DE60113865T2 - Piperazin derivate - Google Patents
Piperazin derivate Download PDFInfo
- Publication number
- DE60113865T2 DE60113865T2 DE60113865T DE60113865T DE60113865T2 DE 60113865 T2 DE60113865 T2 DE 60113865T2 DE 60113865 T DE60113865 T DE 60113865T DE 60113865 T DE60113865 T DE 60113865T DE 60113865 T2 DE60113865 T2 DE 60113865T2
- Authority
- DE
- Germany
- Prior art keywords
- indole
- methyl
- hexahydropyrazino
- compound
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 384
- 239000000203 mixture Substances 0.000 claims description 137
- -1 1H-pyrrolo (2,3-b) pyridin-3-ylmethyl Chemical group 0.000 claims description 133
- 125000000217 alkyl group Chemical group 0.000 claims description 68
- 239000001257 hydrogen Substances 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 125000006239 protecting group Chemical group 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 35
- 150000002431 hydrogen Chemical class 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 238000011282 treatment Methods 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 208000008589 Obesity Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 235000020824 obesity Nutrition 0.000 claims description 20
- 208000035475 disorder Diseases 0.000 claims description 18
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound 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 18
- 229960001243 orlistat Drugs 0.000 claims description 16
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 15
- 150000002148 esters Chemical class 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- 239000003638 chemical reducing agent Substances 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 210000003169 central nervous system Anatomy 0.000 claims description 10
- 230000009467 reduction Effects 0.000 claims description 10
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 9
- 238000011321 prophylaxis Methods 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 230000003542 behavioural effect Effects 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 7
- 208000011580 syndromic disease Diseases 0.000 claims description 7
- OFZCNKHDZGJKCK-VXGBXAGGSA-N (4r,10ar)-7-bromo-4-ethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(Br)C=C2N3[C@H](CC)CNC[C@H]3CC2=C1 OFZCNKHDZGJKCK-VXGBXAGGSA-N 0.000 claims description 6
- 208000024172 Cardiovascular disease Diseases 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
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
- 208000015114 central nervous system disease Diseases 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 239000000460 chlorine Substances 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- XTQKZPARPUBXCZ-LDYMZIIASA-N (4r,10ar)-7-chloro-4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(Cl)C=C2N3[C@H](C)CNC[C@H]3CC2=C1 XTQKZPARPUBXCZ-LDYMZIIASA-N 0.000 claims description 5
- ZFJVQQQPMHYSOA-NEPJUHHUSA-N (4r,10as)-4,6,9-trimethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound CC1=CC=C(C)C2=C1N1[C@H](C)CNC[C@@H]1C2 ZFJVQQQPMHYSOA-NEPJUHHUSA-N 0.000 claims description 5
- TVNXTKSDLQSLAY-KOLCDFICSA-N (4r,10as)-6-chloro-4,7-dimethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(C)C(Cl)=C2N3[C@H](C)CNC[C@@H]3CC2=C1 TVNXTKSDLQSLAY-KOLCDFICSA-N 0.000 claims description 5
- SZWVUASESVZMCY-KCJUWKMLSA-N (4r,10as)-7-chloro-4,6-dimethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(Cl)C(C)=C2N3[C@H](C)CNC[C@@H]3CC2=C1 SZWVUASESVZMCY-KCJUWKMLSA-N 0.000 claims description 5
