JP2002510290A - 複素環化合物、それらの製造方法及びそれらを含む製薬学的組成物 - Google Patents
複素環化合物、それらの製造方法及びそれらを含む製薬学的組成物Info
- Publication number
- JP2002510290A JP2002510290A JP55002898A JP55002898A JP2002510290A JP 2002510290 A JP2002510290 A JP 2002510290A JP 55002898 A JP55002898 A JP 55002898A JP 55002898 A JP55002898 A JP 55002898A JP 2002510290 A JP2002510290 A JP 2002510290A
- Authority
- JP
- Japan
- Prior art keywords
- group
- branched
- linear
- formula
- substituted
- 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.)
- Ceased
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 238000004519 manufacturing process Methods 0.000 title claims description 11
- 150000002391 heterocyclic compounds Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 293
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 68
- 238000000034 method Methods 0.000 claims abstract description 56
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 39
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 39
- 239000003814 drug Substances 0.000 claims abstract description 4
- -1 cyano, nitro, amino Chemical group 0.000 claims description 123
- 125000000217 alkyl group Chemical group 0.000 claims description 100
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 87
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 82
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 79
- 239000002253 acid Substances 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 61
- 150000003839 salts Chemical class 0.000 claims description 58
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
- 150000001412 amines Chemical class 0.000 claims description 39
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 36
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 33
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 32
- 125000000304 alkynyl group Chemical group 0.000 claims description 30
- 229910052727 yttrium Inorganic materials 0.000 claims description 30
- 150000007513 acids Chemical class 0.000 claims description 29
- 125000003282 alkyl amino group Chemical group 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 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 claims description 21
- 125000004429 atom Chemical group 0.000 claims description 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000000623 heterocyclic group Chemical group 0.000 claims description 16
- 239000003795 chemical substances by application Substances 0.000 claims description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 238000000926 separation method Methods 0.000 claims description 12
- 239000004202 carbamide Substances 0.000 claims description 10
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical group CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 8
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 7
- 230000002378 acidificating effect Effects 0.000 claims description 7
- 230000029936 alkylation Effects 0.000 claims description 7
- 238000005804 alkylation reaction Methods 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 238000006467 substitution reaction Methods 0.000 claims description 7
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 6
- 230000003301 hydrolyzing effect Effects 0.000 claims description 6
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 150000008065 acid anhydrides Chemical class 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 230000004913 activation Effects 0.000 claims description 4
- 150000001263 acyl chlorides Chemical class 0.000 claims description 3
- 150000008371 chromenes Chemical class 0.000 claims description 3
- 239000007822 coupling agent Substances 0.000 claims description 3
- 150000008050 dialkyl sulfates Chemical class 0.000 claims description 3
- 238000006698 hydrazinolysis reaction Methods 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 125000005543 phthalimide group Chemical group 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims description 3
- 239000000539 dimer Substances 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims 2
- 229920002807 Thiomer Polymers 0.000 claims 1
- 150000003869 acetamides Chemical class 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- ZESCIVLAFYRPOD-UHFFFAOYSA-N n-[(6-methoxy-2h-chromen-3-yl)methyl]butanamide Chemical compound COC1=CC=C2OCC(CNC(=O)CCC)=CC2=C1 ZESCIVLAFYRPOD-UHFFFAOYSA-N 0.000 claims 1
- 238000007280 thionation reaction Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 374
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 320
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 276
- 239000000243 solution Substances 0.000 description 199
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 174
- 239000002904 solvent Substances 0.000 description 164
- 238000002844 melting Methods 0.000 description 144
- 230000008018 melting Effects 0.000 description 144
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 141
- 239000003480 eluent Substances 0.000 description 137
- 239000000377 silicon dioxide Substances 0.000 description 136
- 239000000203 mixture Substances 0.000 description 121
- 239000007787 solid Substances 0.000 description 114
- 239000012074 organic phase Substances 0.000 description 113
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 112
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 108
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 103
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 100
- 239000000047 product Substances 0.000 description 98
- 238000003756 stirring Methods 0.000 description 97
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 87
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 87
- 235000019341 magnesium sulphate Nutrition 0.000 description 87
- 238000002360 preparation method Methods 0.000 description 86
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 66
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 64
- 230000002829 reductive effect Effects 0.000 description 63
- 239000008346 aqueous phase Substances 0.000 description 62
- 238000010992 reflux Methods 0.000 description 60
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 57
- 239000011541 reaction mixture Substances 0.000 description 57
- 239000003921 oil Substances 0.000 description 55
- 229910052786 argon Inorganic materials 0.000 description 54
- 150000002825 nitriles Chemical class 0.000 description 52
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 150000002148 esters Chemical class 0.000 description 50
- 239000012429 reaction media Substances 0.000 description 47
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 44
- 239000012298 atmosphere Substances 0.000 description 43
- 238000000921 elemental analysis Methods 0.000 description 42
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- 238000001704 evaporation Methods 0.000 description 38
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- 239000012047 saturated solution Substances 0.000 description 33
- 235000017557 sodium bicarbonate Nutrition 0.000 description 31
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 31
- 150000001408 amides Chemical class 0.000 description 29
- 239000000706 filtrate Substances 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 238000001914 filtration Methods 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
- 230000008020 evaporation Effects 0.000 description 21
- 239000003208 petroleum Substances 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 20
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 20
- 239000007868 Raney catalyst Substances 0.000 description 18
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 18
- 229910000564 Raney nickel Inorganic materials 0.000 description 18
- 150000001299 aldehydes Chemical class 0.000 description 18
- 239000000725 suspension Substances 0.000 description 18
- 238000001816 cooling Methods 0.000 description 17
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 16
- 239000002585 base Substances 0.000 description 16
- 230000007062 hydrolysis Effects 0.000 description 16
- 238000006460 hydrolysis reaction Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 239000000741 silica gel Substances 0.000 description 16
- 229910002027 silica gel Inorganic materials 0.000 description 16
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 16
- 239000006188 syrup Substances 0.000 description 16
