CA2533639A1 - Amino acid diamides in non alpha position useful as adjuvants for the administration of active biological agents - Google Patents
Amino acid diamides in non alpha position useful as adjuvants for the administration of active biological agents Download PDFInfo
- Publication number
- CA2533639A1 CA2533639A1 CA002533639A CA2533639A CA2533639A1 CA 2533639 A1 CA2533639 A1 CA 2533639A1 CA 002533639 A CA002533639 A CA 002533639A CA 2533639 A CA2533639 A CA 2533639A CA 2533639 A1 CA2533639 A1 CA 2533639A1
- Authority
- CA
- Canada
- Prior art keywords
- aromatic
- mmol
- compound
- add
- cooh
- 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.)
- Abandoned
Links
- 239000002671 adjuvant Substances 0.000 title claims abstract description 10
- -1 Amino acid diamides Chemical class 0.000 title claims abstract description 7
- 239000003124 biologic agent Substances 0.000 title abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 238000011282 treatment Methods 0.000 claims abstract description 8
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 6
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 3
- 206010061218 Inflammation Diseases 0.000 claims abstract description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 3
- 208000026935 allergic disease Diseases 0.000 claims abstract description 3
- 230000007815 allergy Effects 0.000 claims abstract description 3
- 201000011510 cancer Diseases 0.000 claims abstract description 3
- 125000000524 functional group Chemical group 0.000 claims abstract description 3
- 230000004054 inflammatory process Effects 0.000 claims abstract description 3
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims abstract 3
- 239000003814 drug Substances 0.000 claims abstract 3
- 238000004519 manufacturing process Methods 0.000 claims abstract 3
- 201000010099 disease Diseases 0.000 claims abstract 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 31
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 24
- 229960003616 bemiparin Drugs 0.000 claims description 12
- 229960002897 heparin Drugs 0.000 claims description 11
- 229920000669 heparin Polymers 0.000 claims description 11
- 229920001542 oligosaccharide Polymers 0.000 claims description 8
- 150000002482 oligosaccharides Chemical class 0.000 claims description 7
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 3
- 239000003146 anticoagulant agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims 2
- FPJHWYCPAOPVIV-VOZMEZHOSA-N (2R,3S,4R,5R,6R)-6-[(2R,3R,4R,5R,6R)-5-acetamido-2-(hydroxymethyl)-6-methoxy-3-sulfooxyoxan-4-yl]oxy-4,5-dihydroxy-3-methoxyoxane-2-carboxylic acid Chemical compound CO[C@@H]1O[C@H](CO)[C@H](OS(O)(=O)=O)[C@H](O[C@@H]2O[C@H]([C@@H](OC)[C@H](O)[C@H]2O)C(O)=O)[C@H]1NC(C)=O FPJHWYCPAOPVIV-VOZMEZHOSA-N 0.000 claims 1
- 229920000045 Dermatan sulfate Polymers 0.000 claims 1
- 229920002971 Heparan sulfate Chemical class 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical class [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 230000002785 anti-thrombosis Effects 0.000 claims 1
- 229910021653 sulphate ion Inorganic materials 0.000 claims 1
- 150000001470 diamides Chemical class 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 description 138
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 132
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 69
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 69
- 229910052739 hydrogen Inorganic materials 0.000 description 45