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- 208000002193 Pain Diseases 0.000 claims description 5
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 5
- 125000004448 alkyl carbonyl 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
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 5
- 208000015181 infectious disease Diseases 0.000 claims description 5
- 230000002458 infectious effect Effects 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- 231100000331 toxic Toxicity 0.000 claims description 5
- 230000002588 toxic effect Effects 0.000 claims description 5
- XWXVGQFTZHFUNL-LDYMZIIASA-N (4r,10ar)-7-bromo-4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(Br)C=C2N3[C@H](C)CNC[C@H]3CC2=C1 XWXVGQFTZHFUNL-LDYMZIIASA-N 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- NGNJCNYNDBMXSG-ZWNOBZJWSA-N (4r,10ar)-4,6,7-trimethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(C)C(C)=C2N3[C@H](C)CNC[C@H]3CC2=C1 NGNJCNYNDBMXSG-ZWNOBZJWSA-N 0.000 claims description 3
- GKCUTGZGZISWAV-MWLCHTKSSA-N (4r,10ar)-4,8-dimethyl-7-(trifluoromethyl)-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound CC1=C(C(F)(F)F)C=C2N3[C@H](C)CNC[C@H]3CC2=C1 GKCUTGZGZISWAV-MWLCHTKSSA-N 0.000 claims description 3
- 125000001960 7 membered carbocyclic group Chemical group 0.000 claims description 3
- 206010001488 Aggression Diseases 0.000 claims description 3
- 208000007848 Alcoholism Diseases 0.000 claims description 3
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 3
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 3
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 3
- 206010012289 Dementia 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
- 208000027626 Neurocognitive 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
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 201000007930 alcohol dependence Diseases 0.000 claims description 3
- 208000025748 atypical depressive disease Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 230000004064 dysfunction Effects 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 230000005176 gastrointestinal motility Effects 0.000 claims description 3
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 206010027599 migraine Diseases 0.000 claims description 3
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 claims description 3
- 230000004770 neurodegeneration Effects 0.000 claims description 3
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 3
- 208000022821 personality disease Diseases 0.000 claims description 3
- 201000000484 premenstrual tension Diseases 0.000 claims description 3
- 208000020016 psychiatric disease Diseases 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 208000012201 sexual and gender identity disease Diseases 0.000 claims description 3
- 208000015891 sexual disease Diseases 0.000 claims description 3
- 201000002859 sleep apnea Diseases 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims 1
- 208000018685 gastrointestinal system disease Diseases 0.000 claims 1
- 201000009941 intracranial hypertension Diseases 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 204
- 238000007429 general method Methods 0.000 description 186
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 179
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 117
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 113
- 239000000243 solution Substances 0.000 description 110
- 239000007787 solid Substances 0.000 description 90
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 72