- 235000020357 syrup Nutrition 0.000 description 16
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 16
- 239000003054 catalyst Substances 0.000 description 15
- 239000013078 crystal Substances 0.000 description 15
- 235000009518 sodium iodide Nutrition 0.000 description 15
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 238000000605 extraction Methods 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 239000001632 sodium acetate Substances 0.000 description 14
- 235000017281 sodium acetate Nutrition 0.000 description 14
- 229910000104 sodium hydride Inorganic materials 0.000 description 14
- 239000012141 concentrate Substances 0.000 description 13
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 13
- 239000012071 phase Substances 0.000 description 13
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- 229960003987 melatonin Drugs 0.000 description 12
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 11
- 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 11
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 235000008504 concentrate Nutrition 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 11
- 229910000027 potassium carbonate Inorganic materials 0.000 description 11
- 229910052708 sodium Inorganic materials 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- 230000033764 rhythmic process Effects 0.000 description 9
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 8
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 8
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 8
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical compound OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 8
- 125000001309 chloro group Chemical group Cl* 0.000 description 8
- 238000009833 condensation Methods 0.000 description 8
- 230000005494 condensation Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 8
- 206010022437 insomnia Diseases 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 229960002317 succinimide Drugs 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- 102000001419 Melatonin receptor Human genes 0.000 description 7
- 108050009605 Melatonin receptor Proteins 0.000 description 7
- 241000700159 Rattus Species 0.000 description 7
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 7
- 239000003610 charcoal Substances 0.000 description 7
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 6
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 6
- 208000024827 Alzheimer disease Diseases 0.000 description 6
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- 208000008589 Obesity Diseases 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 230000027288 circadian rhythm Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- 229910052744 lithium Inorganic materials 0.000 description 6
- 235000020824 obesity Nutrition 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 239000011347 resin Substances 0.000 description 6
- 229920005989 resin Polymers 0.000 description 6
- 230000001932 seasonal effect Effects 0.000 description 6
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 6
- XQKBFQXWZCFNFF-UHFFFAOYSA-K triiodosamarium Chemical compound I[Sm](I)I XQKBFQXWZCFNFF-UHFFFAOYSA-K 0.000 description 6
- HOLMTQJJYPAMDJ-UHFFFAOYSA-N (6-methoxy-2h-chromen-3-yl)methanol Chemical compound O1CC(CO)=CC2=CC(OC)=CC=C21 HOLMTQJJYPAMDJ-UHFFFAOYSA-N 0.000 description 5
- 238000007239 Wittig reaction Methods 0.000 description 5
- 239000012300 argon atmosphere Substances 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- OCXGTPDKNBIOTF-UHFFFAOYSA-N dibromo(triphenyl)-$l^{5}-phosphane Chemical compound C=1C=CC=CC=1P(Br)(C=1C=CC=CC=1)(Br)C1=CC=CC=C1 OCXGTPDKNBIOTF-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- FYRHIOVKTDQVFC-UHFFFAOYSA-M potassium phthalimide Chemical compound [K+].C1=CC=C2C(=O)[N-]C(=O)C2=C1 FYRHIOVKTDQVFC-UHFFFAOYSA-M 0.000 description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 4
- JRNVQLOKVMWBFR-UHFFFAOYSA-N 1,2-benzenedithiol Chemical compound SC1=CC=CC=C1S JRNVQLOKVMWBFR-UHFFFAOYSA-N 0.000 description 4
- UAAUVZOAWNDHLN-UHFFFAOYSA-N 2-(1,4-benzodioxin-3-yl)ethanamine Chemical compound C1=CC=C2OC(CCN)=COC2=C1 UAAUVZOAWNDHLN-UHFFFAOYSA-N 0.000 description 4
- OYUNTGBISCIYPW-UHFFFAOYSA-N 2-chloroprop-2-enenitrile Chemical compound ClC(=C)C#N OYUNTGBISCIYPW-UHFFFAOYSA-N 0.000 description 4
- KWMBADTWRIGGGG-UHFFFAOYSA-N 2-diethoxyphosphorylacetonitrile Chemical compound CCOP(=O)(CC#N)OCC KWMBADTWRIGGGG-UHFFFAOYSA-N 0.000 description 4
- ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 4
- HLGVEQBXIXMISA-UHFFFAOYSA-N 6-hydroxy-2,3-dihydro-1,4-benzodioxine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(O)C(C=O)=C2 HLGVEQBXIXMISA-UHFFFAOYSA-N 0.000 description 4
- APXPLXWAWNVIQX-UHFFFAOYSA-N 9-methoxy-2,3-dihydrobenzo[f]chromen-1-one Chemical compound O1CCC(=O)C2=C1C=CC1=CC=C(OC)C=C12 APXPLXWAWNVIQX-UHFFFAOYSA-N 0.000 description 4
- CJXCVYLJLHVHTI-UHFFFAOYSA-N 9-methoxy-3h-benzo[f]chromene-2-carbonitrile Chemical compound O1CC(C#N)=CC2=C1C=CC1=CC=C(OC)C=C12 CJXCVYLJLHVHTI-UHFFFAOYSA-N 0.000 description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- 208000027534 Emotional disease Diseases 0.000 description 4
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- 241001494479 Pecora Species 0.000 description 4
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- LGRFSURHDFAFJT-UHFFFAOYSA-N Phthalic anhydride Natural products C1=CC=C2C(=O)OC(=O)C2=C1 LGRFSURHDFAFJT-UHFFFAOYSA-N 0.000 description 4
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical compound CC(=O)C(O)=O LCTONWCANYUPML-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229910052776 Thorium Inorganic materials 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
- 230000036592 analgesia Effects 0.000 description 4
- 208000022531 anorexia Diseases 0.000 description 4
- 230000000561 anti-psychotic effect Effects 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 description 4
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical compound C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 4
- JHIWVOJDXOSYLW-UHFFFAOYSA-N butyl 2,2-difluorocyclopropane-1-carboxylate Chemical compound CCCCOC(=O)C1CC1(F)F JHIWVOJDXOSYLW-UHFFFAOYSA-N 0.000 description 4
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 4
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical compound C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 4
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 4
- 206010061428 decreased appetite Diseases 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 125000000950 dibromo group Chemical group Br* 0.000 description 4
- 230000002526 effect on cardiovascular system Effects 0.000 description 4
- 230000002996 emotional effect Effects 0.000 description 4
- HYAIFRZTFJBMMC-UHFFFAOYSA-N ethyl 1,4-benzodioxine-3-carboxylate Chemical compound C1=CC=C2OC(C(=O)OCC)=COC2=C1 HYAIFRZTFJBMMC-UHFFFAOYSA-N 0.000 description 4
- OENICUBCLXKLJQ-UHFFFAOYSA-N ethyl 2,3-dibromopropanoate Chemical compound CCOC(=O)C(Br)CBr OENICUBCLXKLJQ-UHFFFAOYSA-N 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 206010016256 fatigue Diseases 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- 239000012528 membrane Substances 0.000 description 4
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- JVMOWFSQJSBXNM-UHFFFAOYSA-N methyl 6-methoxy-2-phenyl-1,4-benzodioxine-3-carboxylate Chemical compound O1C2=CC=C(OC)C=C2OC(C(=O)OC)=C1C1=CC=CC=C1 JVMOWFSQJSBXNM-UHFFFAOYSA-N 0.000 description 4
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 description 4
- NKGCVBIDCXBBQV-UHFFFAOYSA-N n-(9-methoxy-2,3-dihydro-1h-benzo[f]chromen-2-yl)acetamide Chemical compound O1CC(NC(C)=O)CC2=C1C=CC1=CC=C(OC)C=C12 NKGCVBIDCXBBQV-UHFFFAOYSA-N 0.000 description 4
- BNDFXOFTDZJPHN-UHFFFAOYSA-N n-methyl-3,8-dihydro-2h-pyrano[2,3-h][1,4]benzodioxin-9-amine Chemical compound O1CCOC2=C1C=CC1=C2C=C(NC)CO1 BNDFXOFTDZJPHN-UHFFFAOYSA-N 0.000 description 4
- 230000016087 ovulation Effects 0.000 description 4
- 235000006408 oxalic acid Nutrition 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 208000019116 sleep disease Diseases 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- JNVXRQOSRUDXDY-UHFFFAOYSA-N 1,1-diiodoethane Chemical compound CC(I)I JNVXRQOSRUDXDY-UHFFFAOYSA-N 0.000 description 3
