CN1246319C - 氨基(硫)醚衍生物 - Google Patents
氨基(硫)醚衍生物 Download PDFInfo
- Publication number
- CN1246319C CN1246319C CNB951184857A CN95118485A CN1246319C CN 1246319 C CN1246319 C CN 1246319C CN B951184857 A CNB951184857 A CN B951184857A CN 95118485 A CN95118485 A CN 95118485A CN 1246319 C CN1246319 C CN 1246319C
- Authority
- CN
- China
- Prior art keywords
- amine
- pyridylmethyl
- fluorophenyl
- phenyl
- chroman
- 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
- -1 Amino (thio) ether derivative Chemical class 0.000 title description 76
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- BDZPHQXGOYWJRH-UHFFFAOYSA-N 3-(chloromethyl)-5-(4-fluorophenyl)pyridine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CCl)=C1 BDZPHQXGOYWJRH-UHFFFAOYSA-N 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 17
- 238000002360 preparation method Methods 0.000 claims description 8
- BSRHATGBRQMDRF-SECBINFHSA-N [(2r)-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C1=CC=C2O[C@@H](CN)CCC2=C1 BSRHATGBRQMDRF-SECBINFHSA-N 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- HKFMQJUJWSFOLY-OAQYLSRUSA-N sarizotan Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNC[C@@H]2OC3=CC=CC=C3CC2)=C1 HKFMQJUJWSFOLY-OAQYLSRUSA-N 0.000 claims 5
- 239000007788 liquid Substances 0.000 claims 2
- 239000002671 adjuvant Substances 0.000 claims 1
- 208000015114 central nervous system disease Diseases 0.000 claims 1
- 239000007787 solid Substances 0.000 claims 1
- 210000003169 central nervous system Anatomy 0.000 abstract description 5
- RJCQMRTZKKPRPL-UHFFFAOYSA-N s-aminosulfanyloxythiohydroxylamine Chemical class NSOSN RJCQMRTZKKPRPL-UHFFFAOYSA-N 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 76
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 61
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 25
- ZLGXNIIHDBZMNX-UHFFFAOYSA-N 2-chloro-n-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound ClCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 ZLGXNIIHDBZMNX-UHFFFAOYSA-N 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
- 125000004432 carbon atom Chemical group C* 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- BSRHATGBRQMDRF-UHFFFAOYSA-N 3,4-dihydro-2h-chromen-2-ylmethanamine Chemical compound C1=CC=C2OC(CN)CCC2=C1 BSRHATGBRQMDRF-UHFFFAOYSA-N 0.000 description 13
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- 159000000000 sodium salts Chemical class 0.000 description 13
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- 229910052760 oxygen Inorganic materials 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 238000006722 reduction reaction Methods 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- MPRYFARMZZMORH-UHFFFAOYSA-N (8-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1CC(CN)OC2=C1C=CC=C2OC MPRYFARMZZMORH-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 125000002947 alkylene group Chemical group 0.000 description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- VQUYNUJARXBNPK-UHFFFAOYSA-N 2-chloroethoxybenzene Chemical compound ClCCOC1=CC=CC=C1 VQUYNUJARXBNPK-UHFFFAOYSA-N 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 239000012442 inert solvent Substances 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- ASPSZCAHOMXPBE-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-2-ylmethanamine Chemical compound C1=CC=C2OC(CN)CC2=C1 ASPSZCAHOMXPBE-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 150000002431 hydrogen Chemical class 0.000 description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 6
- NESLWCLHZZISNB-UHFFFAOYSA-M sodium phenolate Chemical compound [Na+].[O-]C1=CC=CC=C1 NESLWCLHZZISNB-UHFFFAOYSA-M 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- 230000029936 alkylation Effects 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 238000009835 boiling Methods 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 239000011976 maleic acid Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- WKHABRRJMGVELW-UHFFFAOYSA-N (3-phenylphenyl)methanamine Chemical group NCC1=CC=CC(C=2C=CC=CC=2)=C1 WKHABRRJMGVELW-UHFFFAOYSA-N 0.000 description 4
- MXJXTNWYRKHFJH-UHFFFAOYSA-N 1-(chloromethyl)-3-(4-fluorophenyl)benzene Chemical group C1=CC(F)=CC=C1C1=CC=CC(CCl)=C1 MXJXTNWYRKHFJH-UHFFFAOYSA-N 0.000 description 4
- FHEGFPVBHPQEAV-UHFFFAOYSA-N 3-(chloromethyl)-5-phenylpyridine Chemical compound ClCC1=CN=CC(C=2C=CC=CC=2)=C1 FHEGFPVBHPQEAV-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 208000006011 Stroke Diseases 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 206010008118 cerebral infarction Diseases 0.000 description 4
- 239000003638 chemical reducing agent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 4
- YKRYFMJQINAEOO-UHFFFAOYSA-N 1-(chloromethyl)-3-phenylbenzene Chemical group ClCC1=CC=CC(C=2C=CC=CC=2)=C1 YKRYFMJQINAEOO-UHFFFAOYSA-N 0.000 description 3
- AYLPNQWPUSUCMH-UHFFFAOYSA-N 2-[2-[(5-phenylpyridin-3-yl)methylamino]ethoxy]benzonitrile Chemical compound N#CC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 AYLPNQWPUSUCMH-UHFFFAOYSA-N 0.000 description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
- GWADUFIGYRVHFU-UHFFFAOYSA-N 4-[2-[(5-phenylpyridin-3-yl)methylamino]ethoxy]benzonitrile Chemical compound C1=CC(C#N)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 GWADUFIGYRVHFU-UHFFFAOYSA-N 0.000 description 3
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical compound [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 3
- MPRYFARMZZMORH-VIFPVBQESA-N [(2s)-8-methoxy-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C1C[C@@H](CN)OC2=C1C=CC=C2OC MPRYFARMZZMORH-VIFPVBQESA-N 0.000 description 3
- XIINCIMTFZJTCR-UHFFFAOYSA-N [5-(4-fluorophenyl)pyridin-3-yl]methanamine Chemical compound NCC1=CN=CC(C=2C=CC(F)=CC=2)=C1 XIINCIMTFZJTCR-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium chloride Substances Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003054 catalyst Substances 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
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 125000001544 thienyl group Chemical group 0.000 description 3
- RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- AXJVRESUYVYSDH-UHFFFAOYSA-N (6-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound O1C(CN)CCC2=CC(OC)=CC=C21 AXJVRESUYVYSDH-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- HHTDFLDGRRRZQO-UHFFFAOYSA-N 1-(chloromethyl)-3-(4-methoxyphenyl)benzene Chemical group C1=CC(OC)=CC=C1C1=CC=CC(CCl)=C1 HHTDFLDGRRRZQO-UHFFFAOYSA-N 0.000 description 2
- SOWUIXJDGINAKM-UHFFFAOYSA-N 1-(chloromethyl)-3-[4-(trifluoromethyl)phenyl]benzene Chemical group C1=CC(C(F)(F)F)=CC=C1C1=CC=CC(CCl)=C1 SOWUIXJDGINAKM-UHFFFAOYSA-N 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- IXQGCWUGDFDQMF-UHFFFAOYSA-N 2-Ethylphenol Chemical compound CCC1=CC=CC=C1O IXQGCWUGDFDQMF-UHFFFAOYSA-N 0.000 description 2
- JZFPIQGMMCUEHB-UHFFFAOYSA-N 2-[3-(chloromethyl)phenyl]pyridine Chemical compound ClCC1=CC=CC(C=2N=CC=CC=2)=C1 JZFPIQGMMCUEHB-UHFFFAOYSA-N 0.000 description 2
- VBFQJXUDSNZZTP-UHFFFAOYSA-N 2-chloro-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCCl)=C1 VBFQJXUDSNZZTP-UHFFFAOYSA-N 0.000 description 2
- GVJHMXWXZBNGRQ-UHFFFAOYSA-N 3-(2-hydroxyphenyl)propanal Chemical compound OC1=CC=CC=C1CCC=O GVJHMXWXZBNGRQ-UHFFFAOYSA-N 0.000 description 2
- JNZYADHPGVZMQK-UHFFFAOYSA-N 3-(aminomethyl)phenol Chemical compound NCC1=CC=CC(O)=C1 JNZYADHPGVZMQK-UHFFFAOYSA-N 0.000 description 2
- RHUHQMPGEPJAAT-UHFFFAOYSA-N 3-(chloromethyl)-5-(4-methoxyphenyl)pyridine Chemical compound C1=CC(OC)=CC=C1C1=CN=CC(CCl)=C1 RHUHQMPGEPJAAT-UHFFFAOYSA-N 0.000 description 2
- HMNKTRSOROOSPP-UHFFFAOYSA-N 3-Ethylphenol Chemical compound CCC1=CC=CC(O)=C1 HMNKTRSOROOSPP-UHFFFAOYSA-N 0.000 description 2
- VWVVICJGKPEGIS-UHFFFAOYSA-N 3-[3-(chloromethyl)phenyl]pyridine Chemical compound ClCC1=CC=CC(C=2C=NC=CC=2)=C1 VWVVICJGKPEGIS-UHFFFAOYSA-N 0.000 description 2
- WULNDUPZYLKLBH-UHFFFAOYSA-N 3-ethylbenzenethiol Chemical compound CCC1=CC=CC(S)=C1 WULNDUPZYLKLBH-UHFFFAOYSA-N 0.000 description 2
- SGHBRHKBCLLVCI-UHFFFAOYSA-N 3-hydroxybenzonitrile Chemical compound OC1=CC=CC(C#N)=C1 SGHBRHKBCLLVCI-UHFFFAOYSA-N 0.000 description 2
- ASHGTJPOSUFTGB-UHFFFAOYSA-N 3-methoxyphenol Chemical compound COC1=CC=CC(O)=C1 ASHGTJPOSUFTGB-UHFFFAOYSA-N 0.000 description 2
- QXEZEAAWHVLCAG-UHFFFAOYSA-N 4-[2-[(5-phenylpyridin-3-yl)methylamino]ethylsulfanyl]benzonitrile Chemical compound C(#N)C1=CC=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=C1 QXEZEAAWHVLCAG-UHFFFAOYSA-N 0.000 description 2
- WXNZTHHGJRFXKQ-UHFFFAOYSA-N 4-chlorophenol Chemical compound OC1=CC=C(Cl)C=C1 WXNZTHHGJRFXKQ-UHFFFAOYSA-N 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 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
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- 101150065749 Churc1 gene Proteins 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102100038239 Protein Churchill Human genes 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 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 2
- BSRHATGBRQMDRF-VIFPVBQESA-N [(2s)-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C1=CC=C2O[C@H](CN)CCC2=C1 BSRHATGBRQMDRF-VIFPVBQESA-N 0.000 description 2
- LEKRFSJCHRYVQJ-UHFFFAOYSA-N [3-(4-fluorophenyl)phenyl]methanamine Chemical group NCC1=CC=CC(C=2C=CC(F)=CC=2)=C1 LEKRFSJCHRYVQJ-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 235000011054 acetic acid Nutrition 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000005917 acylation reaction Methods 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 208000026106 cerebrovascular disease Diseases 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 150000008282 halocarbons Chemical class 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 description 2
- 150000002689 maleic acids Chemical class 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229910052987 metal hydride Inorganic materials 0.000 description 2
- 150000004681 metal hydrides Chemical class 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- OHENIKJJOMSFDD-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-(6-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1CC2=CC(OC)=CC=C2OC1CNCC(C=1)=CN=CC=1C1=CC=C(F)C=C1 OHENIKJJOMSFDD-UHFFFAOYSA-N 0.000 description 2
- HCKAIPLMPTWXPD-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-(2-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC(F)=CC=2)=C1 HCKAIPLMPTWXPD-UHFFFAOYSA-N 0.000 description 2
