CA1218378A - Preparation of novel 1-[2-carbethoxy 4- benzalkylamido phenoxy]3-amino 2-propanols useful in therapeutics - Google Patents
Preparation of novel 1-[2-carbethoxy 4- benzalkylamido phenoxy]3-amino 2-propanols useful in therapeuticsInfo
- Publication number
- CA1218378A CA1218378A CA000449516A CA449516A CA1218378A CA 1218378 A CA1218378 A CA 1218378A CA 000449516 A CA000449516 A CA 000449516A CA 449516 A CA449516 A CA 449516A CA 1218378 A CA1218378 A CA 1218378A
- Authority
- CA
- Canada
- Prior art keywords
- phenoxy
- benzamido
- carbethoxy
- process according
- tert
- 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
Links
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 title claims abstract description 72
- 238000002360 preparation method Methods 0.000 title abstract description 6
- 239000003814 drug Substances 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 116
- 238000000034 method Methods 0.000 claims description 85
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
- 229960004592 isopropanol Drugs 0.000 claims description 39
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims description 33
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 29
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 25
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 239000011737 fluorine Substances 0.000 claims description 22
- 125000001153 fluoro group Chemical group F* 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 19
- -1 alkoxy radical Chemical class 0.000 claims description 15
- 239000000460 chlorine Substances 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 10
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 9
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 6
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 4
- DNMONWLKZBCKSJ-UHFFFAOYSA-N ethyl 5-[(4-fluorobenzoyl)amino]-2-[2-hydroxy-3-(propan-2-ylamino)propoxy]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)C)O)C=CC(=C1)NC(C1=CC=C(C=C1)F)=O DNMONWLKZBCKSJ-UHFFFAOYSA-N 0.000 claims description 3
- XJDXCHLXIOSNSD-UHFFFAOYSA-N ethyl 5-[(4-methylbenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=CC=C(C=C1)C)=O XJDXCHLXIOSNSD-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 239000001294 propane Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims 29
- 238000010438 heat treatment Methods 0.000 claims 21
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 20
- 235000013350 formula milk Nutrition 0.000 claims 10
- 229910052801 chlorine Inorganic materials 0.000 claims 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- VNZMTPDBZTUHCI-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(2,4-difluorobenzoyl)amino]benzoate Chemical compound C1=C(OCC(O)CNC(C)(C)C)C(C(=O)OCC)=CC(NC(=O)C=2C(=CC(F)=CC=2)F)=C1 VNZMTPDBZTUHCI-UHFFFAOYSA-N 0.000 claims 3
- OFKYSRHVUNLCOT-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(2-fluorobenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=C(C=CC=C1)F)=O OFKYSRHVUNLCOT-UHFFFAOYSA-N 0.000 claims 3
- AYNBYSNISOAOHW-UHFFFAOYSA-N 1-(tert-butylamino)propan-2-ol Chemical compound CC(O)CNC(C)(C)C AYNBYSNISOAOHW-UHFFFAOYSA-N 0.000 claims 2
