US3420822A - Quaternary salts of basic esters of beta-(1-naphthyl)-acrylic acid - Google Patents
Quaternary salts of basic esters of beta-(1-naphthyl)-acrylic acid Download PDFInfo
- Publication number
- US3420822A US3420822A US499014A US3420822DA US3420822A US 3420822 A US3420822 A US 3420822A US 499014 A US499014 A US 499014A US 3420822D A US3420822D A US 3420822DA US 3420822 A US3420822 A US 3420822A
- Authority
- US
- United States
- Prior art keywords
- acrylate
- naphthyl
- calc
- percent
- analysis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000003839 salts Chemical group 0.000 title description 8
- 150000002148 esters Chemical class 0.000 title description 3
- WPXMLUUYWNHQOR-UHFFFAOYSA-N 3-naphthalen-1-ylprop-2-enoic acid Chemical compound C1=CC=C2C(C=CC(=O)O)=CC=CC2=C1 WPXMLUUYWNHQOR-UHFFFAOYSA-N 0.000 title 1
- 230000035484 reaction time Effects 0.000 description 42
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
- 150000001875 compounds Chemical class 0.000 description 35
- -1 morpholino, piperidino Chemical group 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 17
- MYMSJFSOOQERIO-UHFFFAOYSA-N 1-bromodecane Chemical compound CCCCCCCCCCBr MYMSJFSOOQERIO-UHFFFAOYSA-N 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 8
- 229940073608 benzyl chloride Drugs 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- 125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 229940102396 methyl bromide Drugs 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 5
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 4
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 4
- VMKOFRJSULQZRM-UHFFFAOYSA-N 1-bromooctane Chemical compound CCCCCCCCBr VMKOFRJSULQZRM-UHFFFAOYSA-N 0.000 description 4
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical group CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 4
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000000843 anti-fungal effect Effects 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 244000005700 microbiome Species 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000000645 desinfectant Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- YXZFFTJAHVMMLF-UHFFFAOYSA-N 1-bromo-3-methylbutane Chemical compound CC(C)CCBr YXZFFTJAHVMMLF-UHFFFAOYSA-N 0.000 description 2
- HNTGIJLWHDPAFN-UHFFFAOYSA-N 1-bromohexadecane Chemical compound CCCCCCCCCCCCCCCCBr HNTGIJLWHDPAFN-UHFFFAOYSA-N 0.000 description 2
- WSULSMOGMLRGKU-UHFFFAOYSA-N 1-bromooctadecane Chemical compound CCCCCCCCCCCCCCCCCCBr WSULSMOGMLRGKU-UHFFFAOYSA-N 0.000 description 2
- 241000222122 Candida albicans Species 0.000 description 2
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Chemical group CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 2
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229940095731 candida albicans Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000004820 halides Chemical group 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910021653 sulphate ion Inorganic materials 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000000003 vaginal tablet Substances 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FDCJDKXCCYFOCV-UHFFFAOYSA-N 1-hexadecoxyhexadecane Chemical compound CCCCCCCCCCCCCCCCOCCCCCCCCCCCCCCCC FDCJDKXCCYFOCV-UHFFFAOYSA-N 0.000 description 1
- UWLHSHAHTBJTBA-UHFFFAOYSA-N 1-iodooctane Chemical compound CCCCCCCCI UWLHSHAHTBJTBA-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 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
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000192041 Micrococcus Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 241000588767 Proteus vulgaris Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical group 0.000 description 1
- 229940082500 cetostearyl alcohol Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003221 ear drop Substances 0.000 description 1
- 229940047652 ear drops Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical group [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
- 229940006461 iodide ion Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-N methyl sulfate Chemical group COS(O)(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-N 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical group COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 229940007042 proteus vulgaris Drugs 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940072358 xylocaine Drugs 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
- C07D295/084—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/088—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 attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/12—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing the group, wherein Cn means a carbon skeleton not containing a ring; Thio analogues thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
Definitions
- This invention relates to quaternary salts of basic esters of fl-(l-naphthyD-acrylic acid having valuable antibacterial and antifungal activities.
- the quaternary salts of the invention possess the general formula wherein R is hydrogen or phenyl, R and R individually represent methyl or ethyl or when taken collectively with the nitrogen atom to which they are attached represent morpholino, piperidino or pyrrolidino; R represents methyl, ethyl, butyl, isoamyl, octyl, decyl, dodecyl, hexadecyl, octadecyl, bromohexyl, benzyl or an acetyl and X represents a bromide, chloride or iodide ion or a methyl sulfate ion.
- the compounds according to the invention have valuable antibacterial and antifungal activities 3,420,822 Patented Jan. 7, 1969 ICC and are particularly intended for the topical treatment of bacterial and fungal infections.
- R represents an aryl group
- it preferably represents a phenyl group.
- R and R represent alkyl groups, they advantageously represent alkyl groups containing from 1 to 6 carbon atoms; where R and R together with the adjacent nitrogen atom represent a heterocyclic group, this is advantageously a 5- or 6-membered saturated heterocyclic group such as for example a pyrrolidino, piperidino or morpholino group.
- R preferably represents an alkyl group containing from 1 to 20 carbon atoms (e.g.
- X preferably represents a chlorine, bromine or iodine atom, or a methyl sulphate group.
- Particularly preferred compounds according to the invention by virtue of their especially valuable antibacterial and antifungal activities are compounds of the Formula I in which R represents an alkyl group containing from 8 to 12 carbon atoms such as, for example, the following:
- compound (b) is particularly preferred for use in medicinal preparations.
- the antibacterial activity of compounds according to the invention may be demonstrated by in vitro tests utilising the dilution technique (1:2 in tryptose phosphate broth [Difco]) against the following microorganisms: Bacillus subtilis ATCC 6633, Micrococcus pyogencs, var. aureus ATCC 6538P, Streptococcus haemolyticus C203 America, Escherichia coli McLeod ATCC 10536, Proteus vulgaris ATCC 7829 and Pscudomonas aeruginosa ATCC 10145.
