JP4180365B2 - ピペラジン誘導体 - Google Patents
ピペラジン誘導体 Download PDFInfo
- Publication number
- JP4180365B2 JP4180365B2 JP2002515898A JP2002515898A JP4180365B2 JP 4180365 B2 JP4180365 B2 JP 4180365B2 JP 2002515898 A JP2002515898 A JP 2002515898A JP 2002515898 A JP2002515898 A JP 2002515898A JP 4180365 B2 JP4180365 B2 JP 4180365B2
- Authority
- JP
- Japan
- Prior art keywords
- pyrazino
- indole
- methyl
- hexahydro
- compound
- 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
- 150000004885 piperazines Chemical class 0.000 title description 2
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 419
- 238000000034 method Methods 0.000 claims description 223
- 239000000203 mixture Substances 0.000 claims description 135
- -1 1H-pyrrolo (2,3-b) pyridin-3-ylmethyl Chemical group 0.000 claims description 130
- 125000000217 alkyl group Chemical group 0.000 claims description 80
- 239000001257 hydrogen Substances 0.000 claims description 75
- 229910052739 hydrogen Inorganic materials 0.000 claims description 75
- 150000002431 hydrogen Chemical class 0.000 claims description 50
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 24
- 208000008589 Obesity Diseases 0.000 claims description 21
- 235000020824 obesity Nutrition 0.000 claims description 21
- 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 18
- 229960001243 orlistat Drugs 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 16
- 150000002148 esters Chemical class 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 229940086609 Lipase inhibitor Drugs 0.000 claims description 13
- 230000009467 reduction Effects 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 208000035475 disorder Diseases 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 239000008194 pharmaceutical composition 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
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 9
- 208000015114 central nervous system disease Diseases 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 8
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 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 7
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 7
- 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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000005242 carbamoyl alkyl group Chemical group 0.000 claims description 7
- 210000003169 central nervous system Anatomy 0.000 claims description 7
- 230000006378 damage Effects 0.000 claims description 7
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 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
- 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 6
- 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 6
- 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 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
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 239000012453 solvate Substances 0.000 claims description 6
- 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 5
- 208000018522 Gastrointestinal disease 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
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 5
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
- 239000003795 chemical substances by application Substances 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
- 238000011321 prophylaxis Methods 0.000 claims description 5
- 239000000018 receptor agonist Substances 0.000 claims description 5
- 231100000331 toxic Toxicity 0.000 claims description 5
- 230000002588 toxic effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 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 4
- OTCYUUXMBOVVSQ-ZYHUDNBSSA-N (4r,10ar)-4,6-dimethyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole Chemical compound C1=CC(C)=C2N3[C@H](C)CNC[C@H]3CC2=C1 OTCYUUXMBOVVSQ-ZYHUDNBSSA-N 0.000 claims description 4
- 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 4
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229940044601 receptor agonist Drugs 0.000 claims description 4
- 208000024891 symptom Diseases 0.000 claims description 4
- SYNUFLXJJGLJER-BXKDBHETSA-N (4r,10ar)-4-methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole-6-carbonitrile Chemical compound C1=CC(C#N)=C2N3[C@H](C)CNC[C@H]3CC2=C1 SYNUFLXJJGLJER-BXKDBHETSA-N 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
- 208000032841 Bulimia Diseases 0.000 claims description 3
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 claims description 3
- 206010012289 Dementia 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
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 3