- ZGEWBKHFXRXBBP-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(2-chlorobenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=C(C=CC=C1)Cl)=O ZGEWBKHFXRXBBP-UHFFFAOYSA-N 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- IIVWHGMLFGNMOW-UHFFFAOYSA-N 2-methylpropane Chemical compound C[C](C)C IIVWHGMLFGNMOW-UHFFFAOYSA-N 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- NKZKDRBJBZGXNI-UHFFFAOYSA-N ethyl 2-(1-amino-2-hydroxy-4,4-dimethylpentoxy)-5-[(2-chlorobenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OC(C(CC(C)(C)C)O)N)C=CC(=C1)NC(C1=C(C=CC=C1)Cl)=O NKZKDRBJBZGXNI-UHFFFAOYSA-N 0.000 claims 1
- GZCATSTYIQVWPT-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(2-methylbenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=C(C=CC=C1)C)=O GZCATSTYIQVWPT-UHFFFAOYSA-N 0.000 claims 1
- YSQRVHYIYVJLER-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(3-chlorobenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC(=CC=C1)Cl)=O YSQRVHYIYVJLER-UHFFFAOYSA-N 0.000 claims 1
- YFPRKTSIZNSDBA-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(3-methoxybenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC(=CC=C1)OC)=O YFPRKTSIZNSDBA-UHFFFAOYSA-N 0.000 claims 1
- FEWZACAQARPDCW-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(3-methylbenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC(=CC=C1)C)=O FEWZACAQARPDCW-UHFFFAOYSA-N 0.000 claims 1
- XMAMASFFHBQNKZ-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(4-chlorobenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC=C(C=C1)Cl)=O XMAMASFFHBQNKZ-UHFFFAOYSA-N 0.000 claims 1
- PTKWAHZXWUVQNO-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(4-methoxybenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC=C(C=C1)OC)=O PTKWAHZXWUVQNO-UHFFFAOYSA-N 0.000 claims 1
- QSODSASYIYTITL-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(4-methylbenzenecarbothioyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC=C(C=C1)C)=S QSODSASYIYTITL-UHFFFAOYSA-N 0.000 claims 1
- RVILIHPVYUMELQ-UHFFFAOYSA-N ethyl 2-[3-(tert-butylamino)-2-hydroxypropoxy]-5-[(4-methylbenzoyl)amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)(C)C)O)C=CC(=C1)NC(C1=CC=C(C=C1)C)=O RVILIHPVYUMELQ-UHFFFAOYSA-N 0.000 claims 1
- JYNWBRMEYGXXHH-UHFFFAOYSA-N ethyl 5-[(3-fluorobenzoyl)amino]-2-[2-hydroxy-3-(propan-2-ylamino)propoxy]benzoate Chemical compound C(=O)(OCC)C1=C(OCC(CNC(C)C)O)C=CC(=C1)NC(C1=CC(=CC=C1)F)=O JYNWBRMEYGXXHH-UHFFFAOYSA-N 0.000 claims 1
- 239000012458 free base Substances 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
- 235000013849 propane Nutrition 0.000 claims 1
- HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical class CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 abstract description 3
- 230000000144 pharmacologic effect Effects 0.000 abstract description 3
- QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 33
- 230000008018 melting Effects 0.000 description 31
- 238000002844 melting Methods 0.000 description 31
- 239000013078 crystal Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 24
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 13
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 150000002118 epoxides Chemical class 0.000 description 7
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
- 229940011051 isopropyl acetate Drugs 0.000 description 7