- 235000019439 ethyl acetate Nutrition 0.000 description 68
- 238000004587 chromatography analysis Methods 0.000 description 66
- 239000000741 silica gel Substances 0.000 description 63
- 229910002027 silica gel Inorganic materials 0.000 description 63
- 239000002904 solvent Substances 0.000 description 63
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 62
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 44
- 238000000034 method Methods 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 36
- 239000012267 brine Substances 0.000 description 35
- 239000012074 organic phase Substances 0.000 description 35
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- 239000012071 phase Substances 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 24
- 239000000543 intermediate Substances 0.000 description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 102000005962 receptors Human genes 0.000 description 21
- 108020003175 receptors Proteins 0.000 description 21
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 20
- 238000007792 addition Methods 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- 239000002253 acid Substances 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000011734 sodium Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 13
- 238000001816 cooling Methods 0.000 description 13
- 239000012280 lithium aluminium hydride Substances 0.000 description 13
- SGNPIGAGPRLGEJ-UHFFFAOYSA-N oxathiazolidine-3-carboxylic acid Chemical compound OC(=O)N1CCOS1 SGNPIGAGPRLGEJ-UHFFFAOYSA-N 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 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 13
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- 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 10
- XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 10
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
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- 230000037406 food intake Effects 0.000 description 8
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- KKVINERVQDWTBN-MRVPVSSYSA-N (10ar)-9-bromo-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound N12CCNC[C@H]2CC2=C1C=CC=C2Br KKVINERVQDWTBN-MRVPVSSYSA-N 0.000 description 7
- 0 *c1c(C(OI*)=O)[n]c2c1c(*)c(*)c(*)c2* Chemical compound *c1c(C(OI*)=O)[n]c2c1c(*)c(*)c(*)c2* 0.000 description 7
- AEIDURNZWCNQIM-UHFFFAOYSA-N 1,2,3,4-tetrahydropyrazino[1,2-a]indole Chemical compound C1=CC=C2N3CCNCC3=CC2=C1 AEIDURNZWCNQIM-UHFFFAOYSA-N 0.000 description 7
- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 7
- OFZCNKHDZGJKCK-UHFFFAOYSA-N 7-bromo-4-ethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=C(Br)C=C2N3C(CC)CNCC3CC2=C1 OFZCNKHDZGJKCK-UHFFFAOYSA-N 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- FMNXFKVTZJWOAD-UHFFFAOYSA-N tert-butyl 1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OC(C)(C)C)=CC2=C1 FMNXFKVTZJWOAD-UHFFFAOYSA-N 0.000 description 7
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- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
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- 201000010099 disease Diseases 0.000 description 2
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- DDHIPOBBFWQWGF-GFCCVEGCSA-N ethyl 1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]-6-(trifluoromethyl)indole-2-carboxylate Chemical compound C1=C(C(F)(F)F)C=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 DDHIPOBBFWQWGF-GFCCVEGCSA-N 0.000 description 2