- XXNMHEIKWWDUSM-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-phenoxyethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C=CC=CC=2)=C1 XXNMHEIKWWDUSM-UHFFFAOYSA-N 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 150000003891 oxalate salts Chemical class 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- WLJVNTCWHIRURA-UHFFFAOYSA-N pimelic acid Chemical compound OC(=O)CCCCCC(O)=O WLJVNTCWHIRURA-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Chemical group 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 2
- 125000001302 tertiary amino group Chemical group 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 229910052723 transition metal Inorganic materials 0.000 description 2
- 150000003624 transition metals Chemical class 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 1
- UDLPZWJCNIRBJZ-UHFFFAOYSA-N (4-chlorothiophen-2-yl)methanamine Chemical compound NCC1=CC(Cl)=CS1 UDLPZWJCNIRBJZ-UHFFFAOYSA-N 0.000 description 1
- CKVMSFWKVKDEHE-UHFFFAOYSA-N (4-ethylthiophen-2-yl)methanamine Chemical compound CCC1=CSC(CN)=C1 CKVMSFWKVKDEHE-UHFFFAOYSA-N 0.000 description 1
- YGQBEIPTDGUSRG-UHFFFAOYSA-N (4-methoxythiophen-2-yl)methanamine Chemical compound COC1=CSC(CN)=C1 YGQBEIPTDGUSRG-UHFFFAOYSA-N 0.000 description 1
- CKQHNKAVFNDGMK-UHFFFAOYSA-N (4-methylthiophen-2-yl)methanamine Chemical compound CC1=CSC(CN)=C1 CKQHNKAVFNDGMK-UHFFFAOYSA-N 0.000 description 1
- AXMUFYSHNXIVKX-UHFFFAOYSA-N (4-thiophen-3-ylthiophen-2-yl)methanamine Chemical compound S1C(CN)=CC(C2=CSC=C2)=C1 AXMUFYSHNXIVKX-UHFFFAOYSA-N 0.000 description 1
- XEFMTYABZVBBJZ-UHFFFAOYSA-N (5-fluoro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=CC=C2OC(CN)CCC2=C1F XEFMTYABZVBBJZ-UHFFFAOYSA-N 0.000 description 1
- XLAPFRUTQHYMHF-UHFFFAOYSA-N (5-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound O1C(CN)CCC2=C1C=CC=C2OC XLAPFRUTQHYMHF-UHFFFAOYSA-N 0.000 description 1
- HGZDYYSMCSCHRZ-UHFFFAOYSA-N (5-phenylpyridin-3-yl)methanamine Chemical compound NCC1=CN=CC(C=2C=CC=CC=2)=C1 HGZDYYSMCSCHRZ-UHFFFAOYSA-N 0.000 description 1
- PILLPDVRFOWQOC-UHFFFAOYSA-N (6-bromo-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound BrC1=CC=C2OC(CN)CCC2=C1 PILLPDVRFOWQOC-UHFFFAOYSA-N 0.000 description 1
- MVAVRMCGIDQFGB-UHFFFAOYSA-N (6-chloro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound ClC1=CC=C2OC(CN)CCC2=C1 MVAVRMCGIDQFGB-UHFFFAOYSA-N 0.000 description 1
- IYPVOSGPLOGNNR-UHFFFAOYSA-N (6-fluoro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound FC1=CC=C2OC(CN)CCC2=C1 IYPVOSGPLOGNNR-UHFFFAOYSA-N 0.000 description 1
- DTVCVLXCWWYFLS-UHFFFAOYSA-N (6-nitro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound [O-][N+](=O)C1=CC=C2OC(CN)CCC2=C1 DTVCVLXCWWYFLS-UHFFFAOYSA-N 0.000 description 1
- LUKNXDIOFDVOMZ-UHFFFAOYSA-N (6-phenyl-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C=1C=C2OC(CN)CCC2=CC=1C1=CC=CC=C1 LUKNXDIOFDVOMZ-UHFFFAOYSA-N 0.000 description 1
- CLWUGRNLPFYQDU-UHFFFAOYSA-N (7-chloro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=C(Cl)C=C2OC(CN)CCC2=C1 CLWUGRNLPFYQDU-UHFFFAOYSA-N 0.000 description 1
- ZQQRVTOMJQOPSA-UHFFFAOYSA-N (7-fluoro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=C(F)C=C2OC(CN)CCC2=C1 ZQQRVTOMJQOPSA-UHFFFAOYSA-N 0.000 description 1
- LSMOFSDBIWYJKZ-UHFFFAOYSA-N (7-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1CC(CN)OC2=CC(OC)=CC=C21 LSMOFSDBIWYJKZ-UHFFFAOYSA-N 0.000 description 1
- ISDQNDJWJALGFN-UHFFFAOYSA-N (8-chloro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=CC(Cl)=C2OC(CN)CCC2=C1 ISDQNDJWJALGFN-UHFFFAOYSA-N 0.000 description 1
- WFTVJLFTPPMEPU-UHFFFAOYSA-N (8-fluoro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=CC(F)=C2OC(CN)CCC2=C1 WFTVJLFTPPMEPU-UHFFFAOYSA-N 0.000 description 1
- TWCLVALPNOBYQF-UHFFFAOYSA-N (8-nitro-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1=CC([N+]([O-])=O)=C2OC(CN)CCC2=C1 TWCLVALPNOBYQF-UHFFFAOYSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- TZHUQTUFZKRYLV-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-2-yl)-N-[[5-(4-methoxyphenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(OC)=CC=C1C1=CN=CC(CNCC2OC3=CC=CC=C3C2)=C1 TZHUQTUFZKRYLV-UHFFFAOYSA-N 0.000 description 1
- JHUHINYYJBEUIB-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-2-yl)-n-[[5-(2,4-dimethoxyphenyl)pyridin-3-yl]methyl]methanamine Chemical compound COC1=CC(OC)=CC=C1C1=CN=CC(CNCC2OC3=CC=CC=C3C2)=C1 JHUHINYYJBEUIB-UHFFFAOYSA-N 0.000 description 1
- WROUXLCLQNBFFP-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-2-yl)-n-[[5-(3,4,5-trifluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound FC1=C(F)C(F)=CC(C=2C=C(CNCC3OC4=CC=CC=C4C3)C=NC=2)=C1 WROUXLCLQNBFFP-UHFFFAOYSA-N 0.000 description 1
- YNACLLXSPCFCPM-UHFFFAOYSA-N 1-(2,3-dihydro-1-benzofuran-2-yl)-n-[[5-(3,4-dimethoxyphenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=CC(CNCC2OC3=CC=CC=C3C2)=C1 YNACLLXSPCFCPM-UHFFFAOYSA-N 0.000 description 1
- CJHKWIFDLHQWCU-UHFFFAOYSA-N 1-(2-chloroethoxy)-2-methoxybenzene Chemical compound COC1=CC=CC=C1OCCCl CJHKWIFDLHQWCU-UHFFFAOYSA-N 0.000 description 1
- IXWSVBPAGSIIHS-UHFFFAOYSA-N 1-(3,4-dihydro-2h-chromen-2-yl)-n-[(5-phenylpyridin-3-yl)methyl]methanamine Chemical compound C1CC2=CC=CC=C2OC1CNCC(C=1)=CN=CC=1C1=CC=CC=C1 IXWSVBPAGSIIHS-UHFFFAOYSA-N 0.000 description 1
- HKFMQJUJWSFOLY-UHFFFAOYSA-N 1-(3,4-dihydro-2h-chromen-2-yl)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC=CC=C3CC2)=C1 HKFMQJUJWSFOLY-UHFFFAOYSA-N 0.000 description 1
- MKSNAJSWAAHAEQ-UHFFFAOYSA-N 1-(3,4-dihydro-2h-chromen-2-yl)-n-[[5-(4-methoxyphenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(OC)=CC=C1C1=CN=CC(CNCC2OC3=CC=CC=C3CC2)=C1 MKSNAJSWAAHAEQ-UHFFFAOYSA-N 0.000 description 1
- CGPHGPCHVUSFFA-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylpyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(C(O)=O)CCC1 CGPHGPCHVUSFFA-UHFFFAOYSA-N 0.000 description 1
- CTHVAAATMYSBEV-UHFFFAOYSA-N 1-(5-fluoro-3,4-dihydro-2H-chromen-2-yl)-N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC=CC(F)=C3CC2)=C1 CTHVAAATMYSBEV-UHFFFAOYSA-N 0.000 description 1
- AQFNLUVTUWECHX-UHFFFAOYSA-N 1-(6-chloro-3,4-dihydro-2H-chromen-2-yl)-N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC=C(Cl)C=C3CC2)=C1 AQFNLUVTUWECHX-UHFFFAOYSA-N 0.000 description 1
- YFKHINUBHZTJJO-UHFFFAOYSA-N 1-(6-fluoro-3,4-dihydro-2h-chromen-2-yl)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC=C(F)C=C3CC2)=C1 YFKHINUBHZTJJO-UHFFFAOYSA-N 0.000 description 1
- ZYAKMQSXEMQSIT-UHFFFAOYSA-N 1-(7-chloro-3,4-dihydro-2H-chromen-2-yl)-N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC(Cl)=CC=C3CC2)=C1 ZYAKMQSXEMQSIT-UHFFFAOYSA-N 0.000 description 1
- GTBROADPKANZRF-UHFFFAOYSA-N 1-(7-fluoro-3,4-dihydro-2H-chromen-2-yl)-N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC(F)=CC=C3CC2)=C1 GTBROADPKANZRF-UHFFFAOYSA-N 0.000 description 1
- YWOCDPFDOSFISS-UHFFFAOYSA-N 1-(8-chloro-3,4-dihydro-2h-chromen-2-yl)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=C(Cl)C=CC=C3CC2)=C1 YWOCDPFDOSFISS-UHFFFAOYSA-N 0.000 description 1
- GOLVBRMXTDJGIN-UHFFFAOYSA-N 1-(8-fluoro-3,4-dihydro-2H-chromen-2-yl)-N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=C(F)C=CC=C3CC2)=C1 GOLVBRMXTDJGIN-UHFFFAOYSA-N 0.000 description 1
- JAPYFFIXEPHTTC-UHFFFAOYSA-N 1-(8-methoxy-3,4-dihydro-2H-chromen-2-yl)-N-[(3-pyridin-3-ylphenyl)methyl]methanamine Chemical compound O1C=2C(OC)=CC=CC=2CCC1CNCC(C=1)=CC=CC=1C1=CC=CN=C1 JAPYFFIXEPHTTC-UHFFFAOYSA-N 0.000 description 1
- GCXOWHQABOYVGI-UHFFFAOYSA-N 1-(8-methoxy-3,4-dihydro-2h-chromen-2-yl)-n-[(3-pyridin-2-ylphenyl)methyl]methanamine Chemical compound O1C=2C(OC)=CC=CC=2CCC1CNCC(C=1)=CC=CC=1C1=CC=CC=N1 GCXOWHQABOYVGI-UHFFFAOYSA-N 0.000 description 1
- XPMRHYMPZMIVEI-UHFFFAOYSA-N 1-(chloromethyl)-3-(3-methylphenyl)benzene Chemical group CC1=CC=CC(C=2C=C(CCl)C=CC=2)=C1 XPMRHYMPZMIVEI-UHFFFAOYSA-N 0.000 description 1
- IMUOKEXXQVUTRZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(4-methylphenyl)benzene Chemical group C1=CC(C)=CC=C1C1=CC=CC(CCl)=C1 IMUOKEXXQVUTRZ-UHFFFAOYSA-N 0.000 description 1
- QUYVTGFWFHQVRO-UHFFFAOYSA-N 1-(chloromethyl)-3-phenoxybenzene Chemical compound ClCC1=CC=CC(OC=2C=CC=CC=2)=C1 QUYVTGFWFHQVRO-UHFFFAOYSA-N 0.000 description 1
- YISZAGRWYWCRLT-HMTLIYDFSA-N 1-[(2s)-3,4-dihydro-2h-chromen-2-yl]-n-methyl-1-(5-phenylpyridin-3-yl)methanamine Chemical compound CNC([C@H]1OC2=CC=CC=C2CC1)C(C=1)=CN=CC=1C1=CC=CC=C1 YISZAGRWYWCRLT-HMTLIYDFSA-N 0.000 description 1
- NWSJNTSIKPGKTP-PSDZMVHGSA-N 1-[5-(4-fluorophenyl)pyridin-3-yl]-1-[(2r)-8-methoxy-3,4-dihydro-2h-chromen-2-yl]-n-methylmethanamine Chemical compound CNC([C@@H]1OC2=C(OC)C=CC=C2CC1)C(C=1)=CN=CC=1C1=CC=C(F)C=C1 NWSJNTSIKPGKTP-PSDZMVHGSA-N 0.000 description 1
- NWSJNTSIKPGKTP-AIBWNMTMSA-N 1-[5-(4-fluorophenyl)pyridin-3-yl]-1-[(2s)-8-methoxy-3,4-dihydro-2h-chromen-2-yl]-n-methylmethanamine Chemical compound CNC([C@H]1OC2=C(OC)C=CC=C2CC1)C(C=1)=CN=CC=1C1=CC=C(F)C=C1 NWSJNTSIKPGKTP-AIBWNMTMSA-N 0.000 description 1
- DLUXAKYABIDWMU-UHFFFAOYSA-N 1-benzofuran-2-ylmethanamine Chemical compound C1=CC=C2OC(CN)=CC2=C1 DLUXAKYABIDWMU-UHFFFAOYSA-N 0.000 description 1
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000004564 2,3-dihydrobenzofuran-2-yl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
- HFZWRUODUSTPEG-UHFFFAOYSA-N 2,4-dichlorophenol Chemical compound OC1=CC=C(Cl)C=C1Cl HFZWRUODUSTPEG-UHFFFAOYSA-N 0.000 description 1
- ZUAKZLXTZXMPEK-UHFFFAOYSA-N 2-(2,4-dichlorophenoxy)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C(=CC(Cl)=CC=2)Cl)=C1 ZUAKZLXTZXMPEK-UHFFFAOYSA-N 0.000 description 1
- ZVQZLJCSBCUXNK-UHFFFAOYSA-N 2-(2-bromophenoxy)-n-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound BrC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 ZVQZLJCSBCUXNK-UHFFFAOYSA-N 0.000 description 1
- CBRUVVLWYRXKTH-UHFFFAOYSA-N 2-(2-chloroethoxy)phenol Chemical compound OC1=CC=CC=C1OCCCl CBRUVVLWYRXKTH-UHFFFAOYSA-N 0.000 description 1
- JGIWOLOIMARFLY-UHFFFAOYSA-N 2-(2-chlorophenoxy)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C(=CC=CC=2)Cl)=C1 JGIWOLOIMARFLY-UHFFFAOYSA-N 0.000 description 1
- BZEZBSSNSYTMAB-UHFFFAOYSA-N 2-(2-chlorophenyl)sulfanyl-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound ClC1=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=CC=C1 BZEZBSSNSYTMAB-UHFFFAOYSA-N 0.000 description 1
- UBQDHKTVOFRVDO-UHFFFAOYSA-N 2-(2-ethylphenoxy)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound CCC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC(F)=CC=2)=C1 UBQDHKTVOFRVDO-UHFFFAOYSA-N 0.000 description 1
- QYKIDCCOCBTLBX-UHFFFAOYSA-N 2-(2-methylphenoxy)-n-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound CC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 QYKIDCCOCBTLBX-UHFFFAOYSA-N 0.000 description 1
