Inorganic materials 0.000 description 1
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- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
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- MLOXNONIGFZNTQ-CYBMUJFWSA-N tert-butyl (4r)-4,7-dimethyl-3,4-dihydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound C1=C(C)C=C2N3[C@H](C)CN(C(=O)OC(C)(C)C)CC3=CC2=C1 MLOXNONIGFZNTQ-CYBMUJFWSA-N 0.000 description 1
- ZGFOJWQAHCHOLG-LURJTMIESA-N tert-butyl (5s)-5-methyl-2,2-dioxooxathiazolidine-3-carboxylate Chemical compound C[C@H]1CN(C(=O)OC(C)(C)C)S(=O)(=O)O1 ZGFOJWQAHCHOLG-LURJTMIESA-N 0.000 description 1
- ALJRPIAYJALVFG-UHFFFAOYSA-N tert-butyl 2,2-dioxooxathiazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOS1(=O)=O ALJRPIAYJALVFG-UHFFFAOYSA-N 0.000 description 1
- VBYPJHLRWKGNAI-UHFFFAOYSA-N tert-butyl aziridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC1 VBYPJHLRWKGNAI-UHFFFAOYSA-N 0.000 description 1
- BRGKFDMYQYKVHU-UHFFFAOYSA-N tert-butyl oxathiazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOS1 BRGKFDMYQYKVHU-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- PCZOZSATUTWXIC-UHFFFAOYSA-N tetraethylazanium;cyanide Chemical compound N#[C-].CC[N+](CC)(CC)CC PCZOZSATUTWXIC-UHFFFAOYSA-N 0.000 description 1
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- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
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- 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
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Anesthesiology (AREA)
- Pulmonology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00116517 | 2000-07-31 | ||
| PCT/EP2001/008520 WO2002010169A1 (en) | 2000-07-31 | 2001-07-24 | Piperazine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MXPA03000906A true MXPA03000906A (es) | 2005-02-24 |
Family
ID=8169405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MXPA03000906A MXPA03000906A (es) | 2000-07-31 | 2001-07-24 | Derivados de piperazina. |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US20020035110A1 (OSRAM) |
| EP (1) | EP1325008B1 (OSRAM) |
| JP (1) | JP4180365B2 (OSRAM) |
| KR (1) | KR100539139B1 (OSRAM) |
| CN (1) | CN1277828C (OSRAM) |
| AR (1) | AR030306A1 (OSRAM) |
| AT (1) | ATE305933T1 (OSRAM) |
| AU (2) | AU8395501A (OSRAM) |
| BR (1) | BR0112918A (OSRAM) |
| CA (1) | CA2417106C (OSRAM) |
| DE (1) | DE60113865T2 (OSRAM) |
| DK (1) | DK1325008T3 (OSRAM) |
| ES (1) | ES2250459T3 (OSRAM) |
| GT (1) | GT200100155A (OSRAM) |
| MX (1) | MXPA03000906A (OSRAM) |
| PA (1) | PA8523601A1 (OSRAM) |
| PE (1) | PE20020366A1 (OSRAM) |
| UY (1) | UY26863A1 (OSRAM) |
| WO (1) | WO2002010169A1 (OSRAM) |
| ZA (1) | ZA200300525B (OSRAM) |
Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1325008B1 (en) * | 2000-07-31 | 2005-10-05 | F. Hoffmann-La Roche Ag | Piperazine derivatives |
| GB0106177D0 (en) | 2001-03-13 | 2001-05-02 | Hoffmann La Roche | Piperazine derivatives |
| US7566728B2 (en) | 2002-03-29 | 2009-07-28 | Mitsubishi Tanabe Pharma Corporation | Remedy for sleep disturbance |