- 206010041250 Social phobia Diseases 0.000 claims description 3
- 208000007536 Thrombosis Diseases 0.000 claims description 3
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 208000025748 atypical depressive disease Diseases 0.000 claims description 3
- 238000010511 deprotection reaction Methods 0.000 claims description 3
- 201000010064 diabetes insipidus Diseases 0.000 claims description 3
- 206010013663 drug dependence Diseases 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 206010015037 epilepsy Diseases 0.000 claims description 3
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims description 3
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 3
- 208000014674 injury Diseases 0.000 claims description 3
- 206010027175 memory impairment 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
- 230000002265 prevention Effects 0.000 claims description 3
- 201000000980 schizophrenia Diseases 0.000 claims description 3
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 3
- 201000002859 sleep apnea Diseases 0.000 claims description 3
- 208000019116 sleep disease Diseases 0.000 claims description 3
- 208000020685 sleep-wake disease Diseases 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 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 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 230000008733 trauma Effects 0.000 claims description 3
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 206010022773 Intracranial pressure increased Diseases 0.000 claims description 2
- 201000009906 Meningitis Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 2
- 208000010643 digestive system disease Diseases 0.000 claims description 2
- 230000004064 dysfunction Effects 0.000 claims description 2
- 230000005176 gastrointestinal motility Effects 0.000 claims description 2
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 208000020016 psychiatric disease Diseases 0.000 claims description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 4
- 206010010904 Convulsion Diseases 0.000 claims 1
- 206010019233 Headaches Diseases 0.000 claims 1
- 125000001246 bromo group Chemical group Br* 0.000 claims 1
- 125000002837 carbocyclic group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 204
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 115
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 113
- 239000007787 solid Substances 0.000 description 90
- 239000000243 solution Substances 0.000 description 86
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 76
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 68
- 235000019439 ethyl acetate Nutrition 0.000 description 68
- 238000004587 chromatography analysis Methods 0.000 description 63
- 239000000741 silica gel Substances 0.000 description 63
- 229910002027 silica gel Inorganic materials 0.000 description 63
- 239000002904 solvent Substances 0.000 description 55
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 52
- 239000012074 organic phase Substances 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 44
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 36
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- 239000000047 product Substances 0.000 description 31
- 239000003921 oil Substances 0.000 description 28
- 235000019198 oils Nutrition 0.000 description 28
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
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- 239000000543 intermediate Substances 0.000 description 25
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class 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
- 235000002639 sodium chloride Nutrition 0.000 description 22
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- 235000019441 ethanol Nutrition 0.000 description 19
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- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 239000012071 phase Substances 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
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- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 238000007429 general method Methods 0.000 description 16
- BRGKFDMYQYKVHU-UHFFFAOYSA-N tert-butyl oxathiazolidine-3-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCOS1 BRGKFDMYQYKVHU-UHFFFAOYSA-N 0.000 description 16
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- UOUFRTFWWBCVPV-UHFFFAOYSA-N tert-butyl 4-(2,4-dioxo-1H-thieno[3,2-d]pyrimidin-3-yl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CC1)n1c(=O)[nH]c2ccsc2c1=O UOUFRTFWWBCVPV-UHFFFAOYSA-N 0.000 description 11
