FR2645019A1 - - Google Patents
Download PDFInfo
- Publication number
- FR2645019A1 FR2645019A1 FR8904139A FR8904139A FR2645019A1 FR 2645019 A1 FR2645019 A1 FR 2645019A1 FR 8904139 A FR8904139 A FR 8904139A FR 8904139 A FR8904139 A FR 8904139A FR 2645019 A1 FR2645019 A1 FR 2645019A1
- Authority
- FR
- France
- Prior art keywords
- group
- sep
- formula
- indicated above
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 104
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 11
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims abstract description 10
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims abstract description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims description 167
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 74
- 238000000034 method Methods 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 51
- -1 lithium aluminum hydride Chemical compound 0.000 claims description 47
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 43
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 31
- 235000019256 formaldehyde Nutrition 0.000 claims description 31
- 230000002829 reductive effect Effects 0.000 claims description 31
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 30
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 25
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 20
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 19
- 239000012429 reaction media Substances 0.000 claims description 19
- 238000005804 alkylation reaction Methods 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 15
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 claims description 14
- 229940073608 benzyl chloride Drugs 0.000 claims description 14
- 230000029936 alkylation Effects 0.000 claims description 13
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 150000002576 ketones Chemical class 0.000 claims description 10
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 10
- 238000006722 reduction reaction Methods 0.000 claims description 9
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims description 6
- 125000003277 amino group Chemical group 0.000 claims description 6
- 238000010511 deprotection reaction Methods 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 238000006268 reductive amination reaction Methods 0.000 claims description 6
- 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 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 4
- 150000001351 alkyl iodides Chemical class 0.000 claims description 4
- 150000008064 anhydrides Chemical class 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 230000032050 esterification Effects 0.000 claims description 4
- 238000005886 esterification reaction Methods 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 208000020401 Depressive disease Diseases 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 230000010933 acylation Effects 0.000 claims description 3
- 238000005917 acylation reaction Methods 0.000 claims description 3
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical group CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 claims description 3
- 230000003412 degenerative effect Effects 0.000 claims description 3
- MCSAJNNLRCFZED-UHFFFAOYSA-N nitroethane Chemical compound CC[N+]([O-])=O MCSAJNNLRCFZED-UHFFFAOYSA-N 0.000 claims description 3
- 230000007170 pathology Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 150000001299 aldehydes Chemical class 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 230000006198 deformylation Effects 0.000 claims description 2
- 238000006344 deformylation reaction Methods 0.000 claims description 2
- 230000017858 demethylation Effects 0.000 claims description 2
- 238000010520 demethylation reaction Methods 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 230000001012 protector Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 2
- 229910052717 sulfur Inorganic materials 0.000 abstract 1
- 239000000047 product Substances 0.000 description 101
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 57
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 56