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- RNFDZDMIFOFNMC-UHFFFAOYSA-N 1-(propan-2-ylamino)propan-2-ol Chemical compound CC(C)NCC(C)O RNFDZDMIFOFNMC-UHFFFAOYSA-N 0.000 description 5
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000000903 blocking effect Effects 0.000 description 3
- 230000001882 diuretic effect Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102100038916 Caspase-5 Human genes 0.000 description 2
- 101100112336 Homo sapiens CASP5 gene Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 101100273286 Mus musculus Casp4 gene Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- GEQORLOEZSDDND-UHFFFAOYSA-N ethyl 5-[(2-methoxybenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=C(C=CC=C1)OC)=O GEQORLOEZSDDND-UHFFFAOYSA-N 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UJUKHOATWVVDER-UHFFFAOYSA-N 1-amino-1-phenoxypropan-1-ol Chemical compound CCC(N)(O)OC1=CC=CC=C1 UJUKHOATWVVDER-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- HNUALPPJLMYHDK-UHFFFAOYSA-N C[CH]C Chemical compound C[CH]C HNUALPPJLMYHDK-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 125000003047 N-acetyl group Chemical group 0.000 description 1
- RFMMMVDNIPUKGG-YFKPBYRVSA-N N-acetyl-L-glutamic acid Chemical class CC(=O)N[C@H](C(O)=O)CCC(O)=O RFMMMVDNIPUKGG-YFKPBYRVSA-N 0.000 description 1
- GZMYLSJUNSCMTD-MOPGFXCFSA-N OC[C@@H](C)NC1=NC(=CC(=C1)C=1C=C(C=CC=1C)NC(=O)N1C[C@@H](CC1)CC(F)(F)F)N1CCOCC1 Chemical compound OC[C@@H](C)NC1=NC(=CC(=C1)C=1C=C(C=CC=1C)NC(=O)N1C[C@@H](CC1)CC(F)(F)F)N1CCOCC1 GZMYLSJUNSCMTD-MOPGFXCFSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001408 amides Chemical group 0.000 description 1
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000006793 arrhythmia Effects 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- XCOCZAKMZXMEPV-UHFFFAOYSA-N ethyl 2-(oxiran-2-ylmethoxy)-5-[[4-(trifluoromethyl)benzoyl]amino]benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=CC=C(C=C1)C(F)(F)F)=O XCOCZAKMZXMEPV-UHFFFAOYSA-N 0.000 description 1
- YMMCVTLWLBSENY-UHFFFAOYSA-N ethyl 2-hydroxy-5-[(2-methylbenzoyl)amino]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C(=CC=CC=2)C)=C1 YMMCVTLWLBSENY-UHFFFAOYSA-N 0.000 description 1
- SBFDMSNQNXCESC-UHFFFAOYSA-N ethyl 2-hydroxy-5-[(3-methoxybenzoyl)amino]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C=C(OC)C=CC=2)=C1 SBFDMSNQNXCESC-UHFFFAOYSA-N 0.000 description 1
- KPJFTRQSAIYAQE-UHFFFAOYSA-N ethyl 2-hydroxy-5-[(4-methylbenzoyl)amino]benzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C=CC(C)=CC=2)=C1 KPJFTRQSAIYAQE-UHFFFAOYSA-N 0.000 description 1
- CHJADGWZZHPRDI-UHFFFAOYSA-N ethyl 2-hydroxy-5-[[4-(trifluoromethyl)benzoyl]amino]benzoate Chemical compound C(=O)(OCC)C1=C(C=CC(=C1)NC(C1=CC=C(C=C1)C(F)(F)F)=O)O CHJADGWZZHPRDI-UHFFFAOYSA-N 0.000 description 1
- JDKWYWNJLPZDQD-UHFFFAOYSA-N ethyl 5-[(2-chlorobenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=C(C=CC=C1)Cl)=O JDKWYWNJLPZDQD-UHFFFAOYSA-N 0.000 description 1
- VKYIHFFSFPPRQO-UHFFFAOYSA-N ethyl 5-[(2-fluorobenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=C(C=CC=C1)F)=O VKYIHFFSFPPRQO-UHFFFAOYSA-N 0.000 description 1
- HGMAGATULBZDOP-UHFFFAOYSA-N ethyl 5-[(2-methylbenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=C(C=CC=C1)C)=O HGMAGATULBZDOP-UHFFFAOYSA-N 0.000 description 1
