NO325321B1 - Piperazinylpyrazinforbindelser, preparat, fremgangsmate for fremstilling samt anvendelse av slike - Google Patents
Piperazinylpyrazinforbindelser, preparat, fremgangsmate for fremstilling samt anvendelse av slike Download PDFInfo
- Publication number
- NO325321B1 NO325321B1 NO20032253A NO20032253A NO325321B1 NO 325321 B1 NO325321 B1 NO 325321B1 NO 20032253 A NO20032253 A NO 20032253A NO 20032253 A NO20032253 A NO 20032253A NO 325321 B1 NO325321 B1 NO 325321B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- hydrogen
- formula
- alkyl
- piperazinyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 19
- 238000002360 preparation method Methods 0.000 title claims description 9
- HCGFLVDMFDHYJD-UHFFFAOYSA-N 2-piperazin-1-ylpyrazine Chemical class C1CNCCN1C1=CN=CC=N1 HCGFLVDMFDHYJD-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 86
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 claims abstract description 30
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 claims abstract description 29
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims abstract description 28
- 229940076279 serotonin Drugs 0.000 claims abstract description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 239000001257 hydrogen Substances 0.000 claims description 20
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 150000003839 salts Chemical class 0.000 claims description 13
- 208000019901 Anxiety disease Diseases 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 208000030814 Eating disease Diseases 0.000 claims description 9
- 208000019454 Feeding and Eating disease Diseases 0.000 claims description 9
- 208000008589 Obesity Diseases 0.000 claims description 9
- 235000014632 disordered eating Nutrition 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 235000020824 obesity Nutrition 0.000 claims description 9
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Natural products C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 201000009032 substance abuse Diseases 0.000 claims description 5
- 231100000736 substance abuse Toxicity 0.000 claims description 5
- 208000011117 substance-related disease Diseases 0.000 claims description 5
- 208000026139 Memory disease Diseases 0.000 claims description 4
- 208000019022 Mood disease Diseases 0.000 claims description 4
- 150000001204 N-oxides Chemical class 0.000 claims description 4
- 208000002193 Pain Diseases 0.000 claims description 4
- 201000001880 Sexual dysfunction Diseases 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 231100000872 sexual dysfunction Toxicity 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- KYUMSNOGPIMDDQ-UHFFFAOYSA-N 2-[2-[3-[(4-methylpiperazin-1-yl)methyl]phenoxy]ethoxy]-3-piperazin-1-ylpyrazine Chemical compound C1CN(C)CCN1CC1=CC=CC(OCCOC=2C(=NC=CN=2)N2CCNCC2)=C1 KYUMSNOGPIMDDQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- IMGWDNKFCPQHLO-UHFFFAOYSA-N 2-piperazin-1-yl-3-[2-[3-(pyrrolidin-1-ylmethyl)phenoxy]ethoxy]pyrazine Chemical compound C=1C=CC(CN2CCCC2)=CC=1OCCOC1=NC=CN=C1N1CCNCC1 IMGWDNKFCPQHLO-UHFFFAOYSA-N 0.000 claims description 3
- JOTZYRURFZTPHV-UHFFFAOYSA-N 4-[[3-[2-(3-piperazin-1-ylpyrazin-2-yl)oxyethoxy]phenyl]methyl]morpholine Chemical compound C=1C=CC(CN2CCOCC2)=CC=1OCCOC1=NC=CN=C1N1CCNCC1 JOTZYRURFZTPHV-UHFFFAOYSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- SGQNDQAVSJOBEL-UHFFFAOYSA-N n-[[3-[2-(3-piperazin-1-ylpyrazin-2-yl)oxyethoxy]phenyl]methyl]propan-2-amine Chemical compound CC(C)NCC1=CC=CC(OCCOC=2C(=NC=CN=2)N2CCNCC2)=C1 SGQNDQAVSJOBEL-UHFFFAOYSA-N 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 208000026723 Urinary tract disease Diseases 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 150000004677 hydrates Chemical class 0.000 claims description 2