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- PTDZGJNEPIRDTH-UHFFFAOYSA-N (2-methylpropan-2-yl)oxycarbonylsulfamic acid Chemical compound CC(C)(C)OC(=O)NS(O)(=O)=O PTDZGJNEPIRDTH-UHFFFAOYSA-N 0.000 description 8
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- VHFVKMTVMIZMIK-UHFFFAOYSA-N 1-(3-chlorophenyl)piperazine Chemical compound ClC1=CC=CC(N2CCNCC2)=C1 VHFVKMTVMIZMIK-UHFFFAOYSA-N 0.000 description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
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- 150000001721 carbon Chemical group 0.000 description 7
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- 150000003840 hydrochlorides Chemical class 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
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- 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
- LSGNITUKEBVOTR-LLVKDONJSA-N ethyl 4-chloro-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=C1Cl LSGNITUKEBVOTR-LLVKDONJSA-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
- NONXIADLXCZUQU-CYBMUJFWSA-N ethyl 5-fluoro-6-methyl-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound FC1=C(C)C=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 NONXIADLXCZUQU-CYBMUJFWSA-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
- WQHIUDDIDWTRBI-UHFFFAOYSA-N ethyl 5-methyl-6-(trifluoromethyl)-1h-indole-2-carboxylate Chemical compound CC1=C(C(F)(F)F)C=C2NC(C(=O)OCC)=CC2=C1 WQHIUDDIDWTRBI-UHFFFAOYSA-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
- MIBFONNBTQRYGN-UHFFFAOYSA-N ethyl 6-(trifluoromethyl)-1h-indole-2-carboxylate Chemical compound C1=C(C(F)(F)F)C=C2NC(C(=O)OCC)=CC2=C1 MIBFONNBTQRYGN-UHFFFAOYSA-N 0.000 description 2
- IKSUHXBPFTYQJQ-GFCCVEGCSA-N ethyl 6-bromo-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=C1 IKSUHXBPFTYQJQ-GFCCVEGCSA-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
- 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
- UJPSFZNFNLMHIV-UHFFFAOYSA-N ethyl 6-chloro-1-(1-cyanoethyl)indole-2-carboxylate Chemical compound C1=C(Cl)C=C2N(C(C)C#N)C(C(=O)OCC)=CC2=C1 UJPSFZNFNLMHIV-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
- PPRAPJONRYJDFE-LLVKDONJSA-N ethyl 6-chloro-5-fluoro-1-[(2r)-1-[(2-methylpropan-2-yl)oxycarbonylamino]propan-2-yl]indole-2-carboxylate Chemical compound FC1=C(Cl)C=C2N([C@H](C)CNC(=O)OC(C)(C)C)C(C(=O)OCC)=CC2=C1 PPRAPJONRYJDFE-LLVKDONJSA-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
- 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
- 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
- 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
- ABBOXOMUELWNEB-UHFFFAOYSA-N ethyl 7-fluoro-4-methyl-1h-indole-2-carboxylate Chemical compound C1=CC(F)=C2NC(C(=O)OCC)=CC2=C1C ABBOXOMUELWNEB-UHFFFAOYSA-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
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- 230000009103 reabsorption Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 230000029556 regulation of feeding behavior Effects 0.000 description 1
- 208000017443 reproductive system disease Diseases 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
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- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000007127 saponification reaction Methods 0.000 description 1
- 230000036186 satiety Effects 0.000 description 1
- 235000019627 satiety Nutrition 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
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- 150000008163 sugars Chemical class 0.000 description 1
- 125000004962 sulfoxyl group Chemical group 0.000 description 1
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- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
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- 229940033134 talc Drugs 0.000 description 1
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FVBCPAHNPGMZBI-SNVBAGLBSA-N tert-butyl (4r)-8-bromo-7-fluoro-4-methyl-3,4-dihydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound BrC1=C(F)C=C2N3[C@H](C)CN(C(=O)OC(C)(C)C)CC3=CC2=C1 FVBCPAHNPGMZBI-SNVBAGLBSA-N 0.000 description 1
- UOHOLLTUJFVJHL-TZMCWYRMSA-N tert-butyl (4r,10ar)-4,8-dimethyl-7-(trifluoromethyl)-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound CC1=C(C(F)(F)F)C=C2N3[C@H](C)CN(C(=O)OC(C)(C)C)C[C@H]3CC2=C1 UOHOLLTUJFVJHL-TZMCWYRMSA-N 0.000 description 1
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- MZHUTFJXTKZUMX-CRAIPNDOSA-N tert-butyl (4r,10ar)-7-(butylcarbamoyl)-4-methyl-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@@H](C)N2C3=CC(C(=O)NCCCC)=CC=C3C[C@@H]21 MZHUTFJXTKZUMX-CRAIPNDOSA-N 0.000 description 1