- 239000007787 solid Substances 0.000 description 45
- 238000003756 stirring Methods 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 238000006243 chemical reaction Methods 0.000 description 36
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 238000005481 NMR spectroscopy Methods 0.000 description 28
- 239000012043 crude product Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
- 238000000921 elemental analysis Methods 0.000 description 22
- 125000000896 monocarboxylic acid group Chemical group 0.000 description 22
- 238000001953 recrystallisation Methods 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- 239000000725 suspension Substances 0.000 description 20
- 239000007795 chemical reaction product Substances 0.000 description 19
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 18
- 238000010992 reflux Methods 0.000 description 18
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 238000010521 absorption reaction Methods 0.000 description 16
- QBRKXURSEZGDNK-UHFFFAOYSA-N 4-[(2-aminobenzoyl)amino]butanoic acid Chemical compound NC1=CC=CC=C1C(=O)NCCCC(O)=O QBRKXURSEZGDNK-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 241000700159 Rattus Species 0.000 description 9
- 230000001858 anti-Xa Effects 0.000 description 7
- 229940127215 low-molecular weight heparin Drugs 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- VZEOZANZDPEPEH-UHFFFAOYSA-N 4-[[2-[(2-hydroxybenzoyl)amino]benzoyl]amino]butanoic acid Chemical compound OC(=O)CCCNC(=O)C1=CC=CC=C1NC(=O)C1=CC=CC=C1O VZEOZANZDPEPEH-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- DSGKWFGEUBCEIE-UHFFFAOYSA-N (2-carbonochloridoylphenyl) acetate Chemical compound CC(=O)OC1=CC=CC=C1C(Cl)=O DSGKWFGEUBCEIE-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 239000003055 low molecular weight heparin Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 230000000112 colonic effect Effects 0.000 description 4
- CPRRHERYRRXBRZ-SRVKXCTJSA-N methyl n-[(2s)-1-[[(2s)-1-hydroxy-3-[(3s)-2-oxopyrrolidin-3-yl]propan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound COC(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CO)C[C@@H]1CCNC1=O CPRRHERYRRXBRZ-SRVKXCTJSA-N 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- DVIHKVWYFXLBEM-UHFFFAOYSA-N 2-hydroxybenzoyl chloride Chemical compound OC1=CC=CC=C1C(Cl)=O DVIHKVWYFXLBEM-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 2
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- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
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- 229940125898 compound 5 Drugs 0.000 description 2
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- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- WAPLXGPARWRGJO-UHFFFAOYSA-N 2-(4-aminophenyl)butanoic acid Chemical compound CCC(C(O)=O)C1=CC=C(N)C=C1 WAPLXGPARWRGJO-UHFFFAOYSA-N 0.000 description 1
- DEFPNMKDESPGBA-UHFFFAOYSA-N 2-Aminohippuric acid Chemical compound NC1=CC=CC=C1C(=O)NCC(O)=O DEFPNMKDESPGBA-UHFFFAOYSA-N 0.000 description 1
- NZCKTGCKFJDGFD-UHFFFAOYSA-N 2-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Br NZCKTGCKFJDGFD-UHFFFAOYSA-N 0.000 description 1
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 1
- LNNDXQSWYNEJAS-UHFFFAOYSA-N 2-hydroxy-4-methoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C(O)=C1 LNNDXQSWYNEJAS-UHFFFAOYSA-N 0.000 description 1
- GIXCHTWQWLWUCY-UHFFFAOYSA-N 2-hydroxy-4-nitrobenzoyl chloride Chemical compound OC1=CC([N+]([O-])=O)=CC=C1C(Cl)=O GIXCHTWQWLWUCY-UHFFFAOYSA-N 0.000 description 1