- the antifungal activity of compounds according to the invention has been demonstrated by in vitro tests utilising the dilution technique (1:2 in Sabourauds medium) against the following microorganisms: Candida albicans ATCC 10231. T ricophyton mentagrophytes ATCC 8757 and Saccharomyces cerevisiae ATCC 9763. With Candida albicans and Saccharomyces cerevisiae incubation was offected, after innoculation of the compounds to be tested, for a period of 24 hours prior to estimation of the minimum inhibitory concentration; with Tricophyton mentagrophytes, the incubation period was five days.
- the quaternising agent will in general be a compound of the formula R X', where X is a halide or alkyl sulphate ion. Where it is desired that the final compound have an anion other than halide or alkyl sulphate this may be achieved by conventional ion-exchange techniques.
- the reaction is conveniently carried out in the presence of an organic solvent such as, for example, benzene, toluene, acetone or acetonitrile, advantageously at a temperature between and 50 C.
- the reaction time will generally vary between 2 and 60 days according to the nature of the reactants used.
- the quaternary salts of Formula I are in general relatively insoluble in the organic solvent medium and slowly precipitate in crystalline form; in some cases, however, it is desirable to remove the solvent in order to isolate the product.
- the compounds of Formula I obtained may be purified in any convenient way, for example by washing with ether.
- the compounds of Formula II used as starting materials in the above-described process according to the invention may be prepared in any convenient manner, e.g. by one of the following methods:
- R2 HOCH-CHr-N 1 1 ⁇ R3 (IV) (wherein R R and R are as hereinbefore defined).
- the reaction is preferably carried out in the presence of an organic solvent such as for example ether, benzene or dioxan under substantially anhydrous conditions and in the presence of an acid-binding agent such as, for example, an excess of the aminoalcoholof Formula IV.
- the reaction mixture is advantageously refluxed for 24 hours to effect the reaction.
- vent such as for example ethanol or propanol, refluxing the reaction mixture for l5-24 hours.
- the compounds of Formula II may be viscous liquids of pale yellow colour or white crystalline solids, insoluble in Water but soluble in the common organic solvents and in aqueous acid solutions.
- Several of the compounds of Formula II useful as starting materials are now compounds.
- the compounds of Formula I according to the inven tion are in general colourless crystalline solids having varying solubilities in water.
- the quaternary salts formed with benzyl chloride, methyl chloride, butyl bromide and isoamyl bromide are for example soluble in Water whilst the salts formed with longer chain alkyl halides are either insoluble or only sparingly soluble in water.
- compositions which comprise at least one compound of the Formula I in association with a pharmaceutical carrier or excipient.
- the compositions according to the invention may for example be suitable for application to the skin, or alternatively may be adapted for use in the nose, ear or mouth.
- the compositions may for example be in the form of ointments, creams, mouth washes, nasal and otological drop solutions, alcoholic tinctures, powders for topical use, vaginal tablets and suppositories, spray solutions and the like.
- Preferred compositions according to the invention contain from 0.02 to 1.5% by weight of the compound or compounds of Formula I.
- compositions according to the invention may also contain :further therapeutic compounds in addition to compounds of the Formula I, for example anti-inflammatory steroids (e.g. prednisolone, triamcinolone, betamethazone or dexamethasone), antibiotics especially suitable for topical administration (e.g. neomycin) and local anaesthetics (e.g. xylocaine).
- anti-inflammatory steroids e.g. prednisolone, triamcinolone, betamethazone or dexamethasone
- antibiotics especially suitable for topical administration e.g. neomycin
- local anaesthetics e.g. xylocaine
- EXAMPLE 1 19.8 g. of B-(l-naphthyD-acrylic acid and 50 ml. of thionyl chloride are refluxed for 1 hour. The excess of thionyl chloride is distilled off at reduced pressure and the oily residue is redissolved in 20 ml. of anhydrous benzene. 14.5 g. of 2-(N-piperidino)-ethanol in 20 ml. of anhydrous benzene are then slowly added to the benzene solution which is externally cooled during the addition in order not to allow the temperature to rise above 20 C. A further 20 ml. of anhydrous benzene are then added and the reaction mixture is refluxed for 3 hours.
- the free base obtained by treatment of an aqueous solution of the hydrochloride with alkali, is a viscous liquid of pale yellow colour boiling at 189l91 C./ 0.1 mm. Hg.
- EXAMPLE 2 A suspension of 50 g. of sodium fi-(l-naphthyD-acrylate and 33.9 g. of 2-(N-morpholino)-1-chloroethane in 400 ml. of isopropanol is refluxed for 20 hours. The sodium chloride, formed during the reaction, is then filtered off in the warm. The crude 2-(N-morpholino)-ethyl fl- (1-naphthyl)-acrylate crystallizes upon cooling and, after recrystallisation from isopropanol, melts at 80-82 C.
- EXAMPLE 3 11 ml. of a 18% solution of methyl bromide in benzene are added to 4.1 g. of 2-dimethylaminoethyl fl-(l-naphthyl)-acrylate in ml. of anhydrous benzene and the mixture is maintained at room temperature for 2 days. The precipitate thus formed is separated by filtration, Washed with benzene and then With ether. Z-dimethylaminoethyl fl-(l-naphthyD-acrylate methyl bromide is thus obtained as a white crystalline solid melting at 174 C.
- EXAMPLE 4 3.62 g. of hexadecyl bromide are added, at 50 C., to 2.9 g. of Z-dimethylaminoethyl -(1-naphthyl)-acrylate dissolved in a mixture of ml. of anhydrous acetonitrile and 10 ml. of anhydrous benzene and the solution thus obtained is maintained at 50 C. for 20 days.
- the solid thus formed is separated by filtration and then Washed first with benzene and then with ether.
- the 2- dirnethylaminoethyl ,8(1-naphthyl)-acrylate hexadecyl bromide is thus obtained as a White crystalline solid melting at 157-160 C.
- EXAMPLE 128 g. of benzyl chloride are added to a solution of 2.87 g. of 2-dimethylaminoethyl fi-(l-naphthyD-acrylate in 5 ml. of anhydrous acetone and the solution maintained at room temperature for 2 days. The solid which thus separates is separated by filtration and Washed with ether.