- GYQGPHQSESZOJQ-CQSZACIVSA-N ethyl 1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]-7,8-dihydro-6h-cyclopenta[g]indole-2-carboxylate Chemical compound C1=C2CCCC2=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 GYQGPHQSESZOJQ-CQSZACIVSA-N 0.000 description 2
- HVJJYOAPXBPQQV-UHFFFAOYSA-N ethyl 2-azidoacetate Chemical compound CCOC(=O)CN=[N+]=[N-] HVJJYOAPXBPQQV-UHFFFAOYSA-N 0.000 description 2
- AGRYNMDAWIYGNJ-LLVKDONJSA-N ethyl 4,6-dichloro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(Cl)C=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1Cl AGRYNMDAWIYGNJ-LLVKDONJSA-N 0.000 description 2
- PLWDLOJYWDOVEE-OAHLLOKOSA-N ethyl 4,6-dimethyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(C)C=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1C PLWDLOJYWDOVEE-OAHLLOKOSA-N 0.000 description 2
- IGQVZYUDZAZINC-LLVKDONJSA-N ethyl 4,7-difluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC(F)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1F IGQVZYUDZAZINC-LLVKDONJSA-N 0.000 description 2
- KPMMXXNDHSLVKM-OAHLLOKOSA-N ethyl 4,7-dimethyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC(C)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1C KPMMXXNDHSLVKM-OAHLLOKOSA-N 0.000 description 2
- WOXZXFHKNUXCFA-UHFFFAOYSA-N ethyl 4-bromo-1-(cyanomethyl)indole-2-carboxylate Chemical compound C1=CC=C2N(CC#N)C(C(=O)OCC)=CC2=C1Br WOXZXFHKNUXCFA-UHFFFAOYSA-N 0.000 description 2
- ACGHZCMAXSMPRH-GFCCVEGCSA-N ethyl 4-chloro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1Cl ACGHZCMAXSMPRH-GFCCVEGCSA-N 0.000 description 2
- WBOYVWVJGBZKEG-GFCCVEGCSA-N ethyl 5-fluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound FC1=CC=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 WBOYVWVJGBZKEG-GFCCVEGCSA-N 0.000 description 2
- JRRBRESTTKCGLB-UHFFFAOYSA-N ethyl 5-fluoro-6-methyl-1h-indole-2-carboxylate Chemical compound FC1=C(C)C=C2NC(C(=O)OCC)=CC2=C1 JRRBRESTTKCGLB-UHFFFAOYSA-N 0.000 description 2
- QHMRETDVOPIVAM-CQSZACIVSA-N ethyl 5-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound CC1=CC=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 QHMRETDVOPIVAM-CQSZACIVSA-N 0.000 description 2
- PZWGXOOANLOZNX-LLVKDONJSA-N ethyl 6,7-difluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(F)C(F)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 PZWGXOOANLOZNX-LLVKDONJSA-N 0.000 description 2
- CFZCWHAKGSCQLC-UHFFFAOYSA-N ethyl 6,7-difluoro-1h-indole-2-carboxylate Chemical compound C1=C(F)C(F)=C2NC(C(=O)OCC)=CC2=C1 CFZCWHAKGSCQLC-UHFFFAOYSA-N 0.000 description 2
- FVMZWWFKRMBNSZ-UHFFFAOYSA-N ethyl 6-bromo-1h-indole-2-carboxylate Chemical compound C1=C(Br)C=C2NC(C(=O)OCC)=CC2=C1 FVMZWWFKRMBNSZ-UHFFFAOYSA-N 0.000 description 2
- WQWHUTHKOAFIHW-LLVKDONJSA-N ethyl 6-bromo-4-fluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(Br)C=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1F WQWHUTHKOAFIHW-LLVKDONJSA-N 0.000 description 2
- CWMMDFDMQCDTAB-UHFFFAOYSA-N ethyl 6-bromo-4-fluoro-1h-indole-2-carboxylate Chemical compound C1=C(Br)C=C2NC(C(=O)OCC)=CC2=C1F CWMMDFDMQCDTAB-UHFFFAOYSA-N 0.000 description 2
- FSMZLIBWSAMADK-UHFFFAOYSA-N ethyl 6-chloro-1h-indole-2-carboxylate Chemical compound C1=C(Cl)C=C2NC(C(=O)OCC)=CC2=C1 FSMZLIBWSAMADK-UHFFFAOYSA-N 0.000 description 2
- GCHIGJXRRNHXRV-LLVKDONJSA-N ethyl 6-chloro-7-fluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(Cl)C(F)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 GCHIGJXRRNHXRV-LLVKDONJSA-N 0.000 description 2
- RXTPBFBVTOXJHO-UHFFFAOYSA-N ethyl 6-chloro-7-fluoro-1h-indole-2-carboxylate Chemical compound C1=C(Cl)C(F)=C2NC(C(=O)OCC)=CC2=C1 RXTPBFBVTOXJHO-UHFFFAOYSA-N 0.000 description 2