- JCEFEVXGZQADDU-UHFFFAOYSA-N 2-(3,4-dihydro-2h-chromen-2-yl)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCC2OC3=CC=CC=C3CC2)=C1 JCEFEVXGZQADDU-UHFFFAOYSA-N 0.000 description 1
- MPCGKUJGBOYLEE-UHFFFAOYSA-N 2-(3,4-dihydro-2h-chromen-2-yl)ethanamine Chemical compound C1=CC=C2OC(CCN)CCC2=C1 MPCGKUJGBOYLEE-UHFFFAOYSA-N 0.000 description 1
- QUZYQBFLWLOSNS-UHFFFAOYSA-N 2-(3-chlorophenoxy)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C=C(Cl)C=CC=2)=C1 QUZYQBFLWLOSNS-UHFFFAOYSA-N 0.000 description 1
- XAJSTJHMCQWMEK-UHFFFAOYSA-N 2-(3-ethylphenoxy)-n-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound CCC1=CC=CC(OCCNCC=2C=C(C=NC=2)C=2C=CC=CC=2)=C1 XAJSTJHMCQWMEK-UHFFFAOYSA-N 0.000 description 1
- HBUGEKPXHARYQY-UHFFFAOYSA-N 2-(3-ethylphenyl)sulfanyl-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound C(C)C=1C=C(SCCNCC=2C=NC=C(C2)C2=CC=CC=C2)C=CC1 HBUGEKPXHARYQY-UHFFFAOYSA-N 0.000 description 1
- ZYOWWNJODLRYKA-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound C1=CC(Cl)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 ZYOWWNJODLRYKA-UHFFFAOYSA-N 0.000 description 1
- SHCAWRGWUVOASN-UHFFFAOYSA-N 2-(4-chlorophenoxy)-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]ethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C=CC(Cl)=CC=2)=C1 SHCAWRGWUVOASN-UHFFFAOYSA-N 0.000 description 1
- QMXDXFWAJVHTPO-UHFFFAOYSA-N 2-(4-methoxyphenyl)sulfanyl-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound COC1=CC=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=C1 QMXDXFWAJVHTPO-UHFFFAOYSA-N 0.000 description 1
- FIEPEINVYFDAPP-UHFFFAOYSA-N 2-(aminomethyl)-3,4-dihydro-2h-chromen-8-ol Chemical compound C1=CC(O)=C2OC(CN)CCC2=C1 FIEPEINVYFDAPP-UHFFFAOYSA-N 0.000 description 1
- SLHQLBHLHQVDRS-UHFFFAOYSA-N 2-(aminomethyl)-3,4-dihydro-2h-chromene-5-carbonitrile Chemical compound C1=CC=C(C#N)C2=C1OC(CN)CC2 SLHQLBHLHQVDRS-UHFFFAOYSA-N 0.000 description 1
- LMDUZKNXILWPNF-UHFFFAOYSA-N 2-(aminomethyl)-3,4-dihydro-2h-chromene-8-carbonitrile Chemical compound C1=CC(C#N)=C2OC(CN)CCC2=C1 LMDUZKNXILWPNF-UHFFFAOYSA-N 0.000 description 1
- KWYDGSCNANPBRG-UHFFFAOYSA-N 2-(aminomethyl)benzenethiol Chemical compound NCC1=CC=CC=C1S KWYDGSCNANPBRG-UHFFFAOYSA-N 0.000 description 1
- JXQZTESQGQBTIV-UHFFFAOYSA-N 2-(chloromethyl)-4-phenylpyridine Chemical class C1=NC(CCl)=CC(C=2C=CC=CC=2)=C1 JXQZTESQGQBTIV-UHFFFAOYSA-N 0.000 description 1
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 1
- LXUNZSDDXMPKLP-UHFFFAOYSA-N 2-Methylbenzenethiol Chemical compound CC1=CC=CC=C1S LXUNZSDDXMPKLP-UHFFFAOYSA-N 0.000 description 1
- QEWNDKVWVNHEMP-UHFFFAOYSA-N 2-[(3-chloro-2-methyl-3H-thiophen-2-yl)oxy]-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound C=1N=CC(C=2C=CC=CC=2)=CC=1CNCCOC1(C)SC=CC1Cl QEWNDKVWVNHEMP-UHFFFAOYSA-N 0.000 description 1
- BZRSADMMPKJCRM-UHFFFAOYSA-N 2-[2-(aminomethyl)phenyl]sulfanyl-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound NCC1=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=CC=C1 BZRSADMMPKJCRM-UHFFFAOYSA-N 0.000 description 1
- FKFAWDWJDWLKIT-UHFFFAOYSA-N 2-[2-[(5-phenylpyridin-3-yl)methylamino]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 FKFAWDWJDWLKIT-UHFFFAOYSA-N 0.000 description 1
- QSDSJFFTASDXHN-UHFFFAOYSA-N 2-[3-(aminomethyl)phenyl]sulfanyl-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound NCC=1C=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=CC=1 QSDSJFFTASDXHN-UHFFFAOYSA-N 0.000 description 1
- WASQMNYRZGVXOG-UHFFFAOYSA-N 2-[4-(aminomethyl)phenyl]sulfanyl-N-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound NCC1=CC=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=C1 WASQMNYRZGVXOG-UHFFFAOYSA-N 0.000 description 1
- OENGCKGYMZPERW-UHFFFAOYSA-N 2-[[[5-(4-fluorophenyl)pyridin-3-yl]methylamino]methyl]-3,4-dihydro-2H-chromene-6-carbonitrile Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC=C(C=C3CC2)C#N)=C1 OENGCKGYMZPERW-UHFFFAOYSA-N 0.000 description 1
- OYGWYYJVLROANT-UHFFFAOYSA-N 2-[[[5-(4-fluorophenyl)pyridin-3-yl]methylamino]methyl]-3,4-dihydro-2h-chromene-8-carbonitrile Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=C(C#N)C=CC=C3CC2)=C1 OYGWYYJVLROANT-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- YUQUNWNSQDULTI-UHFFFAOYSA-N 2-bromobenzenethiol Chemical compound SC1=CC=CC=C1Br YUQUNWNSQDULTI-UHFFFAOYSA-N 0.000 description 1
- VADKRMSMGWJZCF-UHFFFAOYSA-N 2-bromophenol Chemical compound OC1=CC=CC=C1Br VADKRMSMGWJZCF-UHFFFAOYSA-N 0.000 description 1
- PWOBDMNCYMQTCE-UHFFFAOYSA-N 2-chlorobenzenethiol Chemical compound SC1=CC=CC=C1Cl PWOBDMNCYMQTCE-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- ISPYQTSUDJAMAB-UHFFFAOYSA-N 2-chlorophenol Chemical compound OC1=CC=CC=C1Cl ISPYQTSUDJAMAB-UHFFFAOYSA-N 0.000 description 1
- AYKJNUKVVLAVFJ-UHFFFAOYSA-N 2-fluoroethoxybenzene Chemical compound FCCOC1=CC=CC=C1 AYKJNUKVVLAVFJ-UHFFFAOYSA-N 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- HFHFGHLXUCOHLN-UHFFFAOYSA-N 2-fluorophenol Chemical compound OC1=CC=CC=C1F HFHFGHLXUCOHLN-UHFFFAOYSA-N 0.000 description 1
- FWWOWPGPERBCNJ-UHFFFAOYSA-N 2-hydroxy-4-(2-hydroxyethoxy)-4-oxobutanoic acid Chemical compound OCCOC(=O)CC(O)C(O)=O FWWOWPGPERBCNJ-UHFFFAOYSA-N 0.000 description 1
- CHZCERSEMVWNHL-UHFFFAOYSA-N 2-hydroxybenzonitrile Chemical compound OC1=CC=CC=C1C#N CHZCERSEMVWNHL-UHFFFAOYSA-N 0.000 description 1
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 1
- 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- WJRXWJKDARDOKT-UHFFFAOYSA-N 2-phenoxy-n-[(3-pyridin-2-ylphenyl)methyl]ethanamine Chemical compound C=1C=CC(C=2N=CC=CC=2)=CC=1CNCCOC1=CC=CC=C1 WJRXWJKDARDOKT-UHFFFAOYSA-N 0.000 description 1
- VFVXPORKHJRWNW-UHFFFAOYSA-N 2-phenoxy-n-[(3-pyridin-3-ylphenyl)methyl]ethanamine Chemical compound C=1C=CC(C=2C=NC=CC=2)=CC=1CNCCOC1=CC=CC=C1 VFVXPORKHJRWNW-UHFFFAOYSA-N 0.000 description 1
- NFNHECIVHBTKAT-UHFFFAOYSA-N 2-phenoxy-n-[(4-thiophen-3-ylthiophen-2-yl)methyl]ethanamine Chemical compound C=1C(C2=CSC=C2)=CSC=1CNCCOC1=CC=CC=C1 NFNHECIVHBTKAT-UHFFFAOYSA-N 0.000 description 1
- LXWDUDYTVWGNQL-UHFFFAOYSA-N 2-phenoxy-n-[(5-phenylpyridin-3-yl)methyl]ethanamine Chemical compound C=1N=CC(C=2C=CC=CC=2)=CC=1CNCCOC1=CC=CC=C1 LXWDUDYTVWGNQL-UHFFFAOYSA-N 0.000 description 1
- SFLFCQJQOIZMHF-UHFFFAOYSA-N 3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)CCC2=C1 SFLFCQJQOIZMHF-UHFFFAOYSA-N 0.000 description 1
- IYWYLHUQGUIKHO-UHFFFAOYSA-N 3-(2-chloroethoxy)benzonitrile Chemical compound ClCCOC1=CC=CC(C#N)=C1 IYWYLHUQGUIKHO-UHFFFAOYSA-N 0.000 description 1
- MQRMWSYMUKSODL-UHFFFAOYSA-N 3-(aminomethyl)benzenethiol Chemical compound NCC1=CC=CC(S)=C1 MQRMWSYMUKSODL-UHFFFAOYSA-N 0.000 description 1
- NTYKUDHKMXZULD-UHFFFAOYSA-N 3-(chloromethyl)-5-(2,3,4,5,6-pentafluorophenyl)pyridine Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1C1=CN=CC(CCl)=C1 NTYKUDHKMXZULD-UHFFFAOYSA-N 0.000 description 1
- NZHBGSCTKWTYOZ-UHFFFAOYSA-N 3-(chloromethyl)-5-(2,4-dimethoxyphenyl)pyridine Chemical compound COC1=CC(OC)=CC=C1C1=CN=CC(CCl)=C1 NZHBGSCTKWTYOZ-UHFFFAOYSA-N 0.000 description 1
- HZLRAKIGCDSPIA-UHFFFAOYSA-N 3-(chloromethyl)-5-(3,4,5-trifluorophenyl)pyridine Chemical compound FC1=C(F)C(F)=CC(C=2C=C(CCl)C=NC=2)=C1 HZLRAKIGCDSPIA-UHFFFAOYSA-N 0.000 description 1
- SKIMVKJQAZIKIO-UHFFFAOYSA-N 3-(chloromethyl)-5-(3,4-dimethoxyphenyl)pyridine Chemical compound C1=C(OC)C(OC)=CC=C1C1=CN=CC(CCl)=C1 SKIMVKJQAZIKIO-UHFFFAOYSA-N 0.000 description 1
- CNQCWYFDIQSALX-UHFFFAOYSA-N 3-(chloromethyl)pyridine Chemical compound ClCC1=CC=CN=C1 CNQCWYFDIQSALX-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- YTIANFVBOVZUFL-UHFFFAOYSA-N 3-chloro-n-[(5-phenylpyridin-3-yl)methyl]propan-1-amine Chemical compound ClCCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 YTIANFVBOVZUFL-UHFFFAOYSA-N 0.000 description 1
- JYZXUYGTVJDUQN-UHFFFAOYSA-N 3-chloro-n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]propan-1-amine Chemical class C1=CC(F)=CC=C1C1=CN=CC(CNCCCCl)=C1 JYZXUYGTVJDUQN-UHFFFAOYSA-N 0.000 description 1
- HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 description 1
- XZBXAYCCBFTQHH-UHFFFAOYSA-N 3-chloropropylbenzene Chemical compound ClCCCC1=CC=CC=C1 XZBXAYCCBFTQHH-UHFFFAOYSA-N 0.000 description 1
- SYHJILPZUNKNHQ-UHFFFAOYSA-N 3-phenylbenzonitrile Chemical group N#CC1=CC=CC(C=2C=CC=CC=2)=C1 SYHJILPZUNKNHQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- HALYSFYBJQPLOC-UHFFFAOYSA-N 4-(aminomethyl)benzenethiol Chemical compound NCC1=CC=C(S)C=C1 HALYSFYBJQPLOC-UHFFFAOYSA-N 0.000 description 1
- WCMLRSZJUIKVCW-UHFFFAOYSA-N 4-(trifluoromethyl)benzenethiol Chemical compound FC(F)(F)C1=CC=C(S)C=C1 WCMLRSZJUIKVCW-UHFFFAOYSA-N 0.000 description 1
- BAYGVMXZJBFEMB-UHFFFAOYSA-N 4-(trifluoromethyl)phenol Chemical compound OC1=CC=C(C(F)(F)F)C=C1 BAYGVMXZJBFEMB-UHFFFAOYSA-N 0.000 description 1
- RQJDUEKERVZLLU-UHFFFAOYSA-N 4-Hydroxybenzylamine Chemical compound NCC1=CC=C(O)C=C1 RQJDUEKERVZLLU-UHFFFAOYSA-N 0.000 description 1
- PLAWHYFTZJUAGN-UHFFFAOYSA-N 4-chloro-n-[(5-phenylpyridin-3-yl)methyl]butan-1-amine Chemical compound ClCCCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 PLAWHYFTZJUAGN-UHFFFAOYSA-N 0.000 description 1
- VZXOZSQDJJNBRC-UHFFFAOYSA-N 4-chlorobenzenethiol Chemical compound SC1=CC=C(Cl)C=C1 VZXOZSQDJJNBRC-UHFFFAOYSA-N 0.000 description 1
- NIFAOMSJMGEFTQ-UHFFFAOYSA-N 4-methoxybenzenethiol Chemical compound COC1=CC=C(S)C=C1 NIFAOMSJMGEFTQ-UHFFFAOYSA-N 0.000 description 1
- MVPUXVBBHWUOFS-UHFFFAOYSA-N 4-sulfanylbenzonitrile Chemical compound SC1=CC=C(C#N)C=C1 MVPUXVBBHWUOFS-UHFFFAOYSA-N 0.000 description 1
- LDCYZAJDBXYCGN-VIFPVBQESA-N 5-hydroxy-L-tryptophan Chemical compound C1=C(O)C=C2C(C[C@H](N)C(O)=O)=CNC2=C1 LDCYZAJDBXYCGN-VIFPVBQESA-N 0.000 description 1
- KPFDABVKWKOIME-UHFFFAOYSA-N 6-bromo-3,4-dihydro-2h-chromene Chemical compound O1CCCC2=CC(Br)=CC=C21 KPFDABVKWKOIME-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FSCZYYONSDTBCW-UHFFFAOYSA-N 8-methoxy-3,4-dihydro-2h-chromene Chemical compound C1CCOC2=C1C=CC=C2OC FSCZYYONSDTBCW-UHFFFAOYSA-N 0.000 description 1
- 206010000599 Acromegaly Diseases 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 201000000736 Amenorrhea Diseases 0.000 description 1
- 206010001928 Amenorrhoea Diseases 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- GONOSLWRRSBWFH-UHFFFAOYSA-N BrC1=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=CC=C1 Chemical compound BrC1=C(SCCNCC=2C=NC=C(C=2)C2=CC=CC=C2)C=CC=C1 GONOSLWRRSBWFH-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- YZDJNIRBASNZRU-UHFFFAOYSA-N C1=CC(CN)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 Chemical compound C1=CC(CN)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 YZDJNIRBASNZRU-UHFFFAOYSA-N 0.000 description 1