- EXAMPLE 6 n-decyl bromide g 0.5 5 70% alcohol, q.s. to ml 100
- EXAMPLE 7.-AQUEOUS SOLUTIONS (a) For pro-operative skin disinfectant:
- R is selected from the group consisting of a hydrogen atom and a phenyl group; R and R taken individually represent a group selected from the group consisting of methyl and ethyl, or when taken collectively with the nitrogen atom to which they are attached represent a heterocycle selected from the group consisting of piperidino, morpholino and pyrrolidino; R is selected References Cited UNITED STATES PATENTS 2,415,079 2/1947 Magnoliae 260-469 3,077,470 2/1963 Burckhalter 260239 FOREIGN PATENTS 581,532 8/1959 Canada.
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Description
United States Patent 3,420,822 QUATERNARY SALTS 0F BASIC ESTERS 0F fi-(l-NAPHTHYD-ACRYLIC ACID Silvano Casadio, Milan, Italy, assignor to Istituto de Angeli S.p.A., Milan, Italy, an Italian body corporate No Drawing. Filed Oct. 20, 1965, Ser. No. 499,014 Claims priority, application Italy, Nov. 2, 1964, 44,572 US. Cl. 260240 Claims Int. Cl. C091) 23/00; C09b 55/00; C07c 69/76 ABSTRACT OF THE DISCLOSURE This invention relates to quaternary salts of basic esters of fl-(l-naphthyD-acrylic acid having valuable antibacterial and antifungal activities. The quaternary salts of the invention possess the general formula wherein R is hydrogen or phenyl, R and R individually represent methyl or ethyl or when taken collectively with the nitrogen atom to which they are attached represent morpholino, piperidino or pyrrolidino; R represents methyl, ethyl, butyl, isoamyl, octyl, decyl, dodecyl, hexadecyl, octadecyl, bromohexyl, benzyl or an acetyl and X represents a bromide, chloride or iodide ion or a methyl sulfate ion.
According to the present invention, there are provided compounds of the general formula:
in which:
As stated above, the compounds according to the invention have valuable antibacterial and antifungal activities 3,420,822 Patented Jan. 7, 1969 ICC and are particularly intended for the topical treatment of bacterial and fungal infections. In compounds of the Formula I in which R represents an aryl group, it preferably represents a phenyl group. When R and R represent alkyl groups, they advantageously represent alkyl groups containing from 1 to 6 carbon atoms; where R and R together with the adjacent nitrogen atom represent a heterocyclic group, this is advantageously a 5- or 6-membered saturated heterocyclic group such as for example a pyrrolidino, piperidino or morpholino group. R preferably represents an alkyl group containing from 1 to 20 carbon atoms (e.g. a methyl, ethyl, butyl, isoamyl, octyl, decyl, dodecyl, hexadecyl or octadecyl group), a bromoalkyl group such as for example a 6-bromo-hexyl group; a benzyl group; or an acetyl group. X preferably represents a chlorine, bromine or iodine atom, or a methyl sulphate group.
Particularly preferred compounds according to the invention by virtue of their especially valuable antibacterial and antifungal activities are compounds of the Formula I in which R represents an alkyl group containing from 8 to 12 carbon atoms such as, for example, the following:
(a) 2- dimethylamino ethyl [3- l-naphthyl) -acrylate dodecyl bromide,
(b 2- (N-pyrrolidino) ethyl )3- l-naphthyl) -acrylate decyl bromide,
(c) 2- (N-morpholino) ethyl p-( 1-naphthyl)-acrylate decyl bromide, and
(d) 1-phenyl-2 (N-piperidino) ethyl fil-naphthyl) acrylate decyl bromide.
Of these compounds, compound (b) is particularly preferred for use in medicinal preparations.
The antibacterial activity of compounds according to the invention may be demonstrated by in vitro tests utilising the dilution technique (1:2 in tryptose phosphate broth [Difco]) against the following microorganisms: Bacillus subtilis ATCC 6633, Micrococcus pyogencs, var. aureus ATCC 6538P, Streptococcus haemolyticus C203 America, Escherichia coli McLeod ATCC 10536, Proteus vulgaris ATCC 7829 and Pscudomonas aeruginosa ATCC 10145. 18-24 hours old cultures of the microorganisms, suitably diluted, were inoculated with the compounds to be tested and, after incubation for 24 hours at 37 C., the minimum concentration of compound which effected in hibition of the growth of the microorganisms was estimated.
The antifungal activity of compounds according to the invention has been demonstrated by in vitro tests utilising the dilution technique (1:2 in Sabourauds medium) against the following microorganisms: Candida albicans ATCC 10231. T ricophyton mentagrophytes ATCC 8757 and Saccharomyces cerevisiae ATCC 9763. With Candida albicans and Saccharomyces cerevisiae incubation was offected, after innoculation of the compounds to be tested, for a period of 24 hours prior to estimation of the minimum inhibitory concentration; with Tricophyton mentagrophytes, the incubation period was five days.
In the following table, the results of tests carried out on the compounds (a), (b), (c) and (d) according to the invention are summarised. These tests were carried out by means of the suspension technique according to the method of Said and coll. described in Annales pharmv franc. 21, 187, 1963, and the results demonstrate the bactericidal and fungicidal activities of the four compounds even at very low concentrations.
(wherein R R and R are as hereinbefore defined). The reaction is advantageously carried out in an organic sol- Compounds according to the invention have also been tested on rabbits eyes and by subcutaneous injection into the abdomen of mice in order to ascertain the suitability of the compounds for topical application. These tests demonstrated that the compounds according to the invention have good skin compatibility.
Further according to the invention, there is provided a process for the preparation of compounds of the Formula I which comprises reacting an amine of the general formula with a quaternising agent to introduce the substituent R and the anion X.
The quaternising agent will in general be a compound of the formula R X', where X is a halide or alkyl sulphate ion. Where it is desired that the final compound have an anion other than halide or alkyl sulphate this may be achieved by conventional ion-exchange techniques.
The reaction is conveniently carried out in the presence of an organic solvent such as, for example, benzene, toluene, acetone or acetonitrile, advantageously at a temperature between and 50 C. The reaction time will generally vary between 2 and 60 days according to the nature of the reactants used. The quaternary salts of Formula I are in general relatively insoluble in the organic solvent medium and slowly precipitate in crystalline form; in some cases, however, it is desirable to remove the solvent in order to isolate the product. The compounds of Formula I obtained may be purified in any convenient way, for example by washing with ether.