| AU2003243089B2 (en) | 2002-06-19 | 2010-01-07 | Biovitrum Ab (Publ) | Novel compounds, their use and preparation |
| US7105526B2 (en) | 2002-06-28 | 2006-09-12 | Banyu Pharmaceuticals Co., Ltd. | Benzimidazole derivatives |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| DE10319612A1 (de) | 2003-05-02 | 2004-11-18 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline |
| DE10320780A1 (de) * | 2003-05-09 | 2005-01-20 | Bayer Healthcare Ag | Heterocyclyl-substituierte Dihydrochinazoline |
| GB0314967D0 (en) * | 2003-06-26 | 2003-07-30 | Hoffmann La Roche | Piperazine derivatives |
| US20050032930A1 (en) * | 2003-07-02 | 2005-02-10 | Christian Jackson | Inkjet ink |
| US7547693B2 (en) | 2003-09-22 | 2009-06-16 | Banyu Pharmaceutical Co. Ltd. | Piperidine derivative |
| DE10352499A1 (de) * | 2003-11-11 | 2005-06-09 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline II |
| EP1734963A4 (en) | 2004-04-02 | 2008-06-18 | Merck & Co Inc | METHOD FOR TREATING PEOPLE WITH METABOLIC AND ANTHROPOMETRIC DISORDER |
| DE102004022672A1 (de) * | 2004-05-07 | 2005-11-24 | Bayer Healthcare Ag | Substituierte Azachinazoline |
| EP1792629A4 (en) | 2004-08-25 | 2010-08-25 | Takeda Pharmaceutical | MEANS FOR THE PREVENTION / TREATMENT OF STRESS-RELATED HARNINE INCONTINENCE AND PRECAUTIONARY METHOD FOR THIS |
| ES2325773T5 (es) | 2004-11-01 | 2014-02-24 | Amylin Pharmaceuticals, Llc. | Tratamiento de la obesidad y de los trastornos relacionados |
| EP2314688B1 (en) | 2004-11-12 | 2014-07-16 | Asuragen, Inc. | Methods and compositions involving miRNA and miRNA inhibitor molecules |
| US7790712B2 (en) | 2005-03-17 | 2010-09-07 | Boehringer Ingelheim Pharmaceutical, Inc. | Substituted [1,4]diazepino[1,2-A]indoles and azepino[1,2-A]indoles as anti-cytokine inhibitors |
| EP1888585B1 (en) * | 2005-05-03 | 2011-06-29 | F. Hoffmann-La Roche AG | Tetracyclic azapyrazinoindolines as 5-ht2 ligands |
| US7737155B2 (en) | 2005-05-17 | 2010-06-15 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
| EP1892241B1 (en) | 2005-05-30 | 2016-03-30 | Msd K.K. | Novel piperidine derivative |
| DE102005027517A1 (de) | 2005-06-15 | 2006-12-21 | Bayer Healthcare Ag | Verfahren zur Herstellung von Dihydrochinazolinen |
| EP1916239A4 (en) | 2005-08-10 | 2009-10-21 | Banyu Pharma Co Ltd | PYRIDOLVERBINDUNG |
| EP2330124B1 (en) | 2005-08-11 | 2015-02-25 | Amylin Pharmaceuticals, LLC | Hybrid polypeptides with selectable properties |
| EP2330125A3 (en) | 2005-08-11 | 2012-12-12 | Amylin Pharmaceuticals, Inc. | Hybrid polypeptides with selectable properties |
| JPWO2007024004A1 (ja) | 2005-08-24 | 2009-03-05 | 萬有製薬株式会社 | フェニルピリドン誘導体 |
| EP1939194A4 (en) | 2005-09-07 | 2010-12-08 | Banyu Pharma Co Ltd | BICYCLIC AROMATIC SUBSTITUTED PYRIDONE DERIVATIVE |
| KR20080048502A (ko) | 2005-09-29 | 2008-06-02 | 머크 앤드 캄파니 인코포레이티드 | 멜라노코르틴-4 수용체 조절제로서의 아실화스피로피페리딘 유도체 |
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| US652018A (en) * | 1900-02-15 | 1900-06-19 | John C Duner | Gate. |