- PTYMQNSISJWXOB-UHFFFAOYSA-N C1=CC(OC)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 Chemical compound C1=CC(OC)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 PTYMQNSISJWXOB-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000018152 Cerebral disease Diseases 0.000 description 1
- HEBNHOAFPIQYRI-UHFFFAOYSA-N ClC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 Chemical compound ClC1=CC=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 HEBNHOAFPIQYRI-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010058359 Hypogonadism Diseases 0.000 description 1
- 229910021576 Iron(III) bromide Inorganic materials 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N Monoamide-Oxalic acid Natural products NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- IZCGYDRITKHVNI-UHFFFAOYSA-N N-[(5-phenylpyridin-3-yl)methyl]-2-[4-(trifluoromethyl)phenyl]sulfanylethanamine Chemical compound FC(C1=CC=C(SCCNCC=2C=NC=C(C2)C2=CC=CC=C2)C=C1)(F)F IZCGYDRITKHVNI-UHFFFAOYSA-N 0.000 description 1
- PIOGJJUGBVKASJ-UHFFFAOYSA-N N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-(6-nitro-3,4-dihydro-2H-chromen-2-yl)methanamine Chemical compound C1CC2=CC([N+](=O)[O-])=CC=C2OC1CNCC(C=1)=CN=CC=1C1=CC=C(F)C=C1 PIOGJJUGBVKASJ-UHFFFAOYSA-N 0.000 description 1
- PVDAGVGVGKMTMC-UHFFFAOYSA-N N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-(7-nitro-3,4-dihydro-2H-chromen-2-yl)methanamine Chemical compound O1C2=CC([N+](=O)[O-])=CC=C2CCC1CNCC(C=1)=CN=CC=1C1=CC=C(F)C=C1 PVDAGVGVGKMTMC-UHFFFAOYSA-N 0.000 description 1
- JAJOJTQJISVAHP-UHFFFAOYSA-N N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-(8-nitro-3,4-dihydro-2H-chromen-2-yl)methanamine Chemical compound O1C=2C([N+](=O)[O-])=CC=CC=2CCC1CNCC(C=1)=CN=CC=1C1=CC=C(F)C=C1 JAJOJTQJISVAHP-UHFFFAOYSA-N 0.000 description 1
- LCTFEPBMPJDOJB-UHFFFAOYSA-N N-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-N-[(5-phenylpyridin-3-yl)methyl]-4-phenylsulfanylbutan-1-amine Chemical compound S(C1=CC=CC=C1)CCCCN(CC=1C=NC=C(C=1)C1=CC=C(C=C1)F)CC=1C=NC=C(C=1)C1=CC=CC=C1 LCTFEPBMPJDOJB-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 229910000990 Ni alloy Inorganic materials 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- 229940123796 Prolactin inhibitor Drugs 0.000 description 1
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- JRXBKFWEEBIXRR-UHFFFAOYSA-N S(C1=CC=CC=C1)CCCCNCC=1C=NC=C(C1)C1=CC=CC=C1 Chemical compound S(C1=CC=CC=C1)CCCCNCC=1C=NC=C(C1)C1=CC=CC=C1 JRXBKFWEEBIXRR-UHFFFAOYSA-N 0.000 description 1
- GMVZOKUKXXEPKG-UHFFFAOYSA-N S(C1=CC=CC=C1)CCCNCC=1C=NC=C(C=1)C1=CC=CC=C1 Chemical compound S(C1=CC=CC=C1)CCCNCC=1C=NC=C(C=1)C1=CC=CC=C1 GMVZOKUKXXEPKG-UHFFFAOYSA-N 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 239000005864 Sulphur Chemical group 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 238000006856 Wolf-Kishner-Huang Minlon reduction reaction Methods 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- OVUHGTNSFHCUDV-UHFFFAOYSA-N [6-(trifluoromethyl)-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound FC(F)(F)C1=CC=C2OC(CN)CCC2=C1 OVUHGTNSFHCUDV-UHFFFAOYSA-N 0.000 description 1
- FMNPCKCLXPKKJQ-UHFFFAOYSA-N [8-(trifluoromethyl)-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C1=CC(C(F)(F)F)=C2OC(CN)CCC2=C1 FMNPCKCLXPKKJQ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 150000001348 alkyl chlorides Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 231100000540 amenorrhea Toxicity 0.000 description 1
- 150000003862 amino acid derivatives Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 150000001448 anilines Chemical class 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940125684 antimigraine agent Drugs 0.000 description 1
- 239000002282 antimigraine agent Substances 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 159000000032 aromatic acids Chemical class 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 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
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 description 1
- AZWXAPCAJCYGIA-UHFFFAOYSA-N bis(2-methylpropyl)alumane Chemical compound CC(C)C[AlH]CC(C)C AZWXAPCAJCYGIA-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 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
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
- 239000000920 calcium hydroxide Substances 0.000 description 1
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- QAWTYRYXDYHQNU-UHFFFAOYSA-N diazathiane Chemical class NSN QAWTYRYXDYHQNU-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- MHUWZNTUIIFHAS-CLFAGFIQSA-N dioleoyl phosphatidic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(COP(O)(O)=O)OC(=O)CCCCCCC\C=C/CCCCCCCC MHUWZNTUIIFHAS-CLFAGFIQSA-N 0.000 description 1
- DXPIZCZNFUTPEI-UHFFFAOYSA-N diphenylphosphane;azide Chemical compound [N-]=[N+]=[N-].C=1C=CC=CC=1PC1=CC=CC=C1 DXPIZCZNFUTPEI-UHFFFAOYSA-N 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- PSOZUQKKUGXCEN-UHFFFAOYSA-N ethyl 3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)CCC2=C1 PSOZUQKKUGXCEN-UHFFFAOYSA-N 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
- 238000000605 extraction Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
- YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([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
- 230000006651 lactation Effects 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 125000004401 m-toluyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C(*)=O 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- MJGFBOZCAJSGQW-UHFFFAOYSA-N mercury sodium Chemical compound [Na].[Hg] MJGFBOZCAJSGQW-UHFFFAOYSA-N 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- YNLFEVAOQLXINF-UHFFFAOYSA-N methylsulfanylmethane;tribromoborane Chemical compound CSC.BrB(Br)Br YNLFEVAOQLXINF-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- BVWCVUBJALDUAA-UHFFFAOYSA-N n,n-bis[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-(2-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC=C1OCCN(CC=1C=C(C=NC=1)C=1C=CC(F)=CC=1)CC1=CN=CC(C=2C=CC(F)=CC=2)=C1 BVWCVUBJALDUAA-UHFFFAOYSA-N 0.000 description 1
- OWFALUNDSZEADU-PBHICJAKSA-N n-[(2r,4s)-2-butyl-4-[(2-fluorophenyl)carbamoylamino]-5-methyl-3-oxohexyl]-n-hydroxyformamide Chemical compound CCCC[C@H](CN(O)C=O)C(=O)[C@H](C(C)C)NC(=O)NC1=CC=CC=C1F OWFALUNDSZEADU-PBHICJAKSA-N 0.000 description 1
- OQZHNNDIFVIBPE-UHFFFAOYSA-N n-[(4-chlorothiophen-2-yl)methyl]-2-phenoxyethanamine Chemical compound ClC1=CSC(CNCCOC=2C=CC=CC=2)=C1 OQZHNNDIFVIBPE-UHFFFAOYSA-N 0.000 description 1
- RVFSQKQEKVZUDU-UHFFFAOYSA-N n-[(4-ethylthiophen-2-yl)methyl]-2-phenoxyethanamine Chemical compound CCC1=CSC(CNCCOC=2C=CC=CC=2)=C1 RVFSQKQEKVZUDU-UHFFFAOYSA-N 0.000 description 1
- YNGRWVCZDDWBCY-UHFFFAOYSA-N n-[(4-methoxythiophen-2-yl)methyl]-2-phenoxyethanamine Chemical compound COC1=CSC(CNCCOC=2C=CC=CC=2)=C1 YNGRWVCZDDWBCY-UHFFFAOYSA-N 0.000 description 1
- NKOAJWHRCJJKSB-UHFFFAOYSA-N n-[(4-methylthiophen-2-yl)methyl]-2-phenoxyethanamine Chemical compound CC1=CSC(CNCCOC=2C=CC=CC=2)=C1 NKOAJWHRCJJKSB-UHFFFAOYSA-N 0.000 description 1
- DSPYYYGZECOTPK-UHFFFAOYSA-N n-[(5-phenylpyridin-3-yl)methyl]-2-[4-(trifluoromethyl)phenoxy]ethanamine Chemical compound C1=CC(C(F)(F)F)=CC=C1OCCNCC1=CN=CC(C=2C=CC=CC=2)=C1 DSPYYYGZECOTPK-UHFFFAOYSA-N 0.000 description 1
- WUHLBWYQGJGWDZ-UHFFFAOYSA-N n-[(5-phenylpyridin-3-yl)methyl]-2-thiophen-2-yloxypropan-2-amine Chemical compound C=1C=CSC=1OC(C)(C)NCC(C=1)=CN=CC=1C1=CC=CC=C1 WUHLBWYQGJGWDZ-UHFFFAOYSA-N 0.000 description 1
- AABNSIPWXLKFPZ-UHFFFAOYSA-N n-[[5-(2,4-difluorophenyl)pyridin-3-yl]methyl]-2-naphthalen-2-yloxyethanamine Chemical compound FC1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C=C3C=CC=CC3=CC=2)=C1 AABNSIPWXLKFPZ-UHFFFAOYSA-N 0.000 description 1
- MOHANQATAZMIJJ-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-(5-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound C1CC=2C(OC)=CC=CC=2OC1CNCC(C=1)=CN=CC=1C1=CC=C(F)C=C1 MOHANQATAZMIJJ-UHFFFAOYSA-N 0.000 description 1
- KBMOQXWLUQAPOC-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-(7-methoxy-3,4-dihydro-2h-chromen-2-yl)methanamine Chemical compound O1C2=CC(OC)=CC=C2CCC1CNCC(C=1)=CN=CC=1C1=CC=C(F)C=C1 KBMOQXWLUQAPOC-UHFFFAOYSA-N 0.000 description 1
- XMOYESFPMGCCQP-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-[6-(trifluoromethyl)-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=CC=C(C=C3CC2)C(F)(F)F)=C1 XMOYESFPMGCCQP-UHFFFAOYSA-N 0.000 description 1
- ZMUCRAQGTITTOA-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-1-[8-(trifluoromethyl)-3,4-dihydro-2h-chromen-2-yl]methanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCC2OC3=C(C=CC=C3CC2)C(F)(F)F)=C1 ZMUCRAQGTITTOA-UHFFFAOYSA-N 0.000 description 1
- PSXBJHDCVYATJL-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-(3-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC(OCCNCC=2C=C(C=NC=2)C=2C=CC(F)=CC=2)=C1 PSXBJHDCVYATJL-UHFFFAOYSA-N 0.000 description 1
- ZNVCFHSWJSWVEJ-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-(3-methylphenoxy)ethanamine Chemical compound CC1=CC=CC(OCCNCC=2C=C(C=NC=2)C=2C=CC(F)=CC=2)=C1 ZNVCFHSWJSWVEJ-UHFFFAOYSA-N 0.000 description 1
- PKBXAWDFLLTELQ-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-(4-methoxyphenoxy)ethanamine Chemical compound C1=CC(OC)=CC=C1OCCNCC1=CN=CC(C=2C=CC(F)=CC=2)=C1 PKBXAWDFLLTELQ-UHFFFAOYSA-N 0.000 description 1
- GSJYVKALYAWDSW-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-naphthalen-1-yloxyethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C3=CC=CC=C3C=CC=2)=C1 GSJYVKALYAWDSW-UHFFFAOYSA-N 0.000 description 1
- PZHRZKDTJGDPDA-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-naphthalen-2-yloxyethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCOC=2C=C3C=CC=CC3=CC=2)=C1 PZHRZKDTJGDPDA-UHFFFAOYSA-N 0.000 description 1
- XXCGVGJEBPVKBM-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-2-phenylsulfanylethanamine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCSC=2C=CC=CC=2)=C1 XXCGVGJEBPVKBM-UHFFFAOYSA-N 0.000 description 1
- CJRVCXAOQNOOOK-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-4-phenoxybutan-1-amine Chemical compound C1=CC(F)=CC=C1C1=CN=CC(CNCCCCOC=2C=CC=CC=2)=C1 CJRVCXAOQNOOOK-UHFFFAOYSA-N 0.000 description 1
- WQGXXRODJLLJGY-UHFFFAOYSA-N n-[[5-(4-fluorophenyl)pyridin-3-yl]methyl]-n-methyl-2-phenoxyethanamine Chemical compound C=1N=CC(C=2C=CC(F)=CC=2)=CC=1CN(C)CCOC1=CC=CC=C1 WQGXXRODJLLJGY-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- FCPGLSSNBUVLLD-UHFFFAOYSA-N naphthalen-1-ol;sodium Chemical compound [Na].C1=CC=C2C(O)=CC=CC2=C1 FCPGLSSNBUVLLD-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- SBOJXQVPLKSXOG-UHFFFAOYSA-N o-amino-hydroxylamine Chemical compound NON SBOJXQVPLKSXOG-UHFFFAOYSA-N 0.000 description 1