- BVQWOGVOYYEQPB-GFCCVEGCSA-N ethyl 6-chloro-7-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(Cl)C(C)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 BVQWOGVOYYEQPB-GFCCVEGCSA-N 0.000 description 2
- MWMVPKZJEBCEFZ-GFCCVEGCSA-N ethyl 6-fluoro-7-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(F)C(C)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 MWMVPKZJEBCEFZ-GFCCVEGCSA-N 0.000 description 2
- NPRDQOSFBHFWDI-UHFFFAOYSA-N ethyl 6-fluoro-7-methyl-1h-indole-2-carboxylate Chemical compound C1=C(F)C(C)=C2NC(C(=O)OCC)=CC2=C1 NPRDQOSFBHFWDI-UHFFFAOYSA-N 0.000 description 2
- FNQPUXSVCJWKBO-UHFFFAOYSA-N ethyl 7-(trifluoromethoxy)-1h-indole-2-carboxylate Chemical compound C1=CC(OC(F)(F)F)=C2NC(C(=O)OCC)=CC2=C1 FNQPUXSVCJWKBO-UHFFFAOYSA-N 0.000 description 2
- MAZVDDKFMWFTBT-GFCCVEGCSA-N ethyl 7-bromo-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC(Br)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 MAZVDDKFMWFTBT-GFCCVEGCSA-N 0.000 description 2
- UXQODLHHBWTHRQ-LLVKDONJSA-N ethyl 7-bromo-5-fluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound FC1=CC(Br)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 UXQODLHHBWTHRQ-LLVKDONJSA-N 0.000 description 2
- ZAUJOWOCPLOJNM-UHFFFAOYSA-N ethyl 7-bromo-5-fluoro-1h-indole-2-carboxylate Chemical compound FC1=CC(Br)=C2NC(C(=O)OCC)=CC2=C1 ZAUJOWOCPLOJNM-UHFFFAOYSA-N 0.000 description 2
- NIEZZGZEEDVZND-CYBMUJFWSA-N ethyl 7-bromo-6-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(C)C(Br)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 NIEZZGZEEDVZND-CYBMUJFWSA-N 0.000 description 2
- LLWGGHFPDPDGBB-UHFFFAOYSA-N ethyl 7-bromo-6-methyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C(Br)=C2NC(C(=O)OCC)=CC2=C1 LLWGGHFPDPDGBB-UHFFFAOYSA-N 0.000 description 2
- LROVGXRQNHHZPC-CYBMUJFWSA-N ethyl 7-chloro-5-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound CC1=CC(Cl)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 LROVGXRQNHHZPC-CYBMUJFWSA-N 0.000 description 2
- MXQDPJDKGXHPGI-CYBMUJFWSA-N ethyl 7-chloro-6-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(C)C(Cl)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 MXQDPJDKGXHPGI-CYBMUJFWSA-N 0.000 description 2
- MSAFHAPZXWNMSH-UHFFFAOYSA-N ethyl 7-chloro-6-methyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C(Cl)=C2NC(C(=O)OCC)=CC2=C1 MSAFHAPZXWNMSH-UHFFFAOYSA-N 0.000 description 2
- BIDSNGIZBRLNBA-UHFFFAOYSA-N ethyl 7-ethyl-1h-indole-2-carboxylate Chemical compound C1=CC(CC)=C2NC(C(=O)OCC)=CC2=C1 BIDSNGIZBRLNBA-UHFFFAOYSA-N 0.000 description 2
- RQHCZSXKZCFWDO-GFCCVEGCSA-N ethyl 7-fluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC(F)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 RQHCZSXKZCFWDO-GFCCVEGCSA-N 0.000 description 2
- IBPOGSPFWFEXSK-CYBMUJFWSA-N ethyl 7-fluoro-4-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC(F)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1C IBPOGSPFWFEXSK-CYBMUJFWSA-N 0.000 description 2
- LQFBVARIHIMSAC-CYBMUJFWSA-N ethyl 7-fluoro-6-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=C(C)C(F)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 LQFBVARIHIMSAC-CYBMUJFWSA-N 0.000 description 2
- KURXPNVVFATLMH-UHFFFAOYSA-N ethyl 7-fluoro-6-methyl-1h-indole-2-carboxylate Chemical compound C1=C(C)C(F)=C2NC(C(=O)OCC)=CC2=C1 KURXPNVVFATLMH-UHFFFAOYSA-N 0.000 description 2
- QIBFTKJVYOSQBG-CQSZACIVSA-N ethyl 7-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound C1=CC(C)=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 QIBFTKJVYOSQBG-CQSZACIVSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
