DE69203797T2 - Amidino-Verbindungen, ihre Herstellung und Verwendung als Arzneimittel. - Google Patents
Amidino-Verbindungen, ihre Herstellung und Verwendung als Arzneimittel.Info
- Publication number
- DE69203797T2 DE69203797T2 DE69203797T DE69203797T DE69203797T2 DE 69203797 T2 DE69203797 T2 DE 69203797T2 DE 69203797 T DE69203797 T DE 69203797T DE 69203797 T DE69203797 T DE 69203797T DE 69203797 T2 DE69203797 T2 DE 69203797T2
- Authority
- DE
- Germany
- Prior art keywords
- phenyl
- formula
- pentoxy
- phenoxy
- substituted
- 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 - Fee Related
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 239000003814 drug Substances 0.000 title description 6
- 229940079593 drug Drugs 0.000 title description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 title description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 140
- 150000001875 compounds Chemical class 0.000 claims abstract description 114
- -1 aliphatic hydrocarbon radical Chemical class 0.000 claims abstract description 104
- 150000003839 salts Chemical class 0.000 claims abstract description 71
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 39
- 150000002367 halogens Chemical group 0.000 claims abstract description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 35
- 239000001257 hydrogen Substances 0.000 claims abstract description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 34
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 29
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 28
- 125000001424 substituent group Chemical group 0.000 claims abstract description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 25
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 17
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 12
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims abstract description 10
- 239000004215 Carbon black (E152) Substances 0.000 claims abstract description 10
- 241000124008 Mammalia Species 0.000 claims abstract description 10
- 229930195733 hydrocarbon Natural products 0.000 claims abstract description 10
- 102000003680 Leukotriene B4 receptors Human genes 0.000 claims abstract description 7
- 108090000093 Leukotriene B4 receptors Proteins 0.000 claims abstract description 7
- 125000003118 aryl group Chemical group 0.000 claims abstract description 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims abstract description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims abstract description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims abstract description 4
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims abstract description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000001301 oxygen Substances 0.000 claims abstract description 3
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 49
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 49
- 238000000034 method Methods 0.000 claims description 39
- 230000008569 process Effects 0.000 claims description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 24
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 24
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 16
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 14
- 239000000203 mixture Substances 0.000 claims description 13
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 12
- 238000002360 preparation method Methods 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 8
- FXHCGMCQIDSTAB-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 FXHCGMCQIDSTAB-UHFFFAOYSA-N 0.000 claims description 7
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 7
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- 239000005557 antagonist Substances 0.000 claims description 5
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 230000003042 antagnostic effect Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 3
- 210000000224 granular leucocyte Anatomy 0.000 claims description 3
- BJYQVASSUAUACF-UHFFFAOYSA-N 4-[5-[4-[(benzoylhydrazinylidene)methyl]phenoxy]pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC(C=C1)=CC=C1C=NNC(=O)C1=CC=CC=C1 BJYQVASSUAUACF-UHFFFAOYSA-N 0.000 claims description 2
- MMBKRKJUARVURA-UHFFFAOYSA-N benzyl (nz)-n-[amino-[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylidene]carbamate Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(N)=NC(=O)OCC=2C=CC=CC=2)C=C1 MMBKRKJUARVURA-UHFFFAOYSA-N 0.000 claims description 2
- 238000012545 processing Methods 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- 239000012050 conventional carrier Substances 0.000 claims 2
- INSYGKFVWGVYRJ-UHFFFAOYSA-N 2-hydroxy-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound C1=C(O)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 INSYGKFVWGVYRJ-UHFFFAOYSA-N 0.000 claims 1
- KMZAGMHCSMQTCA-UHFFFAOYSA-N 3-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound CC(C)N(C(C)C)C(=O)C1=CC=CC(OCCCCCOC=2C=CC(C=NN)=CC=2)=C1 KMZAGMHCSMQTCA-UHFFFAOYSA-N 0.000 claims 1
- KJTXVIVHUMYCJV-UHFFFAOYSA-N n,n-diethyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)N(CC)CC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 KJTXVIVHUMYCJV-UHFFFAOYSA-N 0.000 claims 1