- 229910052772 Samarium Inorganic materials 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- 125000003963 dichloro group Chemical group Cl* 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000037023 motor activity Effects 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- KZUNJOHGWZRPMI-UHFFFAOYSA-N samarium atom Chemical compound [Sm] KZUNJOHGWZRPMI-UHFFFAOYSA-N 0.000 description 3
- 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 2
- JAJHDSDUQFYZQE-UHFFFAOYSA-N (6-methoxy-2,3-dihydro-1,4-benzodioxin-3-yl)methanol Chemical compound O1CC(CO)OC2=CC(OC)=CC=C21 JAJHDSDUQFYZQE-UHFFFAOYSA-N 0.000 description 2
- DKAWDIOUSDRSEF-UHFFFAOYSA-N (6-methoxy-2,3-dihydro-1,4-benzodioxin-3-yl)methyl 4-methylbenzenesulfonate Chemical compound O1C2=CC(OC)=CC=C2OCC1COS(=O)(=O)C1=CC=C(C)C=C1 DKAWDIOUSDRSEF-UHFFFAOYSA-N 0.000 description 2
- SDWIJAUDUFYWTD-UHFFFAOYSA-N (6-pentoxy-2h-chromen-3-yl)methanamine Chemical compound O1CC(CN)=CC2=CC(OCCCCC)=CC=C21 SDWIJAUDUFYWTD-UHFFFAOYSA-N 0.000 description 2
- AODSQYZYAGVROA-UHFFFAOYSA-N 1,4-benzodioxin-3-ylmethanamine Chemical compound C1=CC=C2OC(CN)=COC2=C1 AODSQYZYAGVROA-UHFFFAOYSA-N 0.000 description 2
- QNRYTNHAAHDNAG-UHFFFAOYSA-N 1,4-benzodioxin-3-ylmethanol Chemical compound C1=CC=C2OC(CO)=COC2=C1 QNRYTNHAAHDNAG-UHFFFAOYSA-N 0.000 description 2
- HPARLNRMYDSBNO-UHFFFAOYSA-N 1,4-benzodioxine Chemical compound C1=CC=C2OC=COC2=C1 HPARLNRMYDSBNO-UHFFFAOYSA-N 0.000 description 2
- IUIIXCRKXKRQTK-UHFFFAOYSA-N 1,4-benzodioxine-3-carbaldehyde Chemical compound C1=CC=C2OC(C=O)=COC2=C1 IUIIXCRKXKRQTK-UHFFFAOYSA-N 0.000 description 2
- WUHDLWYAZUFLMJ-UHFFFAOYSA-N 1,4-benzodioxine-3-carbonitrile Chemical compound C1=CC=C2OC(C#N)=COC2=C1 WUHDLWYAZUFLMJ-UHFFFAOYSA-N 0.000 description 2
- ROTKCPXNSAQNCI-UHFFFAOYSA-N 1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=COC2=C1 ROTKCPXNSAQNCI-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 2
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical group CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 2
- DBPZCGJRCAALLW-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-ol Chemical compound O1CCOC2=CC(O)=CC=C21 DBPZCGJRCAALLW-UHFFFAOYSA-N 0.000 description 2
- VUFRIRUMGMOOJQ-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-yl acetate Chemical compound O1CCOC2=CC(OC(=O)C)=CC=C21 VUFRIRUMGMOOJQ-UHFFFAOYSA-N 0.000 description 2
- DNLJHDDOVWQQEW-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carbonitrile Chemical compound C1=CC=C2OC(C#N)COC2=C1 DNLJHDDOVWQQEW-UHFFFAOYSA-N 0.000 description 2
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 2
- CLFRCXCBWIQVRN-UHFFFAOYSA-N 2,5-dihydroxybenzaldehyde Chemical compound OC1=CC=C(O)C(C=O)=C1 CLFRCXCBWIQVRN-UHFFFAOYSA-N 0.000 description 2
- PPKHAIRFQKFMLE-UHFFFAOYSA-N 2,7-dimethoxynaphthalene Chemical compound C1=CC(OC)=CC2=CC(OC)=CC=C21 PPKHAIRFQKFMLE-UHFFFAOYSA-N 0.000 description 2
- CKZREOQXSYOCJG-UHFFFAOYSA-N 2-(1,4-benzodioxin-3-yl)ethanol Chemical compound C1=CC=C2OC(CCO)=COC2=C1 CKZREOQXSYOCJG-UHFFFAOYSA-N 0.000 description 2
- KZYXMJQRCNOPEB-UHFFFAOYSA-N 2-(3,4-dihydro-2h-chromen-4-yl)acetonitrile Chemical compound C1=CC=C2C(CC#N)CCOC2=C1 KZYXMJQRCNOPEB-UHFFFAOYSA-N 0.000 description 2
- KKOARYRANOJRTC-UHFFFAOYSA-N 2-(6-methoxy-2,3-dihydrochromen-4-ylidene)acetonitrile Chemical compound O1CCC(=CC#N)C2=CC(OC)=CC=C21 KKOARYRANOJRTC-UHFFFAOYSA-N 0.000 description 2
- WQGADZACBGKOHW-UHFFFAOYSA-N 2-hydroxy-7-methoxynaphthalene-1-carbaldehyde Chemical compound C1=CC(O)=C(C=O)C2=CC(OC)=CC=C21 WQGADZACBGKOHW-UHFFFAOYSA-N 0.000 description 2
- KIPMDPDAFINLIV-UHFFFAOYSA-N 2-nitroethanol Chemical compound OCC[N+]([O-])=O KIPMDPDAFINLIV-UHFFFAOYSA-N 0.000 description 2
- MBPBIDCQLSCQBW-UHFFFAOYSA-N 3,8-dihydro-2h-pyrano[2,3-h][1,4]benzodioxin-9-ylmethanol Chemical compound O1CCOC2=C1C=CC1=C2C=C(CO)CO1 MBPBIDCQLSCQBW-UHFFFAOYSA-N 0.000 description 2
- JQEVDRZMLSDNPS-UHFFFAOYSA-N 3-(2,3-dihydro-1,4-benzodioxin-3-yl)propanenitrile Chemical compound C1=CC=C2OC(CCC#N)COC2=C1 JQEVDRZMLSDNPS-UHFFFAOYSA-N 0.000 description 2
- AGNLWDJQRDESSF-UHFFFAOYSA-N 3-(2-iodoethyl)-1,4-benzodioxine Chemical compound C1=CC=C2OC(CCI)=COC2=C1 AGNLWDJQRDESSF-UHFFFAOYSA-N 0.000 description 2
- SGTCAUQLJIKBMM-UHFFFAOYSA-N 3-(4-methoxyphenoxy)propanoic acid Chemical compound COC1=CC=C(OCCC(O)=O)C=C1 SGTCAUQLJIKBMM-UHFFFAOYSA-N 0.000 description 2
- XOIIUCLUOQODDC-UHFFFAOYSA-N 3-(iodomethyl)-6-methoxy-2,3-dihydro-1,4-benzodioxine Chemical compound O1CC(CI)OC2=CC(OC)=CC=C21 XOIIUCLUOQODDC-UHFFFAOYSA-N 0.000 description 2
- XPQOPFJPEAHFMK-UHFFFAOYSA-N 3-bromo-1,4-benzodioxine Chemical compound C1=CC=C2OC(Br)=COC2=C1 XPQOPFJPEAHFMK-UHFFFAOYSA-N 0.000 description 2
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
- NTVCMEJZWNSEFW-ICSRJNTNSA-N 4-(diaminomethylideneamino)-n-[[(2s)-1-[(2s)-3-hydroxy-2-(naphthalen-2-ylsulfonylamino)propanoyl]pyrrolidin-2-yl]methyl]butanamide Chemical compound NC(N)=NCCCC(=O)NC[C@@H]1CCCN1C(=O)[C@H](CO)NS(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 NTVCMEJZWNSEFW-ICSRJNTNSA-N 0.000 description 2
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 2
- LDZRRWHCVMSXPE-UHFFFAOYSA-N 4-methoxyphenol;3-(4-methoxyphenoxy)propanenitrile Chemical compound COC1=CC=C(O)C=C1.COC1=CC=C(OCCC#N)C=C1 LDZRRWHCVMSXPE-UHFFFAOYSA-N 0.000 description 2
- XZQLSABETMKIGG-UHFFFAOYSA-N 6-Methoxyflavone Chemical compound C=1C(=O)C2=CC(OC)=CC=C2OC=1C1=CC=CC=C1 XZQLSABETMKIGG-UHFFFAOYSA-N 0.000 description 2
- SDTYJKCULNLMCQ-UHFFFAOYSA-N 6-acetyl-2,3-dihydro-1,4-benzodioxine-3-carboxamide Chemical compound O1CC(C(N)=O)OC2=CC(C(=O)C)=CC=C21 SDTYJKCULNLMCQ-UHFFFAOYSA-N 0.000 description 2
- UKSCFPMGORNPMF-UHFFFAOYSA-N 6-hydroxy-2,3-dihydro-1,4-benzodioxine-5-carbaldehyde Chemical compound O1CCOC2=C(C=O)C(O)=CC=C21 UKSCFPMGORNPMF-UHFFFAOYSA-N 0.000 description 2
- ZNSTYIHKRRLAAJ-UHFFFAOYSA-N 6-methoxy-1,4-benzodioxine-3-carboxylic acid Chemical compound O1C=C(C(O)=O)OC2=CC(OC)=CC=C21 ZNSTYIHKRRLAAJ-UHFFFAOYSA-N 0.000 description 2
- BHVMWYAFPVJCTG-UHFFFAOYSA-N 6-methoxy-2,3-dihydro-1,4-benzodioxine Chemical compound O1CCOC2=CC(OC)=CC=C21 BHVMWYAFPVJCTG-UHFFFAOYSA-N 0.000 description 2
- KAMBUYABGSQMFF-UHFFFAOYSA-N 6-methoxy-2,3-dihydro-1,4-benzodioxine-7-carbaldehyde Chemical compound O1CCOC2=C1C=C(OC)C(C=O)=C2 KAMBUYABGSQMFF-UHFFFAOYSA-N 0.000 description 2
- LQIYOSKKKUPTRP-UHFFFAOYSA-N 6-methoxy-2,3-dihydrochromen-4-one Chemical compound O1CCC(=O)C2=CC(OC)=CC=C21 LQIYOSKKKUPTRP-UHFFFAOYSA-N 0.000 description 2
- QFFAZOPNBVZSGX-UHFFFAOYSA-N 6-methoxy-2h-chromene-3-carbonitrile Chemical compound O1CC(C#N)=CC2=CC(OC)=CC=C21 QFFAZOPNBVZSGX-UHFFFAOYSA-N 0.000 description 2
- VOOCQPOSPBMQSK-UHFFFAOYSA-N 6-methoxy-2h-chromene-3-carboxylic acid Chemical compound O1CC(C(O)=O)=CC2=CC(OC)=CC=C21 VOOCQPOSPBMQSK-UHFFFAOYSA-N 0.000 description 2
- AAHAWTSWDHJZBU-UHFFFAOYSA-N 7-methoxy-1,4-dihydronaphthalen-2-ol Chemical compound C1C=C(O)CC2=CC(OC)=CC=C21 AAHAWTSWDHJZBU-UHFFFAOYSA-N 0.000 description 2
- OEMBLXFKJGJEFY-UHFFFAOYSA-N 9-methoxy-2,3-dihydro-1h-benzo[f]chromene-1-carbonitrile Chemical compound O1CCC(C#N)C2=C1C=CC1=CC=C(OC)C=C12 OEMBLXFKJGJEFY-UHFFFAOYSA-N 0.000 description 2
- UJWQCJLDBRFRLH-UHFFFAOYSA-N 9-methoxy-2,3-dihydro-1h-benzo[f]chromene-2-carbonitrile Chemical compound O1CC(C#N)CC2=C1C=CC1=CC=C(OC)C=C12 UJWQCJLDBRFRLH-UHFFFAOYSA-N 0.000 description 2
- PJLFOAINNBHJPG-UHFFFAOYSA-N 9-methoxy-2,3-dihydro-1h-benzo[f]chromene-2-carboxylic acid Chemical compound O1CC(C(O)=O)CC2=C1C=CC1=CC=C(OC)C=C12 PJLFOAINNBHJPG-UHFFFAOYSA-N 0.000 description 2
- FAQQSKGZARBREI-UHFFFAOYSA-N 9-methoxy-3h-benzo[f]chromene-2-carboxylic acid Chemical compound O1CC(C(O)=O)=CC2=C1C=CC1=CC=C(OC)C=C12 FAQQSKGZARBREI-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 208000000044 Amnesia Diseases 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 229910015900 BF3 Inorganic materials 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-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
- 229940121891 Dopamine receptor antagonist Drugs 0.000 description 2
- 208000030814 Eating disease Diseases 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical group CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- 208000019695 Migraine disease Diseases 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 206010033664 Panic attack Diseases 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 2
- 101100184046 Schizosaccharomyces pombe (strain 972 / ATCC 24843) mid1 gene Proteins 0.000 description 2
- 206010039966 Senile dementia Diseases 0.000 description 2
- 208000010340 Sleep Deprivation Diseases 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
- GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 2
- YCJPNFUOHJOEIY-UHFFFAOYSA-J [Cl-].[Cl-].[Cl-].[Cl-].[Ti+4].COC1=C(C2=CC(=CC=C2C=C1)OC)C=O Chemical compound [Cl-].[Cl-].[Cl-].[Cl-].[Ti+4].COC1=C(C2=CC(=CC=C2C=C1)OC)C=O YCJPNFUOHJOEIY-UHFFFAOYSA-J 0.000 description 2
- NJVHJTQSGGRHGP-UHFFFAOYSA-K [Li].[Al+3].[Cl-].[Cl-].[Cl-] Chemical compound [Li].[Al+3].[Cl-].[Cl-].[Cl-] NJVHJTQSGGRHGP-UHFFFAOYSA-K 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000032683 aging Effects 0.000 description 2
- 102000004305 alpha Adrenergic Receptors Human genes 0.000 description 2
- 108090000861 alpha Adrenergic Receptors Proteins 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000019270 ammonium chloride Nutrition 0.000 description 2
- 239000003708 ampul Substances 0.000 description 2
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 2
- 230000000049 anti-anxiety effect Effects 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 239000002249 anxiolytic agent Substances 0.000 description 2
- 125000005418 aryl aryl group Chemical group 0.000 description 2
- 150000001540 azides Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910021538 borax Inorganic materials 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 125000005997 bromomethyl group Chemical group 0.000 description 2
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 2
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 229940047583 cetamide Drugs 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 230000002060 circadian Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- KCDPDMXLIRWFCN-UHFFFAOYSA-N cyano(ethoxy)phosphinic acid Chemical compound CCOP(O)(=O)C#N KCDPDMXLIRWFCN-UHFFFAOYSA-N 0.000 description 2
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 2
- LZEPOJMTQYNFTR-UHFFFAOYSA-N cyclopropanecarbonyl cyclopropanecarboxylate Chemical group C1CC1C(=O)OC(=O)C1CC1 LZEPOJMTQYNFTR-UHFFFAOYSA-N 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 235000014632 disordered eating Nutrition 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012039 electrophile Substances 0.000 description 2
- 230000007368 endocrine function Effects 0.000 description 2
- 206010015037 epilepsy Diseases 0.000 description 2
- PXPGVMDITOAXKP-UHFFFAOYSA-N ethyl 2-(6-hydroxy-1,4-benzodioxin-3-yl)acetate Chemical compound C1=C(O)C=C2OC(CC(=O)OCC)=COC2=C1 PXPGVMDITOAXKP-UHFFFAOYSA-N 0.000 description 2
- SIVGUFGFIVJFGI-UHFFFAOYSA-N ethyl 2-(6-methoxy-1,4-benzodioxin-3-yl)acetate Chemical compound C1=C(OC)C=C2OC(CC(=O)OCC)=COC2=C1 SIVGUFGFIVJFGI-UHFFFAOYSA-N 0.000 description 2
- RLNDWFPVZYHEND-UHFFFAOYSA-N ethyl 6-acetyl-2,3-dihydro-1,4-benzodioxine-3-carboxylate Chemical compound C1=C(C(C)=O)C=C2OC(C(=O)OCC)COC2=C1 RLNDWFPVZYHEND-UHFFFAOYSA-N 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 239000000417 fungicide Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- AKQZEFRALAUBFS-UHFFFAOYSA-N ilamine Natural products COC(C)C(O)(C(=O)OCC1=CCN2CCCC12)C(C)(C)O AKQZEFRALAUBFS-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 150000002513 isocyanates Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 230000003859 lipid peroxidation Effects 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 238000006138 lithiation reaction Methods 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000006984 memory degeneration Effects 0.000 description 2
- 208000023060 memory loss Diseases 0.000 description 2
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
- 230000004089 microcirculation Effects 0.000 description 2
- 206010027599 migraine Diseases 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- TUSIFDIGNSSICL-UHFFFAOYSA-N n-(1,4-benzodioxin-3-ylmethyl)acetamide Chemical compound C1=CC=C2OC(CNC(=O)C)=COC2=C1 TUSIFDIGNSSICL-UHFFFAOYSA-N 0.000 description 2
- MWADXBFIIIGBMX-UHFFFAOYSA-N n-(1,4-benzodithiin-3-ylmethyl)acetamide Chemical compound C1=CC=C2SC(CNC(=O)C)=CSC2=C1 MWADXBFIIIGBMX-UHFFFAOYSA-N 0.000 description 2
- UXTJRICYFSMTOV-UHFFFAOYSA-N n-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)acetamide Chemical compound C1=CC=C2OC(CNC(=O)C)COC2=C1 UXTJRICYFSMTOV-UHFFFAOYSA-N 0.000 description 2
- BTIYDRLBOALGSI-UHFFFAOYSA-N n-[(6-methoxy-2-phenyl-1,4-benzodioxin-3-yl)methyl]acetamide Chemical compound CC(=O)NCC=1OC2=CC(OC)=CC=C2OC=1C1=CC=CC=C1 BTIYDRLBOALGSI-UHFFFAOYSA-N 0.000 description 2
- QYZFTMMPKCOTAN-UHFFFAOYSA-N n-[2-(2-hydroxyethylamino)ethyl]-2-[[1-[2-(2-hydroxyethylamino)ethylamino]-2-methyl-1-oxopropan-2-yl]diazenyl]-2-methylpropanamide Chemical compound OCCNCCNC(=O)C(C)(C)N=NC(C)(C)C(=O)NCCNCCO QYZFTMMPKCOTAN-UHFFFAOYSA-N 0.000 description 2
- CZDFRDGTYVQVAM-UHFFFAOYSA-N n-[2-(6-methoxy-3,4-dihydro-2h-chromen-4-yl)ethyl]-2-phenylacetamide Chemical compound C12=CC(OC)=CC=C2OCCC1CCNC(=O)CC1=CC=CC=C1 CZDFRDGTYVQVAM-UHFFFAOYSA-N 0.000 description 2
- LTSRVQVECHYRNN-UHFFFAOYSA-N n-[2-(6-methoxy-3,4-dihydro-2h-chromen-4-yl)ethyl]acetamide Chemical compound O1CCC(CCNC(C)=O)C2=CC(OC)=CC=C21 LTSRVQVECHYRNN-UHFFFAOYSA-N 0.000 description 2
- UTRJIELMBYYNTG-UHFFFAOYSA-N n-[2-(6-methoxy-3,4-dihydro-2h-chromen-4-yl)ethyl]butanamide Chemical compound C1=C(OC)C=C2C(CCNC(=O)CCC)CCOC2=C1 UTRJIELMBYYNTG-UHFFFAOYSA-N 0.000 description 2
- XCCQOSJXNQVOBV-UHFFFAOYSA-N n-[3-(2,3-dihydro-1,4-benzodioxin-3-yl)propyl]acetamide Chemical compound C1=CC=C2OC(CCCNC(=O)C)COC2=C1 XCCQOSJXNQVOBV-UHFFFAOYSA-N 0.000 description 2
- DFQICHCWIIJABH-UHFFFAOYSA-N naphthalene-2,7-diol Chemical compound C1=CC(O)=CC2=CC(O)=CC=C21 DFQICHCWIIJABH-UHFFFAOYSA-N 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000020477 pH reduction Effects 0.000 description 2
- 208000019906 panic disease Diseases 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940107700 pyruvic acid Drugs 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 235000010339 sodium tetraborate Nutrition 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- OTNVGWMVOULBFZ-UHFFFAOYSA-N sodium;hydrochloride Chemical compound [Na].Cl OTNVGWMVOULBFZ-UHFFFAOYSA-N 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 239000006190 sub-lingual tablet Substances 0.000 description 2
- 150000001420 substituted heterocyclic compounds Chemical class 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 235000012976 tarts Nutrition 0.000 description 2
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- 238000010626 work up procedure Methods 0.000 description 2
- WYDAKJUGCAZUOB-UHFFFAOYSA-N (3-phenyl-1,4-benzodioxin-2-yl)methanamine Chemical compound O1C2=CC=CC=C2OC(CN)=C1C1=CC=CC=C1 WYDAKJUGCAZUOB-UHFFFAOYSA-N 0.000 description 1
- JUIZALBQHNSZTM-UHFFFAOYSA-N (6-methoxy-1,4-benzodioxin-3-yl)methanamine Chemical compound O1C=C(CN)OC2=CC(OC)=CC=C21 JUIZALBQHNSZTM-UHFFFAOYSA-N 0.000 description 1
- OSDGGSKFCSKMSL-UHFFFAOYSA-N (6-methoxy-2-phenyl-2h-chromen-3-yl)methanamine Chemical compound NCC1=CC2=CC(OC)=CC=C2OC1C1=CC=CC=C1 OSDGGSKFCSKMSL-UHFFFAOYSA-N 0.000 description 1
- NNHIXBSRDQJHHL-UHFFFAOYSA-N (6-methoxy-2h-chromen-3-yl)methanamine Chemical compound O1CC(CN)=CC2=CC(OC)=CC=C21 NNHIXBSRDQJHHL-UHFFFAOYSA-N 0.000 description 1
- MQORYJVGBIWBJJ-UHFFFAOYSA-N (6-methoxy-3,4-dihydro-2h-chromen-3-yl)methyl 4-methylbenzenesulfonate Chemical compound C1C2=CC(OC)=CC=C2OCC1COS(=O)(=O)C1=CC=C(C)C=C1 MQORYJVGBIWBJJ-UHFFFAOYSA-N 0.000 description 1
- KQDCXYTVNPPXHQ-UHFFFAOYSA-N (6-pentoxy-2h-chromen-3-yl)methanol Chemical compound O1CC(CO)=CC2=CC(OCCCCC)=CC=C21 KQDCXYTVNPPXHQ-UHFFFAOYSA-N 0.000 description 1
- YJTKZCDBKVTVBY-UHFFFAOYSA-N 1,3-Diphenylbenzene Chemical group C1=CC=CC=C1C1=CC=CC(C=2C=CC=CC=2)=C1 YJTKZCDBKVTVBY-UHFFFAOYSA-N 0.000 description 1
- PUKASFATSCNUJY-UHFFFAOYSA-N 1-[2-(1,4-benzodioxin-3-yl)ethyl]-3-propylthiourea Chemical compound C1=CC=C2OC(CCNC(=S)NCCC)=COC2=C1 PUKASFATSCNUJY-UHFFFAOYSA-N 0.000 description 1
- YQCCRXTUYJFGOF-UHFFFAOYSA-N 1-[2-(1,4-benzodioxin-3-yl)ethyl]-3-propylurea Chemical compound C1=CC=C2OC(CCNC(=O)NCCC)=COC2=C1 YQCCRXTUYJFGOF-UHFFFAOYSA-N 0.000 description 1
- WSEQXVZVJXJVFP-UHFFFAOYSA-N 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile Chemical compound O1CC2=CC(C#N)=CC=C2C1(CCCN(C)C)C1=CC=C(F)C=C1 WSEQXVZVJXJVFP-UHFFFAOYSA-N 0.000 description 1
- LIKMAJRDDDTEIG-UHFFFAOYSA-N 1-hexene Chemical compound CCCCC=C LIKMAJRDDDTEIG-UHFFFAOYSA-N 0.000 description 1
- OQURWGJAWSLGQG-UHFFFAOYSA-N 1-isocyanatopropane Chemical compound CCCN=C=O OQURWGJAWSLGQG-UHFFFAOYSA-N 0.000 description 1
- YEKPYTLNPBHEQM-UHFFFAOYSA-N 2-(6-methoxy-2,3-dihydro-1,4-benzodioxin-3-yl)acetonitrile Chemical compound O1CC(CC#N)OC2=CC(OC)=CC=C21 YEKPYTLNPBHEQM-UHFFFAOYSA-N 0.000 description 1
- MTSRSHGUCAGMNJ-UHFFFAOYSA-N 2-(6-methoxy-2-phenyl-4h-chromen-4-yl)acetonitrile Chemical compound C=1C(CC#N)C2=CC(OC)=CC=C2OC=1C1=CC=CC=C1 MTSRSHGUCAGMNJ-UHFFFAOYSA-N 0.000 description 1
- BLALMKOJAZKUIF-UHFFFAOYSA-N 2-(6-methoxy-3,4-dihydro-2h-chromen-4-yl)acetonitrile Chemical compound O1CCC(CC#N)C2=CC(OC)=CC=C21 BLALMKOJAZKUIF-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- UMUXVKTUPMPZAB-UHFFFAOYSA-N 2-phenyl-1,4-benzodioxine-3-carboxamide Chemical compound O1C2=CC=CC=C2OC(C(=O)N)=C1C1=CC=CC=C1 UMUXVKTUPMPZAB-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- KTVUBISKCYDXMG-UHFFFAOYSA-N 3-(bromomethyl)-6-methoxy-2-phenyl-2h-chromene Chemical compound BrCC1=CC2=CC(OC)=CC=C2OC1C1=CC=CC=C1 KTVUBISKCYDXMG-UHFFFAOYSA-N 0.000 description 1
- XBLRZMDTUKSRRS-UHFFFAOYSA-N 3-(bromomethyl)-6-methoxy-2h-chromene Chemical compound O1CC(CBr)=CC2=CC(OC)=CC=C21 XBLRZMDTUKSRRS-UHFFFAOYSA-N 0.000 description 1
- RDHPLZASUKFPRV-UHFFFAOYSA-N 3-(bromomethyl)-6-pentoxy-2h-chromene Chemical compound O1CC(CBr)=CC2=CC(OCCCCC)=CC=C21 RDHPLZASUKFPRV-UHFFFAOYSA-N 0.000 description 1
- AEGUGDGVUHCGCX-UHFFFAOYSA-N 3-phenyl-1,4-benzodioxine-2-carbonitrile Chemical compound O1C2=CC=CC=C2OC(C#N)=C1C1=CC=CC=C1 AEGUGDGVUHCGCX-UHFFFAOYSA-N 0.000 description 1
- JSPGOHYLKVWWKI-UHFFFAOYSA-N 6-hydroxy-2h-chromene-3-carbaldehyde Chemical compound O1CC(C=O)=CC2=CC(O)=CC=C21 JSPGOHYLKVWWKI-UHFFFAOYSA-N 0.000 description 1
- YQTDCQTXSZHUBN-UHFFFAOYSA-N 6-methoxy-1,4-benzodioxine-3-carbonitrile Chemical compound O1C=C(C#N)OC2=CC(OC)=CC=C21 YQTDCQTXSZHUBN-UHFFFAOYSA-N 0.000 description 1
- OTQDATOWZUKXTQ-UHFFFAOYSA-N 6-methoxy-1,4-benzodioxine-3-carboxamide Chemical compound O1C=C(C(N)=O)OC2=CC(OC)=CC=C21 OTQDATOWZUKXTQ-UHFFFAOYSA-N 0.000 description 1
- YURQMHCZHLMHIB-UHFFFAOYSA-N 6-methoxy-2-phenyl-2,3-dihydrochromen-4-one Chemical compound C1C(=O)C2=CC(OC)=CC=C2OC1C1=CC=CC=C1 YURQMHCZHLMHIB-UHFFFAOYSA-N 0.000 description 1
- OANNCANKELJZSH-UHFFFAOYSA-N 6-methoxy-2-phenyl-4h-chromene-4-carbaldehyde Chemical compound C=1C(C=O)C2=CC(OC)=CC=C2OC=1C1=CC=CC=C1 OANNCANKELJZSH-UHFFFAOYSA-N 0.000 description 1
- MXZBQFBMIIPEKA-UHFFFAOYSA-N 6-methoxy-2-phenyl-4h-chromene-4-carbonitrile Chemical compound C=1C(C#N)C2=CC(OC)=CC=C2OC=1C1=CC=CC=C1 MXZBQFBMIIPEKA-UHFFFAOYSA-N 0.000 description 1
- NGXPIXPJLMQRNP-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-chromene-3-carbonitrile Chemical compound O1CC(C#N)CC2=CC(OC)=CC=C21 NGXPIXPJLMQRNP-UHFFFAOYSA-N 0.000 description 1
- PRFAFVIAGPYEAA-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-chromene-4-carbonitrile Chemical compound O1CCC(C#N)C2=CC(OC)=CC=C21 PRFAFVIAGPYEAA-UHFFFAOYSA-N 0.000 description 1
- ADODESYHWWKMTE-UHFFFAOYSA-N 6-methoxy-4-methylidene-2-phenyl-2,3-dihydrochromene Chemical compound C1C(=C)C2=CC(OC)=CC=C2OC1C1=CC=CC=C1 ADODESYHWWKMTE-UHFFFAOYSA-N 0.000 description 1
- KQXWYVKOOFLWAA-UHFFFAOYSA-N 6-pentoxy-2h-chromene-3-carbaldehyde Chemical compound O1CC(C=O)=CC2=CC(OCCCCC)=CC=C21 KQXWYVKOOFLWAA-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 241001070941 Castanea Species 0.000 description 1
- 235000014036 Castanea Nutrition 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010052804 Drug tolerance Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
- 241000906446 Theraps Species 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 230000008484 agonism Effects 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- LMSNZLCSZWZZGU-UHFFFAOYSA-N butan-1-ol;hydrochloride Chemical compound Cl.CCCCO LMSNZLCSZWZZGU-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-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
- 239000007795 chemical reaction product Substances 0.000 description 1
- 230000008632 circadian clock Effects 0.000 description 1
- 229960001653 citalopram Drugs 0.000 description 1
- 230000009137 competitive binding Effects 0.000 description 1
- 230000002508 compound effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- DLDCKPBXRSRJPV-UHFFFAOYSA-N cyclobutanecarbonyl cyclobutanecarboxylate Chemical compound C1CCC1C(=O)OC(=O)C1CCC1 DLDCKPBXRSRJPV-UHFFFAOYSA-N 0.000 description 1
- ZOOSILUVXHVRJE-UHFFFAOYSA-N cyclopropanecarbonyl chloride Chemical compound ClC(=O)C1CC1 ZOOSILUVXHVRJE-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 1
- SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical compound [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- DLLJVQNYBYOKGS-UHFFFAOYSA-N ethoxyethane;pentane Chemical compound CCCCC.CCOCC DLLJVQNYBYOKGS-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000026781 habituation Effects 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
- 229940090504 iodopen Drugs 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001193 melatoninergic effect Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LMYJRZHSZKJAMS-UHFFFAOYSA-N n-(3,8-dihydro-2h-pyrano[2,3-h][1,4]benzodioxin-9-ylmethyl)acetamide Chemical compound O1CCOC2=C1C=CC1=C2C=C(CNC(=O)C)CO1 LMYJRZHSZKJAMS-UHFFFAOYSA-N 0.000 description 1
- OGAKUDOMIBBAQK-UHFFFAOYSA-N n-(3,8-dihydro-2h-pyrano[2,3-h][1,4]benzodioxin-9-ylmethyl)butanamide Chemical compound O1CCOC2=C1C=CC1=C2C=C(CNC(=O)CCC)CO1 OGAKUDOMIBBAQK-UHFFFAOYSA-N 0.000 description 1
- GPBVWZZEMHMBSG-UHFFFAOYSA-N n-(4-phenylbut-3-ynyl)acetamide Chemical compound CC(=O)NCCC#CC1=CC=CC=C1 GPBVWZZEMHMBSG-UHFFFAOYSA-N 0.000 description 1
- AMOLHQDPVAGWHN-UHFFFAOYSA-N n-[(2-benzyl-6-methoxy-1,4-benzodioxin-3-yl)methyl]acetamide Chemical compound CC(=O)NCC=1OC2=CC(OC)=CC=C2OC=1CC1=CC=CC=C1 AMOLHQDPVAGWHN-UHFFFAOYSA-N 0.000 description 1
- WYDVGGUJGQIAPA-UHFFFAOYSA-N n-[(6-methoxy-2h-chromen-3-yl)methyl]acetamide Chemical compound O1CC(CNC(C)=O)=CC2=CC(OC)=CC=C21 WYDVGGUJGQIAPA-UHFFFAOYSA-N 0.000 description 1
- RTIMESLYVGWXTE-UHFFFAOYSA-N n-[(6-methoxy-3,4-dihydro-2h-chromen-3-yl)methyl]acetamide Chemical compound O1CC(CNC(C)=O)CC2=CC(OC)=CC=C21 RTIMESLYVGWXTE-UHFFFAOYSA-N 0.000 description 1
- HUABYTGZWINGKU-UHFFFAOYSA-N n-[(6-methoxy-3,4-dihydro-2h-chromen-3-yl)methyl]butanamide Chemical compound C1=C(OC)C=C2CC(CNC(=O)CCC)COC2=C1 HUABYTGZWINGKU-UHFFFAOYSA-N 0.000 description 1
- CPKKCWAPQZRMGV-UHFFFAOYSA-N n-[(6-methoxy-3,4-dihydro-2h-chromen-3-yl)methyl]cyclobutanecarboxamide Chemical compound C1C2=CC(OC)=CC=C2OCC1CNC(=O)C1CCC1 CPKKCWAPQZRMGV-UHFFFAOYSA-N 0.000 description 1
- TWICKOXUVBBENE-UHFFFAOYSA-N n-[(6-methoxy-3,4-dihydro-2h-chromen-4-yl)methyl]acetamide Chemical compound O1CCC(CNC(C)=O)C2=CC(OC)=CC=C21 TWICKOXUVBBENE-UHFFFAOYSA-N 0.000 description 1
- PGXBHQOPLNJTCG-UHFFFAOYSA-N n-[(6-methoxy-3,4-dihydro-2h-chromen-4-yl)methyl]butanamide Chemical compound C1=C(OC)C=C2C(CNC(=O)CCC)CCOC2=C1 PGXBHQOPLNJTCG-UHFFFAOYSA-N 0.000 description 1
- YTUPMMGDLLXQSN-UHFFFAOYSA-N n-[2-(1,4-benzodioxin-3-yl)ethyl]acetamide Chemical compound C1=CC=C2OC(CCNC(=O)C)=COC2=C1 YTUPMMGDLLXQSN-UHFFFAOYSA-N 0.000 description 1
- DORYQSMSEWWBAA-UHFFFAOYSA-N n-[2-(1,4-benzodioxin-3-yl)ethyl]cyclopropanecarboxamide Chemical compound C=1OC2=CC=CC=C2OC=1CCNC(=O)C1CC1 DORYQSMSEWWBAA-UHFFFAOYSA-N 0.000 description 1
- IPXUFJVVVPZQKK-UHFFFAOYSA-N n-[2-(2,3-dihydro-1,4-benzodioxin-3-yl)ethyl]acetamide Chemical compound C1=CC=C2OC(CCNC(=O)C)COC2=C1 IPXUFJVVVPZQKK-UHFFFAOYSA-N 0.000 description 1
- QPZRIWNVFCSIIF-UHFFFAOYSA-N n-[2-(2,3-dihydrofuro[2,3-h][1,4]benzodioxin-8-yl)ethyl]acetamide Chemical compound O1CCOC2=CC=C(OC(CCNC(=O)C)=C3)C3=C21 QPZRIWNVFCSIIF-UHFFFAOYSA-N 0.000 description 1
- BHIYOCBGOSYFMN-UHFFFAOYSA-N n-[2-(2,3-dihydrofuro[2,3-h][1,4]benzodioxin-9-yl)ethyl]acetamide Chemical compound O1CCOC2=C3C(CCNC(=O)C)=COC3=CC=C21 BHIYOCBGOSYFMN-UHFFFAOYSA-N 0.000 description 1
- FJDDSMSDZHURBJ-XSBOKVBDSA-N n-[2-(2-iodanyl-5-methoxy-1h-indol-3-yl)ethyl]acetamide Chemical compound COC1=CC=C2NC([125I])=C(CCNC(C)=O)C2=C1 FJDDSMSDZHURBJ-XSBOKVBDSA-N 0.000 description 1
- NKZOIPJIQIPBRC-UHFFFAOYSA-N n-[2-(6-methoxy-2-phenyl-2h-chromen-4-yl)ethyl]acetamide Chemical compound C1=C(CCNC(C)=O)C2=CC(OC)=CC=C2OC1C1=CC=CC=C1 NKZOIPJIQIPBRC-UHFFFAOYSA-N 0.000 description 1
- VUIMOHVMWOOIIX-UHFFFAOYSA-N n-[2-(6-methoxy-2-phenyl-4h-chromen-4-yl)ethyl]acetamide Chemical compound C=1C(CCNC(C)=O)C2=CC(OC)=CC=C2OC=1C1=CC=CC=C1 VUIMOHVMWOOIIX-UHFFFAOYSA-N 0.000 description 1
- ZNVOGNVNBRWHGA-UHFFFAOYSA-N n-[2-(8-phenyl-2,3-dihydrofuro[2,3-h][1,4]benzodioxin-9-yl)ethyl]acetamide Chemical compound O1C2=CC=C3OCCOC3=C2C(CCNC(=O)C)=C1C1=CC=CC=C1 ZNVOGNVNBRWHGA-UHFFFAOYSA-N 0.000 description 1
- UUMVIZQNWORIOW-UHFFFAOYSA-N n-[2-(9-methoxy-2,3-dihydro-1h-benzo[f]chromen-1-yl)ethyl]acetamide Chemical compound O1CCC(CCNC(C)=O)C2=C1C=CC1=CC=C(OC)C=C12 UUMVIZQNWORIOW-UHFFFAOYSA-N 0.000 description 1
- KJQARJRLSLJZPR-UHFFFAOYSA-N n-[2-(9-methoxy-2,3-dihydro-1h-benzo[f]chromen-1-yl)ethyl]butanamide Chemical compound C1=CC(OC)=CC2=C3C(CCNC(=O)CCC)CCOC3=CC=C21 KJQARJRLSLJZPR-UHFFFAOYSA-N 0.000 description 1
- NAYYNDKKHOIIOD-UHFFFAOYSA-N phthalamide Chemical compound NC(=O)C1=CC=CC=C1C(N)=O NAYYNDKKHOIIOD-UHFFFAOYSA-N 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 231100000765 toxin Toxicity 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
- C07D311/60—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with aryl radicals attached in position 2
-
- 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
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D339/00—Heterocyclic compounds containing rings having two sulfur atoms as the only ring hetero atoms
- C07D339/08—Six-membered rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Psychiatry (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Child & Adolescent Psychology (AREA)
- Anesthesiology (AREA)
- Hospice & Palliative Care (AREA)
- Reproductive Health (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式(I): (式中、 R1は、水素原子、置換若しくは非置換の、直鎖若しくは分岐の(C1−C6) アルキル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルケニ ル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルキニル基、 置換若しくは非置換の(C3−C8)シクロアルキル基、置換若しくは非置換の( C3−C8)シクロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は 、直鎖若しくは分岐である)、又はOR4基(ここで、R4は、水素原子、置換若 しくは非置換の、直鎖若しくは分岐の(C1−C6)アルキル基、置換若しくは非 置換の、直鎖若しくは分岐の(C2−C6)アルケニル基、置換若しくは非置換の 、直鎖若しくは分岐の(C2−C6)アルキニル基、アリール基、アリール−(C1 −C6)アルキル基(ここで、アルキル部分は、直鎖若しくは分岐である)、置換 若しくは非置換の(C3−C8)シクロアルキル基、置換若しくは非置換の(C3 −C8)シクロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は、 直鎖若しくは分岐である)を表し、 R2は、水素原子を表すか、又は二つの隣接炭素原子に位置するR1及びR2は 、それらに結合する炭素原子と一緒になって、アリール基、又は1個若しくは2 個の酸素原子を含む6−員環を形成し、 Xは、酸素原子、硫黄原子、CHq基(ここで、qは、0、1又は2に等しい )、SO、若しくはSO2を表すか、又は Xは、二つの隣接炭素原子に位置するR1及びR2が、それらに結合する炭素原 子と一緒になって、アリール基、又は1個若しくは2個の酸素原子を含む6−員 環を形成するとき、単結合を表し、 Yは、酸素原子、硫黄原子、CHq基(ここで、qは、0、1又は2に等しい) 、 SO、若しくはSO2を表し、 XとYは、同時にCHq基(ここで、qは、0、1又は2に等しい)を表すこ とはできないと理解され、 R3は、水素原子、アリール基、アリール−(C1−C6)アルキル基(ここで、 アルキル部分は、直鎖若しくは分岐である)、又は直鎖若しくは分岐の(C1−C6 )アルキル基を表し、 nは、二つの隣接炭素原子に位置するR1及びR2が、それらに結合する炭素原 子と一緒になって、アリール基、又は1個若しくは2個の酸素原子を含む6−員 環を形成するときには、0、1、2、3、4又は5に等しいか、又は nは、R1が上記と同義であり、そしてR2が水素原子を表すとき、1、2、3 、4又は5に等しく、 −(CH2)n−鎖は、1個以上のハロゲン原子又は直鎖若しくは分岐の(C1 −C6)アルキル基、OH、直鎖若しくは分岐の(C1−C6)アルキルカルボニ ル基及び直鎖若しくは分岐の(C1−C6)アルコキシカルボニル基から選択され る、1個以上の同一又は異なる基で置換されていることができ、 Aは、NR5R6基(ここで、R6は、水素原子又は直鎖若しくは分岐の(C1− C6)アルキル基を表し、R5は、−C(=Z)R7基(ここで、Zは、酸素原子 又は硫黄原子を表し、そしてR7は、水素原子、R8基(ここで、R8は、置換若 しくは非置換の、直鎖若しくは分岐の(C1−C6)アルキル基、置換若しくは非 置換の(C3−C8)シクロアルキル基、置換若しくは非置換の(C3−C8)シク ロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は、直鎖若しくは 分岐である)、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルケ ニル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルキニル基 、アリール基、アリール−(C1−C6)アルキル基(ここで、アルキル部分は、 直鎖若しくは分岐である)を表す)を表す)を表す)、又はNR8R9基(ここで、 R9は、水素原子又は直鎖若しくは分岐の(C1−C6)アルキル基を表し、そし てR8は、上記と同義である)、又は−C(=Z)NR8R9基(ここで、Z、R8 及びR9は、上記と同義である)を表し、 下記シンボル: は、結合が単結合又は二重結合であることができることを意味し、二つの隣接結 合は、同時に二重結合であることはできず、原子の結合価が守られると理解され 、 用語「アリール」は、場合により1個以上のハロゲン原子、又はOH、直鎖 若しくは分岐の(C1−C6)アルコキシ基、直鎖若しくは分岐の(C1−C6)ア ルキル基、シアノ、ニトロ、アミノ、アルキルアミノ、ジアルキルアミノ及びト リハロアルキルから選択される、同一又は異なる基の1個以上により置換されて いる、フェニル又はナフチル基を意味し、 「アルキル」、「アルケニル」及び「アルキニル」に関して用いられる用語「 置換」は、基が、1個以上のハロゲン原子、又はOH、直鎖若しくは分岐の(C1 −C6)アルコキシ、アミノ、アルキルアミノ及びジアルキルアミノから選択さ れる、同一又は異なる基の1個以上により置換されていることを意味し、 「シクロアルキル」及び「シクロアルキルアルキル」に関連して用いられる用 語「置換」は、環部分が、1個以上のハロゲン、又は直鎖若しくは分岐の(C1 −C6)アルキル基、直鎖若しくは分岐の(C1−C6)アルコキシ基、ヒドロキ シ、オキソ、アミノ、アルキルアミノ及びジアルキルアミノから選択される、同 一又は異なる基の1個以上により置換されていることを意味すると理解されるが 、但し Aが、X及びYが同時に酸素原子を表し、かつ結合が単結合である複素環の2 −位において、NHCOR7を表すとき、 R1、R2及びR3は、同時に水素原子を表し、そして nが1に等しいとき、 R7は、エチル、3,4,5−トリメトキシフェニル、2,6−ジメトキシ フェニルエチル、フェニルエチル、ベンジル、フェニル、クロロメチル又は トリフルオロメチル基を表すことはできず、そして nが2に等しいとき、 R7は、3,4,5−トリメトキシフェニル基を表すことはできず、 Aが、X及びYが同時に酸素原子を表し、かつ結合が単結合である複素環の2 − 位において、CONHR8を表すとき、 R1、R2及びR3は、同時に水素原子を表し、そして nが1に等しいとき、 R8は、メチル、エチル、n−ブチル、2−ヒドロキシプロピル又は3−メ トキシプロピル基を表すことはできず、そして nが2に等しいとき、 R8は、2−ヒドロキシプロピル、メチル、又は3−ヒドロキシプロピル基 を表すことはできず、 Aが、XがCH2基を表し、そしてYが酸素原子を表し、かつ結合が単結合で ある複素環の2−位において、NHCOR7を表し、そしてnが1に等しい とき、 R7は、シクロアルキル以外であり、 Aが、XがCH2基を表す複素環の4−位において、CONHR8を表すとき、 R8は、水素原子を表し、そしてYは酸素原子を表し、かつ結合が単結合で あり、そしてnが1に等しいとき、 R8は、ベンジル又は1−フェニル−2−ヒドロキシエチル基を表すことは できず、 Aが、NHCSNHR8を表し、そしてnが2に等しいとき、 R8は、アリール基を表すことはできず、 Xが、CH2基を表し、R1が、上記と同義であり、そしてR2が、水素原子を 表すとき、 Aは、置換若しくは非置換フェニル基により置換された、ウレア又はチオウ レア基を表すことはできない)で示される化合物であるが、式(I)の化合 物は、−CH2−C(O)−NR8R9(ここで、R8及びR9は、上記と同義 である)により3−位に置換されたチオクマロン基(Xは、CH2基を表し 、Yは、硫黄原子を表し、R1は、上記と同義であり、そしてR2は、水素原 子である)を表すことはできない化合物、それらのエナンチオマー類、及び ジアステレオマー類、並びに製薬学的に許容し得る酸又は塩基とのそれらの 付加塩類。 2.式(I): (式中、 R1は、水素原子、置換若しくは非置換の、直鎖若しくは分岐の(C1−C6) アルキル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルケニ ル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルキニル基、 置換若しくは非置換の(C3−C8)シクロアルキル基、置換若しくは非置換の( C3−C8)シクロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は 、直鎖若しくは分岐である)、又はOR4基(ここで、R4は、水素原子、置換若 しくは非置換の、直鎖若しくは分岐の(C1−C6)アルキル基、置換若しくは非 置換の、直鎖若しくは分岐の(C2−C6)アルケニル基、置換若しくは非置換の 、直鎖若しくは分岐の(C2−C6)アルキニル基、アリール基、アリール−(C1 −C6)アルキル基(ここで、アルキル部分は、直鎖若しくは分岐である)、置換 若しくは非置換の、(C3−C8)シクロアルキル基又は置換若しくは非置換の( C3−C8)シクロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は 、直鎖若しくは分岐である)を表し、 R2は、水素原子を表すか、又は二つの隣接炭素原子に位置するR1及びR2は 、それらに結合する炭素原子と一緒になって、アリール基、又は1個若しくは2 個の酸素原子を含む6−員環を形成し、 Xは、酸素原子、硫黄原子、CHq基(ここで、qは、0、1又は2に等しい) 、SO、若しくはSO2を表すか、又は Yは、酸素原子、硫黄原子、CHq基(ここで、qは、0、1又は2に等しい) 、SO、若しくはSO2を表し、 XとYは、同時にCHq基(ここで、qは、0、1又は2に等しい)を表すこ とはできないと理解され、 R3は、水素原子、アリール基、アリール−(C1−C6)アルキル基(ここで、 アルキル部分は、直鎖若しくは分岐である)、又は直鎖若しくは分岐の(C1−C6 )アルキル基を表し、 nは、二つの隣接炭素原子に位置するR1及びR2が、それらに結合する炭素原 子と一緒になって、アリール基、又は1個若しくは2個の酸素原子を含む6−員 環を形成するときには、0、1、2、3、4又は5に等しいか、又は nは、R1が上記と同義であり、そしてR2が水素原子を表すとき、1、2、3 、4又は5に等しく、 −(CH2)n−鎖は、1個以上のハロゲン原子又は直鎖若しくは分岐の(C1 −C6)アルキル基、OH、直鎖若しくは分岐の(C1−C6)アルコキシ、直鎖 若しくは分岐の(C1−C6)アルキルカルボニル基及び直鎖若しくは分岐の(C1 −C6)アルコキシカルボニル基から選択される、1個以上の同一又は異なる基 で置換されていることができ、 Aは、NR5R6基(ここで、R6は、水素原子又は直鎖若しくは分岐の(C1− C6)アルキル基を表し、R5は、−C(=Z)R7基(ここで、Zは、酸素原子 又は硫黄原子を表し、そしてR7は、水素原子、R8基(ここで、R8は、置換若 しくは非置換の、直鎖若しくは分岐の(C1−C6)アルキル基、置換若しくは非 置換の(C3−C8)シクロアルキル基、置換若しくは非置換の(C3−C8)シク ロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は、直鎖若しくは 分岐である)、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルケ ニル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルキニル基 、アリール基又はアリール−(C1−C6)アルキル基(ここで、アルキル部分は 、直鎖若しくは分岐である)を表す)を表す)を表す)、又はNR8R9基(ここで 、R9は、水素原子又は直鎖若しくは分岐の(C1−C6)アルキル基を表し、そ してR8は、上記と同義である)、又は−C(=Z)NR8R9基(ここで、Z、R8 及びR9は、上記と同義である)を表し、 下記シンボル: は、結合が単結合又は二重結合であることができることを意味し、二つの隣接結 合は、同時に二重結合であることはできず、原子の結合価が守られると理解され 、 用語「アリール」は、場合により1個以上のハロゲン原子、又はOH、直鎖若 しくは分岐の(C1−C6)アルコキシ基、直鎖若しくは分岐の(C1−C6)アル キル基、シアノ、ニトロ、アミノ、アルキルアミノ、ジアルキルアミノ及びトリ ハロアルキルから選択される、同一又は異なる基の1個以上により置換されてい る、フェニル又はナフチル基を意味し、 「アルキル」、「アルケニル」及び「アルキニル」に関して用いられる用語「置 換」は、基が、1個以上のハロゲン原子、又はOH、直鎖若しくは分岐の(C1 −C6)アルコキシ、アミノ、アルキルアミノ及びジアルキルアミノから選択さ れる、同一又は異なる基の1個以上により置換されていることを意味し、 「シクロアルキル」及び「シクロアルキルアルキル」に関連して用いられる用 語「置換」は、環部分が、1個以上のハロゲン、又は直鎖若しくは分岐の(C1 −C6)アルキル基、直鎖若しくは分岐の(C1−C6)アルコキシ基、ヒドロキ シ、オキソ、アミノ、アルキルアミノ及びジアルキルアミノから選択される、同 一又は異なる基の1個以上により置換されていることを意味すると理解されるが 、但し Aが、X及びYが同時に酸素原子を表し、かつ結合が単結合である複素環の2 −位において、NHCOR7を表すとき、 R1、R2及びR3は、同時に水素原子を表し、そして nが1に等しいとき、 R7は、エチル、3,4,5−トリメトキシフェニル、2,6−ジメトキシ フェニルエチル、フェニルエチル、ベンジル、フェニル、クロロメチル又は トリフルオロメチル基を表すことはできず、そして nが2に等しいとき、 R7は、3,4,5−トリメトキシフェニル基を表すことはできず、 Aが、X及びYが同時に酸素原子を表し、かつ結合が単結合である複素環の2 −位において、CONHR8を表すとき、 R1、R2及びR3は、同時に水素原子を表し、そして nが1に等しいとき、 R8は、メチル、エチル、n−ブチル、2−ヒドロキシプロピル又は3−メ トキシプロピル基を表すことはできず、そして nが2に等しいとき、 R8は、2−ヒドロキシプロピル、メチル、又は3−ヒドロキシプロピル基 を表すことはできず、 Aが、XがCH2基を表し、そしてYが酸素原子を表し、かつ結合が単結合で ある複素環の2−位において、NHCOR7を表し、そしてnが1に等しい とき、 R7は、シクロアルキル以外であり、 Aが、XがCH2基を表す複素環の4−位において、CONHR8を表すとき、 R8は,水素原子を表し、そしてYは酸素原子を表し、かつ結合が単結合で あり、そしてnが1に等しいとき、 R8は、ベンジル又は1−フェニル−2−ヒドロキシエチル基を表すことは できず、 Aが、NHCSNHR8を表し、そしてnが2に等しいとき、 R8は、アリール基を表すことはできず、 Xが、CH2基を表し、R1が、上記と同義であり、そしてR2が、水素原子を 表すとき、 Aは、置換若しくは非置換フェニル基により置換された、ウレア又はチオウ レア基を表すことはできない)で示される化合物であるが、式(I)の化合 物は、−CH2−C(O)−NR8R9(ここで、R8及びR9は、上記と同義 である)により3−位に置換されたチオクマロン基(Xは、CH2基を表し 、Yは硫黄原子を表し、R1は、上記と同義であり、そしてR2は、水素原子 である)を表すことはできない化合物、それらのエナンチオマー類、及びジ アステレオマー類、並びに製薬学的に許容し得る酸又は塩基とのそれらの付 加塩類。 3.式(I): (式中、 二つの隣接炭素原子に位置するR1及びR2は、それらに結合する炭素原子と一 緒になって、アリール基、又は1個若しくは2個の酸素原子を含む6−員環を形 成し、 Xは、単結合を表し、 Yは、酸素原子、硫黄原子、CHq基(ここで、qは、0、1又は2に等しい) 、SO、若しくはSO2を表し、 R3は、水素原子、アリール基、アリール−(C1−C6)アルキル基(ここで、 アルキル部分は、直鎖若しくは分岐である)、又は直鎖若しくは分岐の(C1−C6 )アルキル基を表し、 nは、0、1、2、3、4又は5に等しく、 −(CH2)n−鎖は、1個以上のハロゲン原子又は直鎖若しくは分岐の(C1 −C6)アルキル基、OH、直鎖若しくは分岐の(C1−C6)アルコキシ、直鎖 若しくは分岐の(C1−C6)アルキルカルボニル基及び直鎖若しくは分岐の(C1 −C6)アルコキシカルボニル基から選択される、1個以上の同一又は異なる基 で置換されていることができ、 Aは、NR5R6基(ここで、R6は、水素原子又は直鎖若しくは分岐の(C1− C6)アルキル基を表し、R5は、−C(=Z)R7基(ここで、Zは、酸素原子 又は硫黄原子を表し、そしてR7は、水素原子、R8基(ここで、R8は、置換若 しくは非置換の、直鎖若しくは分岐の(C1−C6)アルキル基、置換若しくは非 置換の(C3−C8)シクロアルキル基、置換若しくは非置換の(C3−C8)シク ロアルキル−(C1−C6)アルキル基(ここで、アルキル部分は、直鎖若しくは 分岐である)、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルケ ニル基、置換若しくは非置換の、直鎖若しくは分岐の(C2−C6)アルキニル基 、アリール基又はアリール−(C1−C6)アルキル基(ここで、アルキル部分 は、直鎖若しくは分岐である)を表す)を表す)を表す)、又はNR8R9基(ここ で、R9は、水素原子又は直鎖若しくは分岐の(C1−C6)アルキル基を表し、 そしてR8は、上記と同義である)、又は−C(=Z)NR8R9基(ここで、Z、 R8及びR9は、上記と同義である)を表し、 下記シンボル: は、結合が単結合又は二重結合であることができることを意味し、二つの隣接結 合は、同時に二重結合であることはできず、原子の結合価が守られると理解され 、 用語「アリール」は、場合により1個以上のハロゲン原子、又はOH、直鎖 若しくは分岐の(C1−C6)アルコキシ基、直鎖若しくは分岐の(C1−C6)ア ルキル基、シアノ、ニトロ、アミノ、アルキルアミノ及びジアルキルアミノから 選択される、同一又は異なる基の1個以上により置換されている、フェニル又は ナフチル基を意味し、 「アルキル」、「アルケニル」及び「アルキニル」に関して用いられる用語「置 換」は、基が、1個以上のハロゲン原子、又は又はOH、直鎖若しくは分岐の( C1−C6)アルコキシ基、アミノ、アルキルアミノ、ジアルキルアミノ及びトリ ハロアルキルから選択される、同一又は異なる基の1個以上により置換されてい ることを意味し、 「シクロアルキル」及び「シクロアルキルアルキル」に関連して用いられる用 語「置換」は、環部分が、1個以上のハロゲン、又は直鎖若しくは分岐の(C1 −C6)アルキル基、直鎖若しくは分岐の(C1−C6)アルコキシ基、ヒドロキ シ、オキソ、アミノ、アルキルアミノ及びジアルキルアミノ選択される、同一又 は異なる基の1個以上により置換されていることを意味すると理解されるが、但 し AがNHCSNHR8を表し、nが2に等しいとき、 R8は、アリール基を表すことはできない)で示される化合物、それらのエ ナンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は 塩基とのそれらの付加塩類。 4.二つの隣接炭素原子に位置するR1及びR2が、それらに結合する炭素原子 と一緒になって、フェニル又は置換フェニルである、請求項1記載の式(I)の 化合物、それらのエナンチオマー類、及びジアステレオマー類、並びに製薬学的 に許容し得る酸又は塩基とのそれらの付加塩類。 5.二つの隣接炭素原子に位置するR1及びR2が、それらに結合する炭素原子と 一緒になって、1個以上の酸素原子を有する6−員環である、請求項1記載の式 (I)の化合物、それらのエナンチオマー類、及びジアステレオマー類、並びに 製薬学的に許容し得る酸又は塩基とのそれらの付加塩類。 6.R1が、OR4基を表す、請求項1記載の式(I)の化合物、それらのエナン チオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は塩基 とのそれらの付加塩類。 7.Xが、CHq基(ここで、qは、0、1又は2に等しい)を表し、そしてY が、酸素又は硫黄原子を表す、請求項1記載の式(I)の化合物、それらのエナ ンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は塩 基とのそれらの付加塩類。 8.X及びYが、同時に酸素又は硫黄原子を表す、請求項1記載の式(I)の化 合物、それらのエナンチオマー類、及びジアステレオマー類、並びに製薬学的に 許容し得る酸又は塩基とのそれらの付加塩類。 9.Xが、単結合を表す、請求項1記載の式(I)の化合物、それらのエナンチ オマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は塩基と のそれらの付加塩類。 10.R3が、水素原子を表す、請求項1記載の式(I)の化合物、それらのエ ナンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は 塩基とのそれらの付加塩類。 11.R3が、アリール基を表す、請求項1記載の式(I)の化合物、それらの エナンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又 は塩基とのそれらの付加塩類。 12.Aが、式NR5R6を表す、請求項1記載の式(I)の化合物、それらのエ ナンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は 塩基とのそれらの付加塩類。 13.ジヒドロベンゾクロメン類、ジヒドロクロメン類、クロメン類、ジヒドロ −6,7−エチレンジオキシ−クロメン類である、請求項1記載の式(I)の化 合物、それらのエナンチオマー類、及びジアステレオマー類、並びに製薬学的に 許容し得る酸又は塩基とのそれらの付加塩類。 14.N−(9−メトキシ−2,3−ジヒドロ−1H−ベンゾ[f]クロメン− 2−イル)アセトアミドである、請求項1記載の式(I)の化合物、それらのエ ナンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は 塩基とのそれらの付加塩類。 15.N−[2−(6−メトキシ−3,4−ジヒドロ−2H−クロメニル)エチ ル]エチル]アセトアミドである、請求項1記載の式(I)の化合物、そのエナ ンチオマー類、及びジアステレオマー類、並びに製薬学的に許容し得る酸又は塩 基とのそれらの付加塩類。 16.N−[(6−メトキシ−2H−3−クロメニル)メチル]ブタンアミドで ある、請求項1記載の式(I)の化合物、そのエナンチオマー類、及びジアステ レオマー類、並びに製薬学的に許容し得る酸又は塩基とのそれらの付加塩類。 17.請求項1記載の式(I)の化合物を製造する方法であって、 出発材料として、式(II): (式中、 R1、R2、R3、X及びYは、上記と同義であり、そしてn’は、0〜4の値 をもつことができる)で示される化合物を用い、還元剤に付して、式(III): (式中、 R1、R2、R3、X、Y及びn’は、上記と同義である)の化合物を得、 式(III)の化合物は、更に式(IV): (式中、 R1、R2、R3、X、Y及びnは、上記と同義である)の化合物の還元による か、又は 式(V): (式中、 R1、R2、R3、X、Y及びnは、上記と同義であり、そして Halは、ハロゲンを表す)で示される化合物から出発し、フタルイミド基で 置換し、次いで加ヒドラジン分解に付して得ることができ、 式(III)の化合物を、 アシルクロリドClCOR8又は相当する酸無水物(混合又は対称)(ここで、 R8は、上記と同義である)で縮合して、式(I)の特定の場合である式(I/a) : (式中、 R1、R2、R3、R8、X、Y及びnは、上記と同義である)で示される化合物 を得、 ローソン試薬(Lawesson's reagent)のようなチオン化試薬に付し、式(I)の 特定の場合である式(I/b): (式中、 R1、R2、R3、R8、X、Y及びnは、上記と同義である)で示される化合物 を得るか、又は 式(VI): (式中、 Z及びR8は、上記と同義である)で示される化合物と縮合させ、式(I)の 特定の場合である式(I/c):(式中、 R1、R2、R3、R8、X、Y、Z及びnは、上記と同義である)で示される化 合物を得、 式(I/a)、(I/b)及び(I/c)の全体は、式(I)の化合物の特定の場 合である式(I/d): (式中、 R1、R2、R3、X、Y及びnは、上記と同義であり、そして Gは、COR8、CSR8又はCZNHR8基(ここで、Z及びR8は、上記と同 義である)を表す)からなり、 式(VII): (式中、 Alkは、直鎖若しくは分岐の(C1−C6)アルキル基を表し、そして Wは、ハロゲン原子又はトシル基のような脱離基を表す)を用いるか、若しく はジアルキルスルファートを用いる通常のアルキル化技術によりアルキル化する ことができ、式(I)の特定の場合である式(I/e): (式中、 R1、R2、R3、X、Y、G、Alk及びnは、上記と同義である)で示され る化合物を得るか、或いは 酸性若しくは塩基性媒体中で加水分解し、式(VIII): (式中、 R1、R2、R3、X、Y及びn’は、上記と同義である)で示される化合物を 得、酸クロリド形態へ活性化した後又はカップリング剤の存在下に、アミンH2 NR8(ここで、R8は、上記と同義である)の作用に付し、式(I)の特定の場 合である式(I/f): (式中、 R1、R2、R3、R8、X、Y及びn’は、上記と同義である)で示される化合 物を得、 ローソン試薬(Lawesson's reagent)のようなチオン化剤に付し、式(I)の特 定の場合である式(I/g): (式中、 R1、R2、R3、R8、X、Y及びn’は、上記と同義である)で示される化合 物を得、 式(I/f)及び(I/g)の化合物の全体は、式(I/h): (式中、 R1、R2、R3、R8、X、Y、Z及びn’は、上記と同義である)で示される 化合物からなり、 通常のアルキル化技術によりアルキル化することができ、式(I/i): (式中、 R1、R2、R3、R8、X、Y、Z、Alk及びn’は、上記と同義である)で 示される化合物を得、 式(I/a)〜(I/i)の化合物は、式(I)の化合物の全体からなり、通 常の分離技術により精製することができ、所望ならば、製薬学的に許容し得る酸 又は塩基とのそれらの付加塩へ転換し、場合により通常の分離技術によりそれら の異性体へ分離することを特徴とする方法。 18.Xが、単結合を表す式(I)の化合物を製造するための方法であって、 式(XVII): (式中、 Y、R1及びR2は、上記と同義であり、そして Halは、ハロゲン原子を表す)で示される化合物を、式(XVIII): (式中、 R3、n及びAは、上記と同義である)で示される化合物と縮合させ、式(I )の特定の場合である式(I/j): (式中、 R1、R2、R3、Y、n及びAは、上記と同義である)で示される化合物を得 、 式(I/j)は、通常の分離技術により精製することができ、所望ならば、製 薬学的に許容し得る酸又は塩基とのそれらの付加塩へ転換し、場合により通常の 分離技術によりそれらの異性体へ分離することを特徴とする方法。 19.製薬学的に許容し得る賦形剤の1種以上と組み合わせて、請求項1〜16 のいずれか1項記載の式(I)の化合物又は製薬学的に許容し得る酸若しくは塩 基とのその付加塩の少なくとも1種を活性成分として含む製薬学的組成物。 20.メラトニン性システムの疾患の処置で使用するための、請求項19記載の 製薬学的組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9706019A FR2763335B1 (fr) | 1997-05-16 | 1997-05-16 | Nouveaux composes heterocycliques substitues, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR97/06019 | 1997-05-16 | ||
PCT/FR1998/000954 WO1998052935A1 (fr) | 1997-05-16 | 1998-05-14 | Composes heterocycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2002510290A true JP2002510290A (ja) | 2002-04-02 |
JP2002510290A5 JP2002510290A5 (ja) | 2005-12-08 |
Family
ID=9506957
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP55002898A Ceased JP2002510290A (ja) | 1997-05-16 | 1998-05-14 | 複素環化合物、それらの製造方法及びそれらを含む製薬学的組成物 |
Country Status (21)
Country | Link |
---|---|
US (2) | US6313160B1 (ja) |
EP (1) | EP0998471B1 (ja) |
JP (1) | JP2002510290A (ja) |
CN (1) | CN1139584C (ja) |
AT (1) | ATE356814T1 (ja) |
AU (1) | AU741753B2 (ja) |
BR (1) | BR9809643A (ja) |
CA (1) | CA2289599C (ja) |
CY (1) | CY1106545T1 (ja) |
DE (1) | DE69837334T2 (ja) |
DK (1) | DK0998471T3 (ja) |
ES (1) | ES2285775T3 (ja) |
FR (1) | FR2763335B1 (ja) |
HK (1) | HK1028028A1 (ja) |
HU (1) | HUP0003127A3 (ja) |
NO (1) | NO324562B1 (ja) |
NZ (1) | NZ500952A (ja) |
PL (1) | PL197156B1 (ja) |
PT (1) | PT998471E (ja) |
WO (1) | WO1998052935A1 (ja) |
ZA (1) | ZA984114B (ja) |
Families Citing this family (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2799757B1 (fr) * | 1999-10-15 | 2001-12-14 | Adir | Nouveaux derives polycycliques azaindoliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
AU1888101A (en) * | 1999-12-13 | 2001-06-18 | Chugai Seiyaku Kabushiki Kaisha | 3-methyl-chroman and -thiochroman derivatives |
DE10344412A1 (de) * | 2003-09-25 | 2005-05-19 | Röhm GmbH & Co. KG | Polymernetzwerke |
RU2007139541A (ru) * | 2005-04-22 | 2009-05-27 | Вайет (Us) | Производные хромана и хромена и их применение |
CN1891687B (zh) * | 2005-07-08 | 2011-08-03 | 中国医学科学院医药生物技术研究所 | 微生物来源的炎症因子受体拮抗活性化合物及其应用 |
DK2123265T3 (da) * | 2008-05-23 | 2012-09-03 | Novaera S R L | Endipalenformuleringer til behandling af psoriasis |
ES2782357T3 (es) | 2009-11-03 | 2020-09-14 | Fosun Orinove Pharmatech Inc | Inhibidores de IRE 1 alfa |
KR102022154B1 (ko) * | 2016-11-24 | 2019-09-18 | 한양대학교 산학협력단 | MBD2-p66α(GATAD2A)의 상호작용을 억제하는 화합물을 포함하는 암 전이 억제 및 암 질환 예방 및 치료용 조성물 |
US10052326B1 (en) | 2017-10-12 | 2018-08-21 | King Saud University | Antihepatotoxic agents |
CN111960970B (zh) * | 2018-08-08 | 2021-08-20 | 中国人民解放军总医院 | 抗肿瘤化合物 |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3663702A (en) * | 1967-05-05 | 1972-05-16 | Colgate Palmolive Co | Pharmaceutical compositions containing amides of beta-(3 - thianaphthenyl)ethylamines |