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 238000002844 melting Methods 0.000 description 41
- 230000008018 melting Effects 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 31
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
- 235000019341 magnesium sulphate Nutrition 0.000 description 28
- 239000003921 oil Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 27
- 239000000155 melt Substances 0.000 description 26
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 24
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 23
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 17
- 238000001953 recrystallisation Methods 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 16
- 239000012312 sodium hydride Substances 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 239000000725 suspension Substances 0.000 description 14
- DDGRAFHHXYIQQR-UHFFFAOYSA-N 1-chloro-3-(chloromethyl)benzene Chemical compound ClCC1=CC=CC(Cl)=C1 DDGRAFHHXYIQQR-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 10
- 102000010909 Monoamine Oxidase Human genes 0.000 description 10
- 108010062431 Monoamine oxidase Proteins 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- 235000011181 potassium carbonates Nutrition 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 235000009518 sodium iodide Nutrition 0.000 description 9
- NJCVPQRHRKYSAZ-UHFFFAOYSA-N 3-(4-Hydroxyphenyl)-1-propanol Chemical compound OCCCC1=CC=C(O)C=C1 NJCVPQRHRKYSAZ-UHFFFAOYSA-N 0.000 description 8
- MQYBVLOZULJGTC-UHFFFAOYSA-N 4-[4-[(3-chlorophenyl)methoxy]phenyl]butan-2-one Chemical compound C1=CC(CCC(=O)C)=CC=C1OCC1=CC=CC(Cl)=C1 MQYBVLOZULJGTC-UHFFFAOYSA-N 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- VWMVAQHMFFZQGD-UHFFFAOYSA-N p-Hydroxybenzyl acetone Natural products CC(=O)CC1=CC=C(O)C=C1 VWMVAQHMFFZQGD-UHFFFAOYSA-N 0.000 description 8
- NJGBTKGETPDVIK-UHFFFAOYSA-N raspberry ketone Chemical compound CC(=O)CCC1=CC=C(O)C=C1 NJGBTKGETPDVIK-UHFFFAOYSA-N 0.000 description 8
- 0 C*c1cc*(*)cc1 Chemical compound C*c1cc*(*)cc1 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- SKUVZGIRVVTSGA-UHFFFAOYSA-N 3-[4-[(3-chlorophenyl)methoxy]phenyl]propan-1-ol Chemical compound C1=CC(CCCO)=CC=C1OCC1=CC=CC(Cl)=C1 SKUVZGIRVVTSGA-UHFFFAOYSA-N 0.000 description 5
- FQAUCFVLIJFHTB-UHFFFAOYSA-N 3-[4-[(3-nitrophenyl)methoxy]phenyl]propan-1-ol Chemical compound C1=CC(CCCO)=CC=C1OCC1=CC=CC([N+]([O-])=O)=C1 FQAUCFVLIJFHTB-UHFFFAOYSA-N 0.000 description 5
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000000377 silicon dioxide Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- OFQCQIGMURIECL-UHFFFAOYSA-N 2-[2-(diethylamino)ethyl]-2',6'-dimethylspiro[isoquinoline-4,4'-oxane]-1,3-dione;phosphoric acid Chemical compound OP(O)(O)=O.O=C1N(CCN(CC)CC)C(=O)C2=CC=CC=C2C21CC(C)OC(C)C2 OFQCQIGMURIECL-UHFFFAOYSA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 235000019270 ammonium chloride Nutrition 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- KUNYAVRFTQKCFQ-UHFFFAOYSA-N 1-[4-[(3-chlorophenyl)methoxy]phenyl]-N-methylpropan-2-amine Chemical compound C1=CC(CC(C)NC)=CC=C1OCC1=CC=CC(Cl)=C1 KUNYAVRFTQKCFQ-UHFFFAOYSA-N 0.000 description 3
- PBVBTTDTDCKKGJ-UHFFFAOYSA-N 1-[4-[(3-chlorophenyl)methoxy]phenyl]-n,n-dimethylpropan-2-amine Chemical compound C1=CC(CC(C)N(C)C)=CC=C1OCC1=CC=CC(Cl)=C1 PBVBTTDTDCKKGJ-UHFFFAOYSA-N 0.000 description 3
- CPRZBKJJVJCJHN-UHFFFAOYSA-N 1-[4-[4-[(3-chlorophenyl)methoxy]phenyl]butan-2-yl]piperidine Chemical compound C1CCCCN1C(C)CCC(C=C1)=CC=C1OCC1=CC=CC(Cl)=C1 CPRZBKJJVJCJHN-UHFFFAOYSA-N 0.000 description 3
- FVIJFVXSUVPDDA-UHFFFAOYSA-N 2-[4-[4-[(3-chlorophenyl)methoxy]phenyl]butan-2-ylamino]ethanol Chemical compound C1=CC(CCC(C)NCCO)=CC=C1OCC1=CC=CC(Cl)=C1 FVIJFVXSUVPDDA-UHFFFAOYSA-N 0.000 description 3
- MSTCRLLQFLZQHN-UHFFFAOYSA-N 3-[4-[(3-chlorophenyl)methoxy]phenyl]-n-ethylpropan-1-amine Chemical compound C1=CC(CCCNCC)=CC=C1OCC1=CC=CC(Cl)=C1 MSTCRLLQFLZQHN-UHFFFAOYSA-N 0.000 description 3
- ZRXWPSHOTUITAQ-UHFFFAOYSA-N 3-[[4-[3-(methylamino)butyl]phenoxy]methyl]benzonitrile Chemical compound C1=CC(CCC(C)NC)=CC=C1OCC1=CC=CC(C#N)=C1 ZRXWPSHOTUITAQ-UHFFFAOYSA-N 0.000 description 3