- 208000014001 urinary system disease Diseases 0.000 claims description 2
- 230000009466 transformation Effects 0.000 claims 1
- 239000003446 ligand Substances 0.000 abstract description 3
- 239000000203 mixture Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- -1 methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy Chemical group 0.000 description 12
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000000018 receptor agonist Substances 0.000 description 8
- 229940044601 receptor agonist Drugs 0.000 description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
- 208000035475 disorder Diseases 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-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
- IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 4
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 235000019439 ethyl acetate Nutrition 0.000 description 4
- 235000019253 formic acid Nutrition 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 230000000862 serotonergic effect Effects 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 101710138093 5-hydroxytryptamine receptor 2C Proteins 0.000 description 3
- 102100024959 5-hydroxytryptamine receptor 2C Human genes 0.000 description 3
- 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 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 230000036506 anxiety Effects 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000003387 indolinyl group Chemical class N1(CCC2=CC=CC=C12)* 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 230000002485 urinary effect Effects 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 101000761348 Homo sapiens 5-hydroxytryptamine receptor 2C Proteins 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 206010046543 Urinary incontinence Diseases 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000000883 anti-obesity agent Substances 0.000 description 2
- 229940125710 antiobesity agent Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 208000015114 central nervous system disease Diseases 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 102000045993 human HTR2C Human genes 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 150000002473 indoazoles Chemical class 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000003449 preventive effect Effects 0.000 description 2
- 150000003233 pyrroles Chemical class 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 208000012672 seasonal affective disease Diseases 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000013585 weight reducing agent Substances 0.000 description 2
- DBGIVFWFUFKIQN-VIFPVBQESA-N (+)-Fenfluramine Chemical compound CCN[C@@H](C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-VIFPVBQESA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 description 1
- VLSDXINSOMDCBK-BQYQJAHWSA-N (E)-1,1'-azobis(N,N-dimethylformamide) Chemical compound CN(C)C(=O)\N=N\C(=O)N(C)C VLSDXINSOMDCBK-BQYQJAHWSA-N 0.000 description 1
- FRZDVWUAWCOHDI-UHFFFAOYSA-N 1,2,3,4,4a,6-hexahydropyrazino[1,2-a]quinoxalin-5-one Chemical compound C1CNCC2C(=O)NC3=CC=CC=C3N21 FRZDVWUAWCOHDI-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- LFWCEWLQBGZAGG-UHFFFAOYSA-N 1-(1-benzofuran-2-yl)piperazine Chemical class C1CNCCN1C1=CC2=CC=CC=C2O1 LFWCEWLQBGZAGG-UHFFFAOYSA-N 0.000 description 1
- QUERAHCHJWZYJF-UHFFFAOYSA-N 1-(1h-indol-2-yl)ethanamine Chemical class C1=CC=C2NC(C(N)C)=CC2=C1 QUERAHCHJWZYJF-UHFFFAOYSA-N 0.000 description 1
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical class C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