- ZMBFMFFWJLIGBJ-UHFFFAOYSA-N n-benzyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n-propan-2-ylbenzamide Chemical compound COC1=CC(C(=O)N(CC=2C=CC=CC=2)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 ZMBFMFFWJLIGBJ-UHFFFAOYSA-N 0.000 claims 1
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 230000008485 antagonism Effects 0.000 abstract description 5
- 208000011580 syndromic disease Diseases 0.000 abstract description 4
- 239000002464 receptor antagonist Substances 0.000 abstract description 3
- 229940044551 receptor antagonist Drugs 0.000 abstract description 3
- 239000005864 Sulphur Substances 0.000 abstract 1
- 229910052757 nitrogen Inorganic materials 0.000 description 111
- 229910052799 carbon Inorganic materials 0.000 description 109
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 60
- 239000006260 foam Substances 0.000 description 53
- 229910001868 water Inorganic materials 0.000 description 50
- 239000000243 solution Substances 0.000 description 41
- 150000002148 esters Chemical class 0.000 description 40
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000002253 acid Substances 0.000 description 27
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
- DXMDFERFEVQYKX-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 DXMDFERFEVQYKX-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 125000000217 alkyl group Chemical group 0.000 description 20
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 12
- 125000004423 acyloxy group Chemical group 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 125000003342 alkenyl group Chemical group 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 10
- 150000007513 acids Chemical class 0.000 description 10
- 125000000304 alkynyl group Chemical group 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 210000000440 neutrophil Anatomy 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 6
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 6
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 6
- 125000003302 alkenyloxy group Chemical group 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 125000001589 carboacyl group Chemical group 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
- 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 5
- SIIAMRRNVVUWGE-BTJKTKAUSA-N OC(=O)\C=C/C(O)=O.COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 Chemical compound OC(=O)\C=C/C(O)=O.COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 SIIAMRRNVVUWGE-BTJKTKAUSA-N 0.000 description 5
- 241000700159 Rattus Species 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 230000002776 aggregation Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 239000006285 cell suspension Substances 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 235000019698 starch Nutrition 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- PQYRJJWHSHDOAN-UHFFFAOYSA-N 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxybenzoic acid Chemical compound COC1=CC(C(O)=O)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 PQYRJJWHSHDOAN-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 4
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Natural products OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N Lactic Acid Natural products CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 201000004681 Psoriasis Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 150000008064 anhydrides Chemical class 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000011777 magnesium Substances 0.000 description 4
- 229910052749 magnesium Inorganic materials 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- 229940098779 methanesulfonic acid Drugs 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 125000003396 thiol group Chemical class [H]S* 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 3
- DEERVLFWMLSUSM-UHFFFAOYSA-N 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 DEERVLFWMLSUSM-UHFFFAOYSA-N 0.000 description 3
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 125000002252 acyl group Chemical group 0.000 description 3
- 235000001014 amino acid Nutrition 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
- 208000006673 asthma Diseases 0.000 description 3
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 150000001991 dicarboxylic acids Chemical class 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 238000001631 haemodialysis Methods 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000000322 hemodialysis Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 208000010125 myocardial infarction Diseases 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 239000012044 organic layer Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 150000003460 sulfonic acids Chemical class 0.000 description 3
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 2
- CBLWYOIYUDKFGQ-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 CBLWYOIYUDKFGQ-UHFFFAOYSA-N 0.000 description 2
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 2
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical class [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-UHFFFAOYSA-N Aspartic acid Chemical compound OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VNYSSYRCGWBHLG-GEWAPNICSA-N Delta(6)-trans,Delta(8)-cis-leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C/C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-GEWAPNICSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Natural products OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000012895 Gastric disease Diseases 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 235000003704 aspartic acid Nutrition 0.000 description 2