- JAELUZUHVJUOMW-CRAIPNDOSA-N tert-butyl (4r,10ar)-7-(diethylcarbamoyl)-4-methyl-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)C[C@@H](C)N2C3=CC(C(=O)N(CC)CC)=CC=C3C[C@@H]21 JAELUZUHVJUOMW-CRAIPNDOSA-N 0.000 description 1
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- ZBHCYXVITMUPIY-IUODEOHRSA-N tert-butyl (4r,10ar)-7-cyano-4-methyl-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound C1=C(C#N)C=C2N3[C@H](C)CN(C(=O)OC(C)(C)C)C[C@H]3CC2=C1 ZBHCYXVITMUPIY-IUODEOHRSA-N 0.000 description 1
- ACDATRMZFDURGU-RISCZKNCSA-N tert-butyl (4r,10as)-4-methyl-7-(trifluoromethyl)-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound C1=C(C(F)(F)F)C=C2N3[C@H](C)CN(C(=O)OC(C)(C)C)C[C@@H]3CC2=C1 ACDATRMZFDURGU-RISCZKNCSA-N 0.000 description 1
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- JRQQHEOFNZZLJL-UHFFFAOYSA-N tert-butyl 7,8-dibromo-4-ethyl-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound BrC1=C(Br)C=C2N3C(CC)CN(C(=O)OC(C)(C)C)CC3CC2=C1 JRQQHEOFNZZLJL-UHFFFAOYSA-N 0.000 description 1
- JINJSCPYMOTCDY-UHFFFAOYSA-N tert-butyl 7-bromo-4-ethyl-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound C1=C(Br)C=C2N3C(CC)CN(C(=O)OC(C)(C)C)CC3CC2=C1 JINJSCPYMOTCDY-UHFFFAOYSA-N 0.000 description 1
- TUGNIKPUTPELOF-UHFFFAOYSA-N tert-butyl 7-ethylindole-1-carboxylate Chemical compound CCC1=CC=CC2=C1N(C(=O)OC(C)(C)C)C=C2 TUGNIKPUTPELOF-UHFFFAOYSA-N 0.000 description 1
- PBROLGBGLSMWSS-UHFFFAOYSA-N tert-butyl 8-bromo-4-methyl-7-(trifluoromethyl)-3,4,10,10a-tetrahydro-1h-pyrazino[1,2-a]indole-2-carboxylate Chemical compound BrC1=C(C(F)(F)F)C=C2N3C(C)CN(C(=O)OC(C)(C)C)CC3CC2=C1 PBROLGBGLSMWSS-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
- 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
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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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- 238000000844 transformation Methods 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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- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical class CCCN(CCC)CCC YFTHZRPMJXBUME-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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
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- A—HUMAN NECESSITIES
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- A61P25/08—Antiepileptics; Anticonvulsants
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- A—HUMAN NECESSITIES
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- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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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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- A61P25/28—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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- 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)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Reproductive Health (AREA)
- Emergency Medicine (AREA)
- Anesthesiology (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (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 (3)
| Publication Number | Publication Date |
|---|---|
| JP2004505085A JP2004505085A (ja) | 2004-02-19 |
| JP2004505085A5 JP2004505085A5 (enExample) | 2008-09-04 |
| JP4180365B2 true JP4180365B2 (ja) | 2008-11-12 |
Family
ID=8169405
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002515898A Expired - Fee Related JP4180365B2 (ja) | 2000-07-31 | 2001-07-24 | ピペラジン誘導体 |
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) |
Families Citing this family (87)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE305933T1 (de) * | 2000-07-31 | 2005-10-15 | Hoffmann La Roche | Piperazin derivate |
| GB0106177D0 (en) * | 2001-03-13 | 2001-05-02 | Hoffmann La Roche | Piperazine derivatives |
| EP1491212B1 (en) * | 2002-03-29 | 2012-08-08 | Mitsubishi Tanabe Pharma Corporation | Remedy for sleep disturbance |
| JP4460450B2 (ja) | 2002-06-19 | 2010-05-12 | ビオヴィトルム・アクチボラゲット（プブリクト） | 新規化合物、その使用および製造法 |
| 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 |
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| ATE305933T1 (de) * | 2000-07-31 | 2005-10-15 | Hoffmann La Roche | Piperazin derivate |
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| US20050239789A1 (en) | 2005-10-27 |
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| US20020035110A1 (en) | 2002-03-21 |
| AU2001283955B2 (en) | 2006-05-18 |
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