- 125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- IVCGJOSPVGENCT-UHFFFAOYSA-N 1h-pyrrolo[2,3-f]quinoline Chemical class N1=CC=CC2=C(NC=C3)C3=CC=C21 IVCGJOSPVGENCT-UHFFFAOYSA-N 0.000 description 1
- MLCNOCRGSBCAGH-UHFFFAOYSA-N 2,3-dichloropyrazine Chemical compound ClC1=NC=CN=C1Cl MLCNOCRGSBCAGH-UHFFFAOYSA-N 0.000 description 1
- BUYVVPMIOHNILW-UHFFFAOYSA-N 2-(2-phenylethenyl)-1-piperazin-1-yl-2h-quinoxaline Chemical class C1CNCCN1N1C2=CC=CC=C2N=CC1C=CC1=CC=CC=C1 BUYVVPMIOHNILW-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- AVCUCRZTRJHDIR-UHFFFAOYSA-N 2-[[3-[2-(3-piperazin-1-ylpyrazin-2-yl)oxyethoxy]phenyl]methylamino]ethanol Chemical compound OCCNCC1=CC=CC(OCCOC=2C(=NC=CN=2)N2CCNCC2)=C1 AVCUCRZTRJHDIR-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- OIXRZHFZHRSXMN-UHFFFAOYSA-N 3-(2h-indazol-3-yl)propan-1-amine Chemical class C1=CC=C2C(CCCN)=NNC2=C1 OIXRZHFZHRSXMN-UHFFFAOYSA-N 0.000 description 1
- FTSXGQSLUBYQAZ-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)-1-phenoxy-2h-quinoxaline Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2N(OC=2C=CC=CC=2)C1 FTSXGQSLUBYQAZ-UHFFFAOYSA-N 0.000 description 1
- WWIUBZGZLNDEPR-UHFFFAOYSA-N 3-methoxy-n-[[3-[2-(3-piperazin-1-ylpyrazin-2-yl)oxyethoxy]phenyl]methyl]aniline Chemical compound COC1=CC=CC(NCC=2C=C(OCCOC=3C(=NC=CN=3)N3CCNCC3)C=CC=2)=C1 WWIUBZGZLNDEPR-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 102000035038 5-HT1 receptors Human genes 0.000 description 1
- 108091005478 5-HT1 receptors Proteins 0.000 description 1
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 1
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
- 108010072584 5-HT2B Serotonin Receptor Proteins 0.000 description 1
- 102000006969 5-HT2B Serotonin Receptor Human genes 0.000 description 1
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- QKEBGAUJUHZNNU-UHFFFAOYSA-N 9h-pyrrolo[2,3-f]quinoxaline Chemical class N1=CC=NC2=C(NC=C3)C3=CC=C21 QKEBGAUJUHZNNU-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- SLHCMPVPVQSTBV-UHFFFAOYSA-N C1=CNC2=C3C=CN=C3C=CC2=C1 Chemical class C1=CNC2=C3C=CN=C3C=CC2=C1 SLHCMPVPVQSTBV-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- OZLGRUXZXMRXGP-UHFFFAOYSA-N Fluo-3 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=C(C=2)C2=C3C=C(Cl)C(=O)C=C3OC3=CC(O)=C(Cl)C=C32)N(CC(O)=O)CC(O)=O)=C1 OZLGRUXZXMRXGP-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101150013372 Htr2c gene Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- UEQUQVLFIPOEMF-UHFFFAOYSA-N Mianserin Chemical compound C1C2=CC=CC=C2N2CCN(C)CC2C2=CC=CC=C21 UEQUQVLFIPOEMF-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 238000006751 Mitsunobu reaction Methods 0.000 description 1
- 206010029333 Neurosis Diseases 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 241000978776 Senegalia senegal Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 102000015007 alpha-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006816 alpha-adrenergic receptor activity proteins Proteins 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 229940125709 anorectic agent Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 235000021229 appetite regulation Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 208000025307 bipolar depression Diseases 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 150000001907 coumarones Chemical class 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960004597 dexfenfluramine Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 235000011167 hydrochloric acid Nutrition 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000009863 impact test Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical group C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229960003955 mianserin Drugs 