- 235000010233 benzoic acid Nutrition 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
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 2
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000001640 fractional crystallisation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- PGVJGICDFNEAQY-UHFFFAOYSA-N methyl 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 PGVJGICDFNEAQY-UHFFFAOYSA-N 0.000 description 2
- BVWTXUYLKBHMOX-UHFFFAOYSA-N methyl vanillate Chemical compound COC(=O)C1=CC=C(O)C(OC)=C1 BVWTXUYLKBHMOX-UHFFFAOYSA-N 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 208000004235 neutropenia Diseases 0.000 description 2
- VFXVAXFIFHSGNR-UHFFFAOYSA-N octyl carbonochloridate Chemical compound CCCCCCCCOC(Cl)=O VFXVAXFIFHSGNR-UHFFFAOYSA-N 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 208000018556 stomach disease Diseases 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- PAYRXVIOXVUCPY-UHFFFAOYSA-N (5-methyl-2-propan-2-ylcyclohexyl) (ne)-n-[amino-[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylidene]carbamate Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(N)=NC(=O)OC2C(CCC(C)C2)C(C)C)C=C1 PAYRXVIOXVUCPY-UHFFFAOYSA-N 0.000 description 1
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 1
- WOGITNXCNOTRLK-VOTSOKGWSA-N (e)-3-phenylprop-2-enoyl chloride Chemical compound ClC(=O)\C=C\C1=CC=CC=C1 WOGITNXCNOTRLK-VOTSOKGWSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical group CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- BDKNZFMGRUHBGI-UHFFFAOYSA-N 1-[4-[5-(4-methanehydrazonoylphenoxy)pentoxy]benzoyl]-2,2,6,6-tetramethylcyclohex-3-ene-1-carboxamide hydrochloride Chemical compound Cl.NN=CC1=CC=C(OCCCCCOC2=CC=C(C(=O)C3(C(=O)N)C(CC=CC3(C)C)(C)C)C=C2)C=C1 BDKNZFMGRUHBGI-UHFFFAOYSA-N 0.000 description 1
- PHHNNDKXQVKJEP-UHFFFAOYSA-N 1-bromo-5-chloropentane Chemical compound ClCCCCCBr PHHNNDKXQVKJEP-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000001088 1-naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 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
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical class C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical group CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- 125000005976 1-phenylethyloxy group Chemical group 0.000 description 1
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 1
- ZAMGFVXCWFZNGX-UHFFFAOYSA-N 2,6-dichloro-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(Cl)C(C(=O)N(C(C)C)C(C)C)=C(Cl)C=C1OCCCCCOC1=CC=C(C=NN)C=C1 ZAMGFVXCWFZNGX-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- NAOFLPZJKYLHFP-UHFFFAOYSA-N 2-bromo-5-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(Br)C(C(=O)N(C(C)C)C(C)C)=CC(OCCCCCOC=2C=CC(C=NN)=CC=2)=C1 NAOFLPZJKYLHFP-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 1
- BAGMYWSPQCENNO-UHFFFAOYSA-N 2-chloro-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(Cl)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 BAGMYWSPQCENNO-UHFFFAOYSA-N 0.000 description 1
- XYLBKPCFAWUPRC-UHFFFAOYSA-N 2-hydroxy-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(O)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 XYLBKPCFAWUPRC-UHFFFAOYSA-N 0.000 description 1
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000005975 2-phenylethyloxy group Chemical group 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- MPSXGPCFLAGJOM-UHFFFAOYSA-M 2-tert-butyl-5-methyl-1,2-oxazol-2-ium;perchlorate Chemical compound [O-]Cl(=O)(=O)=O.CC1=CC=[N+](C(C)(C)C)O1 MPSXGPCFLAGJOM-UHFFFAOYSA-M 0.000 description 1
- VIOBGCWEHLRBEP-UHFFFAOYSA-N 3,4-dimethoxybenzoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1OC VIOBGCWEHLRBEP-UHFFFAOYSA-N 0.000 description 1
- RHZCUYXJISLAEB-UHFFFAOYSA-N 3,5-dichloro-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.ClC1=CC(C(=O)N(C(C)C)C(C)C)=CC(Cl)=C1OCCCCCOC1=CC=C(C=NN)C=C1 RHZCUYXJISLAEB-UHFFFAOYSA-N 0.000 description 1
- AGWNCXHSQGBTGE-UHFFFAOYSA-N 3-[5-(3-chloro-4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.CC(C)N(C(C)C)C(=O)C1=CC=CC(OCCCCCOC=2C=C(Cl)C(C=NN)=CC=2)=C1 AGWNCXHSQGBTGE-UHFFFAOYSA-N 0.000 description 1
- KWXBKQWTUNGTGT-UHFFFAOYSA-N 3-[5-(4-methanehydrazonoylphenoxy)pentoxy]-4-methoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.COC1=CC=C(C(=O)N(C(C)C)C(C)C)C=C1OCCCCCOC1=CC=C(C=NN)C=C1 KWXBKQWTUNGTGT-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- XDBPHQIILUXMKL-UHFFFAOYSA-N 3-bromo-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.BrC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 XDBPHQIILUXMKL-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- OJAKPVKFENQAON-UHFFFAOYSA-N 3-chloro-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.ClC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 OJAKPVKFENQAON-UHFFFAOYSA-N 0.000 description 1
- LDHFVXSKBVCNMF-UHFFFAOYSA-N 3-methoxy-4-[5-[4-[(z)-n'-(methylcarbamoyl)carbamimidoyl]phenoxy]pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(N)=NC(=O)NC)=CC=C1OCCCCCOC1=CC=C(C(=O)N(C(C)C)C(C)C)C=C1OC LDHFVXSKBVCNMF-UHFFFAOYSA-N 0.000 description 1
- YCYMIEQWFCFYPA-UHFFFAOYSA-N 3-methoxy-4-[5-[4-[(z)-n'-(phenylcarbamoyl)carbamimidoyl]phenoxy]pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(\N)=N\C(=O)NC=2C=CC=CC=2)C=C1 YCYMIEQWFCFYPA-UHFFFAOYSA-N 0.000 description 1
- GXTYJRQCBCWSQM-UHFFFAOYSA-N 3-methoxy-4-[5-[4-[(z)-n'-methylsulfonylcarbamimidoyl]phenoxy]pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(N)=NS(C)(=O)=O)C=C1 GXTYJRQCBCWSQM-UHFFFAOYSA-N 0.000 description 1
- JDBYNYVALIQPIG-UHFFFAOYSA-N 3-methoxy-4-[5-[4-[n'-(3-phenylprop-2-enoyl)carbamimidoyl]phenoxy]pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(N)=NC(=O)C=CC=2C=CC=CC=2)C=C1 JDBYNYVALIQPIG-UHFFFAOYSA-N 0.000 description 1
- QGXQKGLWWDUOEY-UHFFFAOYSA-N 3-n-hydroxybicyclo[2.2.1]hept-5-ene-2,3-dicarboxamide Chemical compound C1C2C=CC1C(C(=O)N)C2C(=O)NO QGXQKGLWWDUOEY-UHFFFAOYSA-N 0.000 description 1
- 125000005977 3-phenylpropyloxy group Chemical group 0.000 description 1
- DHJNXHWSAZEOPI-UHFFFAOYSA-N 4-[5-(4-cyanophenoxy)pentoxy]-3-methoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 DHJNXHWSAZEOPI-UHFFFAOYSA-N 0.000 description 1
- OHYHZURDXYZHJH-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoyl-3-methoxyphenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound C1=C(C=NN)C(OC)=CC(OCCCCCOC=2C=CC(=CC=2)C(=O)N(C(C)C)C(C)C)=C1 OHYHZURDXYZHJH-UHFFFAOYSA-N 0.000 description 1
- IDJIOXRLIMEBSM-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2,3-dimethoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)N(C(C)C)C(C)C)=C(OC)C(OC)=C1OCCCCCOC1=CC=C(C=NN)C=C1 IDJIOXRLIMEBSM-UHFFFAOYSA-N 0.000 description 1
- LHFUQIRNVAAJJV-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2,6-dimethoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.COC1=C(C(=O)N(C(C)C)C(C)C)C(OC)=CC(OCCCCCOC=2C=CC(C=NN)=CC=2)=C1 LHFUQIRNVAAJJV-UHFFFAOYSA-N 0.000 description 1
- WUAULEPVYNNYEA-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2,6-dimethyl-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(C)C(C(=O)N(C(C)C)C(C)C)=C(C)C=C1OCCCCCOC1=CC=C(C=NN)C=C1 WUAULEPVYNNYEA-UHFFFAOYSA-N 0.000 description 1
- JTQIPSWKSBQPHM-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2-methoxy-6-methyl-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.CC1=C(C(=O)N(C(C)C)C(C)C)C(OC)=CC(OCCCCCOC=2C=CC(C=NN)=CC=2)=C1 JTQIPSWKSBQPHM-UHFFFAOYSA-N 0.000 description 1
- GLKYCSXXUNQJAL-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2-methoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(C(=O)N(C(C)C)C(C)C)C(OC)=CC(OCCCCCOC=2C=CC(C=NN)=CC=2)=C1 GLKYCSXXUNQJAL-UHFFFAOYSA-N 0.000 description 1
- YWRUGWFPGYUERR-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2-methyl-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(C)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 YWRUGWFPGYUERR-UHFFFAOYSA-N 0.000 description 1
- KXRVORSPXRTMKV-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3,5-dimethoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(C(C)C)C(C)C)=CC(OC)=C1OCCCCCOC1=CC=C(C=NN)C=C1 KXRVORSPXRTMKV-UHFFFAOYSA-N 0.000 description 1
- VSMKQEYIGSJFPK-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-N,N-di(propan-2-yl)benzamide methanesulfonic acid Chemical compound CS(=O)(=O)O.NN=CC1=CC=C(OCCCCCOC2=C(C=C(C(=O)N(C(C)C)C(C)C)C=C2)OC)C=C1 VSMKQEYIGSJFPK-UHFFFAOYSA-N 0.000 description 1
- PRUHDCBNSSANTN-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n,n-dimethylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 PRUHDCBNSSANTN-UHFFFAOYSA-N 0.000 description 1
- JVXDNHAWFSSBMX-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n,n-dipropylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(CCC)CCC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 JVXDNHAWFSSBMX-UHFFFAOYSA-N 0.000 description 1
- NODLMPWCNZSARU-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n-methylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)NC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 NODLMPWCNZSARU-UHFFFAOYSA-N 0.000 description 1
- OGCUOYFFMOIHLK-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n-propylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)NCCC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 OGCUOYFFMOIHLK-UHFFFAOYSA-N 0.000 description 1
- SBXGUVSPOHLYHS-UHFFFAOYSA-N 4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n-methyl-n-phenylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1N(C)C(=O)C(C=C1)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 SBXGUVSPOHLYHS-UHFFFAOYSA-N 0.000 description 1
- ODZHGQNQNXHFEA-UHFFFAOYSA-N 4-[5-[4-[(acetylhydrazinylidene)methyl]phenoxy]pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NNC(C)=O)C=C1 ODZHGQNQNXHFEA-UHFFFAOYSA-N 0.000 description 1
- WDXISWDCMIOSEV-UHFFFAOYSA-N 4-[5-[4-[(butanoylhydrazinylidene)methyl]phenoxy]pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C=NNC(=O)CCC)=CC=C1OCCCCCOC1=CC=C(C(=O)N(C(C)C)C(C)C)C=C1OC WDXISWDCMIOSEV-UHFFFAOYSA-N 0.000 description 1
- JQZPLNWGBMDTJX-UHFFFAOYSA-N 4-[5-[4-[(z)-n'-(benzenesulfonyl)carbamimidoyl]phenoxy]pentoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(N)=NS(=O)(=O)C=2C=CC=CC=2)C=C1 JQZPLNWGBMDTJX-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- UGPRLYCCVCFYGT-UHFFFAOYSA-N 4-hydroxy-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1O UGPRLYCCVCFYGT-UHFFFAOYSA-N 0.000 description 1
- QSCDILGDQJGUKM-UHFFFAOYSA-N 5-[5-(4-methanehydrazonoylphenoxy)pentoxy]-2-methoxy-n,n-di(propan-2-yl)benzamide;hydrochloride Chemical compound Cl.C1=C(C(=O)N(C(C)C)C(C)C)C(OC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 QSCDILGDQJGUKM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- FPHYJTLSONGOJL-UHFFFAOYSA-N CS(=O)(=O)O.NN=CC1=CC=C(OCCCCCOC2=CC=C(C(=O)N(C3=CC=CC=C3)C(C)C)C=C2)C=C1 Chemical compound CS(=O)(=O)O.NN=CC1=CC=C(OCCCCCOC2=CC=C(C(=O)N(C3=CC=CC=C3)C(C)C)C=C2)C=C1 FPHYJTLSONGOJL-UHFFFAOYSA-N 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-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
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 229920001612 Hydroxyethyl starch Polymers 0.000 description 1
- 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 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 240000001307 Myosotis scorpioides Species 0.000 description 1
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
- NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
- CRUCURXKOQBKOU-UHFFFAOYSA-N OCCS(=O)(=O)O.NN=CC1=CC=C(OCCCCCOC2=C(C=C(C(=O)N(C(C)C)C(C)C)C=C2)OC)C=C1 Chemical compound OCCS(=O)(=O)O.NN=CC1=CC=C(OCCCCCOC2=C(C=C(C(=O)N(C(C)C)C(C)C)C=C2)OC)C=C1 CRUCURXKOQBKOU-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- XTTZLYIHQBFNKK-UHFFFAOYSA-N [4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxyphenyl]-(2-methylpiperidin-1-yl)methanone;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N2C(CCCC2)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 XTTZLYIHQBFNKK-UHFFFAOYSA-N 0.000 description 1
- QMMPWAJAKAMRPC-UHFFFAOYSA-N [4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxyphenyl]-piperidin-1-ylmethanone;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N2CCCCC2)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 QMMPWAJAKAMRPC-UHFFFAOYSA-N 0.000 description 1
- JLNNGZPKEKNEAJ-UHFFFAOYSA-N [4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxyphenyl]-pyrrolidin-1-ylmethanone;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N2CCCC2)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 JLNNGZPKEKNEAJ-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 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
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 150000003973 alkyl amines Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- PZZYQPZGQPZBDN-UHFFFAOYSA-N aluminium silicate Chemical compound O=[Al]O[Si](=O)O[Al]=O PZZYQPZGQPZBDN-UHFFFAOYSA-N 0.000 description 1
- 229910000323 aluminium silicate Inorganic materials 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- LLOHIFXFHGMBNO-UHFFFAOYSA-N azane;2-hydroxyethanesulfonic acid Chemical compound [NH4+].OCCS([O-])(=O)=O LLOHIFXFHGMBNO-UHFFFAOYSA-N 0.000 description 1
- 238000010533 azeotropic distillation Methods 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- SNIABFMMCKVXSY-UHFFFAOYSA-N benzoylazanium;chloride Chemical compound Cl.NC(=O)C1=CC=CC=C1 SNIABFMMCKVXSY-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000005170 cycloalkyloxycarbonyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- QUNALZGLMQIJHN-UHFFFAOYSA-N diethylphosphorylcyanamide Chemical compound CCP(=O)(CC)NC#N QUNALZGLMQIJHN-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012997 ficoll-paque Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- IRXSLJNXXZKURP-UHFFFAOYSA-N fluorenylmethyloxycarbonyl chloride Chemical compound C1=CC=C2C(COC(=O)Cl)C3=CC=CC=C3C2=C1 IRXSLJNXXZKURP-UHFFFAOYSA-N 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940064366 hespan Drugs 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- HVYRATYTWBCYAI-UHFFFAOYSA-N methyl (nz)-n-[amino-[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylidene]carbamate Chemical compound C1=CC(C(N)=NC(=O)OC)=CC=C1OCCCCCOC1=CC=C(C(=O)N(C(C)C)C(C)C)C=C1OC HVYRATYTWBCYAI-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- GMKKXPVXUKEOFA-ZEWJHAJUSA-N molport-000-784-311 Chemical compound C1=C(OCC)C(OCCC)=CC=C1C1C(C2=CC=CC=C2N2)=C2[C@@]2(C)C(=O)N(CCCN3CCOCC3)CC(=O)N2C1 GMKKXPVXUKEOFA-ZEWJHAJUSA-N 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- YEQFREPTCWBUEF-UHFFFAOYSA-N n,n-dicyclohexyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(C2CCCCC2)C2CCCCC2)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 YEQFREPTCWBUEF-UHFFFAOYSA-N 0.000 description 1
- RFVFNLHOUFSQRM-UHFFFAOYSA-N n,n-diethyl-1-[4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzoyl]piperidine-3-carboxamide;hydrochloride Chemical compound Cl.C1C(C(=O)N(CC)CC)CCCN1C(=O)C(C=C1OC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 RFVFNLHOUFSQRM-UHFFFAOYSA-N 0.000 description 1
- ACWLQLWTJLDHJT-UHFFFAOYSA-N n,n-diethyl-2-[5-(4-methanehydrazonoylphenoxy)pentoxy]benzamide;hydrochloride Chemical compound Cl.CCN(CC)C(=O)C1=CC=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 ACWLQLWTJLDHJT-UHFFFAOYSA-N 0.000 description 1
- BCZXBYMPQBDHIF-UHFFFAOYSA-N n,n-diethyl-3-[5-(4-methanehydrazonoylphenoxy)pentoxy]benzamide;hydrochloride Chemical compound Cl.CCN(CC)C(=O)C1=CC=CC(OCCCCCOC=2C=CC(C=NN)=CC=2)=C1 BCZXBYMPQBDHIF-UHFFFAOYSA-N 0.000 description 1
- VWPHJOPTCHHUJZ-UHFFFAOYSA-N n,n-diethyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(CC)CC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 VWPHJOPTCHHUJZ-UHFFFAOYSA-N 0.000 description 1
- HTJOOZDQUPIYDJ-UHFFFAOYSA-N n,n-diethyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]benzamide;hydrochloride Chemical compound Cl.C1=CC(C(=O)N(CC)CC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 HTJOOZDQUPIYDJ-UHFFFAOYSA-N 0.000 description 1
- AJUXDFHPVZQOGF-UHFFFAOYSA-N n,n-dimethyl-1-naphthylamine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1 AJUXDFHPVZQOGF-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- CKQPWWKCXBYMJV-UHFFFAOYSA-N n-[[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylideneamino]pyridine-3-carboxamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC(C=C1)=CC=C1C=NNC(=O)C1=CC=CN=C1 CKQPWWKCXBYMJV-UHFFFAOYSA-N 0.000 description 1
- IAGZEVATIHBVGT-UHFFFAOYSA-N n-[[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylideneamino]pyridine-4-carboxamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC(C=C1)=CC=C1C=NNC(=O)C1=CC=NC=C1 IAGZEVATIHBVGT-UHFFFAOYSA-N 0.000 description 1
- BJVWQOUGWMMEGL-UHFFFAOYSA-N n-[amino-[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylidene]-3,4-dimethoxybenzamide Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)N=C(N)C(C=C1)=CC=C1OCCCCCOC1=CC=C(C(=O)N(C(C)C)C(C)C)C=C1OC BJVWQOUGWMMEGL-UHFFFAOYSA-N 0.000 description 1
- CRHUYMHNCGYVBK-UHFFFAOYSA-N n-benzyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n-methylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(C)CC=2C=CC=CC=2)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 CRHUYMHNCGYVBK-UHFFFAOYSA-N 0.000 description 1
- OPEBPZWFGBMGMD-UHFFFAOYSA-N n-benzyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n-propan-2-ylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(CC=2C=CC=CC=2)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 OPEBPZWFGBMGMD-UHFFFAOYSA-N 0.000 description 1
- OTUMXVRAMRKJMH-UHFFFAOYSA-N n-benzyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)NCC=2C=CC=CC=2)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 OTUMXVRAMRKJMH-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- RYMIECCPQGQQCZ-UHFFFAOYSA-N n-cyclohexyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxy-n-propan-2-ylbenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)N(C(C)C)C2CCCCC2)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 RYMIECCPQGQQCZ-UHFFFAOYSA-N 0.000 description 1
- GMAPELJOVDIFSO-UHFFFAOYSA-N n-ethyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)NCC)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 GMAPELJOVDIFSO-UHFFFAOYSA-N 0.000 description 1
- RFLLNPQVVOYRJF-UHFFFAOYSA-N n-ethyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-n-phenylbenzamide;hydrochloride Chemical compound Cl.C=1C=CC=CC=1N(CC)C(=O)C(C=C1)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 RFLLNPQVVOYRJF-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- PIZPQTRIWKLWCG-UHFFFAOYSA-N n-tert-butyl-4-[5-(4-methanehydrazonoylphenoxy)pentoxy]-3-methoxybenzamide;hydrochloride Chemical compound Cl.COC1=CC(C(=O)NC(C)(C)C)=CC=C1OCCCCCOC1=CC=C(C=NN)C=C1 PIZPQTRIWKLWCG-UHFFFAOYSA-N 0.000 description 1
- 210000004493 neutrocyte Anatomy 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000003791 organic solvent mixture Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229910003445 palladium oxide Inorganic materials 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- OGPLXNVXRLUDBY-UHFFFAOYSA-N phenyl n-[2-(dimethylamino)ethyl]-n-methylcarbamate Chemical compound CN(C)CCN(C)C(=O)OC1=CC=CC=C1 OGPLXNVXRLUDBY-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 210000003281 pleural cavity Anatomy 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- IVRIRQXJSNCSPQ-UHFFFAOYSA-N propan-2-yl carbonochloridate Chemical compound CC(C)OC(Cl)=O IVRIRQXJSNCSPQ-UHFFFAOYSA-N 0.000 description 1
- OTSXUVHHRRJVDY-UHFFFAOYSA-N propan-2-yl n-[[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylideneamino]carbamate Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NNC(=O)OC(C)C)C=C1 OTSXUVHHRRJVDY-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-N sodium;5-ethyl-5-pentan-2-yl-1,3-diazinane-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)NC1=O QGMRQYFBGABWDR-UHFFFAOYSA-N 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- GOVKBVAUFSHFHK-UHFFFAOYSA-N tert-butyl n-[[4-[5-[4-[di(propan-2-yl)carbamoyl]-2-methoxyphenoxy]pentoxy]phenyl]methylideneamino]carbamate Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C=NNC(=O)OC(C)(C)C)C=C1 GOVKBVAUFSHFHK-UHFFFAOYSA-N 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000007966 viscous suspension Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/02—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups
- C07C251/04—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/10—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton
- C07C251/16—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of an unsaturated carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/62—Compounds containing any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylcarbamates
- C07C271/64—Y being a hydrogen or a carbon atom, e.g. benzoylcarbamates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
- C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
- C07C257/18—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Cardiology (AREA)