- ALSHQNKLYSPIER-UHFFFAOYSA-N 3-amino-n-[4-[(3-chlorophenyl)methoxy]phenyl]propanamide Chemical compound C1=CC(NC(=O)CCN)=CC=C1OCC1=CC=CC(Cl)=C1 ALSHQNKLYSPIER-UHFFFAOYSA-N 0.000 description 3
- BYJZSWBXXNKIQJ-UHFFFAOYSA-N 4-[4-[(2-chlorophenyl)methoxy]phenyl]-N-methylbutan-2-amine Chemical compound C1=CC(CCC(C)NC)=CC=C1OCC1=CC=CC=C1Cl BYJZSWBXXNKIQJ-UHFFFAOYSA-N 0.000 description 3
- UGIUXNWEVOQTAJ-UHFFFAOYSA-N 4-[4-[(3-chlorophenyl)methoxy]phenyl]-n,n-dimethylbutan-2-amine Chemical compound C1=CC(CCC(C)N(C)C)=CC=C1OCC1=CC=CC(Cl)=C1 UGIUXNWEVOQTAJ-UHFFFAOYSA-N 0.000 description 3
- BPSHOYJOGXGRMI-UHFFFAOYSA-N 4-[4-[(3-chlorophenyl)methoxy]phenyl]-n-ethylbutan-2-amine Chemical compound C1=CC(CCC(C)NCC)=CC=C1OCC1=CC=CC(Cl)=C1 BPSHOYJOGXGRMI-UHFFFAOYSA-N 0.000 description 3
- AYLMRCKXJPZJSY-UHFFFAOYSA-N 4-[4-[(3-chlorophenyl)methoxy]phenyl]-n-propylbutan-2-amine Chemical compound C1=CC(CCC(C)NCCC)=CC=C1OCC1=CC=CC(Cl)=C1 AYLMRCKXJPZJSY-UHFFFAOYSA-N 0.000 description 3
- XCBZUMLGUBATNB-UHFFFAOYSA-N 4-[4-[(3-fluorophenyl)methoxy]phenyl]butan-2-one Chemical compound C1=CC(CCC(=O)C)=CC=C1OCC1=CC=CC(F)=C1 XCBZUMLGUBATNB-UHFFFAOYSA-N 0.000 description 3
- VAEHJLQTLJUHRK-UHFFFAOYSA-N 4-[4-[(3-nitrophenyl)methoxy]phenyl]butan-2-one Chemical compound C1=CC(CCC(=O)C)=CC=C1OCC1=CC=CC([N+]([O-])=O)=C1 VAEHJLQTLJUHRK-UHFFFAOYSA-N 0.000 description 3
- JKGHUSCDDXITPZ-UHFFFAOYSA-N 4-[4-[(4-fluorophenyl)methoxy]phenyl]butan-2-one Chemical compound C1=CC(CCC(=O)C)=CC=C1OCC1=CC=C(F)C=C1 JKGHUSCDDXITPZ-UHFFFAOYSA-N 0.000 description 3
- XWXNUYMGCNQCNJ-UHFFFAOYSA-N 4-[4-[2-(3-chlorophenyl)ethoxy]phenyl]-n-ethylbutan-2-amine Chemical compound C1=CC(CCC(C)NCC)=CC=C1OCCC1=CC=CC(Cl)=C1 XWXNUYMGCNQCNJ-UHFFFAOYSA-N 0.000 description 3
- NCKUCZJNOPMLIB-UHFFFAOYSA-N 5-[4-[(3-chlorophenyl)methoxy]phenyl]-n-methylpentan-2-amine Chemical compound C1=CC(CCCC(C)NC)=CC=C1OCC1=CC=CC(Cl)=C1 NCKUCZJNOPMLIB-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 3
- 229910000085 borane Inorganic materials 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 150000002367 halogens Chemical class 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000012047 saturated solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
- KPMYPLGXVXXRDR-UHFFFAOYSA-N 1-[4-[(3-chlorophenyl)methoxy]phenoxy]propan-2-one Chemical compound C1=CC(OCC(=O)C)=CC=C1OCC1=CC=CC(Cl)=C1 KPMYPLGXVXXRDR-UHFFFAOYSA-N 0.000 description 2
- ZDYUBTRKRRXWHY-UHFFFAOYSA-N 1-chloro-3-(phenoxymethyl)benzene;ethanol Chemical compound CCO.ClC1=CC=CC(COC=2C=CC=CC=2)=C1 ZDYUBTRKRRXWHY-UHFFFAOYSA-N 0.000 description 2
- FWJXEGXINQLTOC-UHFFFAOYSA-N 1-chloro-3-(phenoxymethyl)benzene;methanol Chemical compound OC.ClC1=CC=CC(COC=2C=CC=CC=2)=C1 FWJXEGXINQLTOC-UHFFFAOYSA-N 0.000 description 2
- LRMIQGATNJDLHM-UHFFFAOYSA-N 1-chloro-3-[[4-(3-methoxypropyl)phenoxy]methyl]benzene Chemical compound C1=CC(CCCOC)=CC=C1OCC1=CC=CC(Cl)=C1 LRMIQGATNJDLHM-UHFFFAOYSA-N 0.000 description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 description 2
- YBVIQSRNZYTANQ-UHFFFAOYSA-N 3-[4-[[3-(trifluoromethyl)phenyl]methoxy]phenyl]propan-1-ol Chemical compound C1=CC(CCCO)=CC=C1OCC1=CC=CC(C(F)(F)F)=C1 YBVIQSRNZYTANQ-UHFFFAOYSA-N 0.000 description 2
- XFHRSBKRGRDMHB-UHFFFAOYSA-N 3-[[4-(3-hydroxypropyl)phenoxy]methyl]benzonitrile Chemical compound C1=CC(CCCO)=CC=C1OCC1=CC=CC(C#N)=C1 XFHRSBKRGRDMHB-UHFFFAOYSA-N 0.000 description 2
- NFNJXVBMMBORCP-UHFFFAOYSA-N 3-[[4-(3-oxobutyl)phenoxy]methyl]benzonitrile Chemical compound C1=CC(CCC(=O)C)=CC=C1OCC1=CC=CC(C#N)=C1 NFNJXVBMMBORCP-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VUTGJGCXBFKEGB-UHFFFAOYSA-N 4-[4-[(3-chlorophenyl)methoxy]phenyl]butan-1-ol Chemical compound C1=CC(CCCCO)=CC=C1OCC1=CC=CC(Cl)=C1 VUTGJGCXBFKEGB-UHFFFAOYSA-N 0.000 description 2
- IMUXPPGRBIVUJH-UHFFFAOYSA-N 4-[4-[(3-chlorophenyl)methoxy]phenyl]butan-2-ol Chemical compound C1=CC(CCC(O)C)=CC=C1OCC1=CC=CC(Cl)=C1 IMUXPPGRBIVUJH-UHFFFAOYSA-N 0.000 description 2
- FHLZIQLFSLNMHZ-UHFFFAOYSA-N 4-[4-[(3-methoxyphenyl)methoxy]phenyl]butan-2-one Chemical compound COC1=CC=CC(COC=2C=CC(CCC(C)=O)=CC=2)=C1 FHLZIQLFSLNMHZ-UHFFFAOYSA-N 0.000 description 2