- FHGLPYAUTNUECU-UHFFFAOYSA-N ethyl 5-[(3-chlorobenzoyl)amino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C=C(Cl)C=CC=2)=C1 FHGLPYAUTNUECU-UHFFFAOYSA-N 0.000 description 1
- HBATYHCBWVWGAM-UHFFFAOYSA-N ethyl 5-[(3-fluorobenzoyl)amino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C=C(F)C=CC=2)=C1 HBATYHCBWVWGAM-UHFFFAOYSA-N 0.000 description 1
- MGTOCLZRCKZUPG-UHFFFAOYSA-N ethyl 5-[(4-chlorobenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=CC=C(C=C1)Cl)=O MGTOCLZRCKZUPG-UHFFFAOYSA-N 0.000 description 1
- OVTVSZYXHARDLZ-UHFFFAOYSA-N ethyl 5-[(4-fluorobenzoyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=CC=C(C=C1)F)=O OVTVSZYXHARDLZ-UHFFFAOYSA-N 0.000 description 1
- KEJWCJDEVANFMQ-UHFFFAOYSA-N ethyl 5-[(4-fluorobenzoyl)amino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C=CC(F)=CC=2)=C1 KEJWCJDEVANFMQ-UHFFFAOYSA-N 0.000 description 1
- WTJIPLOGQHHARP-UHFFFAOYSA-N ethyl 5-[(4-methylbenzenecarbothioyl)amino]-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C(=O)(OCC)C1=C(OCC2CO2)C=CC(=C1)NC(C1=CC=C(C=C1)C)=S WTJIPLOGQHHARP-UHFFFAOYSA-N 0.000 description 1
- VKSZFXFMGVXMFP-UHFFFAOYSA-N ethyl 5-benzamido-2-(oxiran-2-ylmethoxy)benzoate Chemical compound C=1C=C(OCC2OC2)C(C(=O)OCC)=CC=1NC(=O)C1=CC=CC=C1 VKSZFXFMGVXMFP-UHFFFAOYSA-N 0.000 description 1
- BCVWQAICWYZQCY-UHFFFAOYSA-N ethyl 5-benzamido-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OCC)=CC(NC(=O)C=2C=CC=CC=2)=C1 BCVWQAICWYZQCY-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- KHUXNRRPPZOJPT-UHFFFAOYSA-N phenoxy radical Chemical group O=C1C=C[CH]C=C1 KHUXNRRPPZOJPT-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000009877 rendering Methods 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/18—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by etherified hydroxyl radicals
- C07D303/20—Ethers with hydroxy compounds containing no oxirane rings
- C07D303/22—Ethers with hydroxy compounds containing no oxirane rings with monohydroxy compounds
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR8304150 | 1983-03-14 | ||
| FR8304150A FR2542737B1 (fr) | 1983-03-14 | 1983-03-14 | Nouveaux (carbethoxy-2 benzalkylamido-4 phenoxy)-1 amino-3 propanols-2, leurs preparations et leurs utilisations en therapeutique |
| FR8318509A FR2555169B2 (fr) | 1983-11-21 | 1983-11-21 | Nouveaux (carbethoxy-2 benzalkylamido-4 phenoxyl)-1 amino-3 propanols-2, leurs preparations et leurs utilisations en therapeutique |
| FR8318509 | 1983-11-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1218378A true CA1218378A (en) | 1987-02-24 |
Family
ID=26223333
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000449516A Expired CA1218378A (en) | 1983-03-14 | 1984-03-13 | Preparation of novel 1-[2-carbethoxy 4- benzalkylamido phenoxy]3-amino 2-propanols useful in therapeutics |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0122827B1 (en:Method) |
| KR (1) | KR910002945B1 (en:Method) |
| AT (1) | ATE20879T1 (en:Method) |
| AU (1) | AU567332B2 (en:Method) |
| CA (1) | CA1218378A (en:Method) |
| DE (1) | DE3460323D1 (en:Method) |
| DK (1) | DK117484A (en:Method) |
| ES (1) | ES8504681A1 (en:Method) |
| GR (1) | GR81821B (en:Method) |
| IE (1) | IE57094B1 (en:Method) |
| PH (1) | PH19184A (en:Method) |