- MUVDOKVGVSGBBG-UHFFFAOYSA-N 2-hydroxy-5-methoxybenzoyl chloride Chemical compound COC1=CC=C(O)C(C(Cl)=O)=C1 MUVDOKVGVSGBBG-UHFFFAOYSA-N 0.000 description 1
- FMEWLYXGAMCQSC-UHFFFAOYSA-N 2-hydroxy-5-nitrobenzoyl chloride Chemical compound OC1=CC=C([N+]([O-])=O)C=C1C(Cl)=O FMEWLYXGAMCQSC-UHFFFAOYSA-N 0.000 description 1
- RZNHSEZOLFEFGB-UHFFFAOYSA-N 2-methoxybenzoyl chloride Chemical compound COC1=CC=CC=C1C(Cl)=O RZNHSEZOLFEFGB-UHFFFAOYSA-N 0.000 description 1
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 1
- OCZQPOVJWVLQOT-UHFFFAOYSA-N 3-[(2-aminobenzoyl)amino]propanoic acid Chemical compound NC1=CC=CC=C1C(=O)NCCC(O)=O OCZQPOVJWVLQOT-UHFFFAOYSA-N 0.000 description 1
- WHIHIKVIWVIIER-UHFFFAOYSA-N 3-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC(Cl)=C1 WHIHIKVIWVIIER-UHFFFAOYSA-N 0.000 description 1
- WFOSLZPLFCAXQZ-UHFFFAOYSA-N 4-[[2-[(4-methoxybenzoyl)amino]benzoyl]amino]butanoic acid Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=CC=CC=C1C(=O)NCCCC(O)=O WFOSLZPLFCAXQZ-UHFFFAOYSA-N 0.000 description 1
- NFVSDDQSOXOEPX-UHFFFAOYSA-N 4-[[3-[(2-hydroxybenzoyl)amino]benzoyl]amino]butanoic acid Chemical compound OC(=O)CCCNC(=O)C1=CC=CC(NC(=O)C=2C(=CC=CC=2)O)=C1 NFVSDDQSOXOEPX-UHFFFAOYSA-N 0.000 description 1
- GZRKRCIJEVQLKN-UHFFFAOYSA-N 4-[[4-[(2-hydroxybenzoyl)amino]benzoyl]amino]butanoic acid Chemical compound C1=CC(C(=O)NCCCC(=O)O)=CC=C1NC(=O)C1=CC=CC=C1O GZRKRCIJEVQLKN-UHFFFAOYSA-N 0.000 description 1
- BMTIEYHELZLFOQ-UHFFFAOYSA-N 4-[[4-[benzoyl(hydroxy)amino]benzoyl]amino]butanoic acid Chemical compound C=1C=C(C(=O)NCCCC(O)=O)C=CC=1N(O)C(=O)C1=CC=CC=C1 BMTIEYHELZLFOQ-UHFFFAOYSA-N 0.000 description 1
- CCBOXJLPEZRSSA-UHFFFAOYSA-N 4-chloro-2-hydroxybenzoyl chloride Chemical compound OC1=CC(Cl)=CC=C1C(Cl)=O CCBOXJLPEZRSSA-UHFFFAOYSA-N 0.000 description 1
- SKDHHIUENRGTHK-UHFFFAOYSA-N 4-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=C(C(Cl)=O)C=C1 SKDHHIUENRGTHK-UHFFFAOYSA-N 0.000 description 1
- RROFFLPCSWDVLM-UHFFFAOYSA-N 5-[(2-aminobenzoyl)amino]pentanoic acid Chemical compound NC1=CC=CC=C1C(=O)NCCCCC(O)=O RROFFLPCSWDVLM-UHFFFAOYSA-N 0.000 description 1
- NANJQJRZYOVMLF-UHFFFAOYSA-N 5-chloro-2-hydroxybenzoyl chloride Chemical compound OC1=CC=C(Cl)C=C1C(Cl)=O NANJQJRZYOVMLF-UHFFFAOYSA-N 0.000 description 1
- MGMQGGWBRUMFAG-UHFFFAOYSA-N 6-[(2-aminobenzoyl)amino]hexanoic acid Chemical compound NC1=CC=CC=C1C(=O)NCCCCCC(O)=O MGMQGGWBRUMFAG-UHFFFAOYSA-N 0.000 description 1
- QCAZWLDGXHVLCY-UHFFFAOYSA-N 6-[[2-[(2-hydroxybenzoyl)amino]benzoyl]amino]hexanoic acid Chemical compound OC(=O)CCCCCNC(=O)C1=CC=CC=C1NC(=O)C1=CC=CC=C1O QCAZWLDGXHVLCY-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- NAEZZOAQOMCWKU-UHFFFAOYSA-N 8-[(2-aminobenzoyl)amino]octanoic acid Chemical compound NC1=CC=CC=C1C(=O)NCCCCCCCC(O)=O NAEZZOAQOMCWKU-UHFFFAOYSA-N 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 210000000436 anus Anatomy 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000003149 assay kit Methods 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
- 238000005119 centrifugation Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000013401 experimental design Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000002628 heparin derivative Substances 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid group Chemical group C(CCCCC)(=O)O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- NEDGZCPOEZWHQB-UHFFFAOYSA-N methyl 4-[(3-aminobenzoyl)amino]butanoate Chemical compound COC(=O)CCCNC(=O)C1=CC=CC(N)=C1 NEDGZCPOEZWHQB-UHFFFAOYSA-N 0.000 description 1