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- 239000000945 filler Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 2
- 235000019421 lipase Nutrition 0.000 description 2
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
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- VBYPJHLRWKGNAI-UHFFFAOYSA-N tert-butyl aziridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC1 VBYPJHLRWKGNAI-UHFFFAOYSA-N 0.000 description 1
- KDWNTQCNRHAQBC-UHFFFAOYSA-N tert-butyl n-(2-hydroxybutyl)carbamate Chemical compound CCC(O)CNC(=O)OC(C)(C)C KDWNTQCNRHAQBC-UHFFFAOYSA-N 0.000 description 1
- JXCUNZBRFPVMSS-CYBMUJFWSA-N tert-butyl n-[(2r)-3-[2,3-dimethylbutan-2-yl(dimethyl)silyl]oxy-2-hydroxypropyl]carbamate Chemical compound CC(C)C(C)(C)[Si](C)(C)OC[C@H](O)CNC(=O)OC(C)(C)C JXCUNZBRFPVMSS-CYBMUJFWSA-N 0.000 description 1
- PCZOZSATUTWXIC-UHFFFAOYSA-N tetraethylazanium;cyanide Chemical compound N#[C-].CC[N+](CC)(CC)CC PCZOZSATUTWXIC-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000005490 tosylate group Chemical group 0.000 description 1
- 235000021139 traditional diet Nutrition 0.000 description 1
- 238000012549 training Methods 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
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 125000004784 trichloromethoxy group Chemical group ClC(O*)(Cl)Cl 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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)
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- General Health & Medical Sciences (AREA)
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- Diabetes (AREA)
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- Pain & Pain Management (AREA)
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- Endocrinology (AREA)
- Heart & Thoracic Surgery (AREA)
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- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Urology & Nephrology (AREA)
- Pulmonology (AREA)
- Reproductive Health (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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00116517 | 2000-07-31 | ||
| EP00116517 | 2000-07-31 | ||
| PCT/EP2001/008520 WO2002010169A1 (en) | 2000-07-31 | 2001-07-24 | Piperazine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60113865D1 DE60113865D1 (de) | 2006-02-16 |
| DE60113865T2 true DE60113865T2 (de) | 2006-07-20 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60113865T Expired - Fee Related DE60113865T2 (de) | 2000-07-31 | 2001-07-24 | Piperazin derivate |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US20020035110A1 (enExample) |
| EP (1) | EP1325008B1 (enExample) |
| JP (1) | JP4180365B2 (enExample) |
| KR (1) | KR100539139B1 (enExample) |
| CN (1) | CN1277828C (enExample) |
| AR (1) | AR030306A1 (enExample) |
| AT (1) | ATE305933T1 (enExample) |
| AU (2) | AU2001283955B2 (enExample) |
| BR (1) | BR0112918A (enExample) |
| CA (1) | CA2417106C (enExample) |
| DE (1) | DE60113865T2 (enExample) |
| DK (1) | DK1325008T3 (enExample) |
| ES (1) | ES2250459T3 (enExample) |
| GT (1) | GT200100155A (enExample) |
| MX (1) | MXPA03000906A (enExample) |
| PA (1) | PA8523601A1 (enExample) |
| PE (1) | PE20020366A1 (enExample) |
| UY (1) | UY26863A1 (enExample) |
| WO (1) | WO2002010169A1 (enExample) |
| ZA (1) | ZA200300525B (enExample) |
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| CN1277828C (zh) * | 2000-07-31 | 2006-10-04 | 霍夫曼-拉罗奇有限公司 | 哌嗪衍生物 |