- NGELGWAPMGYQFW-UHFFFAOYSA-N 4-[4-[(4-chlorophenyl)methoxy]phenyl]butan-2-one Chemical compound C1=CC(CCC(=O)C)=CC=C1OCC1=CC=C(Cl)C=C1 NGELGWAPMGYQFW-UHFFFAOYSA-N 0.000 description 2
- CDSNOIQHLSTHQL-UHFFFAOYSA-N 4-[4-[2-(3-chlorophenyl)ethoxy]phenyl]butan-2-one Chemical compound C1=CC(CCC(=O)C)=CC=C1OCCC1=CC=CC(Cl)=C1 CDSNOIQHLSTHQL-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- SGNRHQUNRABDKI-UHFFFAOYSA-N C1=CC(C(=O)NCCN)=CC=C1OCC1=CC=CC(Cl)=C1 Chemical compound C1=CC(C(=O)NCCN)=CC=C1OCC1=CC=CC(Cl)=C1 SGNRHQUNRABDKI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102000004316 Oxidoreductases Human genes 0.000 description 2
- 108090000854 Oxidoreductases Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 238000010876 biochemical test Methods 0.000 description 2
- 230000000035 biogenic effect Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- MWXJGMLEBMTAHJ-UHFFFAOYSA-N methyl 4-[(3-chlorophenyl)methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OCC1=CC=CC(Cl)=C1 MWXJGMLEBMTAHJ-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- OXZIRDZDLFPASY-UHFFFAOYSA-N n-[4-[(3-chlorophenyl)methoxy]phenyl]-3-hydroxypropanamide Chemical compound C1=CC(NC(=O)CCO)=CC=C1OCC1=CC=CC(Cl)=C1 OXZIRDZDLFPASY-UHFFFAOYSA-N 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004747 1,1-dimethylethoxycarbonyl group Chemical group CC(C)(OC(=O)*)C 0.000 description 1
- PARHMNZPOUVEIQ-UHFFFAOYSA-N 1-(4-hydroxyphenyl)butan-2-one Chemical compound CCC(=O)CC1=CC=C(O)C=C1 PARHMNZPOUVEIQ-UHFFFAOYSA-N 0.000 description 1
- XGASTRVQNVVYIZ-UHFFFAOYSA-N 1-(chloromethyl)-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(CCl)=C1 XGASTRVQNVVYIZ-UHFFFAOYSA-N 0.000 description 1
- XBDXMDVEZLOGMC-UHFFFAOYSA-N 1-(chloromethyl)-3-fluorobenzene Chemical compound FC1=CC=CC(CCl)=C1 XBDXMDVEZLOGMC-UHFFFAOYSA-N 0.000 description 1
- VGISFWWEOGVMED-UHFFFAOYSA-N 1-(chloromethyl)-3-methoxybenzene Chemical compound COC1=CC=CC(CCl)=C1 VGISFWWEOGVMED-UHFFFAOYSA-N 0.000 description 1
- APGGSERFJKEWFG-UHFFFAOYSA-N 1-(chloromethyl)-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(CCl)=C1 APGGSERFJKEWFG-UHFFFAOYSA-N 0.000 description 1
- IZXWCDITFDNEBY-UHFFFAOYSA-N 1-(chloromethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CCl)C=C1 IZXWCDITFDNEBY-UHFFFAOYSA-N 0.000 description 1
- CDLALMGJCLJAOO-UHFFFAOYSA-N 1-[4-[(4-chlorophenyl)methoxy]phenyl]propan-2-amine Chemical compound C1=CC(CC(N)C)=CC=C1OCC1=CC=C(Cl)C=C1 CDLALMGJCLJAOO-UHFFFAOYSA-N 0.000 description 1
- BICGKFXXLYABSH-UHFFFAOYSA-N 1-chloro-3-[[4-(2-nitroprop-1-enyl)phenoxy]methyl]benzene Chemical compound C1=CC(C=C(C)[N+]([O-])=O)=CC=C1OCC1=CC=CC(Cl)=C1 BICGKFXXLYABSH-UHFFFAOYSA-N 0.000 description 1
- JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 1
- NDWAVJKRSASRPH-UHFFFAOYSA-N 2-(3-chlorophenyl)ethanol Chemical compound OCCC1=CC=CC(Cl)=C1 NDWAVJKRSASRPH-UHFFFAOYSA-N 0.000 description 1
- YCCILVSKPBXVIP-UHFFFAOYSA-N 2-(4-hydroxyphenyl)ethanol Chemical compound OCCC1=CC=C(O)C=C1 YCCILVSKPBXVIP-UHFFFAOYSA-N 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- AKOPNWAGXMASTH-UHFFFAOYSA-N 2-[(4-chlorophenyl)methoxy]benzaldehyde Chemical compound C1=CC(Cl)=CC=C1COC1=CC=CC=C1C=O AKOPNWAGXMASTH-UHFFFAOYSA-N 0.000 description 1
- 125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- PMUNIMVZCACZBB-UHFFFAOYSA-N 2-hydroxyethylazanium;chloride Chemical compound Cl.NCCO PMUNIMVZCACZBB-UHFFFAOYSA-N 0.000 description 1
- QTHQWNGTMOQYMZ-UHFFFAOYSA-N 3-[4-[(3-chlorophenyl)methoxy]phenyl]propanoic acid Chemical compound C1=CC(CCC(=O)O)=CC=C1OCC1=CC=CC(Cl)=C1 QTHQWNGTMOQYMZ-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- ROLMZTIHUMKEAI-UHFFFAOYSA-N 4,5-difluoro-2-hydroxybenzonitrile Chemical compound OC1=CC(F)=C(F)C=C1C#N ROLMZTIHUMKEAI-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- QWEDBUUPMLVCDP-UHFFFAOYSA-N 4-(4-hydroxybutyl)phenol Chemical compound OCCCCC1=CC=C(O)C=C1 QWEDBUUPMLVCDP-UHFFFAOYSA-N 0.000 description 1
- LOQLDQJTSMKBJU-UHFFFAOYSA-N 4-(chloromethyl)benzonitrile Chemical compound ClCC1=CC=C(C#N)C=C1 LOQLDQJTSMKBJU-UHFFFAOYSA-N 0.000 description 1