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- MHTMNQQTGBGJKD-UHFFFAOYSA-N n-[3-(4-phenylpiperazin-1-yl)propyl]pyridin-2-amine Chemical compound C1CN(C=2C=CC=CC=2)CCN1CCCNC1=CC=CC=N1 MHTMNQQTGBGJKD-UHFFFAOYSA-N 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 208000015238 neurotic disease Diseases 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000004526 pharmaceutical effect Effects 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- MQDVUDAZJMZQMF-UHFFFAOYSA-N pyridin-2-ylurea Chemical class NC(=O)NC1=CC=CC=N1 MQDVUDAZJMZQMF-UHFFFAOYSA-N 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 150000003235 pyrrolidines Chemical class 0.000 description 1
- ISZIQZCZKOFSBT-UHFFFAOYSA-N pyrrolo[2,3-g][1]benzazepine Chemical class N1=CC=CC=C2C3=NC=CC3=CC=C21 ISZIQZCZKOFSBT-UHFFFAOYSA-N 0.000 description 1
- 150000005592 pyrroloindoles Chemical class 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000002821 scintillation proximity assay Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- MABNMNVCOAICNO-UHFFFAOYSA-N selenophene Chemical group C=1C=C[se]C=1 MABNMNVCOAICNO-UHFFFAOYSA-N 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000003215 serotonin 5-HT2 receptor antagonist Substances 0.000 description 1
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- IJINSJSWDSHUBL-UHFFFAOYSA-N tert-butyl 4-(3-chloropyrazin-2-yl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=CN=C1Cl IJINSJSWDSHUBL-UHFFFAOYSA-N 0.000 description 1
- ATCSWYASYIDBBB-UHFFFAOYSA-N tert-butyl 4-[3-(2-hydroxyethoxy)pyrazin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=CN=C1OCCO ATCSWYASYIDBBB-UHFFFAOYSA-N 0.000 description 1
- ALZOHEJNMFXRJK-UHFFFAOYSA-N tert-butyl 4-[3-[2-(3-formylphenoxy)ethoxy]pyrazin-2-yl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=NC=CN=C1OCCOC1=CC=CC(C=O)=C1 ALZOHEJNMFXRJK-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical group 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical group C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Chemical group 0.000 description 1
- 150000003852 triazoles Chemical group 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/20—Nitrogen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0004244A SE0004244D0 (sv) | 2000-11-20 | 2000-11-20 | Novel compounds and their use |
| US25370200P | 2000-11-28 | 2000-11-28 | |
| PCT/SE2001/002570 WO2002040457A1 (en) | 2000-11-20 | 2001-11-20 | Piperazinylpyrazines compounds as antagonists of serotonin 5-ht2 receptor |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20032253D0 NO20032253D0 (no) | 2003-05-19 |
| NO20032253L NO20032253L (no) | 2003-07-18 |
| NO325321B1 true NO325321B1 (no) | 2008-03-31 |
Family
ID=26655310
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20032253A NO325321B1 (no) | 2000-11-20 | 2003-05-19 | Piperazinylpyrazinforbindelser, preparat, fremgangsmate for fremstilling samt anvendelse av slike |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP1337518B1 (zh) |
| JP (1) | JP4204315B2 (zh) |
| KR (1) | KR100831909B1 (zh) |
| CN (1) | CN1227237C (zh) |
| AT (1) | ATE433962T1 (zh) |
| AU (1) | AU1529402A (zh) |
| BR (1) | BR0115436A (zh) |
| CA (2) | CA2449899C (zh) |
| DE (1) | DE60139021D1 (zh) |
| DK (1) | DK1337518T3 (zh) |
| EA (1) | EA005975B1 (zh) |
| ES (1) | ES2328671T3 (zh) |
| HK (1) | HK1066810A1 (zh) |
| IL (2) | IL155875A0 (zh) |
| MX (1) | MXPA03004391A (zh) |
| NO (1) | NO325321B1 (zh) |
| NZ (1) | NZ525699A (zh) |
| PL (1) | PL360982A1 (zh) |
| WO (1) | WO2002040457A1 (zh) |
Families Citing this family (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6825198B2 (en) | 2001-06-21 | 2004-11-30 | Pfizer Inc | 5-HT receptor ligands and uses thereof |