| 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 |
| EP1513831B1 (en) | 2002-06-19 | 2010-01-06 | 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 |
| CA2551037A1 (en) | 2003-09-22 | 2005-03-31 | Banyu Pharmaceutical Co., Ltd. | Novel piperidine derivative |
| DE10352499A1 (de) * | 2003-11-11 | 2005-06-09 | Bayer Healthcare Ag | Substituierte Dihydrochinazoline II |
| EP2305352A1 (en) | 2004-04-02 | 2011-04-06 | Merck Sharp & Dohme Corp. | 5-alpha-reductase inhibitors for use in the treatment of men with metabolic and anthropometric disorders |
| DE102004022672A1 (de) * | 2004-05-07 | 2005-11-24 | Bayer Healthcare Ag | Substituierte Azachinazoline |
| EP2400300A1 (en) | 2004-08-25 | 2011-12-28 | Takeda Pharmaceutical Company Limited | Method of screening preventives/remedies for stress urinary incontinence |
| BRPI0518241A (pt) | 2004-11-01 | 2008-04-22 | Amylin Pharmaceuticals Inc | métodos para tratar obesidade e doenças e distúrbios relacionados à obesidade |
| EP2302053A1 (en) | 2004-11-12 | 2011-03-30 | 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 |
| CN101171252B (zh) * | 2005-05-03 | 2011-06-01 | 霍夫曼-拉罗奇有限公司 | 作为5-ht2配体的四环氮杂吡嗪并二氢吲哚类化合物 |
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| EP1892241B1 (en) | 2005-05-30 | 2016-03-30 | Msd K.K. | Novel piperidine derivative |
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| JPWO2007018248A1 (ja) | 2005-08-10 | 2009-02-19 | 萬有製薬株式会社 | ピリドン化合物 |
| AU2006279680B2 (en) | 2005-08-11 | 2012-12-06 | Amylin Pharmaceuticals, Llc | Hybrid polypeptides with selectable properties |
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| US7875633B2 (en) | 2005-08-24 | 2011-01-25 | Banyu Pharmaceutical Co., Ltd. | Phenylpyridone derivative |
| JPWO2007029847A1 (ja) | 2005-09-07 | 2009-03-19 | 萬有製薬株式会社 | 二環性芳香族置換ピリドン誘導体 |
| WO2007041052A2 (en) | 2005-09-29 | 2007-04-12 | Merck & Co., Inc. | Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators |
| EA200801081A1 (ru) * | 2005-10-14 | 2008-10-30 | Х. Лундбекк А/С | Способы лечения расстройств центральной нервной системы комбинацией малых доз эсциталопрама и бупропиона |
| US20080255084A1 (en) | 2005-10-21 | 2008-10-16 | Randy Lee Webb | Combination of Organic Compounds |
| JPWO2007049798A1 (ja) | 2005-10-27 | 2009-04-30 | 萬有製薬株式会社 | 新規ベンゾオキサチイン誘導体 |
| WO2007055418A1 (ja) | 2005-11-10 | 2007-05-18 | Banyu Pharmaceutical Co., Ltd. | アザ置換スピロ誘導体 |
| DE602006010433D1 (de) | 2005-12-09 | 2009-12-24 | Hoffmann La Roche | Für die behandlung von obesitas geeignete tricyclische amidderivate |
| UA95788C2 (en) | 2005-12-15 | 2011-09-12 | Ф. Хоффманн-Ля Рош Аг | Fused pyrrole derivatives |
| WO2007132841A1 (ja) | 2006-05-16 | 2007-11-22 | Takeda Pharmaceutical Company Limited | 縮合複素環化合物およびその用途 |
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| WO2008038692A1 (en) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | Diaryl ketimine derivative |
| TR201802359T4 (tr) | 2007-01-16 | 2018-03-21 | Ipintl Llc | Metabolik sendromun tedavi edilmesine yönelik yeni bileşim. |
| FR2912145B1 (fr) * | 2007-02-02 | 2009-03-06 | Servier Lab | Nouveaux derives tricycliques,leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| JP5319518B2 (ja) | 2007-04-02 | 2013-10-16 | Ｍｓｄ株式会社 | インドールジオン誘導体 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US652018A (en) * | 1900-02-15 | 1900-06-19 | John C Duner | Gate. |
| US3317524A (en) | 1965-02-04 | 1967-05-02 | American Home Prod | Substituted 1, 2, 3, 4-tetrahydro-pyrazino[1, 2-a]indoles |