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| EP1325008B1 (en) * | 2000-07-31 | 2005-10-05 | F. Hoffmann-La Roche Ag | Piperazine derivatives |
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2001
- 2001-07-24 EP EP01962869A patent/EP1325008B1/en not_active Expired - Lifetime
- 2001-07-24 BR BR0112918-0A patent/BR0112918A/pt not_active IP Right Cessation
- 2001-07-24 CA CA002417106A patent/CA2417106C/en not_active Expired - Fee Related
- 2001-07-24 ES ES01962869T patent/ES2250459T3/es not_active Expired - Lifetime
- 2001-07-24 KR KR10-2003-7001439A patent/KR100539139B1/ko not_active Expired - Fee Related
- 2001-07-24 DE DE60113865T patent/DE60113865T2/de not_active Expired - Fee Related
- 2001-07-24 DK DK01962869T patent/DK1325008T3/da active
- 2001-07-24 AU AU8395501A patent/AU8395501A/xx active Pending
- 2001-07-24 JP JP2002515898A patent/JP4180365B2/ja not_active Expired - Fee Related
- 2001-07-24 WO PCT/EP2001/008520 patent/WO2002010169A1/en not_active Ceased
- 2001-07-24 MX MXPA03000906A patent/MXPA03000906A/es active IP Right Grant
- 2001-07-24 CN CNB018152260A patent/CN1277828C/zh not_active Expired - Fee Related
- 2001-07-24 AU AU2001283955A patent/AU2001283955B2/en not_active Ceased
- 2001-07-24 AT AT01962869T patent/ATE305933T1/de not_active IP Right Cessation
- 2001-07-25 US US09/912,949 patent/US20020035110A1/en not_active Abandoned
- 2001-07-25 PE PE2001000749A patent/PE20020366A1/es not_active Application Discontinuation
- 2001-07-27 AR ARP010103589A patent/AR030306A1/es unknown
- 2001-07-30 GT GT200100155A patent/GT200100155A/es unknown
- 2001-07-30 UY UY26863A patent/UY26863A1/es not_active Application Discontinuation
- 2001-07-30 PA PA20018523601A patent/PA8523601A1/es unknown
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- 2003-03-25 US US10/396,242 patent/US6933387B2/en not_active Expired - Fee Related
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| CN1277828C (zh) | 2006-10-04 |
| KR20030020954A (ko) | 2003-03-10 |
| GT200100155A (es) | 2002-05-16 |
| DK1325008T3 (da) | 2006-02-13 |
| CN1452622A (zh) | 2003-10-29 |
| PA8523601A1 (es) | 2002-10-24 |
| BR0112918A (pt) | 2003-07-01 |
| ZA200300525B (en) | 2004-04-20 |
| UY26863A1 (es) | 2002-01-31 |
| US6933387B2 (en) | 2005-08-23 |
| US7253281B2 (en) | 2007-08-07 |
| JP2004505085A (ja) | 2004-02-19 |
| AR030306A1 (es) | 2003-08-20 |
| US20020035110A1 (en) | 2002-03-21 |
| ES2250459T3 (es) | 2006-04-16 |
| JP4180365B2 (ja) | 2008-11-12 |
| WO2002010169A1 (en) | 2002-02-07 |
| CA2417106A1 (en) | 2002-02-07 |
| PE20020366A1 (es) | 2002-05-17 |
| EP1325008B1 (en) | 2005-10-05 |
| KR100539139B1 (ko) | 2005-12-26 |
| CA2417106C (en) | 2007-09-18 |
| US20050239789A1 (en) | 2005-10-27 |
| EP1325008A1 (en) | 2003-07-09 |
| US20070106076A1 (en) | 2007-05-10 |
| DE60113865T2 (de) | 2006-07-20 |
| AU2001283955B2 (en) | 2006-05-18 |
| ATE305933T1 (de) | 2005-10-15 |
| DE60113865D1 (de) | 2006-02-16 |
| AU8395501A (en) | 2002-02-13 |
| US20030216401A1 (en) | 2003-11-20 |
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