| US6858615B2 (en) | 2002-02-19 | 2005-02-22 | Parion Sciences, Inc. | Phenyl guanidine sodium channel blockers |
| SI1645558T1 (sl) * | 2002-06-19 | 2008-10-31 | Biovitrum Ab Publ | Piperazinilpirazini kot modulatorji serotonin 5-HT2C receptorja |
| US7226925B2 (en) | 2002-06-19 | 2007-06-05 | Biovitrum Ab | Compounds, their use and preparation |
| CA2485537A1 (en) * | 2002-06-19 | 2003-12-31 | Biovitrum Ab | 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 |
| CL2004000826A1 (es) * | 2003-04-25 | 2005-03-04 | Pfizer | Uso de un agonista para el receptor 5-ht2c para preparar un medicamento util en el tratamiento de la incontinencia urinaria provocada por estres, con la condicion de que el agonista no sea 1-[6-cloro-5-(trifluorometil)-2-piridinil]piperazina (org-129 |
| WO2005028438A1 (ja) | 2003-09-22 | 2005-03-31 | Banyu Pharmaceutical Co., Ltd. | 新規ピペリジン誘導体 |
| 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 |
| CA2577060A1 (en) | 2004-08-13 | 2006-02-23 | Amgen Inc. | Substituted benzofused heterocycles |
| EP2400300A1 (en) | 2004-08-25 | 2011-12-28 | Takeda Pharmaceutical Company Limited | Method of screening preventives/remedies for stress urinary incontinence |
| EP1814590B2 (en) | 2004-11-01 | 2013-12-11 | Amylin Pharmaceuticals, Inc. | Treatment of obesity and related disorders |
| US20090286723A1 (en) | 2005-02-11 | 2009-11-19 | Amylin Pharmaceuticals, Inc. | Hybrid Polypeptides with Selectable Properties |
| US7737155B2 (en) | 2005-05-17 | 2010-06-15 | Schering Corporation | Nitrogen-containing heterocyclic compounds and methods of use thereof |
| ES2574014T3 (es) | 2005-05-30 | 2016-06-14 | Msd K.K. | Derivado de piperidina novedoso |
| EP1916239A4 (en) | 2005-08-10 | 2009-10-21 | Banyu Pharma Co Ltd | PYRIDONE COMPOUND |
| BRPI0614649A2 (pt) | 2005-08-11 | 2011-04-12 | Amylin Pharmaceuticals Inc | polipeptìdeos hìbridos com propriedades selecionáveis |
| EP1921065B1 (en) | 2005-08-24 | 2010-10-20 | Banyu Pharmaceutical Co., Ltd. | Phenylpyridone derivative |
| WO2007029847A1 (ja) | 2005-09-07 | 2007-03-15 | Banyu Pharmaceutical Co., Ltd. | 二環性芳香族置換ピリドン誘導体 |
| EP1940842B1 (en) | 2005-09-29 | 2012-05-30 | Merck Sharp & Dohme Corp. | Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators |
| BRPI0617621A2 (pt) | 2005-10-21 | 2011-08-02 | Novartis Ag | combinação de compostos orgánicos |
| AU2006307046A1 (en) | 2005-10-27 | 2007-05-03 | Msd K.K. | Novel benzoxathiin derivative |
| MY146564A (en) | 2005-11-10 | 2012-08-30 | Msd Kk | Aza-substituted spiro 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 |
| EP2698157B1 (en) | 2006-09-22 | 2015-05-20 | Merck Sharp & Dohme Corp. | Method of treatment using fatty acid synthesis inhibitors |
| WO2008038692A1 (fr) | 2006-09-28 | 2008-04-03 | Banyu Pharmaceutical Co., Ltd. | dÉrivÉ de diarylcÉtimine |
| US8431552B2 (en) | 2007-01-16 | 2013-04-30 | Chien-Hung Chen | Composition for treating metabolic syndrome |
| AU2008233662B2 (en) | 2007-04-02 | 2012-08-23 | Msd K.K. | Indoledione derivative |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| US7879802B2 (en) | 2007-06-04 | 2011-02-01 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP2216023A4 (en) | 2007-11-15 | 2013-03-13 | Takeda Pharmaceutical | CONDENSED PYRIDINE DERIVATIVE AND USE THEREOF |
| CA2714617A1 (en) | 2008-03-06 | 2009-09-11 | Banyu Pharmaceutical Co., Ltd. | Alkylaminopyridine derivative |
| US20110015198A1 (en) | 2008-03-28 | 2011-01-20 | Banyu Pharmaceutical Co., Inc. | Diarylmethylamide derivative having melanin-concentrating hormone receptor antagonism |
| CA2666036C (en) | 2008-05-16 | 2017-09-12 | Chien-Hung Chen | Novel compositions and methods for treating hyperproliferative diseases |