- 125000005441 o-toluyl group Chemical group [H]C1=C([H])C(C(*)=O)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 238000006053 organic reaction Methods 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- RLXDCJUIXHSXQD-UHFFFAOYSA-N oxalic acid;hydrate Chemical compound O.OC(=O)C(O)=O.OC(=O)C(O)=O RLXDCJUIXHSXQD-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 125000005440 p-toluyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C(*)=O)C([H])([H])[H] 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000010647 peptide synthesis reaction Methods 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003138 primary alcohols Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 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
- 239000000952 serotonin receptor agonist Substances 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910001023 sodium amalgam Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup 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
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 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
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229910052720 vanadium Inorganic materials 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- A61P25/22—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
- A61P25/24—Antidepressants
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/16—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring not being further substituted
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/20—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/64—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with oxygen atoms directly attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Hydrogenated Pyridines (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
Abstract
式1的氨基(硫)醚衍生物,其中,R0,R1,R2,R3,R6,R7,R8,R9,X和Z如权利要求1中的定义,以及该衍生物的盐,它们对于中枢神经系统有治疗作用。
Description
本发明涉及新的式1氨基(硫)醚衍生物,及其生理上可接受的盐
其中,
X 是氧、硫、亚硫酰基、磺酰基或,当R0和R1不相连时,1-3个碳原子的亚烷基链,以及CH2,
Z 是-(CH2)n1-(CH2)n2-(CH3)n3,其中
n1=0,1,2,或3
n2=0或1
n3=0,1,2或3并满足
n1+n2+n3<4
R0 是氢或A
R1 是氢,A,OA,苯氧基,Ph,OH,F,Cl,Br,CN,CF3,COOH,COOA,1-4个碳原子的酰氧基,羧基酰胺基,-CH2NH2,-CH2NHA,-CH2NA2,-CH2NHAc,
-CH2NHSO2CH3,或
R0与R1 一起是一个具有1-3个碳原子的亚烷基链或一个具有2-3个碳原子的亚链烯基链,
R2是氢,A,Ac或-CH2-R4,
R3是-CH2-R4,或-CHA-R4,
R4是Ph,未取代或被R5单取代的2-,3-,或4-吡啶基,或者未取代的或被A,OA,OH,F,Cl,Br,CN和/或CF3单或双取代的,或被另一个噻吩基取代的噻吩,
R5是未取代的或被F,CF3部分或完全氟化的A,A和/或OA单,双,三,四,五取代的苯基,
R6,R7,R8和R9彼此独立地是H,A,OA,苯氧基,OH,F,Cl,Br,I,CN,CF3,NO2,NH2,NHA,NA2,Ac,Ph,有3-7个碳原子的环烷基,-CH2NH2,-CH2NHA,-CH2NA2,-CH2NHAc或-CH2NHSO2CH3或两个相邻的残基一起是一个有3或4个碳原子的亚烷基链,和/或
R1和R6一起是一个有3或4个碳原子的亚烷基链。
A 是一个具有1-6个碳原子的烷基。
Ac 是有1-10个碳原子的烷酰基或有7-11个碳原子的芳酰基。
Ph 是未取代的或被R5,2-,3-,或4-吡啶基或苯氧基取代的苯基。
本发明的目的是开发能用于制备药品的新型化合物。
已发现,式I的化合物及其生物相容酸加成盐具有有价值的药物特性。因此,特别是,它们对中枢神经系统有活性,尤其作为5-羟色胺兴奋剂和拮抗剂。它们抑制了氚标记5-羟色铵配位体与海马(hippocampal)受体的结合(Cossery et al.,European J.Pharmaco1.140(1987),143-155)。它们也改善了DOPA在纹状体内的积累以及5-HTP在核缝内的积累(Seyfried et al.,European J.Pharmacol.160(1989),31-41)。它们还有止痛和降压的效果;因此,在插入导管的神志清醒的自发高血压的老鼠(品种:SHR/Okamoto/NIH-MO-CHB-Kisslegg;方法:q.v.Weeks and Jones,Proc.Soc.Exptl.Biol.Med.
104(1960),G46-648)口服诸化合物后,直接测量的血压降低了。它们对于预防和控制大脑梗塞(脑中风)的后遗症,如中风和脑缺血也是有用的。
这些物质可用在与5-羟色胺和多巴胺能的系统的紊乱相关的疾病以及涉及对5-羟基色胺(5HTIA类)有高亲和性的受体和多巴胺(D2类)受体的疾病的治疗。
它们适用于治疗中央神经系统的机能失调,如焦虑、紧张和抑郁症,中央神经系统引起的性功能障碍,睡眠或食物吸收失调。而且,它们适用于消除识别缺陷,改善学习和记忆能力,并治疗Alzheimer疾病。它们也适用于精神病(精神分裂症)
式I的化合物及其生物相容酸加成盐可因此用作焦虑缓解剂(anxiolytics)、抗抑郁剂,安定剂,和/或抗高血压剂的活性成分,而且也可用作制备其它药物活性成分的中间体。
本发明涉及式I的氨基(硫)醚衍生物及其生物相容的酸加成盐。
A基是具有1,2,3,4,5或6个碳原子,特别是1或2个碳原子的烷基,优选甲基以及乙基,正丙基,异丙基,正丁基,异丁基,仲丁基或叔丁基,OA优选甲氧基以及乙氧基,正丙氧基,异丙氧基,正丁氧基,异丁氧基,仲丁氧基或叔丁氧基。NHA优选甲氨基以及乙氨基,正丙氨基,异丙氧基,正丁氨基,异丁氨基,仲丁氨基或叔丁氨基。NA2优选二甲氨基以及N-乙基-N-甲基氨基,二乙氨基,二正丙氨基,二异丙氨基或二正丁氨基。
Ac优选有1-6个,特别是1,2,3或4个碳原子的烷酰,具体地说优选甲酰或乙酰,而且,优选丙酰,丁酰,异丁酰,戊酰或己酰,且另外优选苯甲酰,邻、间或对甲苯酰,1-或2-萘酰。
X优选氧或硫,而Z主要代表-CH2-,-(CH2)2-,-(CH2)3-,-(CHCH3)-,而且也优选-CH2-,-(CHCH3)-,-(CH2)2-(CHCH3)-,-CH2-(CHCH3)-CH2-或-(CHCH3)-(CH2)2-。
残基R0优选H或甲基,但大多数情况下,R0和R1一起形成一个亚烷基链,优选包括2个碳原子。如果R1与前边给出的定义不同,它优选氢,A,OA,CONH2或CN。
R2优选H或A且R3优选被另一个苯基取代的2-,3-或4-吡啶甲基或苯基,或者,另外R3是优选被另一个噻吩基取代的噻吩基。
R3主要代表2-,3-,4-吡啶甲基,5-苯基-3-呲啶甲基,5-(氟苯基)-3-吡啶甲基,5-(甲氧苯基)-3-吡啶甲基,4’-氟-3-联苯基甲基,3-联苯基甲基或4-(噻吩基)-2-噻吩甲基。另外,R3优选2-,4-,5-或6-(m-氟苯基)-3-吡啶甲基,3-,4-,5-或6-(m-氟苯基)-2-吡啶甲基或2-或3-(m-氟苯基)-4-吡啶甲基,其中m代表前缀一、二、三、四或五。
R6,R7,R8和R9优选互相无关地为H,A,OA,Cl,CN或CF3。另外,R1和R6优选一起为一个具有4个碳原子的亚烷基链。而且,另一种优选定义是:从R6,R7,R8和R9选出的两个相邻残基一起形成一个有3或4个碳原子的亚烷基链。
因此,具体地说,本发明涉及式I的那些化合物及其盐,其中至少一个所述基团具有上述的一个含义,特别是上述的一个优选含义。化合物的一些优选基可由下边的分式Ia和Ii来表示,这些分式符合式I而且其中没有更详细介绍的各基团和参数按式I定义,但在其中:
Ia中:X是氧,R0和R1一起形成-(CH2)2-,Z是亚甲基且R6,R7,R8和R9是氢。
Ib中:X是氧,R0和R1一起形成-(CH2)2-,Z是亚甲基且R4是未取代或单取代的吡啶基或联苯基。
IC中:X是氧,R0和R1一起形成-(CH2)2-,Z是亚甲基且R4是5-(4-氟苯基)-3-吡啶基
Id中:X是氧,R0和R1一起形成亚甲基,且R4是5-(4-氟苯基)-3-吡啶基。
Ie中:X是氧,R0是氢,Z是亚甲基且R4是5-(4-氟苯基)-3-吡啶基。
If中:X是氧,R0和R1是氢,Z是亚甲基且R4是5-(4-氟苯基)-3-吡啶基,
Ig中:X是氧,R0是氢,R1是氯,乙基或甲氧基,Z是亚甲基且R4是4-(4-氟苯基)-3-吡啶基,
Ih中:X是氧,Z是亚甲基且R4是5-苯基-3-吡啶基,
Ii中:X是氧,Z是-(CH2)2-,-(CH2)3-,或-(CHCH3)-且R4是5-(4-氟苯基)-3-吡啶基。
特别优选的化合物是式Ik和Iak至Iik的那些,它们与分式I和Ia至Ii相对应,但另在其中:
X 是硫,亚磺酰或磺酰。
本发明进一步涉及制备式I的衍生物及其盐的方法,其特征在于:式II的化合物
其中,
G是Cl,Br,I,OH或在官能改性成一个活性基团、特别是一个离去基团的OH基,而且R0,R1,R6,R7,R8,R9,X和Z定义如上,与式III的胺反应
HNR2R3 III,
其中,
R2和R3定义如上。
或者其特征在于:式IV的化合物
其中,
M 是H,Li+,Na+,K+,NH4 +或其它合适的金属离子,而且X,R1,R6,R7,R8和R9定义如上,
与式V的化合物反应
其中,
G’按G给出定义并且R0,R2,R3和Z定义如上。
或者其特征在于:式VI的化合物
其中R0和R1一起为C1-C3亚烷基链,且R2,R3,R6,R7,R8,R9,X,Z,M和G定义如上,
环化成式I的氨基醚或氨基硫醚衍生物,或其特征在于:式I中一个或多个氢原子已经被一个或多个还原性基团和/或一个或多个C-C和/或C-N链所取代的化合物用一种还原剂处理,或者其特征在于:式I中一个或多个氢原子已经被一个或多个可溶性基团取代的化合物用一种溶解剂处理,和/或其特征在于:OA基可有选择性地裂键成OH基,和/或Ar基转化成另一个Ar基,和/或其特征在于:得到的式I的碱或酸通过与酸或碱处理转化成它的一种盐。
另外,式I的化合物用公知的方法例如文献中介绍的那些(如,在标准著作中:Houben-Weyl,Methoden der Organischen Chemie(Methods of Organic Chemistry),Georg-Thieme-Verlag,Stuttgart;Or-ganic Reactions,John Wiley & Sons,Inc.,New York)制备,即在例如已知的且适于所述反应的反应条件下制备。也可以利用一些本来已知的变通方法,这里不再更详细叙述。
如果需要,用于要求保护的方法的起始物也可以就地形成,即它们不从反应混合物中分离而是立即进一步反应得到式I的化合物。
在式II的衍生物中,G优选Cl或Br,但它也可以是I,OH或官能改性成一种活性基团,尤其是具有1-6个碳原子的烷基磺酰氧基(如,甲磺酰氧基)或具有6-10个碳原子的芳基磺酰氧基(如,苯酰氧基,对甲苯磺酰氧基,萘-1-或-2-磺酰氧基)的OH基。
一些式II、特别是式III的化合物是已知的;式II和III的未知化合物类可按已知化合物的类似方法容易地制备出。
式II的伯醇可以例如通过还原适当的羧酸或其酯来得到。用亚硫酰氯、溴化氢、三溴化磷或相似的卤素化合物的处理产生了与式II的化合物相应的卤化物。相应的磺酰氧基化合物可从式II的醇与合适的磺酰氯反应得到。
式7的碘化合物可以例如通过碘化钾与合适的对甲苯磺酸酯反应而得到。
大多数胺衍生物III是公知的并可通过如已知胺的烷化或酰化而得到。
化合物II和III的反应根据从有关胺的烷基化的文献中可知的那些方法而进行。诸组分可以在不存在溶剂的条件下,在密封管或,如果需要的话,在高压釜中一起熔化。但是,也可以在惰性溶剂存在的情况下反应诸化合物。合适的溶剂的例子是烃,如苯,甲苯或二甲苯;酮,如丙酮或丁酮;醇,如甲醇,乙醇,异丙醇或正丁醇;醚,如四氢呋喃(THF)或二恶烷;酰胺,如二甲基甲酰胺(DMF)或N-甲基吡咯烷酮;或腈,如乙腈,或如果需要,这些溶剂彼此之间的混合物或与水的混合物。这样也是有利的:即加入一种酸结合剂,如碱金属或碱土金属的氢氧化物,碳酸盐或重碳酸盐或另外一种弱酸的碱金属或碱土金属的盐,优选钾、钠或钙盐,或者加入一种有机碱,如三乙胺,二甲基苯胺,吡啶或喹啉,或过量的胺组分。反应时间在几分钟至14天之间,这取决于使用条件,而且反应温度在约0至150℃,通常在20至130℃之间。
也可以通过将式IV的化合物与式G’(CHR0)-Z-NR2R3(V)的化合物反应得到式I的化合物。
已经知道一些式V,特别是式IV的化合物;未知化合物类似已知化合物可被容易地制备出。例如,式IV的化合物可通过苯酚或苯硫酚与例如NaH,KH的氢化物,或苯基锂或甲基锂的金属化作用而被容易地制备。也可通过苯硫酚的氧化而产生亚磺酰或磺酰化合物来制备IV类的化合物。
式V的胺可自伯胺开始,借助已知的胺的烷基化或酰化的多种可能性而制备出。也可以通过还原和随后的烷基化将适当取代的硝基化合物转化成式V的胺。
化合物IV和V的反应根据从有关醚,硫醚或酯的生成的文献中可知的方法进行。这些组分可以在无溶剂存在的情况下,如果合适在封闭的管中或在高压釜中,于常压或升高的压力下(加入惰性气体,如N2,以提高压力),彼此直接互熔。但是也可以在有惰性溶剂存在的情况下将这些化合物进行反应。合适的溶剂是前边提到的用于II与III反应的那些。将酸结合剂加入到反应混合物中也可产生有利的效果。与前述的用于化合物II和III反应中同样的碱也是适用的。
取决于所选反应条件,最佳反应时间在几分钟至14天之间,且反应温度介于约0℃和150℃之间,通常在20℃至130℃之间。
另外,通过式VI(其中,R0和R1一起形成一个有1至3个碳原子的亚烷基链)的化合物的环化可得到式I的化合物。
式VI的化合物可通过如酮的还原而得到。这些酮与化合物VI相似,但其中CHG基团由羰基取代。
式VI的化合物的环化反应根据前述的用于化合物IV和V的反应中的方法并在相同的反应条件下进行。
式I的化合物也可借助还原剂,最好在介于-80℃和+250℃之间的温度下,和存在至少一种惰性溶剂的情况下,处理前体(其中,氢原子被一个或多个可还原的基团和/或一个或多个附带的C-C和/或C-N键所取代)而得到,
具体地说,可还原基团(可由氢取代的基团)是,羰基中的氧,羟基,芳基磺酰氧基(如,对甲苯磺酰氧基),N-苯磺酰,N-苄基或O-苄基。
原则上,只包含一个上述基团或附带价键的化合物,或包含两个或更多彼此相邻的上述基团或附带价键的化合物,可以通过还原转化成式I的化合物,即可能同时还原起始化合物中存在的Ind基团中的取代基。例如,可使用初生态氢或配位金属氢化物,或借助Wolff-Kishner还原或在过渡金属催化剂存在下采用氢气的还原来进行此反应。
用于还原反应的优选起始物具有结构式VII
其中,
Z’是一满足Z基的链,只是一个或多个-CH2基团已被-CO-取代和/或一个或多个氢原子已被Cl,Br,F,SH或OH基团取代。
式VII的化合物可通过用伯或仲胺酰胺酸、酰基卤、酐或酯得到。优选游离羧酸与胺在肽合成的条件下进行反应。最好当有脱水剂存在,如碳化二亚胺(如二环己基碳化二亚胺,或者N-(3-二甲基氨丙基)-N-乙基碳化二亚胺)或丙烷膦酸酐(q.v.Angew.Chen.
92,129(1980)),二苯基膦酰叠氮化物或2-乙氧基-N-乙氧基碳酰基-1,2-二氢喹啉,在一种惰性溶剂中,如卤化烃(如亚甲基氯),醚(如二噁烷),酰胺(如DMF或二甲基乙酰胺),或腈(如乙腈),在介于-10至40℃之间,优选0和30℃之间的温度下,进行这个反应。
如果初生态氢用作还原剂,这可以通过如将金属或弱酸或与碱处理得到。这样,可使用锌与碱金属氢氧化物溶液的混合物或铁与乙酸的混合物。在乙醇、异丙醇、丁醇、戊或异戊醇或苯酚之类的醇中使用钠或另一种碱金属也是合适的。也可以在碱性水溶液中使用铝-镍合金,如需要加入乙醇,含水醇或水溶液中的钠汞齐和铝汞齐也适于产生初生态氢。该反应也可在多相中进行,在多相的情况下,使用水相和苯或甲苯相很方便。
其它可特别有利地使用的还原剂是配位金属氢化物,如LiAlH4,NaBH4,氢化二异丁铝或NaAl(OCH2CH2OCH3)2H2,和乙硼烷,如果需要,加入催化剂,如BF3,AlCl3或LiBr。适于此目的的溶剂特别是醚乙醚、二正丁醚,THF,二噁烷,二甘醇二甲醚或1,2-二甲氧基乙烷,以及烃如苯。适于采用NaBH4进行还原的溶剂主要是醇,例如甲醇或乙醇,也可以是水或含水醇。通过这些方法进行还原优选在-80和+150℃之间,特别是在0和大约100℃之间的温度下进行。
酰胺中的-CO基(如,式V1中Z’是-(CH2)n1(CHA)n2-CO基的那些基团)还原成CH2基可以使用THF中的LiAlH4在约0和66℃之间的温度下进行,这特别有利。
也可以根据Wolff-Kishner方法,将一个或多个羰基还原成CH2基,例如,在无水醇中,在压力作用下,并在约150和250℃之间的温度下使用无水肼进行处理。最好使用醇钠作为催化剂。还原反应也可根据Huang-Minlon方法通过在高沸可与水混溶的溶剂(如二甘醇或三甘醇)中,并在碱(如氢氧化钠)存在的情况下使用水合肼进行反应而变通。反应混合物通常沸腾3-4小时。随后,蒸去水并将生成的腙在高达200℃的温度下分解。Wolff-Kishner反应也可在二甲基亚砜中,于室温下使用肼而进行。
而且,也可以通过使用H2气,在过渡金属,如阮内镍或钯的催化作用下,进行某些还原反应。通过这种方法,如Cl,Br,I,SH或在某些情况下,甚至OH基也可由氢取代。通过在甲醇中使用Pd/H2产生的催化氢化也可将硝基转换成NH2基。
式I中一个或多个H原子已被一个或多个可溶剂分解的基团取代的化合物也可被溶剂分解,特别是水解,而生成式I的化合物。
用于溶剂分解的起始物可例如通过将III与式II中一个或多个H原子已被一个或多个可溶剂分解的基团取代的化合物反应而得到。因此,特别是,1-酰胺衍生物(它们具有结构式I,只是在基团的1-位,它们含一个酰基,优选烷酰基,烷基磺酰基或每种情况下有多至10个碳原子的芳基磺酰基,如甲磺酰基,苯磺酰基或对甲苯磺酰基)可在酸性,或优选中性或碱性的介质中,于0和200℃之间的温度下进行水解而得到相应的仲胺衍生物。氢氧化钠、氢氧化钾、或氢氧化钙,碳酸钠或碳酸钾,或氨,可方便地用作碱。所选的溶剂优选水;低分子量的醇,如甲醇或乙醇;醚,如THF或二恶烷;砜,如四亚甲基砜;或它们的混合物,特别是包含水的混合物。水解也可简单地通过仅用水处理,特别是在沸点下而进行。
通过公知的方法,可把式I的一种化合物转化成式I的另一种化合物。
在惰性溶剂中,如卤代烃如二氯甲烷,醚如FHF或二噁烷,酰胺如DMF或二甲基乙酰,或腈如乙腈中,在介于-10℃和溶剂沸点的温度之间,优选0和70℃之间,通过对仲氨基残基烷基化或酰化可将式I中例如R2是氢的化合物转化成带有叔氨基的化合物。而且,通过已知的烷基化反应可将其它伯氨基转化成仲或叔氨基。
式I的化合物也可通过在基团Ar处的转化而转变成式I的其它衍生物。
式I中Ph基O-邻烷基单或双取代的醚可以解离成相应的羟基衍生物。也可以通过在甲苯,醚如THF或二甲基亚砜中,使用二甲基硫醚-三溴化硼进行处理,或通过在约150-250℃下与吡啶或氢卤化苯胺,优选盐酸吡啶一起熔融,而解离醚。
如果排除式I的化合物中其它付反应,在Friedel-Crafts-反应条件下,在路易斯酸,如AlCl3,FeBr3或Fe的催化下,在30℃和150℃之间,最好在50℃和150℃之间的温度下,于一种惰性溶剂中,如烃,FHF或四氯化碳中,通过将合适的卤素或烷基氯或烷基溴与衍生出的式I的化合物进行反应,而将Ph基团氯化、溴化或烷基化。另外,例如可通过公知的反应将硝基还原成氨基。
式I的化合物可具有一个或多个不对称中心。当制备时,如果使用旋光原料,它们可作为外消旋物或以旋光形式得到。当合成时,具有两个或多个不对称中心的化合物通常以外消旋物的混合物形式得到,从这些混合物中可以分离出各个纯的外消旋物,例如采用从惰性溶剂中的重结晶的方法。如果需要,得到的外消旋物可通过已知的方法借助化学方法或凝聚物的结晶而拆分成其光学对映体。最好是,通过旋光拆解剂从外消旋物形成非对映异构体。合适的拆解剂的例子是旋光酸,如D和L形的被护氨基酸衍生物(如对甲苯磺酰脯氨酸,酒石酸,二苯甲酰酒石酸,二乙酰酒石酸,樟脑-磺酸,扁桃酸,苹果酸或乳酸。不同形式的非对映异构体可通过已知的方式,如分步结晶而被拆分,而且式I的旋光化合物可由公知的方式从非对映异构体中释放出。
式I的碱可用酸转换成相应的酸加成盐,产生生物相容盐的酸适于这个反应。因此可使用无机酸,如硫酸,氢卤酸(如盐酸或氢溴酸,磷酸(如正磷酸),硝酸和氨磺酸,以及有机酸,特别是脂肪酸,脂环酸,芳脂酸,芳香酸或多环一元或多元羧酸,磺酸或硫酸,例如甲酸,乙酸,丙酸,新戊酸,二乙基乙酸,丙二酸,琥珀酸,庚二酸,富马酸,马来酸,乳酸,酒石酸,苹果酸,苯甲酸,水杨酸,2-苯基丙酸,柠檬酸,葡糖酸,抗坏血酸,烟酸,异烟酸,甲磺酸或乙磺酸,乙烷二磺酸,2-羟基乙磺酸,苯磺酸,对甲苯磺酸,萘单磺酸和萘二磺酸,以及月桂基磺酸。
如果需要,通过用强碱,如氢氧化钠、氢氧化钾或碳酸钠,碳酸钾处理可从其盐中释放出式I的游离碱,条件是分子中不存在其它酸基。在式I的化合物含有游离酸基的情况下,通过用碱处理也可成盐。合适的碱是碱金属氢氧化物,碱土金属氢氧化物或伯、仲、叔胺形式的有机碱。
本发明进一步涉及式I的化合物和其生物相容盐用于制备药物制剂、特别是通过一种非化学的途径的用途。为此,它们可与至少一种配料或赋形剂一起转变成一种合适剂量形式;如果合适,可与一种或多种附加活性成分合用。