- SSJSHCMGUKSNKE-UHFFFAOYSA-N 4-[(3-chlorophenyl)methoxy]aniline Chemical compound C1=CC(N)=CC=C1OCC1=CC=CC(Cl)=C1 SSJSHCMGUKSNKE-UHFFFAOYSA-N 0.000 description 1
- QMXPJNHJNFUZAT-UHFFFAOYSA-N 4-[(3-chlorophenyl)methoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=CC(Cl)=C1 QMXPJNHJNFUZAT-UHFFFAOYSA-N 0.000 description 1
- IAOYKLCKOHMZNN-UHFFFAOYSA-N 4-[(3-chlorophenyl)methoxy]phenol Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC(Cl)=C1 IAOYKLCKOHMZNN-UHFFFAOYSA-N 0.000 description 1
- NYGUDDSVLJHLPK-UHFFFAOYSA-N 4-[4-[(4-fluorophenyl)methoxy]phenyl]butan-2-amine Chemical compound C1=CC(CCC(N)C)=CC=C1OCC1=CC=C(F)C=C1 NYGUDDSVLJHLPK-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- FNRWFXUDZHCJNG-UHFFFAOYSA-N 5-(2-methoxyphenyl)pentan-2-one Chemical compound COC1=CC=CC=C1CCCC(C)=O FNRWFXUDZHCJNG-UHFFFAOYSA-N 0.000 description 1
- FSTNRQYLBMRPQZ-UHFFFAOYSA-N 5-(4-methoxyphenyl)-n-methylpentan-2-amine Chemical compound CNC(C)CCCC1=CC=C(OC)C=C1 FSTNRQYLBMRPQZ-UHFFFAOYSA-N 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102220508011 Gasdermin-E_N24D_mutation Human genes 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- 238000006547 Leuckart Thiophenol synthesis reaction Methods 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- AAHKTJVLFUYJHF-UHFFFAOYSA-N [4-[(3-chlorophenyl)methoxy]phenyl]methanol Chemical compound C1=CC(CO)=CC=C1OCC1=CC=CC(Cl)=C1 AAHKTJVLFUYJHF-UHFFFAOYSA-N 0.000 description 1
- BVJSGOYEEDZAGW-UHFFFAOYSA-N [chloro(nitro)methyl]benzene Chemical compound [O-][N+](=O)C(Cl)C1=CC=CC=C1 BVJSGOYEEDZAGW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- VEZXCJBBBCKRPI-UHFFFAOYSA-N beta-propiolactone Chemical compound O=C1CCO1 VEZXCJBBBCKRPI-UHFFFAOYSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- NHADDZMCASKINP-HTRCEHHLSA-N decarboxydihydrocitrinin Natural products C1=C(O)C(C)=C2[C@H](C)[C@@H](C)OCC2=C1O NHADDZMCASKINP-HTRCEHHLSA-N 0.000 description 1
- XHFGWHUWQXTGAT-UHFFFAOYSA-N dimethylamine hydrochloride Natural products CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
- IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- XWBDWHCCBGMXKG-UHFFFAOYSA-N ethanamine;hydron;chloride Chemical compound Cl.CCN XWBDWHCCBGMXKG-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- JXYZHMPRERWTPM-UHFFFAOYSA-N hydron;morpholine;chloride Chemical compound Cl.C1COCCN1 JXYZHMPRERWTPM-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- UBYSXLZLPQONBN-UHFFFAOYSA-N n-[1-[4-[(3-chlorophenyl)methoxy]phenyl]ethyl]acetamide Chemical compound C1=CC(C(NC(C)=O)C)=CC=C1OCC1=CC=CC(Cl)=C1 UBYSXLZLPQONBN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- BVJSUAQZOZWCKN-UHFFFAOYSA-N p-hydroxybenzyl alcohol Chemical compound OCC1=CC=C(O)C=C1 BVJSUAQZOZWCKN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000011837 pasties Nutrition 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical compound OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 239000001120 potassium sulphate Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 229960000380 propiolactone Drugs 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L sodium sulphate Substances [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- ZQSOYUYQHRGXAA-UHFFFAOYSA-N tert-butyl N-(propanoylamino)carbamate Chemical compound CCC(=O)NNC(=O)OC(C)(C)C ZQSOYUYQHRGXAA-UHFFFAOYSA-N 0.000 description 1
- JCIJZXUVKRMOJR-UHFFFAOYSA-N tert-butyl n-[1-[4-[(3-chlorophenyl)methoxy]phenyl]propan-2-yl]-n-methylcarbamate Chemical compound C1=CC(CC(C)N(C)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC(Cl)=C1 JCIJZXUVKRMOJR-UHFFFAOYSA-N 0.000 description 1
- DJUNQDMDICDUNN-UHFFFAOYSA-N tert-butyl n-[1-[4-[(3-chlorophenyl)methoxy]phenyl]propan-2-yl]carbamate Chemical compound C1=CC(CC(C)NC(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC(Cl)=C1 DJUNQDMDICDUNN-UHFFFAOYSA-N 0.000 description 1
- KFOOREVHBBOLOT-UHFFFAOYSA-N tert-butyl n-[5-(4-hydroxyphenyl)pentan-2-yl]-n-methylcarbamate Chemical compound CC(C)(C)OC(=O)N(C)C(C)CCCC1=CC=C(O)C=C1 KFOOREVHBBOLOT-UHFFFAOYSA-N 0.000 description 1
- KHOQDBOLSYAMKV-UHFFFAOYSA-N tert-butyl n-[5-[4-[(3-chlorophenyl)methoxy]phenyl]pentan-2-yl]-n-methylcarbamate Chemical compound C1=CC(CCCC(C)N(C)C(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC(Cl)=C1 KHOQDBOLSYAMKV-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/32—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups bound to acyclic carbon atoms and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/27—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups
- C07C205/35—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by etherified hydroxy groups having nitro groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
- C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
- C07C217/18—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted
- C07C217/20—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring being further substituted by halogen atoms, by trihalomethyl, nitro or nitroso groups, or by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/58—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/16—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/48—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/50—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by nitrogen atoms not being part of nitro or nitroso groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
- C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/70—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form
- C07C45/71—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction with functional groups containing oxygen only in singly bound form being hydroxy groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/20—Unsaturated compounds containing keto groups bound to acyclic carbon atoms
- C07C49/255—Unsaturated compounds containing keto groups bound to acyclic carbon atoms containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
- C07C49/76—Ketones containing a keto group bound to a six-membered aromatic ring
- C07C49/84—Ketones containing a keto group bound to a six-membered aromatic ring containing ether groups, groups, groups, or groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/367—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/007—Esters of unsaturated alcohols having the esterified hydroxy group bound to an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
- C07C69/84—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring
- C07C69/92—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring of monocyclic hydroxy carboxylic acids, the hydroxy groups and the carboxyl groups of which are bound to carbon atoms of a six-membered aromatic ring with etherified hydroxyl groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8904139A FR2645019A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1989-03-30 | 1989-03-30 | |
EP19900906244 EP0477184A1 (fr) | 1989-03-30 | 1990-03-28 | Inhibiteurs de la mono-amine oxydase, leur procede de preparation et leur utilisation en therapeutique |
PCT/FR1990/000209 WO1990011997A2 (fr) | 1989-03-30 | 1990-03-28 | Inhibiteurs de la mono-amine oxydase, leur procede de preparation et leur utilisation en therapeutique |
CA002050590A CA2050590A1 (fr) | 1989-03-30 | 1990-03-28 | Inhibiteurs de la mono-amine oxydase, leur procede de preparation et leur utilisation en therapeutique |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR8904139A FR2645019A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1989-03-30 | 1989-03-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
FR2645019A1 true FR2645019A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1990-10-05 |
Family
ID=9380182
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
FR8904139A Withdrawn FR2645019A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1989-03-30 | 1989-03-30 |
Country Status (4)
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6900354B2 (en) * | 2002-07-15 | 2005-05-31 | Hoffman-La Roche Inc. | 3-phenyl-propionamido, 3-phenyl-acrylamido and 3-phenyl-propynamido derivatives |
US7173023B2 (en) | 2003-10-23 | 2007-02-06 | Hoffmann-La Roche Inc. | Bicyclic compounds |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100187952B1 (ko) * | 1991-10-04 | 1999-06-01 | 우에하라 아끼라 | 알콕시페닐알킬아민 유도체 |
US5380755A (en) * | 1992-07-24 | 1995-01-10 | The Du Pont Merck Pharmaceutical Company | Alkyl and alkylbenzyl ethers of substituted hydroquinones |
WO1997000238A1 (fr) * | 1995-06-14 | 1997-01-03 | Taisho Pharmaceutical Co., Ltd. | Derives de phenylalkylamine substitues optiquement actifs |
Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1125434B (de) * | 1959-06-11 | 1962-03-15 | Eprova Ag | Verfahren zur Herstellung basischer Amide |
US4051173A (en) * | 1974-04-02 | 1977-09-27 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Phenoxyalkanol derivatives |
EP0002408A1 (fr) * | 1977-11-26 | 1979-06-13 | SOCIETE DE RECHERCHES INDUSTRIELLES S.O.R.I. Société anonyme dite: | Nouveaux composés phénoxy-alcanols substitués, leur procédé de préparation et leur application en thérapeutique |
DE2820612A1 (de) * | 1978-05-11 | 1979-11-15 | Ciba Geigy Ag | Verfahren zur herstellung des neuen l-1- eckige klammer auf 4-(3-trifluoromethyl-benzyloxy)-phenyl eckige klammer zu -2-(3,3-diphenylpropylamino)-propans |
EP0009683A1 (de) * | 1978-09-30 | 1980-04-16 | MERCK PATENT GmbH | Neue basische Phenyläther, diese enthaltende pharmazeutische Zubereitungen und die Herstellung dieser Äther und Zubereitungen |
GB2068952A (en) * | 1980-02-07 | 1981-08-19 | Richardson Merrell Inc | Phenyl Hydroxyalkyl Ethers and Thioethers |
US4329367A (en) * | 1974-08-05 | 1982-05-11 | Ciba-Geigy Corporation | 1-(Aralkoxyphenyl)-2-(bis-arylalkylamino)-alkanes |
WO1984000106A1 (en) * | 1982-06-21 | 1984-01-19 | Stiefel Laboratories | Anesthetic-antipruritic n-(3-(4-(3-fluorobenzyloxy)phenoxy)propyl)morpholine compounds, compositions and use |
FR2626877A1 (fr) * | 1988-02-05 | 1989-08-11 | Delalande Sa | Ethers alkyliques ou benzyliques du phenol, leurs procedes de preparation et leur application en therapeutique |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA782420B (en) * | 1978-04-27 | 1979-04-25 | Ciba Geigy Ag | 1-(aralkoxyphenyl)-2-(bisarylalkylamino)-alkanes |
-
1989
- 1989-03-30 FR FR8904139A patent/FR2645019A1/fr not_active Withdrawn
-
1990
- 1990-03-28 EP EP19900906244 patent/EP0477184A1/fr not_active Withdrawn
- 1990-03-28 CA CA002050590A patent/CA2050590A1/fr not_active Abandoned
- 1990-03-28 WO PCT/FR1990/000209 patent/WO1990011997A2/fr not_active Application Discontinuation
Patent Citations (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1125434B (de) * | 1959-06-11 | 1962-03-15 | Eprova Ag | Verfahren zur Herstellung basischer Amide |
US4051173A (en) * | 1974-04-02 | 1977-09-27 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Phenoxyalkanol derivatives |
US4329367A (en) * | 1974-08-05 | 1982-05-11 | Ciba-Geigy Corporation | 1-(Aralkoxyphenyl)-2-(bis-arylalkylamino)-alkanes |
EP0002408A1 (fr) * | 1977-11-26 | 1979-06-13 | SOCIETE DE RECHERCHES INDUSTRIELLES S.O.R.I. Société anonyme dite: | Nouveaux composés phénoxy-alcanols substitués, leur procédé de préparation et leur application en thérapeutique |
DE2820612A1 (de) * | 1978-05-11 | 1979-11-15 | Ciba Geigy Ag | Verfahren zur herstellung des neuen l-1- eckige klammer auf 4-(3-trifluoromethyl-benzyloxy)-phenyl eckige klammer zu -2-(3,3-diphenylpropylamino)-propans |
EP0009683A1 (de) * | 1978-09-30 | 1980-04-16 | MERCK PATENT GmbH | Neue basische Phenyläther, diese enthaltende pharmazeutische Zubereitungen und die Herstellung dieser Äther und Zubereitungen |
GB2068952A (en) * | 1980-02-07 | 1981-08-19 | Richardson Merrell Inc | Phenyl Hydroxyalkyl Ethers and Thioethers |
WO1984000106A1 (en) * | 1982-06-21 | 1984-01-19 | Stiefel Laboratories | Anesthetic-antipruritic n-(3-(4-(3-fluorobenzyloxy)phenoxy)propyl)morpholine compounds, compositions and use |
FR2626877A1 (fr) * | 1988-02-05 | 1989-08-11 | Delalande Sa | Ethers alkyliques ou benzyliques du phenol, leurs procedes de preparation et leur application en therapeutique |
Non-Patent Citations (2)
Title |
---|
CHEMICAL ABSTRACTS, vol. 92, no. 3, 21 janvier 1980, page 659, r�sum� no. 22236h, Columbus, Ohio, US; & ZA-A-7 802 420 (CIBA-GEIGY AG) 06-03-1979 * |