- FCJLYYUEXHKAIK-UHFFFAOYSA-N methyl 4-[(4-aminobenzoyl)amino]butanoate Chemical compound COC(=O)CCCNC(=O)C1=CC=C(N)C=C1 FCJLYYUEXHKAIK-UHFFFAOYSA-N 0.000 description 1
- JTXQQWCDNBYCOW-UHFFFAOYSA-N methyl 6-[(4-aminobenzoyl)amino]hexanoate Chemical compound COC(=O)CCCCCNC(=O)C1=CC=C(N)C=C1 JTXQQWCDNBYCOW-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
-
- 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
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/17—Amides, e.g. hydroxamic acids having the group >N—C(O)—N< or >N—C(S)—N<, e.g. urea, thiourea, carmustine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07C233/83—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom of an acyclic saturated carbon skeleton
-
- 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
- C07C235/56—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 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
- C07C235/58—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 with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/64—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 with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position 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 a carbon atom of a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pain & Pain Management (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Diabetes (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)
- Medicinal Preparation (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ES200301781A ES2222822B1 (es) | 2003-07-28 | 2003-07-28 | Diamidas de aminoacidos en posicion no alfa utiles como adyuvantes para la administracion de agentes biologicos activos. |
| ESP200301781 | 2003-07-28 | ||
| PCT/ES2004/000346 WO2005012230A1 (es) | 2003-07-28 | 2004-07-23 | DIAMIDAS DE AMINOACIDOS EN POSICION NO α UTILES COMO ADYUVANTES PARA LA ADMINISTRACION DE AGENTES BIOLOGICOS ACTIVOS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2533639A1 true CA2533639A1 (en) | 2005-02-10 |
Family
ID=34112519
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002533639A Abandoned CA2533639A1 (en) | 2003-07-28 | 2004-07-23 | Amino acid diamides in non alpha position useful as adjuvants for the administration of active biological agents |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US7462735B2 (enExample) |
| EP (1) | EP1652836B1 (enExample) |
| JP (1) | JP4343227B2 (enExample) |
| KR (1) | KR100970216B1 (enExample) |
| CN (1) | CN100475776C (enExample) |
| AT (1) | ATE367373T1 (enExample) |
| AU (1) | AU2004261417C1 (enExample) |
| BR (1) | BRPI0413032A (enExample) |
| CA (1) | CA2533639A1 (enExample) |
| DE (1) | DE602004007665T2 (enExample) |
| DK (1) | DK1652836T3 (enExample) |
| ES (2) | ES2222822B1 (enExample) |
| PL (1) | PL1652836T3 (enExample) |
| PT (1) | PT1652836E (enExample) |
| RU (1) | RU2368599C2 (enExample) |
| WO (1) | WO2005012230A1 (enExample) |
| ZA (1) | ZA200600165B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2060253A1 (en) | 2007-11-14 | 2009-05-20 | Laboratorios Farmaceuticos Rovi, S.A. | Pharmaceutical forms for the release of active compounds |
| ES2296529B1 (es) * | 2006-08-07 | 2009-04-01 | Laboratorios Farmaceuticos Rovi, S.A. | Composicion farmaceutica con promotores de absorcion. |
| US8802156B2 (en) | 2007-11-14 | 2014-08-12 | Laboratorios Farmacéuticos Rovi, S.A. | Pharmaceutical forms for the release of active compounds |
| EP2213282A1 (en) | 2009-01-30 | 2010-08-04 | Laboratorios Farmaceuticos Rovi, S.A. | Pharmaceutical forms for the release of active compounds |
| CN104230745B (zh) * | 2014-07-10 | 2016-06-22 | 南京医科大学 | 一类n-苄基取代的氨基水杨酸与4-氨基丁酸的酰胺衍生物及其药物用途 |
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| US6001347A (en) | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5965121A (en) * | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) * | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| US6358504B1 (en) * | 1997-02-07 | 2002-03-19 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO2000007979A2 (en) * | 1998-08-07 | 2000-02-17 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO2000031536A2 (en) * | 1998-11-23 | 2000-06-02 | President And Fellows Of Harvard College | Detecting structural or synthetic information about chemical compounds |
| SE0102764D0 (sv) * | 2001-08-17 | 2001-08-17 | Astrazeneca Ab | Compounds |
-
2003
- 2003-07-28 ES ES200301781A patent/ES2222822B1/es not_active Expired - Lifetime
-
2004
- 2004-07-23 PL PL04742074T patent/PL1652836T3/pl unknown
- 2004-07-23 RU RU2006101630/04A patent/RU2368599C2/ru not_active IP Right Cessation
- 2004-07-23 US US10/563,994 patent/US7462735B2/en not_active Expired - Fee Related
- 2004-07-23 WO PCT/ES2004/000346 patent/WO2005012230A1/es not_active Ceased
- 2004-07-23 AU AU2004261417A patent/AU2004261417C1/en not_active Ceased
- 2004-07-23 BR BRPI0413032-4A patent/BRPI0413032A/pt not_active IP Right Cessation
- 2004-07-23 CA CA002533639A patent/CA2533639A1/en not_active Abandoned
- 2004-07-23 JP JP2006521597A patent/JP4343227B2/ja not_active Expired - Fee Related
- 2004-07-23 DE DE602004007665T patent/DE602004007665T2/de not_active Expired - Lifetime
- 2004-07-23 DK DK04742074T patent/DK1652836T3/da active
- 2004-07-23 KR KR1020067001803A patent/KR100970216B1/ko not_active Expired - Fee Related
- 2004-07-23 CN CNB2004800220400A patent/CN100475776C/zh not_active Expired - Fee Related
- 2004-07-23 PT PT04742074T patent/PT1652836E/pt unknown
- 2004-07-23 EP EP04742074A patent/EP1652836B1/en not_active Expired - Lifetime
- 2004-07-23 ES ES04742074T patent/ES2289534T3/es not_active Expired - Lifetime
- 2004-07-23 ZA ZA200600165A patent/ZA200600165B/xx unknown
- 2004-07-23 AT AT04742074T patent/ATE367373T1/de active
Also Published As
| Publication number | Publication date |
|---|---|
| KR100970216B1 (ko) | 2010-07-16 |
| AU2004261417B2 (en) | 2010-07-01 |
| ATE367373T1 (de) | 2007-08-15 |
| ES2222822A1 (es) | 2005-02-01 |
| CN100475776C (zh) | 2009-04-08 |
| DE602004007665D1 (de) | 2007-08-30 |
| EP1652836B1 (en) | 2007-07-18 |
| RU2368599C2 (ru) | 2009-09-27 |
| US7462735B2 (en) | 2008-12-09 |
| AU2004261417A1 (en) | 2005-02-10 |
| PT1652836E (pt) | 2007-10-23 |
| ZA200600165B (en) | 2007-03-28 |
| DE602004007665T2 (de) | 2008-05-15 |
| AU2004261417C1 (en) | 2011-02-24 |
| KR20060079184A (ko) | 2006-07-05 |
| ES2289534T3 (es) | 2008-02-01 |
| RU2006101630A (ru) | 2007-09-10 |
| ES2222822B1 (es) | 2005-12-16 |
| US20070191302A1 (en) | 2007-08-16 |
| PL1652836T3 (pl) | 2007-12-31 |
| DK1652836T3 (da) | 2007-11-05 |
| JP2007533600A (ja) | 2007-11-22 |
| CN1829682A (zh) | 2006-09-06 |
| EP1652836A1 (en) | 2006-05-03 |
| BRPI0413032A (pt) | 2006-10-03 |
| JP4343227B2 (ja) | 2009-10-14 |
| WO2005012230A1 (es) | 2005-02-10 |
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| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |
Effective date: 20130108 |