| EP2301936A1 (en) | 2008-06-19 | 2011-03-30 | Banyu Pharmaceutical Co., Ltd. | Spirodiamine-diarylketoxime derivative |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| EP2319841A1 (en) | 2008-07-30 | 2011-05-11 | Msd K.K. | (5-membered)-(5-membered) or (5-membered)-(6-membered) fused ring cycloalkylamine derivative |
| CA2741125A1 (en) | 2008-10-22 | 2010-04-29 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| CA2741644C (en) | 2008-10-30 | 2013-05-07 | Merck Sharp & Dohme Corp. | Isonicotinamide orexin receptor antagonists |
| WO2010051206A1 (en) | 2008-10-31 | 2010-05-06 | Merck Sharp & Dohme Corp. | Novel cyclic benzimidazole derivatives useful anti-diabetic agents |
| US20110243940A1 (en) | 2008-12-16 | 2011-10-06 | Schering Corporation | Bicyclic pyranone derivatives and methods of use thereof |
| EP2379547A1 (en) | 2008-12-16 | 2011-10-26 | Schering Corporation | Pyridopyrimidine derivatives and methods of use thereof |
| CN102458579B (zh) | 2009-06-15 | 2014-11-05 | 武田药品工业株式会社 | 吡嗪并氧氮杂*衍生物 |
| US20120253036A1 (en) | 2009-12-11 | 2012-10-04 | Yukinori Nagakura | Agent for treating fibromyalgia |
| US8895596B2 (en) | 2010-02-25 | 2014-11-25 | Merck Sharp & Dohme Corp | Cyclic benzimidazole derivatives useful as anti-diabetic agents |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| EP2677869B1 (en) | 2011-02-25 | 2017-11-08 | Merck Sharp & Dohme Corp. | Novel cyclic azabenzimidazole derivatives useful as anti-diabetic agents |
| CN108676076A (zh) | 2011-03-01 | 2018-10-19 | 辛纳吉制药公司 | 制备鸟苷酸环化酶c激动剂的方法 |
| AR086745A1 (es) | 2011-06-27 | 2014-01-22 | Parion Sciences Inc | 3,5-diamino-6-cloro-n-(n-(4-(4-(2-(hexil(2,3,4,5,6-pentahidroxihexil)amino)etoxi)fenil)butil)carbamimidoil)pirazina-2-carboxamida |
| AR088352A1 (es) | 2011-10-19 | 2014-05-28 | Merck Sharp & Dohme | Antagonistas del receptor de 2-piridiloxi-4-nitrilo orexina |
| AU2013296470B2 (en) | 2012-08-02 | 2016-03-17 | Merck Sharp & Dohme Corp. | Antidiabetic tricyclic compounds |
| US9029382B2 (en) * | 2012-12-17 | 2015-05-12 | Parion Sciences, Inc. | 3,5-diamino-6-chloro-N-(N-(4-phenylbutyl)carbamimidoyl) pyrazine-2-carboxamide compounds |
| HUE032891T2 (hu) | 2012-12-17 | 2017-11-28 | Parion Sciences Inc | Klórpirazin-karboxamid-származékok nem kielégítõ nyálkahártya-hidratáció által elõsegített megbetegedések kezelésére |
| WO2014139388A1 (en) | 2013-03-14 | 2014-09-18 | Merck Sharp & Dohme Corp. | Novel indole derivatives useful as anti-diabetic agents |
| US9708367B2 (en) | 2013-03-15 | 2017-07-18 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase and their uses |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| JP6606491B2 (ja) | 2013-06-05 | 2019-11-13 | シナジー ファーマシューティカルズ インコーポレイテッド | グアニル酸シクラーゼｃの超高純度アゴニスト、その作成および使用方法 |
| US9102633B2 (en) | 2013-12-13 | 2015-08-11 | Parion Sciences, Inc. | Arylalkyl- and aryloxyalkyl-substituted epithelial sodium channel blocking compounds |
| JP6769963B2 (ja) | 2014-08-29 | 2020-10-14 | ティエエッセ ファルマ ソチエタ レスポンサビリタ リミタータ | α−アミノ−β−カルボキシムコン酸セミアルデヒド脱炭酸酵素の阻害剤 |
| TW201729814A (zh) * | 2015-12-24 | 2017-09-01 | 武田藥品工業股份有限公司 | 固形製劑 |
| AU2017342083A1 (en) | 2016-10-14 | 2019-04-11 | Tes Pharma S.R.L. | Inhibitors of alpha-amino-beta-carboxymuconic acid semialdehyde decarboxylase |
| EP3733204A4 (en) | 2017-12-27 | 2021-09-15 | Takeda Pharmaceutical Company Limited | THERAPEUTIC FOR EXERCISE INCONTINENCE AND STAIR INCONTINENCE |
| KR20210111248A (ko) | 2018-11-20 | 2021-09-10 | 테스 파마 에스.알.엘. | α-아미노-β-카르복시뮤콘산 세미알데하이드 데카르복실라제의 저해제 |
| WO2020167706A1 (en) | 2019-02-13 | 2020-08-20 | Merck Sharp & Dohme Corp. | 5-alkyl pyrrolidine orexin receptor agonists |
| WO2021026047A1 (en) | 2019-08-08 | 2021-02-11 | Merck Sharp & Dohme Corp. | Heteroaryl pyrrolidine and piperidine orexin receptor agonists |