本发明进一步涉及组合物、尤其是药物制剂,它们含有至少一种式I的化合物和/或一种其生物相容盐。这些制剂可用做人用或兽用的药物。可能的赋形剂是一些有机或无机物,它们适于肠胃给药(如,口服),非肠胃给药,或局部给药并且它们不与该新型化合物反应。这些赋形剂的例子是水,植物油,苯甲醇,聚乙二醇,明胶,碳水化合物,如乳糖或淀粉,硬脂酸镁,滑石或石油胶冻。药片,糖衣药片,胶囊,糖浆,糖汁,滴剂或栓剂特别适用于肠胃给药,溶液、优选油或水溶液,以及悬浮液,乳化液或植入物用于非肠胃给药,油,膏或粉用于局部给药。该新型化合物也可被冻干,产生的冻干物用于制造可注射的制剂。所示制剂可被消毒和/或包含配料,如润滑剂,防腐剂,稳定剂和/或润湿剂,乳化剂,影响渗透压的盐,缓冲物质,着色剂,调味剂和/或香料。如果需要,它们也可包括一种或多种附加活性成份,如一种或多种维生素。
式I的化合物及其生物相容盐可用于对人或动物的治疗和防治疾病。它们可用于治疗中枢神经系统的紊乱,如紧张,抑郁和/或精神病,以及治疗高血压(如,使用甲基多巴)产生的副作用。该化合物也可用于内分泌和妇科,如用于治疗肢端肥大症,性腺机能减退,继发性闭经,经前期综合症和自发性产期泌乳,而且也可用于预防和治疗大脑紊乱(如偏头痛),特别是采用与麦角生物碱相似的方式用于老年病症并用于控制大脑梗塞(脑中风)的后遗症,如中风和脑缺血。
而且,它们适用于消除识别缺限,改善学习和记忆能力并治疗Alzheimer病。
在这些治疗中,本发明中式I的化合物通常类似于已知的市售剂(如催乳激素抑制剂,二氢麦角考尔宁)给药,优选以每剂量单位大约0.2和500mg的剂量、特别是0.2和50mg给药。每日剂量优选为约0.001和10mg/kg体重。小剂量(约0.2至1mg/每剂量单位;约0.001至0.005mg/kg体重)特别适于用作防偏头痛药剂;每剂量单位10和50mg的用量优选用于其它症状。但是,对每个病人的特定剂量取决于许多因素,例如所用特定化合物的活性,体重,一般健康状况,性别,饮食,时间和给药方法,排泄率,药物结合以及所治疗特定疾病的严重程度。优选口服。
在下述实施例中,“以传统方式处理”意思是:如果需要,加入水,使用二氯甲烷进行萃取,分离出有机相,通过硫酸钠干燥并过滤,蒸发滤液,残余物在硅胶上通过色谱法和/或通过结晶纯化。温度以℃给出。
实施例1
2.8g 2-氨基甲基-苯并二氢呲喃[通过将3-(2-羟基-苯基)-丙醛与氰化钾反应,并随后催化还原2-氰基-苯并二氢呲喃而得到]与2.2g 3-(氯甲基)-吡啶的250ml DMF溶液与1g N-甲基-吗啉一起在20℃下搅拌12小时,并以传统方式处理得到N-(3-吡啶基甲基)-N-(2-苯并二氢呲喃基-甲基)-胺。与溶于100ml乙醇中的0.5当量马来酸一起搅拌得到马来酸盐,其中m.p.为163-164°。
以相似的方式得到下列物质:
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-5-(4-甲氧基苯基)-吡啶
得到N-[5-(4-甲氧基苯基)-3-呲啶基甲基]-N-(2-苯并二氢吡喃基-甲基)-胺,马来酸盐。m.p.177-178°。
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-5-苯基-吡啶
得到N-(5-苯基-3-吡啶基甲基)-N-(2-苯并二氢吡喃基-甲基)-胺,马来酸盐,m.p.184°。
从2-氨基乙基-苯并二氢吡喃和3-(氯甲基)-联苯得到N-3-联苯基乙基-N-(2-苯并二氢呲喃基-甲基)-胺,马来酸盐m.p.162°。
从2-氨基甲基-6-苯基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶,
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(6-苯基-2-苯并二氢吡喃基-甲基)-胺,马来酸盐m.p.222-224°。
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-呲啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并二氢吡喃基-甲基)-胺,马来酸盐m.p.182-183°。
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-联苯得到N-3-联苯基甲基-N-(2-苯并二氢吡喃基-甲基)-胺,马来酸盐m.p.174-175°。
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-4’-氟联苯,得到N-(4’-氟-3-联苯基甲基)-N-(2-苯并二氢吡喃基-甲基)-胺,马来酸盐m.p.183-184°。
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(8-甲氧基-2-苯并二氢呲喃基)-甲基]-胺,马来酸盐m.p.160-165。
从2-氨基甲基-7-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(7-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,马来酸盐m.p.170.5-172°。
从2-氨基甲基-6-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-甲氧基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐。
从2-氨基甲基-5-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(5-甲氧基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐m.p.181-183°。
从2-氨基甲基-8-硝基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(8-硝基-苯并二氢吡喃基-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-2,3,4,5-四氢-1-苯氧杂环庚三烯和3-(氯甲基)-5-(4-氟苯基)-呲啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[2-(2,3,4,5-四氢-1-苯氧杂环庚三烯基)-甲基]-胺,马来酸盐m.p.194-195°;
从2-氨基乙基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并二氢吡喃基乙基)-胺,马来酸盐m.p.160°;
从3-氨基-2,3,4,5-四氢-1-苯氧杂环庚三烯和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-3-(2,3,4,5-四氢-1-苯氧杂环庚三烯基)-胺,马来酸盐m.p.179-180°
从2-氨基甲基-8-羟基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟联苯)吡啶
得到N-[5-(4-氟-3-联苯基甲基]-N-[(8-羟基-2-苯并二氢吡喃基)-甲基]-胺,马来酸盐m.p.173°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-4’-氟联苯
得到N-(4’-氟-3-联苯基甲基)-N-[(8-甲氧基-2-苯并二氢吡喃)-甲基]-胺,马来酸盐m.p.176°;
从2-氨基甲基-6-氟苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-氟-2-苯并二氢吡喃基)-甲基]-胺,马来酸盐m.p.169-170°;
从2-氨基甲基-苯并二氢吡喃和3-(2-吡啶基)-氯甲基-苯
得到N-[3-(2-呲啶基)-苯基甲基]-N-2-苯并二氢呲喃-甲基-胺,马来酸盐m.p.201°;
从2-氨基甲基-苯并二氢呲喃和3-(3-吡啶基)-氯甲基-苯
得到N-[3-(3-吡啶基)-苯基甲基]-N-2-苯并二氢吡喃-甲基-胺,马来酸氢盐m.p.120°
从2-氨基甲基-8-甲氧基-苯并二氢呲喃和3-(3-呲啶基)-氯甲基-苯
得到N-[3-(3-吡啶基)-苯基甲基]-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,马来酸盐m.p.85°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(2-吡啶基)-氯甲基-苯
得到N-[3-(2-吡啶基)-苯基甲基]-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,马来酸盐m.p.167°;
采用相似方式得到下列物质(不用马来酸,而用0.1N的盐酸溶液处理该化合物,得到盐酸盐);
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-4’-甲基-联苯
得到N-(4’-甲基-3-联苯基甲基)-N-2-苯并二氢吡喃基-甲基-胺,盐酸盐,m.p.206-207°;
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-4’-甲氧基-联苯。
得到N-(4’-甲氧基-3-联苯基甲基)-N-2-苯并二氢吡喃-甲基-胺,盐酸盐,m.p.191-192°;
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-4’-三氟甲基-联苯
得到N-(4’-三氟甲基-3-联苯基甲基)-N-(2-苯并二氢吡喃基甲基-胺,盐酸盐,m.p.181-182°;
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-3’-三氟甲基-联苯
得到N-(3’-三氟甲基-3-联苯基甲基)-N-2-苯并二氢吡喃基-甲基-胺,盐酸盐,m.p.161-162°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-4’-三氟甲基-联苯
得到N-(4’-三氟甲基-3-联苯基甲基)-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,盐酸盐,m.p.206°-207°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-3’-甲基-联苯
得到N-(3’-三氟甲基-3-联苯基甲基)-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,盐酸盐,m.p.206°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-4’-甲基-联苯
得到N-(4’-甲基-3-联苯基甲基)-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,盐酸盐,m.p.188-189°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-4’-甲氧基-联苯
得到N-(4’-甲氧基-3-联苯基甲基)-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,盐酸盐,m.p.186-187°;
从2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-联苯
得到N-(3-联苯基甲基)-N-[(8-甲氧基-2-苯并二氢吡喃基)-甲基]-胺,盐酸盐,m.p.211-212°;
从2-氨基甲基-6-硝基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-硝基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-7-硝基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-呲啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(7-硝基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-8-氯-苯并二氢呲喃和3-(氯甲基)-5-(4-氟苯基)吡啶
得到N-[5-(4-氟苯基)-3-吡啶甲基]-N-[(8-氯苯并二氢吡喃-2-基)甲基]-胺,马来酸盐;
从2-氨基甲基-6-氯-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-氯-苯并二氢吡喃-2-基)-甲基]-胺,m.p.87-80℃;
从2-氨基甲基-7-氯-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(7-氯-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-8-氰基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(8-氰基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-6-氰基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-呲啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-氰基-苯并二氢呲喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-5-氰基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(5-氰基苯并二氢吡喃-2-基]-甲基]-胺,马来酸盐;
从2-氨基甲基-5-氟-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-呲啶基甲基]-N-[(5-氟-苯并二氢吡喃基-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-6-氟-苯并二氢呲喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-氟-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-5-(3,4-二氟-联苯)-吡啶
得到N-[5-(3,1-二氟苯基)-3-吡啶甲基]-N-(2-苯并二氢吡喃-甲基)-胺,马来酸盐,m.p.175-177°;
从2-氨基甲基-苯并二氢吡喃和3-苯氧基-苄基氯,得到:N-(3-苯氧基-苄基)-N-(2-苯并二氢吡喃-甲基)-胺,马来酸盐,m.p.150-152°下;
从2-氨基甲基-苯并二氢吡喃和2-(氯甲基)-4-苯基-吡啶
得到N-(4-苯基-2-吡啶基甲基)-N-(2-苯并二氢吡喃-甲基)-胺,马来酸盐,m.p.156-158°;
从2-氨基甲基-6-溴-苯并二氢吡喃和3-(氯甲基)-5-(4-氟-苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[2-(6-溴-苯并二氢吡喃)-甲基]-胺,马来酸盐;
从2-氨基甲基-苯并呋喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并呋喃-甲基)-胺,马来酸盐,m.p.147°
从2-氨基甲基-7-氟-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(7-氟-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-8-氟-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基-甲基]-N-[(8-氟-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-6-三氟甲基-苯并二氢呲喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-三氟甲基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-8-三氟甲基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶
得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(8-三氟甲基-苯并二氢吡喃-2-基)-甲基]-胺,马来酸盐;
实施例2
类似于实施例1,通过2-氨基甲基-2,3-二氢苯并呋喃和3-(氯甲基)-5-(4-氟苯基)-吡啶的反应,得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(2,3-二氢苯并呋喃-2-基)-甲基]-胺,马来酸盐,m.p.178-180°。
以相似的方式得到下列物质:
从2-氨基甲基-2,3-二氢苯并呋喃和3-(氯甲基)-5-(4-甲氧基苯基)-吡啶
得到N-[5-(4-甲氧基苯基)-3-吡啶基甲基]-N-[(2,3-二氢-苯并呋喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-2,3-二氢苯并呋喃和3-(氯甲基)-5-(3,4-二甲氧基苯基)-吡啶
得到N-[5-(3,4-二甲氧基苯基)-3-呲啶基甲基]-N-[(2,3-二氢-苯并呋喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-2,3-二氢苯并呋喃和3-(氯甲基)-5-(2,4-二甲氧基苯基)-吡啶
得到N-[5-(2,4-二甲氧基苯基)-3-吡啶基甲基]-N-[(2,3-二氢-苯并呋喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-2,3-二氢苯并呋喃和3-(氯甲基)-5-(3,4,5-三氟苯基)-吡啶
得到N-[5-(3,4,5-三氟苯基)-3-吡啶基甲基]-N-[(2,3-二氢-苯并呋喃-2-基)-甲基]-胺,马来酸盐;
从2-氨基甲基-2,3-二氢苯并呋喃和3-(氯甲基)-5-(2,3,4,5,6-五氟苯基)-吡啶
得到N-[5-(2,3,4,5,6-五氟苯基)-3-呲啶基甲基]-N-[(2,3-二氢-苯并呋喃-2-基]-胺,马来酸盐。
实施例3
2.2g 3-甲基苯酚,优选其钠盐,和5.6g N-(2-氯乙基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺(“A”)[可由邻苯二甲酰亚胺的钾盐和5-(4-氟苯基)-3-氯甲基-吡啶反应,产物用肼裂键并随后与1,2-二氯乙烷反应得到]的50ml乙腈混合物于50°搅拌5小时并以传统方式处理,得到N-[2-(3-甲基苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺。与溶于100ml乙醇的0.5当量的马来酸搅拌得到马来酸酯,m.p.152-154°。
以类似的方法得到下述物质:
从2,4-二氯苯酚的钠盐与“A”
得到N-[2-(2,4-二氯苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.148-150°;
从3-甲氧基苯酚的钠盐和“A”
得到N-[2-(3-甲氧基苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.122-124°;
从4-甲氧基苯酚的钠盐和“A”
得到N-[2-(4-甲氧基苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,m.p.94-96°;
从3-氯苯酚的钠盐和“A”
得到N-[2-(3-氯苯氧基)-乙基]-N-[5-(4-氟苯基)-3-呲啶基甲基]-胺,马来酸盐,m.p.150-152°
从2-氟苯酚的钠盐和“A”
得到N-[2-(2-氯苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.153-155°;
从2-甲氧基苯酚的钠盐和“A”
得到N-[2-(2-甲氧基苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶甲基]-胺,马来酸盐,m.p.134-136°;
从4-氯苯酚的钠盐和“A”
得到N-[2-(4-氯苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.163-164°;
从2-乙基苯酚的钠盐和“A”
得到N-[2-(2-乙基苯氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.128-130°;
从3-氰基苯酚的钠盐和“A”
得到N-[2-(3-氰基苯酚)-乙基]-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,草酸盐,m.p.245°;
从4-氰基苯酚的钠盐和“A”
得到N-[2-(4-氰基苯酚)-乙基]-N-[5-(4-氟苯基)-3-呲啶基甲基]-胺,草酸盐,m.p.25°;
从苯酚的钠盐和N-[3-苯氧基-苄基)-胺
得到N-(2-苯氧基)-乙基)-N-(3-苯氧基-苄基)-胺,马来酸盐,m.p.166-168°;
从苯酚的钠盐和“A”
得到N-(2-苯氧基-乙基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,m.p.84-86°。
实施例4
类似于实施例1,通过2-氨基甲基-6-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶反应,得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[(6-甲氧基-2-苯并二氢呲喃基)-甲基]-胺。与盐酸搅拌得到二盐酸盐,m.p.205-206°。
实施例5
类似于实施例1,通过2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟苯基)-吡啶的反应,得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并二氢吡喃-甲基)-胺。与盐酸搅拌,得到二盐酸盐一半水合物,m.p.210-213°
实施例6
1.8g 3-氨基甲基-联苯[通过还原3-氰基-联苯得到]和1.6g 2-氟乙基-苯基醚[通过苯酚钠与二氯乙烷反应得到]的200ml乙腈溶液在室温下搅拌8小时,并以传统方式处理得到N-(3-联苯基甲基)-N-2-苯氧基乙基-胺。与溶于100ml乙醇的0.5当量的马来酸搅拌得到马来酸盐,m.p.178-180°。
以类似的方式得到下列物质:
从3-氨基甲基-4’-氟-联苯和2-氯乙基-苯基醚
得到N-(4’-氟-3-联苯基甲基)-N-2-苯氧基乙基-胺,马来酸盐,m.p.194-196°;
从3-氨基甲基-2’,4’-二氯-联苯和2-氯乙基-苯基醚
得到N-(2’,4’-二氟-3-联苯基甲基)-N-2-苯氧基乙基-胺;
从3-氨基甲基-5-苯基吡啶和2-氯乙基-苯基醚
得到N-(5-苯基-3-吡啶基甲基)-N-2-苯氧基乙基-胺,m.p.77-79°;
从2-氨基甲基-4-(3-噻吩基)-噻吩和2-氯乙基-苯基醚
得到N-[4-(3-噻吩基)-2-噻吩基甲基]-N-2-苯氧基乙基-胺,m.p.96-98°;
从2-氨基甲基-4-甲基-噻吩和2-氯乙基-苯基醚
得到N-(4-甲基-2-噻吩基甲基)-N-2-苯氧基乙基-胺;
从2-氨基甲基-4-甲氧基-噻吩和2-氯乙基-苯基醚
得到N-(4-甲氧基-2-噻吩基甲基)-N-2-苯氧基乙基-胺;
从2-氨基甲基-4-乙基-噻吩和2-氯乙基-苯基醚
得到N-(4-乙基-2-噻吩基甲基)-N-2-苯氧基乙基-胺;
从2-氨基甲基-4-氯-噻吩和2-氯乙基-苯基醚
得到N-(4-氯-2-噻吩基甲基)-N-2-苯氧基乙基-胺;
从3-氨基甲基-4’-氟-联苯和2-氯乙基-(3-氰-苯基)-醚
得到N-(4’-氟-3-联苯基甲基)-N-2-(3-氰基-苯氧基-乙基)-胺,马来酸盐,m.p.158-160°;
从3-氨基甲基-联苯和2-氯乙基-(2-甲氧基-苯基)-醚
得到N-(3-联苯基甲基)-N-2-(2-甲氧基-苯氧基)-乙基-胺,m.p.72-74°
从3-氨基甲基-联苯和2-氯乙基-2-联苯基-醚
得到N-(3-联苯基甲基)-N-2-(2-联苯氧基)-乙基胺,马来酸盐,m.p.146-148°;
从3-氨基甲基-5-(4-氟-苯基)-吡啶和2-氯乙基-(2-联苯基)-醚
得到N-[5-(4-氟苯基-3-吡啶基甲基)]-N-2-(2-联苯氧基)-乙基-胺,m.p.134-136°;
从3-氨基甲基-联苯和2-氯乙基-(2-羟基苯基)-醚
得到N-(3-联苯基甲基)-N-2-(2-羟基苯氧基)-乙基胺,m.p.88-90°
实施例7
1.2g 2-羟基-苯甲腈和2.5g N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺[通过2-羟基-乙胺与3-氯甲基-5-苯基-吡啶反应并随后使用PCl3将产物转变成2-氯乙基化合物而得到]的200ml乙腈溶液在室温下搅拌5小时,并以传统方式处理得到N-[2-(2-氰基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺。与溶于100ml乙醇中的0.5当量草酸搅拌得到草酸盐,m.p.208°。以类似的方式得到下述物质:
从2-氯-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-氯苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从2-甲基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-甲基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-氯-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氯苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-氰基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氰基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从3-乙基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(3-乙基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-三氟甲基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-三氟甲基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从2-溴-苯酚和N-2-氯乙基-N-(5-苯基-3-呲啶基甲基)-胺
得到N-[2-(2-溴苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从2-氨基甲基-苯和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-氨基乙基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-甲氧基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-甲氧基苯氧基)-乙基]-N-(5-苯基-3-吡啶基-甲基)-胺;
从3-氨基甲基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(3-氨基乙基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-氨基甲基-苯酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氨基甲基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺。
实施例8
3.1g N-[2-(2-氰基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺,3g NaOH,50ml水和40ml二甘醇单乙醚的混合物在140°的浴温下搅拌3小时。将混合物冷却并以传统方式处理,得到N-[2-(2-甲酰胺基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺。与溶在100ml乙醇中的0.5当量的草酸一起搅拌得到草酸盐,m.p.230°。
实施例9
类似于实施例8,通过部分水解N-[2-(4-氰基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺,得到N-[2-(4-甲酰胺基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺。
实施例10
类似于实施例8,自N-[2-(4-氰基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺开始,沸腾16小时并随后以传统方式处理,得到N-[2-(4-羧基苯氧基]-乙基-N-[5-苯基-3-呲啶基甲基]-胺。
实施例11
类似于实施例8,自N-[2-(2-氰基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺开始,沸腾16小时并随后以传统方式处理,得到N-[2-(2-羧基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺。
实施例12
类似于实施例7,2.3g苯酚钠和2.5g N-3-氯丙基-N-[5-(4-氟苯基)-3-吡啶甲基]-胺[通过3-羟基丙胺与3-氯甲基-5-(4-氟-苯基)-吡啶反应并随后使用PCl3将产物转变成3-氯丙基-化合物而得到]溶于200ml的乙腈中,在室温下搅拌5小时并以传统方式处理,得到N-(3-苯氧基-丙基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺。与溶于100ml乙醇/水的0.5当量草酸一起搅拌得到草酸盐半水合物,m.p.217°。
以类似的方式得到下述物质:
从苯酚钠和N-4-氯丁基-N-[5-(4-氟苯基)-3-呲啶基甲基]-胺
得到N-(4-苯氧基-丁基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.143°
从苯酚钠和N-2-氯异丙基-N-[5-(4-氟苯基)-3-呲啶基甲基]-胺
得到N-(2-苯氧基-异丙基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,马来酸盐,m.p.123-125°;
从苯硫酚钠和N-2-氯乙基-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺
得到N-(2-硫苯氧基-乙基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺,草酸盐,m.p.230°;
从苯硫酚钠和N-4-氯丁基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-(4-硫苯氧基-丁基)-N-(5-苯基-3-吡啶基甲基)-胺
从苯硫酚钠和N-3-氯丙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-(3-硫苯氧基-丙基)-N-(5-苯基-3-吡啶基甲基)-胺;
从苯硫酚钠和N-2-氯异丙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-(2-硫苯氧基-异丙基)-N-(5-苯基-3-吡啶基甲基)-胺。
实施例13
根据实施例7,以类例的方式得到下述物质:
从2-氯-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-氯硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从2-甲基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-甲基氯硫苯氧基)-乙基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺
从4-氯-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氟硫苯氧堪)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-氰基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氰基硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从3-乙基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氰基硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从3-乙基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(3-乙基硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-三氟甲基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-呲啶基甲基)-胺
得到N-[2-(4-三氟甲基硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从2-溴-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-溴硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从2-氨基甲基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(2-氨基甲基硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-甲氧基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-甲氧基硫苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从3-氨基甲基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(3-氨基甲硫基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
从4-氨基甲基-苯硫酚和N-2-氯乙基-N-(5-苯基-3-吡啶基甲基)-胺
得到N-[2-(4-氨基甲硫基苯氧基)-乙基]-N-(5-苯基-3-吡啶基甲基)-胺;
实施例14
2.8g N-[2-(2-甲氧基苯氧基)-乙基]-N-[5-(4-氟苯基)-3-呲啶基甲基]-胺[依实施例3得到]和1当量的3-氧甲基-5-(4-氟苯基)-吡啶的125ml乙腈溶液在40°下搅拌6小时,并以传统方式处理,得到N-[2-(2-甲氧基苯氧基)-乙基]-N,N-双-[5-(4-氟苯基)-3-吡啶基甲基]-胺,m.p.90-92°。
通过3-氯甲基-5-(4-氟苯基)-吡啶与以下物质反应,以类似的方式得到。
与N-(4-苯氧基)-丁基)-N-(5-苯基-3-吡啶基甲基)-胺
得到N-(4-苯氧基)-丁基)-N-(5-苯基-3-吡啶基甲基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-胺;
与N-(2-苯氧基-异丙基)-N-(5-苯基-3-吡啶基甲基)-胺
得到N-(2-苯氧基-异丙基)-N-(5-苯基-3-吡啶基甲基)-N-[5-(4-氟-苯基)-3-吡啶基甲基]-胺;与N-(2-硫苯氧基-丁基)-N-(5-苯基-3-吡啶基甲基)-胺;
得到N-(2-硫苯氧基-丁基)-N-(5-苯基-3-呲啶基甲基)-N-[5-(4-氟-苯基)-3-吡啶基甲基]-胺;
与N-(4-硫苯氧基-丁基)-N-(5-苯基-3-吡啶基甲基)-胺
得到N-(4-硫苯氧基-丁基)-N-(5-苯基-3-吡啶基甲基)-N-[5-(4-氟-苯基)-3-吡啶基甲基]-胺;
实施例15
类似于实施例7,2.3g 1-萘酚钠和2.9gN-2-氯乙基-N-[5-(4-氟苯基-3-吡啶基甲基)-胺[通过2-羟基乙胺与3-氯甲基-5-(4-氟苯基)-吡啶反应随后通过与PCL3的反应将产物转变成2-氯乙基-化合物而得到]溶于200ml乙腈中的溶液在室温下搅拌5小时并以传统方式处理得到N-[2-(1-萘氧基)-乙基]-N-[5-(4-氟苯基)-3-呲啶基甲基]-胺,m.p.92-94°。
通过2-萘酚盐与下述物质反应得到:
与N-2-氯乙基-N-[5-(4-氟苯基-3-吡啶基甲基)-胺
得到N-[2-(2-萘氧基)-乙基]-N-[5-(4-氟苯基)-3-吡啶基-甲基]-胺,m.p.128-130°
与N-2-氯乙基-N-[5-(2,4-二氯苯基-3-吡啶基甲基)-胺,
得到N-[2-(2-萘氧基)-乙基]-N-[5-(2,4-二氟苯基)-3-吡啶基甲基]-胺,
实施例16
2.1g N-(2-苯氧基-乙基)-N-[5-(4-氟-苯基)-3-吡啶基甲基]-胺[可根据实施例3得到]的100ml THF溶液在搅拌下用2ml碘甲烷处理,历时3小时。以传统方式处理,得到N-(2-苯氧基-乙基)-N-[5-(4-氟苯基)-3-吡啶基甲基]-N-甲基-胺,草酸盐,m.p.159-161°。
类似地,烷基化仲胺得到以下物质:
N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并二氢吡喃-甲基)-N-甲基-胺,m.p.71°;
N-3-联苯基甲基-N-(2-苯并二氢吡喃基-甲基)-N-甲基-胺。
实施例17
类似于实施例1,通过N-[5-(4-氟苯基)-3-吡啶基甲基]-胺与1-氯-3-苯基丙烷的反应得到N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(3-苯基丙基)-胺,m.p.<50°。
实施例18
类似于实施例3,通过苯酚钠盐与N-(2-氟乙基)-N-3-(2-吡啶基)-氯甲基-苯反应得到N-[3-(2-吡啶基)-苯基甲基]-N-[2-(苯氧基)-乙基]-胺,马来酸盐,m.p.170°;
苯酚钠盐与N-(2-氯乙基)-N-3-(3-吡啶基)-氯甲基-苯反应得到N-[3-(3-吡啶基)-苯基甲基]-N-[2-(苯氧基)-乙基]-胺,马来酸盐,m.p.123-125°。
制备对应体化合物:
实施例19
4.5g 2-氨基甲基-苯并二氢吡喃[可通过将3-(2-羟基-苯基)-丙醛与KCN反应并随后催化还原2-氰基苯并二氢呲喃而得到]和3.9g甲苯磺酰脯氨酸的190ml乙醇溶液回流15分钟。随后,边搅拌边将溶液冷却到5°。在冷却过程中,加入几块纯的(R)-2-氨基甲基-苯并二氢吡喃的晶体。将溶液保持在5°下搅拌18小时,并随后分离出纯的对应体(R)-2-氮基甲基-苯并二氢吡喃。对第一次结晶产生的晶体反复两次结晶过程以得到一种纯度超过99%的对应体。
随后,类似于实施例1,将(R)-2-氨基甲基-苯并二氢吡喃
与3-(氯甲基)-5-(4-氟苯基)-吡啶反应以得到(R)-(一)-2-[5-(4-氟苯基)-3-吡啶基-甲基氨基甲基]-苯并二氢吡喃[=(R)-(一)-1N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并二氢吡喃基二甲基)-胺]。与0.1N的盐酸溶液一起搅拌得到二盐酸盐,m.p.234-235°;[α20]=-65°(C=1,甲醇)。
类似地,通过(S)-2-氨基甲基-苯并二氢吡喃和3-(苯并二氢呲喃基)-5-(4-氟-苯基)-吡啶的反应,得到(S)-(+)-2-[5-(4-氟苯基)-3-吡啶基-甲基氨基甲基]-苯并二氢吡喃[=(S)-(+)-1N-[5-(4-氟苯基)-3-吡啶基甲基]-N-(2-苯并二氢吡喃基-甲基)-胺]。与0.1N的盐酸溶液一起搅拌得到二盐酸盐,m.p.227-228°,[α20]=+62°(C=1,甲醇)。
类似地,通过(S)-2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟-苯基)-吡啶的反应得到(S)-(+)-2-[5-(4-氟苯基)-3-吡啶基-甲基氨基甲基]-8-甲氧基-苯并二氢吡喃[=(S)-(+)-1-N-[5-(4-氟苯基)-3-呲啶基甲基]-N-[2-(8-甲氧基-苯并二氢吡喃)-甲基]-胺。与0.1N的盐酸溶液搅拌得到二盐酸盐,m.p.214-215°。
类似地,通过(S)-2-氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-5-(4-氟-苯基)-吡啶的反应得到(R)-(-)-2-[5-(4-氟苯基)-3-吡啶基-甲基氨基甲基]-8-甲氧基-苯并二氢吡喃[=(R)-(-)-1-N-[5-(4-氟苯基)-3-吡啶基甲基]-N-[2-(8-甲氧基-苯并二氢吡喃基)-甲基]-胺]。与0.1N盐酸溶液一起搅拌得到二盐酸盐,m.p.214°。
实施例20
类似于实施例1,5g(R)-2-氨基甲基-苯并二氢吡喃[通过2-羧基-苯并二氢吡喃和(+)-苯基乙基胺反应,分离出主要的结晶的非对映体,通过用乙醇重结晶纯化,转变成苯并二氢吡喃酸乙酯,通过HPLC手性相(Chiracel OJTM)进一步纯化,转变成酰胺。通过在FHF中用LiAlH4或VitrideTM还原成(R)-2-氨基甲基-苯并二氢吡喃而得到]的溶液与3-(氯甲基)-5-苯基-吡啶反应生成(R)-(-)-2-[5-苯基-3-吡啶基-甲基氨基甲基]-苯并二氢吡喃[=(R)-(-)-1N-(5-苯基-3-吡啶基甲基)-N-(2-苯并二氢吡喃基-甲基)-胺]。与0.1N盐酸溶液一起搅拌得到二盐酸盐,m.p.243-244°。
类似地,通过(S)-2-氨基甲基-苯并二氢吡喃和3-(氯甲基)-5-苯基-吡啶的反应得到(S)-(+)-2-(5-苯基-3-吡啶基-甲基氨基甲基)-苯并二氢吡喃[=(S)-(+)-1N-(5-苯基-3-吡啶基甲基)-N-(2-苯并二氢呲喃基-甲基)-胺]。与0.1N盐酸溶液一起搅拌得到二盐酸盐,m.p.244-245°。
类似地,通过(S)-2-氨基甲基-8-甲氧基-苯丙二氢吡喃和3-(氯甲基)-4’-氟-联苯的反应得到(S)-(+)-2-[4’-氟-3-联苯基-甲基氨基甲基]-8-甲氧基-苯并二氢吡喃[=(S)-(+)-1N-[4’-氟-3-联苯基-甲基]-N-[2-(8-甲氧基-苯并二氢吡喃基)-甲基]-胺]。与0.1N盐酸溶液一起搅拌得到二盐酸盐,m.p.189-190°;[α20]=+74°(C=1,甲醇)。
类似地,通过(R)-2-(氨基甲基-8-甲氧基-苯并二氢吡喃和3-(氯甲基)-4’-氟-联苯反应得到(R)-(-)-2-[4’-氟-3-联苯基-甲基氨基甲基]-8-甲氧基-苯并二氢呲喃[=(R)-(-)-1N-[4’-氟-3-联苯基-甲基]-N-[2-(8-甲氧基-苯并二氢吡喃基)-甲基]-胺]。与0.1N盐酸溶液一起搅拌得到二盐酸盐,m.p.189-190°;[α20]=-74.3°(C=1,甲醇)。
下述实施例涉及药品制剂。
实施例A:注射药瓶
100g式I的活性化合物与5g磷酸氢二钠于3L二次蒸馏水中所形成的溶液用2N盐酸调至pH6.5,消毒过滤,装入注射药瓶并在无菌条件下冷冻干燥,以无菌方式封闭药瓶。每一注射药瓶中合5mg活性化合物。
实施例B:栓剂
20g式I的化合物的混合物与100g大豆磷脂和1400g可可油熔合,将该混合物灌入模子中并冷却。每个栓剂包括20mg活性化合物。
实施例C:溶液
1g式I的活性化合物,9.38g NaH2PO4·2H2O,28.48gNa2HPO4·12H2O和0.1g杀藻铵在940ml二次蒸馏水中制备成溶液。该溶液调至pH6.8,冲成1L并通过辐射消毒灭菌。这种溶液可用作眼药水。
实施例D:药膏
500mg式I的化合物在无菌条件下与99.5g凡士林混合。
实施例E:药片
100g式I的活性化合物,1kg乳糖,600g微晶纤维素,600g玉米淀粉,100g聚乙烯吡咯烷酮,80g滑石粉和10g硬脂酸镁以常规方式压成药片,这样,每个药片包含10mg活性化合物。
实施例F:糖衣药片
与实施例E中所述相同方式压成药片并随后以常规方式包上一层蔗糖、玉米淀粉、滑石粉、黄蓍胶精和着色剂涂层。
实施例G:胶囊
硬胶囊以常规方式填入式I的活性化合物,这样,每个胶囊含5mg活性化合物。
实施例H:吸入喷雾剂
14g式I的化合物溶于101等渗压的NaCl溶液中并把该溶液灌入市售带泵机构的喷雾剂罐中。该喷雾剂可喷入嘴中和鼻中。每次喷射(约0.1ml)对应约0.14mg的剂量。
Claims (5)
1.(R)-(-)-2-[5-(4-氟苯基)-3-吡啶基甲基氨基甲基]-苯并二氢吡喃及其生物相容盐。
2.一种制备(R)-(-)-2-[5-(4-氟苯基)-3-吡啶基甲基氨基甲基]-苯并二氢吡喃及其盐的方法,其特征在于使3-(氯甲基)-5-(4-氟苯基)吡啶与(R)-2-氨基甲基苯并二氢吡喃反应和/或其特征在于所得碱通过用酸处理转化为它的一种盐。
3.制备药物制剂的方法,其特征在于使(R)-(-)-2-[5-(4-氟苯基)-3-吡啶基甲基氨基甲基]-苯并二氢吡喃及其一种生物相容盐与至少一种固体、液体或半液体赋型剂或助剂一起转化成适当的剂型。
4.药物制剂,其特征在于它含有(R)-(-)-2-[5-(4-氟苯基)-3-吡啶基甲基氨基甲基]-苯并二氢吡喃和/或其生理上可接受的一种盐。
5.应用(R)-(-)-2-[5-(4-氟苯基)-3-吡啶基甲基氨基甲基]-苯并二氢吡喃或其生物相容盐制备用于治疗中枢神经系统紊乱的药物的用途。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP94116223 | 1994-10-14 | ||
EP94116223.2 | 1994-10-14 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1130180A CN1130180A (zh) | 1996-09-04 |
CN1246319C true CN1246319C (zh) | 2006-03-22 |
Family
ID=8216383
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB951184857A Expired - Fee Related CN1246319C (zh) | 1994-10-14 | 1995-10-13 | 氨基(硫)醚衍生物 |
Country Status (27)
Country | Link |
---|---|
US (1) | US5767132A (zh) |
EP (2) | EP0707007B1 (zh) |
JP (1) | JP3880645B2 (zh) |
KR (1) | KR100389497B1 (zh) |
CN (1) | CN1246319C (zh) |
AT (1) | ATE210657T1 (zh) |
AU (1) | AU703637B2 (zh) |
BR (1) | BR9504379A (zh) |
CA (1) | CA2160447C (zh) |
CO (1) | CO4480021A1 (zh) |
CZ (1) | CZ292104B6 (zh) |
DE (1) | DE69524528T2 (zh) |
DK (1) | DK0707007T3 (zh) |
ES (1) | ES2169102T3 (zh) |
FI (1) | FI116385B (zh) |
HU (1) | HU227883B1 (zh) |
MX (1) | MX9504332A (zh) |
NO (1) | NO308848B1 (zh) |
PL (1) | PL181165B1 (zh) |
PT (1) | PT707007E (zh) |
RU (1) | RU2155753C2 (zh) |
SI (1) | SI0707007T1 (zh) |
SK (1) | SK283870B6 (zh) |
TR (1) | TR199501253A2 (zh) |