CHEMICAL ABSTRACTS, vol. 93, no. 13, 29 septembre 1980, page 637, r�sum� no. 132227j, Columbus, Ohio, US; & JP-A-80 40 651 (DAINIPPON PHARMACEUTICAL CO., LTD) 22-03-1980 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6900354B2 (en) * | 2002-07-15 | 2005-05-31 | Hoffman-La Roche Inc. | 3-phenyl-propionamido, 3-phenyl-acrylamido and 3-phenyl-propynamido derivatives |
CN1305838C (zh) * | 2002-07-15 | 2007-03-21 | 弗·哈夫曼-拉罗切有限公司 | 肉桂酰胺衍生物 |
US7173023B2 (en) | 2003-10-23 | 2007-02-06 | Hoffmann-La Roche Inc. | Bicyclic compounds |
Also Published As
Publication number | Publication date |
---|---|
WO1990011997A3 (fr) | 1990-11-15 |
EP0477184A1 (fr) | 1992-04-01 |
WO1990011997A2 (fr) | 1990-10-18 |
CA2050590A1 (fr) | 1990-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0773937A1 (fr) | Nouvelles piperazides derivees d'aryl piperazine, leurs procedes de preparation, leur utilisation a titre de medicament et les compositions pharmaceutiques les comprenant | |
EP0373998B1 (fr) | Ethers d'oxime de propénone, procédé pour leur préparation et compositions pharmaceutiques les contenant | |
EP0428434A2 (fr) | Composés aromatiques aminés et leurs énantiomères, procédé pour leur préparation et compositions pharmaceutiques les contenant | |
FR2676054A1 (fr) | Nouveaux composes n-alkylenepiperidino et leurs enantiomeres, procede pour leur preparation et compositions pharmaceutiques les contenant. | |
FR2500450A1 (fr) | Nouveaux derives aminomethyl-5 oxazolidiniques, leur procede de preparation et leur application en therapeutique | |
HU221626B1 (hu) | Eljárás fluoxetin előállítására | |
FR2866888A1 (fr) | Derives de alkylpiperazine- et alkylhomopiperazine- carboxylates, leur preparation et leur application en therapeutique | |
EP1214313B1 (fr) | Heteroaryloxypropanolamines comme agonistes du recepteur beta3-adrenergique | |
FR2498596A1 (fr) | Nouvelles phenylalcoylamines, leur preparation et leur utilisation en tant que medicaments | |
EP0213984B1 (fr) | Nouveaux dérivés de l'indole carboxamide, leurs sels, procédé et intermédiaires de préparation, application à titre de médicaments et compositions les renfermant | |
FR2645019A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
FR2617402A1 (fr) | Derives du thiophene et leur procede de fabrication et medicaments les contenant | |
EP0259206B1 (fr) | Dérivés de la dihydro-1,4 pyridine leurs procédés de préparation et les compositions pharmaceutiques qui les contiennent | |
EP0119107B1 (fr) | Nouveaux dérivés du bicyclo(4.2.0)octatriène-1,3,5, leur préparation et leur application en thérapeutique | |
WO1994002473A1 (fr) | Derives de la n-cycloalkylpiperazine, procedes d'obtention et compositions pharmaceutiques les contenant | |
FR2817257A1 (fr) | Cyclohexyl(alkyl)-propanolamines, leur preparation et compositions pharmaceutiques en contenant | |
EP0201400A1 (fr) | Dérivés du 4-phénylpropyl indole et leurs sels, leur procédé de préparation, leur application à titre de médicaments et les compositions pharmaceutiques les renfermant | |
EP0303545A2 (fr) | Procédé pour la préparation de phényléthanolaminotétralines | |
FR2528422A1 (fr) | Nouveaux derives du 1,2,3,4-tetrahydronaphtalene, procede pour leur preparation et composition pharmaceutique contenant ces derives | |
CA1091249A (fr) | Procede de preparation de nouvelles n-acyl glutamines et les nouveaux produits ainsi obtenus | |
CA2267251C (fr) | Nouveaux derives de la phenoxyethylamine, leur procede de preparation, leur application comme medicaments et les compositions pharmaceutiques les contenant | |
FR2584070A1 (fr) | Nouveaux derives de l'hydroxy alkoxy 4-phenyl propyl indole, leurs sels, procede et intermediaires de preparation, application a titre de medicaments et compositions les renfermant. | |
JPS63139179A (ja) | Dl−パントラクトンの光学分割法 | |
FR2505329A1 (fr) | Esters 2-methoxyphenyliques d'amino-acides n-substitues, procede pour leur preparation et compositions pharmaceutiques les contenant | |
EP1539684B1 (en) | Benzenesulphonamides and process for their preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ER | Errata listed in the french official journal (bopi) |
Free format text: 40/90 |
|
ST | Notification of lapse |