US3511851A (en) * | 1967-06-12 | 1970-05-12 | Du Pont | Heterocyclic amino-oxazolines |
US4046762A (en) * | 1972-10-20 | 1977-09-06 | Instituto Luso Farmaco D'italia S.R.L. | Esters and amides of 3-aryl-1,4 benzodioxan-2-carboxylic acids |
IE46676B1 (en) * | 1977-03-17 | 1983-08-24 | Shell Int Research | Lipofenesis-inhibiting compositions |
BE868304A (nl) * | 1977-06-30 | 1978-12-21 | Shell Int Research | Werkwijze ter bereiding van een verbinding voor het tegengaan van lipogenese. |
US4205076A (en) * | 1978-10-16 | 1980-05-27 | Shell Oil Company | Lipogenesis inhibition by certain esters of substituted benzodioxincarboxylic acids |
EP0115142B1 (en) * | 1982-12-23 | 1986-11-05 | Ici Americas Inc. | Chroman compounds |
GB8515389D0 (en) * | 1985-06-18 | 1985-07-17 | Ici Plc | Heterocyclic compounds |
PT84806B (pt) * | 1986-05-03 | 1989-12-29 | Beecham Group Plc | Processo para a preparacao de benzopiranos |
FR2618437B1 (fr) * | 1987-07-23 | 1989-11-17 | Rhone Poulenc Sante | Nouveaux derives du benzopyranne, leur preparation et les medicaments qui les contiennent |
US4868210A (en) * | 1988-03-30 | 1989-09-19 | Warner-Lambert Company | Antihyperlipidemic and antiatherosclerotic compounds and compositions |
JPH04500075A (ja) * | 1988-08-16 | 1992-01-09 | イー・アイ・デユポン・ドウ・ヌムール・アンド・カンパニー | 殺菌性ベンゾジオキサンアミン誘導体 |
ATE121740T1 (de) * | 1989-03-22 | 1995-05-15 | Ciba Geigy Ag | Neue benzothiopyranylamine. |
FR2658818B1 (fr) * | 1990-02-27 | 1993-12-31 | Adir Cie | Nouveaux derives a structure naphtalenique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
FR2661676A1 (fr) * | 1990-05-02 | 1991-11-08 | Lipha | Derives d'amino benzocycloalcanes, procedes de preparation et medicaments les contenant. |
WO1992018462A1 (en) * | 1991-04-12 | 1992-10-29 | Schering Corporation | Bicyclic amides as inhibitors of acyl-coenzyme a: cholesterol acyl transferase |
FR2680366B1 (fr) * | 1991-08-13 | 1995-01-20 | Adir | Nouveaux derives d'arylethylamines, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent. |
FR2696453B1 (fr) * | 1992-10-02 | 1994-12-23 | Adir | Nouveaux arylalkyl(thio)amides, leur procédé de préparation, et les compositions pharmaceutiques qui les contiennent. |
DK0690843T3 (da) * | 1993-03-25 | 2000-11-13 | Upjohn Co | Fornyl- eller cyanosubstituerede indolderivater med dopaninerg aktivitet |
FR2704857B1 (fr) * | 1993-05-07 | 1995-06-23 | Adir | Nouvelles benzodioxines substituées, leur procédé de préparation et les compositions pharmaceutiques les contenant. |
GB9326192D0 (en) * | 1993-12-22 | 1994-02-23 | Glaxo Group Ltd | Chemical compounds |
FR2716680B1 (fr) * | 1994-02-25 | 1996-04-05 | Adir | Nouveaux dérivés de benzodioxane, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
JPH07242655A (ja) * | 1994-03-03 | 1995-09-19 | Taiho Yakuhin Kogyo Kk | 1,4−ベンゾジオキサン誘導体 |
JPH07242543A (ja) * | 1994-03-03 | 1995-09-19 | Taiho Yakuhin Kogyo Kk | 肝疾患治療剤 |
GB9407919D0 (en) * | 1994-04-21 | 1994-06-15 | Glaxo Group Ltd | Chemical compounds |
FR2725985B1 (fr) * | 1994-10-21 | 1996-11-15 | Adir | Nouveaux composes tricycliques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR2729147A1 (fr) * | 1995-01-11 | 1996-07-12 | Adir | Nouveaux composes (hetero) cycliques alkyles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR2732969B1 (fr) * | 1995-04-14 | 1997-05-16 | Adir | Nouveaux composes pyridiniques, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR2734816B1 (fr) * | 1995-05-31 | 1997-07-04 | Adir | Nouveaux aryl (alkyl) propylamides, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
FR2734815B1 (fr) * | 1995-05-31 | 1997-07-04 | Adir | Nouveaux composes arylalkyl (thio) carboxamides, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent |
FR2734814B1 (fr) * | 1995-05-31 | 1997-07-04 | Adir | Nouveaux composes alkoxy-aryles, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
-
1997
- 1997-05-16 FR FR9706019A patent/FR2763335B1/fr not_active Expired - Fee Related
-
1998
- 1998-05-14 HU HU0003127A patent/HUP0003127A3/hu unknown
- 1998-05-14 BR BR9809643-5A patent/BR9809643A/pt not_active Application Discontinuation
- 1998-05-14 US US09/423,745 patent/US6313160B1/en not_active Expired - Fee Related
- 1998-05-14 ES ES98925703T patent/ES2285775T3/es not_active Expired - Lifetime
- 1998-05-14 PL PL336857A patent/PL197156B1/pl unknown
- 1998-05-14 PT PT98925703T patent/PT998471E/pt unknown
- 1998-05-14 CN CNB988062844A patent/CN1139584C/zh not_active Expired - Fee Related
- 1998-05-14 NZ NZ500952A patent/NZ500952A/en unknown
- 1998-05-14 EP EP98925703A patent/EP0998471B1/fr not_active Expired - Lifetime
- 1998-05-14 AT AT98925703T patent/ATE356814T1/de not_active IP Right Cessation
- 1998-05-14 DE DE69837334T patent/DE69837334T2/de not_active Expired - Fee Related
- 1998-05-14 AU AU77723/98A patent/AU741753B2/en not_active Ceased
- 1998-05-14 DK DK98925703T patent/DK0998471T3/da active
- 1998-05-14 CA CA002289599A patent/CA2289599C/fr not_active Expired - Fee Related
- 1998-05-14 JP JP55002898A patent/JP2002510290A/ja not_active Ceased
- 1998-05-14 WO PCT/FR1998/000954 patent/WO1998052935A1/fr active IP Right Grant
- 1998-05-15 ZA ZA984114A patent/ZA984114B/xx unknown
-
1999
- 1999-11-15 NO NO19995594A patent/NO324562B1/no unknown
-
2000
- 2000-11-17 HK HK00107327A patent/HK1028028A1/xx not_active IP Right Cessation
-
2001
- 2001-08-28 US US09/941,016 patent/US6602903B2/en not_active Expired - Fee Related
-
2007
- 2007-04-26 CY CY20071100565T patent/CY1106545T1/el unknown
Also Published As
Publication number | Publication date |
---|---|
ZA984114B (en) | 1998-11-24 |
US6313160B1 (en) | 2001-11-06 |
HUP0003127A3 (en) | 2002-12-28 |
CA2289599C (fr) | 2005-12-06 |
NO995594D0 (no) | 1999-11-15 |
NZ500952A (en) | 2002-03-01 |
PL197156B1 (pl) | 2008-03-31 |
US20020052400A1 (en) | 2002-05-02 |
CN1260789A (zh) | 2000-07-19 |
WO1998052935A1 (fr) | 1998-11-26 |
EP0998471B1 (fr) | 2007-03-14 |
DE69837334T2 (de) | 2008-01-10 |
AU741753B2 (en) | 2001-12-06 |
HK1028028A1 (en) | 2001-02-02 |
DK0998471T3 (da) | 2007-07-02 |
NO995594L (no) | 2000-01-14 |
CA2289599A1 (fr) | 1998-11-26 |
ES2285775T3 (es) | 2007-11-16 |
ATE356814T1 (de) | 2007-04-15 |
FR2763335A1 (fr) | 1998-11-20 |
EP0998471A1 (fr) | 2000-05-10 |
US6602903B2 (en) | 2003-08-05 |
BR9809643A (pt) | 2000-10-03 |
PT998471E (pt) | 2007-06-05 |
FR2763335B1 (fr) | 2000-11-24 |
CN1139584C (zh) | 2004-02-25 |
DE69837334D1 (de) | 2007-04-26 |
HUP0003127A2 (hu) | 2002-05-29 |
PL336857A1 (en) | 2000-07-17 |
AU7772398A (en) | 1998-12-11 |
NO324562B1 (no) | 2007-11-19 |
CY1106545T1 (el) | 2012-01-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2002514620A (ja) | 新しい置換環状化合物、これらの製造方法及びこれらを含む薬剤組成物 | |
JPH08291172A (ja) | 新規なピリジン化合物、それらの製造方法およびそれらを含有する医薬組成物 | |
EP0708099B1 (fr) | Nouveaux composés amides tricycliques, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent | |
AU766322B2 (en) | New substituted dimeric compounds, a process for their preparation and pharmaceutical compositions containing them | |
HU211928A9 (en) | Therapeutically useful 2-aminotetraline derivatives | |
JP2002510290A (ja) | 複素環化合物、それらの製造方法及びそれらを含む製薬学的組成物 | |
US20070191328A1 (en) | Isoquinoline compounds | |
JP4125418B2 (ja) | 新規複素環化合物、その製造方法、およびそれを含有する医薬組成物 | |
JP3361490B2 (ja) | シクロアルキレン鎖を有する新規環式化合物、その製造法、及びそれを含有する製剤組成物 | |
AU779702B2 (en) | New isoindoloindolone compounds, a process for their preparation and pharmaceutical compositions containing them | |
AU2007310769B2 (en) | Novel indole derivatives, process for the preparation thereof and pharmaceutical compositions containing them | |
AU2007203044A1 (en) | New napthalene compounds, a process for their preparation and pharmaceutical compositions containing them | |
JP2002509130A (ja) | 新しい三環系化合物、その製造方法及びこれらを含む医薬組成物 | |
AU761605B2 (en) | New substituted dimeric compounds, a process for their preparation and pharmaceutical compositions containing them | |
JP4015546B2 (ja) | 置換ビフェニル誘導体、その製造方法およびそれを含有する医薬組成物 | |
AU2007203040A1 (en) | New naphthalene compounds, a process for their preparation and pharmaceutical compositions containing them |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20050426 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20050426 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090106 |
|
A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20090427 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20090728 |