| PT (1) | PT78238B (en:Method) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0617020A1 (en) * | 1992-04-02 | 1994-09-28 | Shudo, Koichi, Prof. Dr. | Carboxylic acid derivatives having retinoic acid-like activity |
| DE60013491T2 (de) * | 2000-04-19 | 2005-09-01 | Neurotech Co., Ltd., Suwon | Verbindungen, zusammensetzungen und verfahren zur vorbeugung der neurodegeneration bei akuten oder chronischen verletzungen des zentralen nervensystems |
| US6964982B2 (en) | 2000-04-20 | 2005-11-15 | Neurotech Co., Ltd. | Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system |
| KR100545745B1 (ko) | 2002-06-19 | 2006-01-24 | 주식회사 뉴로테크 | 테트라플루오로벤질 유도체 및 이를 함유하는 급성 및퇴행성 뇌신경계 질환의 예방 및 치료용 약학적 조성물 |
| US8455470B2 (en) | 2006-04-13 | 2013-06-04 | Neurotech Pharmaceuticals Co., Ltd | Pharmaceutical composition for treating or preventing degenerative and inflammatory diseases |
| KR100852962B1 (ko) | 2007-11-12 | 2008-08-20 | 주식회사 뉴로테크 | 2-하이드록시-5-페닐알킬아미노벤조산 유도체 및 이의 염의제조방법 |
| US8596361B2 (en) | 2007-12-14 | 2013-12-03 | 3M Innovative Properties Company | Proppants and uses thereof |
| MX2010006455A (es) | 2007-12-14 | 2010-09-28 | Schlumberger Technology Bv | Metodos de tratamiento de pozos subterraneos utilizando aditivos cambiables. |
| EP3059338A1 (en) | 2007-12-14 | 2016-08-24 | 3M Innovative Properties Company | Fiber aggregate |
| KR101204108B1 (ko) * | 2009-02-09 | 2012-11-22 | 주식회사 지엔티파마 | 5-벤질아미노살리실산 유도체 또는 이의 염의 의약 용도 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3852468A (en) * | 1967-02-27 | 1974-12-03 | Ici Ltd | Alkanolamine derivatives as {62 -adrenergic blocking agents |
| MX158644A (es) * | 1982-07-20 | 1989-02-21 | Menarini Sas | Procedimiento para preparar un derivado 1-alquilamina-3-(4(p-alquiloxibenzamida)-fenoxi)-2propanol |
-
1984
- 1984-02-28 DK DK117484A patent/DK117484A/da not_active Application Discontinuation
- 1984-03-05 IE IE528/84A patent/IE57094B1/en unknown
- 1984-03-12 PT PT78238A patent/PT78238B/pt not_active IP Right Cessation
- 1984-03-12 ES ES530503A patent/ES8504681A1/es not_active Expired
- 1984-03-12 AT AT84400490T patent/ATE20879T1/de active
- 1984-03-12 EP EP84400490A patent/EP0122827B1/fr not_active Expired
- 1984-03-12 GR GR74075A patent/GR81821B/el unknown
- 1984-03-12 DE DE8484400490T patent/DE3460323D1/de not_active Expired
- 1984-03-13 CA CA000449516A patent/CA1218378A/en not_active Expired
- 1984-03-13 KR KR1019840001323A patent/KR910002945B1/ko not_active Expired
- 1984-03-13 AU AU25537/84A patent/AU567332B2/en not_active Ceased
- 1984-03-14 PH PH30393A patent/PH19184A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ATE20879T1 (de) | 1986-08-15 |
| DK117484A (da) | 1984-09-15 |
| ES530503A0 (es) | 1985-05-01 |
| AU567332B2 (en) | 1987-11-19 |
| PT78238A (fr) | 1984-04-01 |
| PH19184A (en) | 1986-01-23 |
| EP0122827A1 (fr) | 1984-10-24 |
| EP0122827B1 (fr) | 1986-07-23 |
| PT78238B (fr) | 1986-04-24 |
| KR910002945B1 (ko) | 1991-05-11 |
| GR81821B (en:Method) | 1984-12-12 |
| DK117484D0 (da) | 1984-02-28 |
| KR840009078A (ko) | 1984-12-24 |
| DE3460323D1 (en) | 1986-08-28 |
| ES8504681A1 (es) | 1985-05-01 |
| IE840528L (en) | 1984-09-14 |
| AU2553784A (en) | 1984-09-20 |
| IE57094B1 (en) | 1992-04-22 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |