JP2013517322A - サリチレート脂肪酸誘導体 - Google Patents
サリチレート脂肪酸誘導体 Download PDFInfo
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- JP2013517322A JP2013517322A JP2012549443A JP2012549443A JP2013517322A JP 2013517322 A JP2013517322 A JP 2013517322A JP 2012549443 A JP2012549443 A JP 2012549443A JP 2012549443 A JP2012549443 A JP 2012549443A JP 2013517322 A JP2013517322 A JP 2013517322A
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- ethyl
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- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 title claims description 7
- 229960001860 salicylate Drugs 0.000 title description 6
- 229940053200 antiepileptics fatty acid derivative Drugs 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 429
- 238000000034 method Methods 0.000 claims abstract description 95
- 239000000203 mixture Substances 0.000 claims abstract description 79
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims abstract description 56
- 238000011282 treatment Methods 0.000 claims abstract description 39
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 30
- 230000004054 inflammatory process Effects 0.000 claims abstract description 30
- 206010061218 Inflammation Diseases 0.000 claims abstract description 28
- 235000012000 cholesterol Nutrition 0.000 claims abstract description 28
- 230000002265 prevention Effects 0.000 claims abstract description 27
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 27
- 208000032928 Dyslipidaemia Diseases 0.000 claims abstract description 19
- 208000017170 Lipid metabolism disease Diseases 0.000 claims abstract description 19
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 17
- 206010022489 Insulin Resistance Diseases 0.000 claims abstract description 15
- 208000001145 Metabolic Syndrome Diseases 0.000 claims abstract description 10
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 10
- 230000002093 peripheral effect Effects 0.000 claims abstract description 10
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 9
- 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 134
- -1 2-ethyl-2-((5Z, 8Z, 11Z, 14Z, 17Z) -icosa-5,8,11,14,17-pentaen-1-ylthio) butanamido Chemical group 0.000 claims description 130
- 125000003342 alkenyl group Chemical group 0.000 claims description 113
- 125000000217 alkyl group Chemical group 0.000 claims description 90
- 125000000304 alkynyl group Chemical group 0.000 claims description 84
- 229910052739 hydrogen Inorganic materials 0.000 claims description 75
- 239000005711 Benzoic acid Substances 0.000 claims description 63
- 235000010233 benzoic acid Nutrition 0.000 claims description 63
- 229910052799 carbon Inorganic materials 0.000 claims description 60
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 58
- 125000003277 amino group Chemical group 0.000 claims description 53
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 52
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 48
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 229910052760 oxygen Inorganic materials 0.000 claims description 46
- 229910052717 sulfur Inorganic materials 0.000 claims description 45
- 125000002252 acyl group Chemical group 0.000 claims description 44
- 150000003839 salts Chemical class 0.000 claims description 44
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 43
- 125000003282 alkyl amino group Chemical group 0.000 claims description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000004423 acyloxy group Chemical group 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 41
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 41
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 41
- 125000004414 alkyl thio group Chemical group 0.000 claims description 41
- 125000005843 halogen group Chemical group 0.000 claims description 41
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims description 40
- 239000000651 prodrug Substances 0.000 claims description 36
- 229940002612 prodrug Drugs 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 33
- 239000012453 solvate Substances 0.000 claims description 33
- 229960004889 salicylic acid Drugs 0.000 claims description 32
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 31
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 27
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 19
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
- 150000001413 amino acids Chemical group 0.000 claims description 16
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 16
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 229910052801 chlorine Inorganic materials 0.000 claims description 11
- 229910052731 fluorine Inorganic materials 0.000 claims description 11
- 125000003386 piperidinyl group Chemical group 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 238000008214 LDL Cholesterol Methods 0.000 claims description 6
- 108010069201 VLDL Cholesterol Proteins 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 235000020660 omega-3 fatty acid Nutrition 0.000 claims description 6
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 5
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 229960000581 salicylamide Drugs 0.000 claims description 4
- QLGLBUMDIRFCLE-AAQCHOMXSA-N 2-[(2-hydroxybenzoyl)amino]ethyl 2-[(5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenoxy]butanoate Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCOC(CC)C(=O)OCCNC(=O)C1=CC=CC=C1O QLGLBUMDIRFCLE-AAQCHOMXSA-N 0.000 claims description 3
- SMMLHZQODOYOJJ-AAQCHOMXSA-N 2-[2-[(5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenoxy]butanoylamino]ethyl 2-hydroxybenzoate Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCOC(CC)C(=O)NCCOC(=O)C1=CC=CC=C1O SMMLHZQODOYOJJ-AAQCHOMXSA-N 0.000 claims description 3
- AWZXNEUJVXHPQZ-AAQCHOMXSA-N 2-[2-[(5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenoxy]butanoyloxy]benzoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCOC(CC)C(=O)OC1=CC=CC=C1C(O)=O AWZXNEUJVXHPQZ-AAQCHOMXSA-N 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- YNFAGIJVXPHDIC-YNUSHXQLSA-N 2-[2-[(4z,7z,10z,13z,16z,19z)-docosa-4,7,10,13,16,19-hexaenoxy]butanoyloxy]benzoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCOC(CC)C(=O)OC1=CC=CC=C1C(O)=O YNFAGIJVXPHDIC-YNUSHXQLSA-N 0.000 claims description 2
- AZIJCDVFPMIUDL-NEUKSRIFSA-N 2-[2-ethyl-2-[(5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenyl]sulfanylbutanoyl]oxybenzoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCSC(CC)(CC)C(=O)OC1=CC=CC=C1C(O)=O AZIJCDVFPMIUDL-NEUKSRIFSA-N 0.000 claims description 2
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 11
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 11
- 125000003368 amide group Chemical group 0.000 claims 4
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims 2
- ACMPWZQOUILVFB-UHFFFAOYSA-N 4-methylpentanamide Chemical compound CC(C)CCC(N)=O ACMPWZQOUILVFB-UHFFFAOYSA-N 0.000 claims 1
- USNVSQSHSQWBMS-NEUKSRIFSA-N 5-[[2-ethyl-2-[(5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenyl]sulfanylbutanoyl]amino]-2-hydroxybenzoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCSC(CC)(CC)C(=O)NC1=CC=C(O)C(C(O)=O)=C1 USNVSQSHSQWBMS-NEUKSRIFSA-N 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 abstract description 14
- 150000003873 salicylate salts Chemical class 0.000 abstract description 14
- 108010010234 HDL Lipoproteins Proteins 0.000 abstract description 11
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 9
- 229930195729 fatty acid Natural products 0.000 abstract description 9
- 239000000194 fatty acid Substances 0.000 abstract description 9
- 150000004665 fatty acids Chemical class 0.000 abstract description 9
- 210000004369 blood Anatomy 0.000 abstract description 7
- 239000008280 blood Substances 0.000 abstract description 7
- 150000002632 lipids Chemical class 0.000 abstract description 7
- 150000003626 triacylglycerols Chemical class 0.000 abstract description 6
- 108010023302 HDL Cholesterol Proteins 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
- 125000006239 protecting group Chemical group 0.000 description 87
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 68
- 239000011734 sodium Substances 0.000 description 55
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 48
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 44
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 0 CCC(C)C(*)*(*)C(C)(C)C(N)S(C)(C)C(*1)OC1*(C)C=C Chemical compound CCC(C)C(*)*(*)C(C)(C)C(N)S(C)(C)C(*1)OC1*(C)C=C 0.000 description 40
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 238000000132 electrospray ionisation Methods 0.000 description 34
- 235000019439 ethyl acetate Nutrition 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 32
- 239000003480 eluent Substances 0.000 description 29
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 26
- 239000002904 solvent Substances 0.000 description 26
- 238000003818 flash chromatography Methods 0.000 description 25
- 239000012074 organic phase Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 22
- 235000019253 formic acid Nutrition 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- 238000003776 cleavage reaction Methods 0.000 description 18
- 230000007017 scission Effects 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 238000004519 manufacturing process Methods 0.000 description 17
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000002360 preparation method Methods 0.000 description 16
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 15
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 14
- 201000010099 disease Diseases 0.000 description 14
- 229960000953 salsalate Drugs 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 12
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 11
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- 230000000694 effects Effects 0.000 description 11
- 230000002757 inflammatory effect Effects 0.000 description 11
- 150000001412 amines Chemical class 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 9
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 8
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 230000003110 anti-inflammatory effect Effects 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 7
- 239000012317 TBTU Substances 0.000 description 7
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 7
- 229960001138 acetylsalicylic acid Drugs 0.000 description 7
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 7
- 239000003054 catalyst Substances 0.000 description 7
- 229910052727 yttrium Inorganic materials 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
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 238000001727 in vivo Methods 0.000 description 6
- 235000020824 obesity Nutrition 0.000 description 6
- 239000012071 phase Substances 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
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- 150000008044 alkali metal hydroxides Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
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- MXUHMQZOATZRIK-UHFFFAOYSA-N methyl 5-amino-2-hydroxybenzoate Chemical compound COC(=O)C1=CC(N)=CC=C1O MXUHMQZOATZRIK-UHFFFAOYSA-N 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
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- 238000002953 preparative HPLC Methods 0.000 description 5
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- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- VOGXDRFFBBLZBT-AAQCHOMXSA-N 2-[(5z,8z,11z,14z,17z)-icosa-5,8,11,14,17-pentaenoxy]butanoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCCOC(CC)C(O)=O VOGXDRFFBBLZBT-AAQCHOMXSA-N 0.000 description 4
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 4
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- 208000032843 Hemorrhage Diseases 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
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- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
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- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
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- C07C235/16—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
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- 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
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- C07C271/20—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by nitrogen atoms not being part of nitro or nitroso groups
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- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
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- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
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| US29671710P | 2010-01-20 | 2010-01-20 | |
| US61/296,717 | 2010-01-20 | ||
| PCT/IB2011/000250 WO2011089529A1 (en) | 2010-01-20 | 2011-01-20 | Salicylate fatty acid derivatives |
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| WO2009061208A1 (en) | 2007-11-09 | 2009-05-14 | Pronova Biopharma Norge As | Lipid compounds for use in cosmetic products, as food supplement or as a medicament |
| KR101708065B1 (ko) | 2008-07-08 | 2017-02-17 | 카타베이시스 파마슈티칼즈, 인코포레이티드 | 지방산 아세틸화 살리실레이트 및 그 용도 |
| US9085527B2 (en) | 2008-07-08 | 2015-07-21 | Catabasis Pharmaceuticals, Inc. | Fatty acid acylated salicylates and their uses |
| EP2147910A1 (en) * | 2008-07-15 | 2010-01-27 | Pronova BioPharma Norge AS | Novel lipid compounds |
| NZ596386A (en) | 2009-05-08 | 2014-01-31 | Pronova Biopharma Norge As | Polyunsaturated fatty acids for the treatment of diseases related to cardiovascular, metabolic and inflammatory disease areas |
| UA111475C2 (uk) * | 2010-11-05 | 2016-05-10 | Пронова Байофарма Нордж Ас | Способи лікування із застосуванням ліпідних сполук |
| WO2014132134A1 (en) * | 2013-02-28 | 2014-09-04 | Pronova Biopharma Norge As | A composition comprising a lipid compound, a triglyceride, and a surfactant, and methods of using the same |
| EP2889286B1 (en) * | 2013-12-30 | 2016-05-18 | Pax Forschung GmbH | Pharmaceutically active compound for use as anti-inflammatory agent |
| KR20240033300A (ko) | 2015-04-28 | 2024-03-12 | 바스프 에이에스 | 비알코올성 지방간염의 예방 및/또는 치료를 위한 구조적으로 강화된 함황 지방산의 용도 |
| EP3720431B1 (en) | 2017-12-06 | 2024-10-30 | Basf As | Fatty acid derivatives for treating non-alcoholic steatohepatitis |
| KR20210015883A (ko) | 2018-05-23 | 2021-02-10 | 노스씨 테라퓨틱스 비.브이. | 당뇨 제어 및 염증성장질환 치료의 향상을 위한 구조적으로 변형된 지방산 |
| AU2021405273A1 (en) | 2020-12-22 | 2023-08-10 | Northsea Therapeutics B.V. | Combination therapies comprising oxygen-containing structurally enhanced fatty acids for treatment of non-alcoholic steatohepatitis |
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| US4036951A (en) * | 1973-03-12 | 1977-07-19 | Synergistics, Inc. | Ultra-violet filtration with certain aminosalicylic acid esters |
| US4264517A (en) * | 1978-12-11 | 1981-04-28 | G.D. Searle & Co. | Alkylphenyl 5Z,8Z,11Z,14Z,17Z-eicosapentaenoates |
| GB9403857D0 (en) * | 1994-03-01 | 1994-04-20 | Scotia Holdings Plc | Fatty acid derivatives |
| ES2400375T3 (es) * | 2006-04-07 | 2013-04-09 | Novartis Ag | Combinación que comprende A) un compuesto de pirimidilaminobenzamida y B)un inhibidor de cinasa THR315LLE |
| ES2391305T3 (es) * | 2006-04-12 | 2012-11-23 | Unilever N.V. | Composición oral que comprende un ácido graso poliinsaturado y ácido salicílico para obtener un efecto antiinflamatorio en la piel |
| KR101708065B1 (ko) * | 2008-07-08 | 2017-02-17 | 카타베이시스 파마슈티칼즈, 인코포레이티드 | 지방산 아세틸화 살리실레이트 및 그 용도 |
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| WO2011089529A4 (en) | 2011-10-27 |
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