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| EP0572863A1 (de) * | 1992-06-05 | 1993-12-08 | F. Hoffmann-La Roche Ag | ZNS Pyrazinoindole |
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| US5622950A (en) * | 1993-03-01 | 1997-04-22 | Merck, Sharp & Dohme Ltd. | Pyrrolo-pyridine derivatives |
| US5576319A (en) * | 1993-03-01 | 1996-11-19 | Merck, Sharp & Dohme Ltd. | Pyrrolo-pyridine derivatives |
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| CZ20012193A3 (cs) * | 1998-12-17 | 2001-12-12 | American Home Products Corporation | Deriváty 2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)chinoxalin-5(6H)onu, způsob jejich výroby a jejich pouľití |
| GB9902047D0 (en) * | 1999-01-29 | 1999-03-17 | Cerebrus Ltd | Chemical compounds XI |
| CN1277828C (zh) * | 2000-07-31 | 2006-10-04 | 霍夫曼-拉罗奇有限公司 | 哌嗪衍生物 |
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2001
- 2001-07-24 CN CNB018152260A patent/CN1277828C/zh not_active Expired - Fee Related
- 2001-07-24 DK DK01962869T patent/DK1325008T3/da active
- 2001-07-24 KR KR10-2003-7001439A patent/KR100539139B1/ko not_active Expired - Fee Related
- 2001-07-24 MX MXPA03000906A patent/MXPA03000906A/es active IP Right Grant
- 2001-07-24 JP JP2002515898A patent/JP4180365B2/ja not_active Expired - Fee Related
- 2001-07-24 EP EP01962869A patent/EP1325008B1/en not_active Expired - Lifetime
- 2001-07-24 CA CA002417106A patent/CA2417106C/en not_active Expired - Fee Related
- 2001-07-24 WO PCT/EP2001/008520 patent/WO2002010169A1/en not_active Ceased
- 2001-07-24 DE DE60113865T patent/DE60113865T2/de 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
- 2001-07-24 BR BR0112918-0A patent/BR0112918A/pt not_active IP Right Cessation
- 2001-07-24 ES ES01962869T patent/ES2250459T3/es not_active Expired - Lifetime
- 2001-07-24 AU AU8395501A patent/AU8395501A/xx active Pending
- 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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- 2003-01-20 ZA ZA200300525A patent/ZA200300525B/en unknown
- 2003-03-25 US US10/396,242 patent/US6933387B2/en not_active Expired - Fee Related
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2005
- 2005-06-28 US US11/169,079 patent/US7253281B2/en not_active Expired - Fee Related
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2007
- 2007-01-03 US US11/649,132 patent/US20070106076A1/en not_active Abandoned
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| MXPA03000906A (es) | 2005-02-24 |
| US20030216401A1 (en) | 2003-11-20 |
| ZA200300525B (en) | 2004-04-20 |
| AU8395501A (en) | 2002-02-13 |
| WO2002010169A1 (en) | 2002-02-07 |
| CA2417106C (en) | 2007-09-18 |
| UY26863A1 (es) | 2002-01-31 |
| PE20020366A1 (es) | 2002-05-17 |
| DE60113865D1 (de) | 2006-02-16 |
| AR030306A1 (es) | 2003-08-20 |
| KR20030020954A (ko) | 2003-03-10 |
| US6933387B2 (en) | 2005-08-23 |
| ATE305933T1 (de) | 2005-10-15 |
| ES2250459T3 (es) | 2006-04-16 |
| DK1325008T3 (da) | 2006-02-13 |
| KR100539139B1 (ko) | 2005-12-26 |
| CN1452622A (zh) | 2003-10-29 |
| EP1325008A1 (en) | 2003-07-09 |
| US20020035110A1 (en) | 2002-03-21 |
| GT200100155A (es) | 2002-05-16 |
| US20050239789A1 (en) | 2005-10-27 |
| JP2004505085A (ja) | 2004-02-19 |
| BR0112918A (pt) | 2003-07-01 |
| CA2417106A1 (en) | 2002-02-07 |
| US20070106076A1 (en) | 2007-05-10 |
| JP4180365B2 (ja) | 2008-11-12 |
| EP1325008B1 (en) | 2005-10-05 |
| AU2001283955B2 (en) | 2006-05-18 |
| US7253281B2 (en) | 2007-08-07 |
| PA8523601A1 (es) | 2002-10-24 |
| CN1277828C (zh) | 2006-10-04 |
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