The compounds of Formula II used as starting materials in the above-described process according to the invention may be prepared in any convenient manner, e.g. by one of the following methods:
(1) Reaction of the corresponding B-(l-naphthyD- acrylic chloride with an aminoalcohol of formula:
R2 HOCH-CHr-N 1 1 \R3 (IV) (wherein R R and R are as hereinbefore defined). The reaction is preferably carried out in the presence of an organic solvent such as for example ether, benzene or dioxan under substantially anhydrous conditions and in the presence of an acid-binding agent such as, for example, an excess of the aminoalcoholof Formula IV. The reaction mixture is advantageously refluxed for 24 hours to effect the reaction.
(2) Reaction of the sodium B-(I-naphthyD-acrylate with a chloroamine of formula:
vent such as for example ethanol or propanol, refluxing the reaction mixture for l5-24 hours.
The compounds of Formula II may be viscous liquids of pale yellow colour or white crystalline solids, insoluble in Water but soluble in the common organic solvents and in aqueous acid solutions. Several of the compounds of Formula II useful as starting materials are now compounds.
The compounds of Formula I according to the inven tion are in general colourless crystalline solids having varying solubilities in water. The quaternary salts formed with benzyl chloride, methyl chloride, butyl bromide and isoamyl bromide are for example soluble in Water whilst the salts formed with longer chain alkyl halides are either insoluble or only sparingly soluble in water.
Further according to the invention there are provided pharmaceutical compositions (and especially compositions adapted for topical use) which comprise at least one compound of the Formula I in association with a pharmaceutical carrier or excipient. The compositions according to the invention may for example be suitable for application to the skin, or alternatively may be adapted for use in the nose, ear or mouth. The compositions may for example be in the form of ointments, creams, mouth washes, nasal and otological drop solutions, alcoholic tinctures, powders for topical use, vaginal tablets and suppositories, spray solutions and the like. Preferred compositions according to the invention contain from 0.02 to 1.5% by weight of the compound or compounds of Formula I. If desired, the compositions according to the invention may also contain :further therapeutic compounds in addition to compounds of the Formula I, for example anti-inflammatory steroids (e.g. prednisolone, triamcinolone, betamethazone or dexamethasone), antibiotics especially suitable for topical administration (e.g. neomycin) and local anaesthetics (e.g. xylocaine).
In order that the invention may be well understood, the following examples are given by way of illustration only:
EXAMPLE 1 19.8 g. of B-(l-naphthyD-acrylic acid and 50 ml. of thionyl chloride are refluxed for 1 hour. The excess of thionyl chloride is distilled off at reduced pressure and the oily residue is redissolved in 20 ml. of anhydrous benzene. 14.5 g. of 2-(N-piperidino)-ethanol in 20 ml. of anhydrous benzene are then slowly added to the benzene solution which is externally cooled during the addition in order not to allow the temperature to rise above 20 C. A further 20 ml. of anhydrous benzene are then added and the reaction mixture is refluxed for 3 hours. After cooling, the suspended solid is filtered, washed with benzene and crystallised from absolute ethanol. The 2- (N-piperidino)-ethyl fi-(l-naphthyD-acrylate hydrochloride is thus obtained (M. Pt. 197 C.).
The free base, obtained by treatment of an aqueous solution of the hydrochloride with alkali, is a viscous liquid of pale yellow colour boiling at 189l91 C./ 0.1 mm. Hg.
Analysis for C H O N (percent). Calc.: C, 77.64; H 7.49; N, 4.53. Found: C, 77.95; H, 7.53; N, 4.49.
The following compounds are prepared in an analogous manner:
Z-dimethylaminoethyl ;3-( l-naphthyl) -acrylate B.P. 170-175 C./0.2 mm. Hg.
Analysis for C1'1H1902N (percent). Calc.: C, 75.81; H, 7.11; N, 5.20. Found: C, 76.3; H, 7.10; N, 5.39. Hydrochloride: M. Pt. 153 C.
2- (N-pyrrolidino -ethyl fl-( 1-naphthyl)-acrylate B.P. 197-199 C./mm. Hg.
Analysis for C H O N (percent). Calc.: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.50; H, 7.18; N, 4.88. Hydrochloride: M.P. 151 C.
1-phenyl-2-dimethylaminoethyl /8-( 1-naphthy1)-acrylate M.P. 82-83 C. (crystallized from isopropanol. Analysis for C H O N (percent). Calc.: C, 79.97; H, 6.71; N, 4.06. Found: C, 79.83; H, 6.82; N, 4.00. Hydrochloride: M.P.181-183 C.
l-phenyl-Z- (N-morpholino) -ethyl [3-( 1-naphthyl)- acrylate M.P. 117 C. (crystallized from 95% ethanol). Analysis for C H O N (percent). Calc.: C, 77.49; H, 6.50; N, 3.62. Found: C, 78.00; H, 6.59; N, 3.61. Hydrochloride: M.P. ZOO-204 C.
1-phenyl-2- (N-piperidino) -ethy1 fi- 1-naphthyl)- acrylate M.P. 78-79 C. (crystallized from 95% ethanol). Analysis for CzeHzqOzN (percent). Calc.: C, 81.01; H, 7.06; N, 3.63. Found: C, 81.46; H, 7.11; N, 3.67. Hydrochloride: M.P. 191192 C.
EXAMPLE 2 A suspension of 50 g. of sodium fi-(l-naphthyD-acrylate and 33.9 g. of 2-(N-morpholino)-1-chloroethane in 400 ml. of isopropanol is refluxed for 20 hours. The sodium chloride, formed during the reaction, is then filtered off in the warm. The crude 2-(N-morpholino)-ethyl fl- (1-naphthyl)-acrylate crystallizes upon cooling and, after recrystallisation from isopropanol, melts at 80-82 C.
Analysis for C H O N (percent). Calc.: C, 73.29; H, 6.80; N, 4.50. Found: C, 73.01; H, 6.81; N, 4.60. Hydrochloride: M.P. 213 C.