- Pulmonology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Vascular Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Cephalosporin Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Diaphragms For Electromechanical Transducers (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US71410891A | 1991-06-11 | 1991-06-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69203797D1 DE69203797D1 (de) | 1995-09-07 |
| DE69203797T2 true DE69203797T2 (de) | 1996-02-08 |
Family
ID=24868773
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69203797T Expired - Fee Related DE69203797T2 (de) | 1991-06-11 | 1992-06-02 | Amidino-Verbindungen, ihre Herstellung und Verwendung als Arzneimittel. |
Country Status (21)
| Country | Link |
|---|---|
| EP (1) | EP0518819B1 (enExample) |
| JP (1) | JP3370998B2 (enExample) |
| KR (1) | KR100249068B1 (enExample) |
| AT (1) | ATE125791T1 (enExample) |
| AU (1) | AU653603B2 (enExample) |
| CA (1) | CA2070795A1 (enExample) |
| CZ (1) | CZ279630B6 (enExample) |
| DE (1) | DE69203797T2 (enExample) |
| DK (1) | DK0518819T3 (enExample) |
| ES (1) | ES2075672T3 (enExample) |
| FI (1) | FI922643A7 (enExample) |
| GR (1) | GR3017028T3 (enExample) |
| HU (1) | HU220226B (enExample) |
| IE (1) | IE67513B1 (enExample) |
| IL (1) | IL102105A (enExample) |
| MX (1) | MX9202749A (enExample) |
| NO (1) | NO178259C (enExample) |
| NZ (1) | NZ243079A (enExample) |
| PH (1) | PH30829A (enExample) |
| TW (1) | TW201298B (enExample) |
| ZA (1) | ZA924220B (enExample) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5488160A (en) * | 1991-06-11 | 1996-01-30 | Ciba-Geigy Corporation | Amidino compounds, their manufacture and method of treatment |
| US5451700A (en) * | 1991-06-11 | 1995-09-19 | Ciba-Geigy Corporation | Amidino compounds, their manufacture and methods of treatment |
| PL173781B1 (pl) * | 1992-02-05 | 1998-04-30 | Boehringer Ingelheim Kg | Sposób wytwarzania nowych pochodnych amidyny |
| DE4219158A1 (de) * | 1992-06-11 | 1993-12-16 | Thomae Gmbh Dr K | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| US5432178A (en) * | 1992-09-18 | 1995-07-11 | Ono Pharmaceutical Co., Ltd. | Amidinophenol derivatives |
| DE4234295A1 (de) * | 1992-10-12 | 1994-04-14 | Thomae Gmbh Dr K | Carbonsäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| DE4309285A1 (de) * | 1993-03-23 | 1994-09-29 | Boehringer Ingelheim Kg | Heterocyclen enthaltende Amidinderivate, ihre Herstellung und Verwendung |
| ATE222100T1 (de) * | 1993-10-21 | 2002-08-15 | Searle & Co | Amidino-derivate nützlich als no synthase-hemmer |
| CA2134192A1 (en) * | 1993-11-12 | 1995-05-13 | Michael L. Denney | 5, 6-bicyclic glycoprotein iib/iiia antagonists |
| DE4424713A1 (de) * | 1994-07-13 | 1996-01-18 | Boehringer Ingelheim Kg | Substituierte Benzamidine, ihre Herstellung und Verwendung als Arnzneistoffe |
| DE69508875T2 (de) | 1994-09-20 | 1999-09-16 | Ono Pharmaceutical Co. Ltd., Osaka | Amidinophenol-Derivate als Protease-hemmende Verbindungen |
| EP0942903A1 (en) | 1996-09-26 | 1999-09-22 | Novartis AG | Aryl-substituted acrylamides with leukotriene b4 (ltb-4) receptor antagonist activity |
| GB9928511D0 (en) * | 1999-12-03 | 2000-02-02 | Secr Defence Brit | Orally administrable pharmaceutical product and method of fabrication therefor |
| US7851486B2 (en) | 2002-10-17 | 2010-12-14 | Decode Genetics Ehf. | Susceptibility gene for myocardial infarction, stroke, and PAOD; methods of treatment |
| US7507531B2 (en) | 2002-10-17 | 2009-03-24 | Decode Genetics Chf. | Use of 5-lipoxygenase activating protein (FLAP) gene to assess susceptibility for myocardial infarction |
| CA2539276A1 (en) * | 2003-09-17 | 2005-03-31 | Decode Genetics Ehf. | Methods of preventing or treating recurrence of myocardial infarction |
| US8158362B2 (en) | 2005-03-30 | 2012-04-17 | Decode Genetics Ehf. | Methods of diagnosing susceptibility to myocardial infarction and screening for an LTA4H haplotype |
| CN101193862B (zh) * | 2005-04-13 | 2013-08-21 | 阿斯特克斯治疗有限公司 | 羟基苯甲酰胺衍生物和其作为hsp90抑制剂的用途 |
| US10336733B2 (en) | 2015-11-30 | 2019-07-02 | Merk Sharp & Dohme Corp. | Aryl acylsulfonamides as BLT1 antagonists |
| US10370368B2 (en) | 2015-11-30 | 2019-08-06 | Merck Sharp & Dohme Corp. | Aryl acylsulfonamides as BLT1 antagonists |
| WO2017095725A1 (en) | 2015-11-30 | 2017-06-08 | Merck Sharp & Dohme Corp. | Aryl sulfonamides as blt1 antagonists |
| WO2017095724A1 (en) | 2015-11-30 | 2017-06-08 | Merck Sharp & Dohme Corp. | Aryl sulfonamides as blt1 antagonists |
| KR102858089B1 (ko) | 2021-02-16 | 2025-09-10 | 스테판 칼레 | 조명 장치 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1243322A (en) * | 1984-01-23 | 1988-10-18 | Joshua Rokach | Antagonists of slow reacting substances of anaphylaxis |
| US4808604A (en) * | 1985-10-03 | 1989-02-28 | Ciba-Geigy Corporation | N-(substituted phenyl) tetrazol-5-yl carboxamides and anti-allergic use thereof |
| AU626033B2 (en) * | 1988-10-25 | 1992-07-23 | Government Of The United States Of America, As Represented By The Secretary Of The Army, The | Methods for the treatment and prophylaxis of pneumocystis carinii pneumonia and other diseases and compounds and formulations for use in said methods |
| EP0518818A3 (en) * | 1991-06-11 | 1993-04-28 | Ciba-Geigy Ag | Arylethers, their manufacture and use as medicament |
-
1992
- 1992-06-02 EP EP92810423A patent/EP0518819B1/en not_active Expired - Lifetime
- 1992-06-02 AT AT92810423T patent/ATE125791T1/de not_active IP Right Cessation
- 1992-06-02 DE DE69203797T patent/DE69203797T2/de not_active Expired - Fee Related
- 1992-06-02 DK DK92810423.1T patent/DK0518819T3/da active
- 1992-06-02 ES ES92810423T patent/ES2075672T3/es not_active Expired - Lifetime
- 1992-06-04 IL IL10210592A patent/IL102105A/en not_active IP Right Cessation
- 1992-06-05 PH PH44466A patent/PH30829A/en unknown
- 1992-06-05 AU AU18073/92A patent/AU653603B2/en not_active Ceased
- 1992-06-08 JP JP14733392A patent/JP3370998B2/ja not_active Expired - Fee Related
- 1992-06-08 FI FI922643A patent/FI922643A7/fi unknown
- 1992-06-09 NZ NZ243079A patent/NZ243079A/en not_active IP Right Cessation
- 1992-06-09 MX MX9202749A patent/MX9202749A/es unknown
- 1992-06-09 KR KR1019920009920A patent/KR100249068B1/ko not_active Expired - Fee Related
- 1992-06-09 CA CA002070795A patent/CA2070795A1/en not_active Abandoned
- 1992-06-10 NO NO922274A patent/NO178259C/no unknown
- 1992-06-10 HU HU9201938A patent/HU220226B/hu not_active IP Right Cessation
- 1992-06-10 ZA ZA924220A patent/ZA924220B/xx unknown
- 1992-06-11 TW TW081104576A patent/TW201298B/zh active
- 1992-06-11 CZ CS921780A patent/CZ279630B6/cs not_active IP Right Cessation
- 1992-07-01 IE IE921878A patent/IE67513B1/en not_active IP Right Cessation
-
1995
- 1995-08-03 GR GR950401946T patent/GR3017028T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JP3370998B2 (ja) | 2003-01-27 |
| ATE125791T1 (de) | 1995-08-15 |
| CA2070795A1 (en) | 1992-12-12 |
| DK0518819T3 (da) | 1995-09-25 |
| EP0518819B1 (en) | 1995-08-02 |
| EP0518819A3 (en) | 1993-04-21 |
| MX9202749A (es) | 1992-12-01 |
| NO922274L (no) | 1992-12-14 |
| GR3017028T3 (en) | 1995-11-30 |
| DE69203797D1 (de) | 1995-09-07 |
| IL102105A0 (en) | 1993-01-14 |
| KR930000470A (ko) | 1993-01-15 |
| IL102105A (en) | 1996-10-31 |
| NZ243079A (en) | 1994-11-25 |
| HU220226B (hu) | 2001-11-28 |
| NO922274D0 (no) | 1992-06-10 |
| HUT62264A (en) | 1993-04-28 |
| ES2075672T3 (es) | 1995-10-01 |
| NO178259B (no) | 1995-11-13 |
| AU1807392A (en) | 1992-12-17 |
| AU653603B2 (en) | 1994-10-06 |
| EP0518819A2 (en) | 1992-12-16 |
| TW201298B (enExample) | 1993-03-01 |
| HU9201938D0 (en) | 1992-08-28 |
| FI922643A0 (fi) | 1992-06-08 |
| ZA924220B (en) | 1993-02-24 |
| CZ178092A3 (en) | 1993-01-13 |
| IE67513B1 (en) | 1996-04-03 |
| FI922643A7 (fi) | 1992-12-12 |
| IE921878A1 (en) | 1992-12-16 |
| JPH05239009A (ja) | 1993-09-17 |
| NO178259C (no) | 1996-02-21 |
| CZ279630B6 (cs) | 1995-05-17 |
| KR100249068B1 (ko) | 2000-03-15 |
| PH30829A (en) | 1997-10-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69316236T2 (de) | Substituierte amidinverbindungen, ihre herstellung und behandlungsmethoden | |
| EP0445796B1 (de) | Peptidbindungen enthaltende Essigsäurederivate | |
| DE60034155T2 (de) | Adamantanderivate zur Behandlung von entzündlichen, immunologischen und kardiovaskulären Erkrankungen | |
| EP0562512B1 (de) | Sulfonamidocarbonylpyridin-2-carbonsäureamide und ihre Verwendung als Arzneimittel | |
| JP3370998B2 (ja) | アミジノ化合物、それらの製造および治療方法 | |
| DE69316367T2 (de) | Natürliche aminosäurederivate als metalloproteinase-inhibitoren | |
| DE60221569T2 (de) | Acrylsulfonamidderivate zur verwendung als ccr3-antagonisten bei der behandlung von inflammatorischen und immunologischen erkrankungen | |
| DE4102024A1 (de) | Biphenylderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung | |
| JPH05239008A (ja) | アリールエーテル、それらの製造方法および治療方法 | |
| DE69105856T2 (de) | Acetamidderivate. | |
| EP0524146A1 (de) | Aminosubstituierte Piperazinderivate | |
| DE602004005016T2 (de) | Biphenylcarboxamidderivate und ihre verwendung als p38 kinase inhibitoren | |
| US5246965A (en) | Arylethers, their manufacture and methods of treatment | |
| DE19544686A1 (de) | Aminosäurederivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung | |
| DE4443390A1 (de) | Neue dipeptidische p-Amidinobenzylamide mit N-terminalen Sulfonyl- bzw. Aminosulfonylresten | |
| DE69307669T2 (de) | Aromatische Hydroxyamidin-Derivate und ihre Verwendung als Leukotriene-B4-Rezeptor Antagonisten | |
| DE69203780T2 (de) | Aminosäurederivate und ihre Verwendung als antiviral Wirkstoffe. | |
| DE69416683T2 (de) | Benzolactam-derivate | |
| KR20100081349A (ko) | 브라디키닌 ｂ１ 길항제인 신규 비펩티드 유도체 | |
| US5488160A (en) | Amidino compounds, their manufacture and method of treatment | |
| DE10132686A1 (de) | Heteroarylcarbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel | |
| DE10019755A1 (de) | Neue Aminoaryl/cycloalkylcarbonsäuren als Integrinantagonisten | |
| DE3779813T2 (de) | 1,4-dihydropyridinderivate. | |
| HK1005720A (en) | Amidino compounds, their manufacture and use as medicament | |
| HK1005720B (en) | Amidino compounds, their manufacture and use as medicament |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: NOVARTIS AG, BASEL, CH |
|
| 8328 | Change in the person/name/address of the agent |
Representative=s name: PFENNING MEINIG & PARTNER GBR, 80339 MUENCHEN |
|
| 8328 | Change in the person/name/address of the agent |
Representative=s name: MAIWALD PATENTANWALTSGESELLSCHAFT MBH, 80335 MUENC |
|
| 8339 | Ceased/non-payment of the annual fee |