| CN112341397B (zh) * | 2019-08-09 | 2023-05-23 | 成都苑东生物制药股份有限公司 | 吡嗪类衍生物或盐、异构体、其制备方法及用途 |
| CR20230089A (es) | 2020-08-18 | 2023-04-11 | Merck Sharp & Dohme Llc | Agonistas de bicicloheptano pirrolidina de los receptores de orexina |
Family Cites Families (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3253989A (en) | 1963-02-11 | 1966-05-31 | American Cyanamid Co | Process for producing anorexia |
| US4081542A (en) | 1975-04-21 | 1978-03-28 | Merck & Co., Inc. | Piperazinylpyrazines |
| EP0572863A1 (de) | 1992-06-05 | 1993-12-08 | F. Hoffmann-La Roche Ag | ZNS Pyrazinoindole |
| TW270114B (zh) | 1993-10-22 | 1996-02-11 | Hoffmann La Roche | |
| TW334423B (en) | 1993-10-22 | 1998-06-21 | Hoffmann La Roche | Tricyclic 1-aminoethylpyrrole-derivatives |
| FR2722788B1 (fr) | 1994-07-20 | 1996-10-04 | Pf Medicament | Nouvelles piperazides derivees d'aryl piperazine, leurs procedes de preparation, leur utilisation a titre de medicament et les compositions pharmaceutiques les comprenant |
| GB9420999D0 (en) | 1994-10-18 | 1994-12-07 | Smithkline Beecham Plc | Novel compounds |
| US5688795A (en) | 1994-11-08 | 1997-11-18 | Syntex (U.S.A.) Inc. | 3-(4-phenylpiperazin-1-yl)propyl-amino, thio and oxy!-pyridine, pyrimidine and benzene derivatives as α1 -adrenoceptor antagonists |
| FR2740134B1 (fr) | 1995-10-18 | 1998-01-09 | Pf Medicament | Derives d'amines cycliques d'aryl-piperazines, leur preparation et les compositions pharmaceutiques les contenant |
| JP3560986B2 (ja) | 1997-01-13 | 2004-09-02 | 山之内製薬株式会社 | ５―ｈｔ２ｃ受容体作用薬及びアミノアルキルインダゾール誘導体 |
| ES2208812T3 (es) | 1997-02-25 | 2004-06-16 | Akzo Nobel N.V. | Derivados de azetidina y de pirrolidina. |
| AU727654B2 (en) | 1997-06-13 | 2000-12-21 | Yamanouchi Pharmaceutical Co., Ltd. | Tricyclic pyrazole derivative |
| WO1999011930A1 (de) | 1997-08-29 | 1999-03-11 | Luk Fahrzeug-Hydraulik Gmbh & Co. Kg | Taumelscheibenkompressor |
| JPH11279159A (ja) * | 1998-03-24 | 1999-10-12 | Nippon Soda Co Ltd | 光学活性なピペラジンカルボン酸エステルの製造方法 |
| AU4037699A (en) | 1998-05-08 | 1999-11-29 | Akzo Nobel N.V. | Novel aryl-hydro naphthalenal kanamines |
| GB9819019D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds II |
| GB9819020D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds III |
| GB9819032D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds IV |
| GB9819033D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Ltd | Chemical compounds VI |
| GB9819035D0 (en) | 1998-09-01 | 1998-10-28 | Cerebrus Res Ltd | Chemical compounds VII |
| GB9820767D0 (en) | 1998-09-23 | 1998-11-18 | Cerebrus Ltd | Chemical compounds VIII |
| WO2000035922A1 (en) | 1998-12-17 | 2000-06-22 | American Home Products Corporation | 2,3,4,4a-tetrahydro-1h-pyrazino(1,2-a)quinoxalin-5(6h)one derivates being 5ht2c agonists |
| JP2002535396A (ja) | 1999-01-27 | 2002-10-22 | イーライ・リリー・アンド・カンパニー | セロトニン（５−ｈｔ（２ｃ））アゴニストとしてのアミノアルキルベンゾフラン類 |
| GB9902047D0 (en) | 1999-01-29 | 1999-03-17 | Cerebrus Ltd | Chemical compounds XI |
| EA005820B1 (ru) | 1999-05-21 | 2005-06-30 | Биовитрум Аб | Агонисты и антагонисты рецепторов 5-ht |
| IL145998A0 (en) | 1999-06-15 | 2002-07-25 | Du Pont Pharm Co | Substituted heterocycle fused gamma-carbolines |
| MXPA02000914A (es) | 1999-07-29 | 2002-07-30 | Lilly Co Eli | Benzofuranos serotonergicos. |
| ES2203498T3 (es) | 1999-07-29 | 2004-04-16 | Eli Lilly And Company | Benzofurilpiperazinas: agonistas de receptor 5-ht2c de la serotonina. |
| PT1204658E (pt) | 1999-07-29 | 2003-08-29 | Lilly Co Eli | Agonistas benzofurilpiperazina de serotonina |
| JP2003506371A (ja) | 1999-07-29 | 2003-02-18 | イーライ・リリー・アンド・カンパニー | セロトニン作動性ベンゾチオフェン |
| GB9918965D0 (en) | 1999-08-11 | 1999-10-13 | Cerebrus Ltd | Chemical compounds xxi |