EXAMPLE 3 11 ml. of a 18% solution of methyl bromide in benzene are added to 4.1 g. of 2-dimethylaminoethyl fl-(l-naphthyl)-acrylate in ml. of anhydrous benzene and the mixture is maintained at room temperature for 2 days. The precipitate thus formed is separated by filtration, Washed with benzene and then With ether. Z-dimethylaminoethyl fl-(l-naphthyD-acrylate methyl bromide is thus obtained as a white crystalline solid melting at 174 C.
Analysis for C H O NBr (percent). Calc.: C, 59.35; H, 6.08; N, 3.84; Br, 21.94. Found: C, 60.12; H, 6.10; N, 3.91; Br, 22.05.
The following quaternary salts are prepared in an analogous manner:
2-dimethylaminoethyl B-( 1-naphthyl)-acry1ate n.butyl bromide Reaction time: 4 days, M.P. 186188 C. Analysis for C H O NBr (percent). Calc.: C, 62.06; H, 6.94; N, 3.45; Br, 19.66. Found: C, 62.36; H, 7.01; N, 3.39; Br, 1915.
Z-dimethylaminoethyl fi- 1-naphthyl)-acrylate isomayl bromide Reaction time: 5 days, M.P. 182186 C. Analysis for C H O NB1" (percent). Calc.: C, 62.87; H, 7.19; N, 3.33; Br, 19.01. Found: c, 62.01; H, 7.00; N, 3.31; Br, 19.11.
6 Z-dimethylaminoethyl ,B-( 1-naphthy1)-acrylate 6-bromohexyl bromide Reaction time: 7 days, M.P. 189190 C. Analysis for C H O NBr (percent) Calc.: C, 53.8; H, 6.09; N, 2.73; Br, 31.14. Found: C, 53.91; H, 6.11; N, 2.69; Br, 31.01.
2-dimethylaminoethyl fil-naphthyl) -acrylate n-octyl bromide Reaction time: 7 days, M.P. 157158 C. Analysis for C H O NBr (percent). Calc. C, 64.93; H, 7.85; N, 3.03; Br, 17.28. Found: C, 64.95; H, 7.77; N, 3.03; Br, 17.41.
Z-dimethylaminoethyl ,B-( 1-naphthyl-) acrylate n-decyl bromide Reaction time: 12 days, M.P. -168 C. Analysis for C H O NBr (percent). Calc.: C, 66.10; H, 8.22; N, 2.86; Br, 16.29; Found: C, 66.01; H, 8.19; N, 2.89; Br, 16.33.
Z-dimethylaminoethyl fl- 1-naphthyl)-acrylate n-dodecyl bromide Reaction time: 12 days, M.P. 156-15 8 C. Analysis for C H O NBr (percent). Calc.: C, 67.20; H, 8.55; N, 2.70; Br, 15.41. Found: C, 67.41; H, 8.56; N, 2.69; Br, 15.45.
2- (N-morpholino -ethyl ,3-( l-naphthyl) -acrylate methyl bromide Reaction time: 3 days, M.P. -177 C. Analysis for C H O NBr (percent). Calc. C, 59.12; H, 5.95; N, 3.45; Br, 19.67. Found: C, 59.91; H, 5.88; N, 3.43; Br, 19.66.
2-(N-piperidino)-ethyl fi- 1-naphthyl)-acrylate methyl bromide Reaction time: 2 days, M.P. 175 C. Analysis for C H O NBr (percent). Calc.: C, 62.38; H, 6.48; N, 3.46; Br, 19.77. Found: C, 62.43; H, 6.43; N, 3.51; Br, 19.60.
2-(N-pyrrolidino)-ethyl fi-( 1-naphthyl)-acrylate methyl bromide Reaction time: 2 days, M.P. 178 C. Analysis for C H O NBr (percent). Calc.: C, 61.54; H, 6.20; N, 3.59; Br, 20.47. Found: C, 61.10; H, 6.18; N, 3.51; Br, 20.39.
2- N-pyrrolidino -ethyl B- l-naphthyl) -acrylate n-butyl bromide Reaction time: 6 days, M.P. 214220 C. Analysis for C H O NBr (percent). Calc.: C, 63.90; H, 6.99; N, 3.24; Br, 18.48. Found: C, 63.10; H, 6.88; N, 3.21; Br, 18.53.
2- (N-pyrrolidino -ethyl fl-( l-naphthyl) -acrylate isoamyl bromide Reaction time: 6 days, M.P. 2132l8 C. Analysis for C H O NBr (percent). Calc.: C, 64.56; H, 7.23; N, 3.14; Br, 17.90. Found: C, 64.59; H, 7.21; N, 3.11; Br, 17.50.
2- N-pyrrolidino) ethyl ,8-( 1-naphthyl)-acrylate 6-bromohexyl bromide Reaction time: 7 days, M.P. 80100 C. Analysis for C H O NBr (percent). Calc.: C, 55.60; H, 6.16; N, 2.59; Br, 29.63. Found: C, 55.99; H, 6.11; N, 2.58; Br, 29.50.
2- (N-pyrrolidino -ethyl ,8-( l-naphthyl -acrylate n.0cty1 bromide Reaction time: 8 days, M.P. 132133 C. Analysis for C27H33O2NBr (percent). Calc.: C, 66.38; H, 7.84; N, 2.87; Br, 16.36. Found: C, 66.55; H, 7.81; N, 2.90; Br, 16.41.
1-penyl-2-dimethylaminoethyl fi-( 1-naphthyl)- acrylate methyl bromide Reaction time: 2 days, M.P. 218 C. Analysis for C H O NB1' (percent) Calc.: C, 65.48; H, 5.95 N, 3.18; Br, 18.15. Found: C, 65.91; H, 5.88; N, 3.18; Br, 18.67.
7 1-pheny1-2-dimethylaminoethyl ,B-( 1-naphthyl)- acrylate dimethylsulphate Reaction time: 14 days, M.P. 168-172 C. Analysis for C H O NS (percent). Calc.: C, 63.68; H, 6.20; N, 2.97. Found: C, 62.9; H, 6.21; N, 2.84.
1-phenyl-2-dimethylarninoethyl /3-( 1 -naphthyl acrylate methyl iodide Reaction time: 2 days, M.P. 173-176 C. Analysis for C H O NI (percent). Calc.: C, 59.12; H, 5.38; N, 2.87; I, 26.06. Found: C, 59.90; H, 5.29; N, 2.89; I, 26.19.
1-phenyl-2-dimethylaminoethyl ,B-(I-naphthyD- acrylate n-butyl bromide Reaction time: 20 days, M.P. 160-165 C. Analysis for CzqHgzOgNBI' (percent). Calc.: C, 67.20; H, 6.69; N, 2.91; Br, 16.57. Found: C, 67.44; H, 6.55; N, 3.01; Br, 16.66.
1-phenyl-2-dirnethylaminoethyl ,8-( 1-n aphthyl acrylate isoamyl bromide Reaction time: 20 days at 50 C. The product was isolated by removal of the solvent. M.P. 84-88 C. Analysis for C H O NBr (percent). Calc.: C, 67.73; H, 6.90; N, 2.82; Br, 16.10. Found: C, 67.91; H, 6.83; N, 2.86; Br, 16.44.
1pheny1-2-dimethylaminoethyl B- 1-naphthyl)-acrylate 6-bromohexyl bromide Reaction time: 7 days, M.P. 70-75 C. Analysis for C H O NBr (percent). Calc.: C, 59.12; H, 5.99; N, 2.38; Br, 27.11. Found: C, 59.01; H, 6.03; N, 2.18; Br, 27.03.
1-phenyl-2-dimethylaminoethyl fl-( 1-naphthyl)-acrylate n-octyl bromide Reaction time: 8 days, M.P. 82 C. Analysis for C H O NB1 (percent). Calc.: C, 69.13; H, 7.49; N, 2.60; Br, 14.84. Found: C, 69.51; H, 7.57; N, 2.59; Br, 14.99.
1-pheny1-2-dimethylaminoethyl fi-( 1-naphthyl)-acrylate n-decyl bromide Reaction time: 20 days, M.P. 74-78 C. Analysis for C H O NBr (percent). Calc.: C, 70.00; H, 7.82; N, 2.47; Br, 14.10. Found: C, 70.61; H, 7.94; N, 2.47; Br, 14.14.
1-phenyl-2-dimethylaminoethyl B-( 1-naphthyl)-acrylate n-dodecyl bromide Reaction time: 25 days, M.P. 98-102 C. Analysis for C H O NB1" (percent). Calc.: C, 70.7; H, 8.14; N, 2.36; Br, 13.44. Found. C, 70.8; H, 8.11; N, 2.40; Br, 13.39.
1-phenyl-2 N-morpholino -ethyl ,8-(1-naphthyl)- acrylate methyl bromide I-phenyl-Z-(N-piperidino)-ethyl ,8-( 1-naphthyl)- acrylate methyl bromide Reaction time: 8 days, M.P. 212 C. Analysis for C27H3 O NBr (percent). Calc.: C, 67.50; H, 6.29; N, 2.91; Br, 16.63. Found: C, 67.39; H, 6.27; N, 2.70; Br, 16.91.
l-phenyl-Z-(N-piperidino)-ethyl B-(l-naphthyD-acrylate acetyl chloride Reaction time: 2 days, M.P. 193-194" C. Analysis for C H O NCI (percent). Calc.: C, 72.50; H, 6.52; N, 3.02; Cl, 7.64. Found: C, 72.81; H, 6.39; N, 3.18; Cl, 7.80.
EXAMPLE 4 3.62 g. of hexadecyl bromide are added, at 50 C., to 2.9 g. of Z-dimethylaminoethyl -(1-naphthyl)-acrylate dissolved in a mixture of ml. of anhydrous acetonitrile and 10 ml. of anhydrous benzene and the solution thus obtained is maintained at 50 C. for 20 days. The solid thus formed is separated by filtration and then Washed first with benzene and then with ether. The 2- dirnethylaminoethyl ,8(1-naphthyl)-acrylate hexadecyl bromide is thus obtained as a White crystalline solid melting at 157-160 C.
Analysis for C H O NBr (percent). Calc.: C, 69.00; H, 9.12; N, 2.44; Br, 13.91. Found: C, 69.21; H, 9.10; N, 2.39; Br. 14.06.
The following quaternary ammonium salts are obtained in an analogous manner:
2-(N-morpholino)-ethyl B-(l-naphthyD-acrylate n-butyl bromide Reaction time: 5 days. The compound was isolated by removal of the solvent. M.P. 177-187 C. Analysis for C H O NBr (percent). Calc.: C, 61.6; H, 6.74; N, 8.12; Br, 17.82. Found: C, 62.0; H, 6.77; N, 3.21; Br, 17.91.
2-(N-morpholino)-ethyl B-(l-naphthyD-acrylate n-octyl bromide Reaction time: 20 days, M.P. 86-88" C. Analysis for C27H3303NBr (percent). Calc.: C, 64.28; H, 7.59; N, 2.78; Br, 15.84. Found: C, 65.00; H, 7.61; N, 2.70; Br. 15.89.
2- Nmorpholino) ethyl fi-( 1-naphthyl)-acrylate n-decyl bromide Reaction time: 60 days. The product was isolated by removal of the solvent. M.P. 88-92 C. Analysis for C H O NBr (percent). Calc.: C, 65.40; H, 7.95; N, 2.63; Br, 15.01. Found: C, 65.10; H, 7.88; N, 2.67; Br, 15.15.
Z-(N-morpholino -et-hyl fl-( 1-naphthyl)-acrylate n-dodecyl bromide Reaction time: 60 days. The product was isolated by removal of the solvent. M.P. 7680 C. Analysis for C H O NBr (percent). Calc.: C, 66.40; H, 8.27; N, 2.50; Br, 14.26. Found: C, 66.93; H, 8.31; N, 2.50; Br, 14.38.
2- N-piperidino -ethyl [i-(1-naphthy1)-acrylate n-octyl bromide Reaction time: 8 days, M.P. -157 C. Analysis for C H O NB1 (percent). Calc.: C, 66.92; H, 8.02; N, 2.79; Br, 15.90. Found: C, 66.18; H, 8.01; N, 2.81; Br, 15.66.
2-(N-pyrro1idino)-ethyl /3-(1-naphthyl)-acrylate n-decyl bromide Reaction time: 20 days, M.P. 92.95 C. Analysis for C H O NBr (percent). Calc.: C, 67.45; H, 8.20; N, 2.71; Br, 15.47. Found: C, 67.91; H, 8.19; N, 2.83; Br, 15.41.
2- (N-pyrro1idino)-ethyl 3-(1-naphthyl)-acrylate n-dodecyl bromide Reaction time: 25 days, M.P. 90-95 C. Analysis for C H O NBr (percent). Calc.: C, 68.40; H, 8.52; N, 2.57; Br, 14.67. Found: C, 68.10; H, 8.55; N, 2.59; Br, 14.55.
2- N-pyrrolidino -ethyl 18- 1-naphthyl)-acrylate n-octadecyl bromide Reaction time: 25 days, M.P. 82-86 C. Analysis for C37H5302NBI' (percent). Calc.: C, 70.68; H, 9.30; N, 2.23; Br, 12.71. Found: C, 70.00; H, 9.19; N, 2.18; Br, 12.75.
1-phenyl-Z-dimethylaminoethyl ,8-(1-naphthyl)-acrylate n-octadecyl bromide Reaction time: 45 days. The compound was isolated by removal of the solvent. M.P. 8286 C. Analysis for 9 C H O NBr (percent). Calc.: C, 72.52; H, 8.92; N, 2.06; Br. 11.77. Found: C, 72.80; H, 8.99; N, 2.15; Br, 11.51.
1-phenyl-2- (N-piperidino) -ethy1 B-( l-naphthyl) -aorylate n-octyl iodide Reaction time: 20 days. The product was isolated by removal of the solvent. M.P. 158-163 C. Analysis for C H O NI (percent). Calc.: C, 65.28; H, 7.09; N, 2.24; I, 20.29. Found: C, 65.53; H, 7.12; N, 2.25; I, 20.23.
1-pheny1-2- (N-piperidino) -ethyl B-( 1-naphthy1)-acry1ate n-decyl bromide Reaction time: 20 days, M.P. 168-171 C. Analysis for C H O NBr (percent) Calc.: C, 71.30; H, 7.98; N, 2.31; Br, 13.17. Found: C, 71.48; H, 8.05; N, 2.47; Br, 13.21.
EXAMPLE 1.28 g. of benzyl chloride are added to a solution of 2.87 g. of 2-dimethylaminoethyl fi-(l-naphthyD-acrylate in 5 ml. of anhydrous acetone and the solution maintained at room temperature for 2 days. The solid which thus separates is separated by filtration and Washed with ether.
The Z-dimethylaminoethyl fi-(l-naphthyD-acrylate benzyl chloride is thus obtained as a white crystalline solid melting at 197198 C.
Analysis for C H O NCI (percent). Calc.: C, 72.80; H, 6.62; N, 3.55; Cl, 8.95. Found: C, 72.51; H, 6.60; N, 3.57; Cl, 9.01.
The following quaternary ammonium salts are obtained in an analogous manner:
2- (N-morpholino -ethyl ,8-( 1-naphthyl)-acrylate benzyl chloride Reaction time; reaction temperature: 5 days at 50 C. M.P. 166167 C. Analysis for C H O NCl (percent). Calc.: C, 71.30; H, 6.44; N, 3.20; Cl, 8.09. Found: C, 70.99; H, 6.43; N, 312; Cl, 8.13.
2-(N-piperidino)-ethyl /3-( l-naphthyl) -acrylate benzyl chloride Reaction time: 5 days, M.P. 189191 C. Analysis for C27H3002NC]. (percent). Calc.: C, 74.38; H, 6.94; N, 3.21; Cl, 8.13. Found: C, 74.42; H, 6.99; N, 3.19; Cl, 8.16.
2-(N-pyrrolidino)-ethyl fl-(l-naphthyD-acrylat benzyl chloride Reaction time: 5 days, M.P. 176 C. Analysis for C H O NCl (percent). Calc.: C, 74.01; H, 6.69; N, 3.32; CI, 8.40. Found: C, 74.62; H, 6.83; N, 3.31; Cl, 8.39.
1-phenyl-2-dimethylaminoethyl ;8-( 1-naphthy1)-acrylate benzyl bromide Reaction time: 15 days. Reaction temperature: 50 C. The compound was isolated by removal of the solvent. M.P. 60-65 C. Analysis for C H O NBr (percent). Calc.: C, 69.75; H, 5.85; N, 2.71; Br, 15.47. Found: C, 69.95, H, 5.72; N, 2.58; Br, 15.39.
1-phenyl-2-dimethylaminoethyl 18- 1-naphthy1)-acrylate benzyl chloride Reaction time: 20 days, M.P. 178181 C. Analysis for C H O NCl (percent). Calc.: C, 76.34; H, 6.41; N, 2.97; Cl, 7.51. Found: C, 76.34; H, 6.31; N, 2.79; Cl, 7.61.
1-phenyl-2- (N-piperidino -ethyl ;8-( 1-naphthyl)-acrylate benzyl chloride Reaction time: 20 days. Reaction temperature: 50 C., M.P. 1051 C. Analysis for C H O NCl (percent). Calc.: C, 77.40; H, 6.69; N, 2.73; Cl, 692. Found: C, 77.10; H, 6.80; N, 2.75; Cl, 6.84.
10 EXAMPLE 6.--TINCTURES n-decyl bromide g 0.5 5 70% alcohol, q.s. to ml 100 (b) 2- (-N-pyrrolidino) -ethyl fl- 1-naphthyl)-acrylate n-decyl bromide 'g 1 Industrial methylated spirits ml 75 Distilled water, q.s. to ml 100 10 EXAMPLE 7.-AQUEOUS SOLUTIONS (a) For pro-operative skin disinfectant:
2- (-N-pyrrolidino -ethyl 3- l-naphthyl -acryla n-decyl bromide -g 1 Propylene glycol ml 5 Distilled water, q.s. to ml 100 (b) Disinfectant for the hands and arms of the surgeon before sungical procedures: A B 2- (N pyrrolidino) -ethyl ,8- 1-naphthyl acrylate n-decyl bromide g 0.5 0.1 Propylene glycol ml 5 5 'Distilled water, q.s. to ml 100 100 (c) Disinfectants for use in obstetrics and for burns and wounds:
2- (N pyrrolidino) -ethyl B- 1-naphthyl -acrylate n-decyl bromide g 0.05 Propropylene lglycol ml 5 Distilled water, q.s. to ml 100 EXAMPLE 8.-CREAMS Grams (a) 2-(N-pyrrolidino)-ethyl fl-(l-naphthyD- ecrylate n-decyl bromide 0. 5 0. 1 Cetostearyl alcohol. 10 10 Liquid parafiin 10 10 Distilled water, q.s. t 100 100 (b) 2-(N-pyrrolidino)-ethyl 40 acrylate n-decyl bromide 0. 5 0. 1 Polyethylene 1000 monocetyl ether. 2 2 Cetostearyl cohol 8 8 Cetyl alcohol 5 5 Yellow soft parafiin 10 10 Liquid paraflin 10 10 Glycerin 5 5 Distilled water, q.s. to 100 100 EXAMPLE 9.-LOTIONS Grams 2-(N-pyrrolidino) ethyl B-(l-naphthyD-acrylate n-decyl bromide 0. 5 0. 1 01 3 3 2 2 20 20 2 2 100 100 EXAMPLE 10.VAGINAL TABLETS Grams Each tablet contains:
2-(N-pyrrolidino)-ethyl fl-(l-naphthybacrylate n-decyl bromide 0. 005 0 0005 Polysorbate 80 0. 010 0 010 Lactose, q.s. to 2 EXAMPLE 11.-VAGI'NAL SUPPOSITOR-IES Grams Each suppository contains:
2-(N-pyrrolidino)-ethyl B-(l-naphthyD- acrylate n-decyl bromide 0. 005 0. 0005 Glycerinated gelatine, q.s. to 2 2 EXAMPLE 12.LOZENGES Grams Each lozenge contains:
acrylate n-decyl bromide. 0. 002 0. 0005 Mannitol 0. 200 0.200
Talc 0.020 0.020
Flavour, q.s
Sugar, q.s. to 1 1 EXAMPLE 13.EAR DROPS 2-(N-pyrrolidino)-ethyl fl-(l-naphthyl) -aeryla-te ndeeyl bromide, g 0. 0. 02
Propylene glycol (ml.), q.s. to 100 100 I claim:
1. A compound of the formula wherein R is selected from the group consisting of a hydrogen atom and a phenyl group; R and R taken individually represent a group selected from the group consisting of methyl and ethyl, or when taken collectively with the nitrogen atom to which they are attached represent a heterocycle selected from the group consisting of piperidino, morpholino and pyrrolidino; R is selected References Cited UNITED STATES PATENTS 2,415,079 2/1947 Blicke 260-469 3,077,470 2/1963 Burckhalter 260239 FOREIGN PATENTS 581,532 8/1959 Canada.
OTHER REFERENCES Chemical Abstracts, vol. 46, col. 11168 (1952) (abstract of Sergievskaya et a1.)
Chemical Abstracts, vol. 65, cols. 1752 to 1754 (1965) (abstract of Crescenzi et a1.)
Chemical Abstracts, vol. 65, col. 2135 (1965 (abstract of Coppi et 211.)
JOHN D. RANDOLPH, Primary Examiner.
US. Cl. X.R. 260469; 424308, 274, 267, 248
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT4457264 | 1964-11-02 | ||
| GB4457264 | 1964-11-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3420822A true US3420822A (en) | 1969-01-07 |
Family
ID=26265419
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US499014A Expired - Lifetime US3420822A (en) | 1964-11-02 | 1965-10-20 | Quaternary salts of basic esters of beta-(1-naphthyl)-acrylic acid |
Country Status (2)
| Country | Link |
|---|---|
| US (1) | US3420822A (en) |
| NL (1) | NL6514041A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2676224A1 (en) * | 1991-05-10 | 1992-11-13 | Gastaud Jean Marie | NOVEL QUATERNARY AMMONIUM SALTS, PROCESSES THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME. |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2415079A (en) * | 1944-02-26 | 1947-02-04 | Regents | Basic-alkyl esters and their salts |
| CA581532A (en) * | 1959-08-18 | Abbott Laboratories | Method of preparing quaternary ammonium salts | |
| US3077470A (en) * | 1961-03-21 | 1963-02-12 | Univ Kansas Res Foundation | 3-[4-hydroxy-3-(aminomethyl)-phenyl]-4-(4-oxyphenyl)-alkanes and alkenes |
-
1965
- 1965-10-20 US US499014A patent/US3420822A/en not_active Expired - Lifetime
- 1965-10-29 NL NL6514041A patent/NL6514041A/xx unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA581532A (en) * | 1959-08-18 | Abbott Laboratories | Method of preparing quaternary ammonium salts | |
| US2415079A (en) * | 1944-02-26 | 1947-02-04 | Regents | Basic-alkyl esters and their salts |
| US3077470A (en) * | 1961-03-21 | 1963-02-12 | Univ Kansas Res Foundation | 3-[4-hydroxy-3-(aminomethyl)-phenyl]-4-(4-oxyphenyl)-alkanes and alkenes |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2676224A1 (en) * | 1991-05-10 | 1992-11-13 | Gastaud Jean Marie | NOVEL QUATERNARY AMMONIUM SALTS, PROCESSES THEREOF AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME. |
| WO1992020646A1 (en) * | 1991-05-10 | 1992-11-26 | Gastaud Jean Marie | Novel quaternary ammonium salts, process for obtaining same and pharmaceutical compositions containing them |
| US5399590A (en) * | 1991-05-10 | 1995-03-21 | Gastaud; Jean M. | Quaternary ammonium salts and pharmaceutical compositions containing them |
Also Published As
| Publication number | Publication date |
|---|---|
| NL6514041A (en) | 1966-05-03 |
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