TW (1) | TW420664B (zh) |
UA (1) | UA45952C2 (zh) |
ZA (1) | ZA958673B (zh) |
Families Citing this family (46)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL119483A (en) * | 1995-11-06 | 1999-06-20 | American Home Prod | 2-(Aminomethyl)-3,4,7,9- tetrahydro- 2H-pyrano-2[3,3-e]indol-8-ones their derivatives and pharmaceutical compositions containing them |
JP2000516210A (ja) | 1996-07-12 | 2000-12-05 | ロイコサイト,インコーポレーテッド | ケモカインレセプターアンタゴニストとその使用方法 |
FR2756284B1 (fr) * | 1996-11-26 | 2000-04-28 | Adir | Nouveaux derives du benzopyrane, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
US6127380A (en) * | 1997-02-18 | 2000-10-03 | American Home Products Corporation | 4-aminoalkoxy-1H-benzoimidazoles |
US5922715A (en) * | 1997-02-18 | 1999-07-13 | American Home Products Corporation | 5-aminoalkoxy-1, 4-dihydroquinoxaline-2, 3-diones |
US5990144A (en) * | 1997-02-18 | 1999-11-23 | American Home Products Corporation | 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-one dopamine autoreceptor agonists |
NZ336971A (en) * | 1997-02-18 | 2000-10-27 | American Home Prod | 5-Aminoalkoxy-1,4-dihydroquinoxaline-2,3-diones useful as dopamine agonists |
CA2278718A1 (en) * | 1997-02-18 | 1998-08-20 | American Home Products Corporation | 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-thiones derivatives, their preparation and their use as dopamine autoreceptor (d2) agonists |
KR20000071129A (ko) * | 1997-02-18 | 2000-11-25 | 이곤 이 버그 | 4-아미노알콕시-1h-벤즈이미다졸 유도체, 이의 제조방법 및도파민 자가수용체(d2) 효능제로서의 이의 용도 |
US5972958A (en) * | 1997-02-18 | 1999-10-26 | American Home Products Corporation | 4-aminoalkoxy-1,3-dihydro-benzoimidazol-2-thiones |
HUP0001262A3 (en) * | 1997-02-18 | 2002-04-29 | American Home Products Corp Ma | 4-aminoalkoxy-1,3-dihydrobenzoimidazol-2-one deriatives, their preparation and their use as dopamine autoreceptor (d2) agonists |
CO5011067A1 (es) * | 1997-11-03 | 2001-02-28 | Novartis Ag | Derivados de bifenilo como productos farmaceuticos, su pre- paracion y composiciones farmaceuticas que los contienen |
US7189753B1 (en) | 1997-11-06 | 2007-03-13 | Cady Roger K | Preemptive prophylaxis of migraine |
FR2786767B1 (fr) * | 1998-12-02 | 2001-02-23 | Pf Medicament | Nouveaux derives de 3-alkoxybenzylamines et leur utilisation a titre de medicaments pour le traitement de la schizophrenie |
DE19858341A1 (de) * | 1998-12-17 | 2000-06-21 | Merck Patent Gmbh | Chromanderivate |
AU3772800A (en) * | 1999-03-24 | 2000-10-09 | Sepracor, Inc. | Diaryl thioethers, compositions and uses thereof |
DE10005150A1 (de) * | 2000-02-07 | 2001-08-09 | Merck Patent Gmbh | Verfahren zur Herstellung von 5-Arylnicotinaldehyden |
GB0004153D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
GB0004152D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel compounds |
GB0004151D0 (en) | 2000-02-23 | 2000-04-12 | Astrazeneca Uk Ltd | Novel use |
UA73981C2 (en) | 2000-03-10 | 2005-10-17 | Merck Patent Gmbh | (r)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane for treatment of extrapyramidal movement disorders (variants), pharmaceutical composition and kit |
DE10029371A1 (de) * | 2000-06-20 | 2002-01-03 | Merck Patent Gmbh | Heterocyclische Aminoalkylpyridinderivate als Psychopharmaka |
DE10044091A1 (de) | 2000-09-07 | 2002-04-04 | Merck Patent Gmbh | Chromanonderivate |
AU2002221744A1 (en) * | 2000-11-14 | 2002-05-27 | Merck Patent Gmbh | Novel uses of combined selective dopamine D2 receptor antagonists and 5-HT1A receptor agonists |
DE10120619A1 (de) * | 2001-04-26 | 2002-10-31 | Merck Patent Gmbh | 2-(5-(4-Fluorphenyl)-3-pyridylmethylaminomethyl-chroman |
ES2280602T3 (es) * | 2001-07-26 | 2007-09-16 | Merck Patent Gmbh | Uso de 2-(5-(4-fluorofenil)-3-piridilmetilaminometil)-cromano y sus sales fisiologicamente aceptables. |
SE0102640D0 (sv) | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
SE0102641D0 (sv) * | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
SE0102639D0 (sv) | 2001-07-31 | 2001-07-31 | Astrazeneca Ab | Novel compounds |
DK1427724T3 (da) * | 2001-09-19 | 2006-08-21 | Merck Patent Gmbh | Hidtil ukendt anvendelse af substituerede aminomethylchromaner |
WO2003029239A1 (en) | 2001-10-04 | 2003-04-10 | Wyeth | Chroman and benzofuran derivatives as 5-hydroxytryptamine-6 ligands |
US20050014818A1 (en) * | 2001-11-09 | 2005-01-20 | Masaru Mitsuda | Process for producing optically active chroman derivative and intermediate |
GB0225548D0 (en) | 2002-11-01 | 2002-12-11 | Glaxo Group Ltd | Compounds |
US7728155B2 (en) | 2003-10-24 | 2010-06-01 | Wyeth Llc | Dihydrobenzofuranyl alkanamines and methods for using same as cns agents |
US20050261347A1 (en) * | 2003-10-24 | 2005-11-24 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
US7435837B2 (en) | 2003-10-24 | 2008-10-14 | Wyeth | Dihydrobenzofuranyl alkanamine derivatives and methods for using same |
AP2006003700A0 (en) | 2004-02-13 | 2006-08-31 | Warner Lambert Co | Androgen receptor modulators |
CA2563291A1 (en) | 2004-04-13 | 2005-10-27 | Warner-Lambert Company Llc | 4-cyano-phenoxy-alkyl carboxyl derivatives as androgen modulators |
WO2005102990A1 (en) | 2004-04-22 | 2005-11-03 | Warner-Lambert Company Llc | Androgen modulators |
BRPI0513020A (pt) | 2004-07-08 | 2008-04-22 | Warner Lambert Co | moduladores de andrÈgenio, seus usos, composição farmacêutica, formulação farmacêutica tópica e artigo de fabricação |
RU2007139541A (ru) * | 2005-04-22 | 2009-05-27 | Вайет (Us) | Производные хромана и хромена и их применение |
WO2006116218A1 (en) * | 2005-04-22 | 2006-11-02 | Wyeth | Crystal forms of {[(2r)-7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine hydrochloride |
TW200724139A (en) | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
TW200811182A (en) | 2006-05-25 | 2008-03-01 | Wyeth Corp | Oxindoledioxans, synthesis thereof, and intermediates thereto |
EP2699543B1 (en) * | 2011-04-19 | 2016-03-02 | Integrative Research Laboratories Sweden AB | Novel modulators of cortical dopaminergic- and nmda-receptor-mediated glutamatergic neurotransmission |
WO2016149765A1 (en) * | 2015-03-26 | 2016-09-29 | The Florey Institute Of Neuroscience And Mental Health | Sodium channel modulators |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2364685C3 (de) * | 1973-12-27 | 1978-06-15 | Beiersdorf Ag, 2000 Hamburg | Phenoxyäthylamine |
FR2397417A1 (fr) * | 1977-07-12 | 1979-02-09 | Parcor | Procede de preparation de derives de la thienopyridine |
JPS55124742A (en) * | 1979-03-20 | 1980-09-26 | Kyowa Hakko Kogyo Co Ltd | Novel aminoalcohol derivative |
CA1337429C (en) * | 1983-12-05 | 1995-10-24 | Guy Rosalia Eugene Van Lommen | Derivatives of 2,2'-iminobisethanol |
DE3901814A1 (de) * | 1988-07-28 | 1990-02-01 | Bayer Ag | Substituierte aminomethylzetraline sowie ihre heterocyclischen analoga |
DE4135474A1 (de) * | 1991-10-28 | 1993-04-29 | Bayer Ag | 2-aminomethyl-chromane |
SI9300097B (en) * | 1992-02-27 | 2001-12-31 | Janssen Pharmaceutica Nv | (benzodioxan, benzofuran or benzopyran) alkylamino) alkyl substituted guanidines |
JPH05255302A (ja) * | 1992-03-09 | 1993-10-05 | Yamanouchi Pharmaceut Co Ltd | 新規なクロマニルオキシアルキルアミン誘導体 |
DE4226527A1 (de) * | 1992-08-11 | 1994-02-17 | Merck Patent Gmbh | 1,4-Benzodioxanderivate |
EP0714396B1 (en) * | 1993-08-19 | 2003-12-10 | Janssen Pharmaceutica N.V. | Vasocontrictive dihydrobenzopyran derivatives |
-
1995
- 1995-10-06 PT PT95115779T patent/PT707007E/pt unknown
- 1995-10-06 SI SI9530574T patent/SI0707007T1/xx unknown
- 1995-10-06 DE DE69524528T patent/DE69524528T2/de not_active Expired - Lifetime
- 1995-10-06 EP EP95115779A patent/EP0707007B1/en not_active Expired - Lifetime
- 1995-10-06 ES ES95115779T patent/ES2169102T3/es not_active Expired - Lifetime
- 1995-10-06 DK DK95115779T patent/DK0707007T3/da active
- 1995-10-06 AT AT95115779T patent/ATE210657T1/de active
- 1995-10-06 EP EP01109746A patent/EP1123933A1/en not_active Withdrawn
- 1995-10-11 SK SK1266-95A patent/SK283870B6/sk not_active IP Right Cessation
- 1995-10-11 BR BR9504379A patent/BR9504379A/pt not_active Application Discontinuation
- 1995-10-12 CZ CZ19952661A patent/CZ292104B6/cs not_active IP Right Cessation
- 1995-10-12 AU AU34218/95A patent/AU703637B2/en not_active Ceased
- 1995-10-12 TR TR95/01253A patent/TR199501253A2/xx unknown
- 1995-10-12 CA CA002160447A patent/CA2160447C/en not_active Expired - Fee Related
- 1995-10-12 MX MX9504332A patent/MX9504332A/es unknown
- 1995-10-13 JP JP29056195A patent/JP3880645B2/ja not_active Expired - Lifetime
- 1995-10-13 ZA ZA958673A patent/ZA958673B/xx unknown
- 1995-10-13 HU HU9502976A patent/HU227883B1/hu unknown
- 1995-10-13 CN CNB951184857A patent/CN1246319C/zh not_active Expired - Fee Related
- 1995-10-13 CO CO95048279A patent/CO4480021A1/es unknown
- 1995-10-13 UA UA95104511A patent/UA45952C2/uk unknown
- 1995-10-13 PL PL95310932A patent/PL181165B1/pl not_active IP Right Cessation
- 1995-10-13 NO NO954080A patent/NO308848B1/no not_active IP Right Cessation
- 1995-10-13 FI FI954874A patent/FI116385B/fi not_active IP Right Cessation
- 1995-10-13 KR KR1019950035240A patent/KR100389497B1/ko not_active IP Right Cessation
- 1995-10-13 RU RU95118105/04A patent/RU2155753C2/ru not_active IP Right Cessation
- 1995-10-16 US US08/543,727 patent/US5767132A/en not_active Expired - Lifetime
- 1995-11-24 TW TW084112553A patent/TW420664B/zh not_active IP Right Cessation
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1246319C (zh) | 氨基(硫)醚衍生物 | |
CN1263755C (zh) | 作为选择性cox-2抑制剂的吡唑并吡啶衍生物 | |
CN1110493C (zh) | 氨基噻吩羧基酰胺及其作为磷酸二酯酶抑制剂的用途 | |
CN1110495C (zh) | 芳烷基二嗪酮,其制备方法及其药物制剂 | |
CN1178917C (zh) | 作为nk1受体拮抗剂前药的4-苯基-吡啶衍生物的n-氧化物 | |
CN1310907C (zh) | 杂环化合物和以其为有效成分的抗肿瘤药 | |
CN1109022C (zh) | 芳基链烷酰基哒嗪衍生物、其制备方法和含有它们的药物以及应用 | |
CN1753884A (zh) | 阿片类受体拮抗剂 | |
CN1906180A (zh) | 新的长效β-2-激动剂及其作为药物的用途 | |
CN1040193A (zh) | 烷氧基-4(1h)-吡啶酮衍生物的制备 | |
CN1642927A (zh) | 环状酰胺 | |
CN1168720C (zh) | 芳基链烷酰基哒嗪化合物 | |
CN1244578C (zh) | 取代的苯并呋喃-2-甲酰胺衍生物 | |
CN1758909A (zh) | 作为新MDM2-p53抑制剂的取代的哌啶类 | |
CN101035533A (zh) | 抗精神分裂症的双重nk1/nk3拮抗剂 | |
CN1478092A (zh) | 苯并噁嗪酮衍生物及其制备和应用 | |
CN1053064A (zh) | 杂环衍生物制法 | |
CN1942434A (zh) | 茚衍生物及其制备方法 | |
CN101043888A (zh) | 制备异噻唑衍生物的方法 | |
CN1665812A (zh) | 用于治疗肥胖的作为选择性黑色素浓缩激素受体拮抗剂的螺取代的哌啶化合物 | |
CN1069640C (zh) | 噁唑烷酮衍生物,其制备方法及含它们的药物组合物 | |
CN1756753A (zh) | 苯并呋喃衍生物 | |
CN1795179A (zh) | 新的咪唑衍生物、其制备方法和其作为药物的用途 | |
CN1662519A (zh) | 新化合物及其作为甘氨酸转运抑制剂的用途 | |
CN1187336C (zh) | 咪唑类衍生物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C06 | Publication | ||
PB01 | Publication | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20060322 Termination date: 20141013 |
|
EXPY | Termination of patent right or utility model |