| GB9918962D0 (en) | 1999-08-11 | 1999-10-13 | Cerebrus Ltd | Chemical compounds xxii |
-
2001
- 2001-11-20 CA CA2449899A patent/CA2449899C/en not_active Expired - Fee Related
- 2001-11-20 DK DK01983901T patent/DK1337518T3/da active
- 2001-11-20 KR KR1020037006822A patent/KR100831909B1/ko not_active IP Right Cessation
- 2001-11-20 MX MXPA03004391A patent/MXPA03004391A/es active IP Right Grant
- 2001-11-20 CN CNB018192416A patent/CN1227237C/zh not_active Expired - Fee Related
- 2001-11-20 JP JP2002542785A patent/JP4204315B2/ja not_active Expired - Fee Related
- 2001-11-20 EA EA200300595A patent/EA005975B1/ru not_active IP Right Cessation
- 2001-11-20 IL IL15587501A patent/IL155875A0/xx active IP Right Grant
- 2001-11-20 NZ NZ525699A patent/NZ525699A/en unknown
- 2001-11-20 AT AT01983901T patent/ATE433962T1/de not_active IP Right Cessation
- 2001-11-20 AU AU1529402A patent/AU1529402A/xx not_active Withdrawn
- 2001-11-20 BR BR0115436-2A patent/BR0115436A/pt not_active IP Right Cessation
- 2001-11-20 ES ES01983901T patent/ES2328671T3/es not_active Expired - Lifetime
- 2001-11-20 PL PL36098201A patent/PL360982A1/xx unknown
- 2001-11-20 EP EP01983901A patent/EP1337518B1/en not_active Expired - Lifetime
- 2001-11-20 CA CA002428905A patent/CA2428905A1/en active Pending
- 2001-11-20 DE DE60139021T patent/DE60139021D1/de not_active Expired - Lifetime
- 2001-11-20 WO PCT/SE2001/002570 patent/WO2002040457A1/en active IP Right Grant
-
2003
- 2003-05-12 IL IL155875A patent/IL155875A/en not_active IP Right Cessation
- 2003-05-19 NO NO20032253A patent/NO325321B1/no not_active IP Right Cessation
-
2004
- 2004-12-14 HK HK04109907A patent/HK1066810A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2449899A1 (en) | 2002-05-23 |
| ES2328671T3 (es) | 2009-11-17 |
| EP1337518A1 (en) | 2003-08-27 |
| KR100831909B1 (ko) | 2008-05-26 |
| EA005975B1 (ru) | 2005-08-25 |
| CN1520404A (zh) | 2004-08-11 |
| DK1337518T3 (da) | 2009-10-19 |
| JP2004531465A (ja) | 2004-10-14 |
| CA2449899C (en) | 2010-04-06 |
| KR20030060946A (ko) | 2003-07-16 |
| EP1337518B1 (en) | 2009-06-17 |
| MXPA03004391A (es) | 2004-05-31 |
| HK1066810A1 (en) | 2005-04-01 |
| IL155875A0 (en) | 2003-12-23 |
| CN1227237C (zh) | 2005-11-16 |
| PL360982A1 (en) | 2004-09-20 |
| ATE433962T1 (de) | 2009-07-15 |
| NO20032253L (no) | 2003-07-18 |
| NO20032253D0 (no) | 2003-05-19 |
| WO2002040457A1 (en) | 2002-05-23 |
| EA200300595A1 (ru) | 2003-10-30 |
| NZ525699A (en) | 2005-03-24 |
| BR0115436A (pt) | 2004-01-06 |
| IL155875A (en) | 2007-06-17 |
| JP4204315B2 (ja) | 2009-01-07 |
| AU1529402A (en) | 2002-05-27 |
| CA2428905A1 (en) | 2002-05-23 |
| DE60139021D1 (de) | 2009-07-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO325321B1 (no) | Piperazinylpyrazinforbindelser, preparat, fremgangsmate for fremstilling samt anvendelse av slike | |
| DE60024986T2 (de) | Pyrazinyl-piperazin-verbindungen, ihre anwendung und herstellung | |
| AU2003228196B2 (en) | Novel compounds and their use | |
| KR100846339B1 (ko) | 세로토닌 5ｈｔ-2 수용체의 아고니스트 또는안타고니스트로서의 피페라지닐피라진 화합물 | |
| US6593330B2 (en) | Compounds and their use | |
| AU2002224266A1 (en) | Piperazinylpyrazine compounds as agonist or antagonist of serotonin 5HT-2 receptor | |
| DE60311822T2 (de) | Neue piperazinyl-pyrazinon-derivate zur behandlung von 5-ht2a rezeptor-bedingten erkrankungen | |
| AU2002215294B2 (en) | Piperazinylpyrazines compounds as antagonists of serotonin 5-HT2 receptor | |
| US6756377B2 (en) | Compounds and their use | |
| JP4831966B2 (ja) | ５−ｈｔ２ａ受容体関連疾患の治療のための新規ピペラジニル−ピラジノン誘導体 | |
| AU2002215294A1 (en) | Piperazinylpyrazines compounds as antagonists of serotonin 5-HT2 receptor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |