CA2110838A1 - Hyrdroxyamidine derivatives - Google Patents
Hyrdroxyamidine derivativesInfo
- Publication number
- CA2110838A1 CA2110838A1 CA002110838A CA2110838A CA2110838A1 CA 2110838 A1 CA2110838 A1 CA 2110838A1 CA 002110838 A CA002110838 A CA 002110838A CA 2110838 A CA2110838 A CA 2110838A CA 2110838 A1 CA2110838 A1 CA 2110838A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- amino
- hydroxy
- alkoxy
- alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 95
- 241000124008 Mammalia Species 0.000 claims abstract description 9
- 102000003680 Leukotriene B4 receptors Human genes 0.000 claims abstract description 8
- 108090000093 Leukotriene B4 receptors Proteins 0.000 claims abstract description 8
- 230000008485 antagonism Effects 0.000 claims abstract description 6
- 208000011580 syndromic disease Diseases 0.000 claims abstract description 5
- -1 aliphatic hydrocarbon radical Chemical class 0.000 claims description 131
- 229910052739 hydrogen Inorganic materials 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 42
- 239000001257 hydrogen Substances 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 27
- 150000002367 halogens Chemical group 0.000 claims description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
- 125000003545 alkoxy group Chemical group 0.000 claims description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 150000002431 hydrogen Chemical group 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000002947 alkylene group Chemical group 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
- 125000004423 acyloxy group Chemical group 0.000 claims description 13
- 230000008569 process Effects 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 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 11
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 9
- 125000001931 aliphatic group Chemical group 0.000 claims description 9
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 239000004215 Carbon black (E152) Substances 0.000 claims description 7
- 229930195733 hydrocarbon Natural products 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 6
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 4
- 241001465754 Metazoa Species 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- BJVVHIVCDWUTEW-UHFFFAOYSA-N 2-hydroxy-4-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenoxy]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(N)=NO)C=C1 BJVVHIVCDWUTEW-UHFFFAOYSA-N 0.000 claims description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 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 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- AESKWGOCAPJJND-UHFFFAOYSA-N 2-chloro-4-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenoxy]pentoxy]-n-phenyl-n-propan-2-ylbenzamide Chemical compound C=1C=CC=CC=1N(C(C)C)C(=O)C(C(=C1)Cl)=CC=C1OCCCCCOC1=CC=C(C(N)=NO)C=C1 AESKWGOCAPJJND-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 239000005864 Sulphur Substances 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- VDUMSOCVLPXFHT-UHFFFAOYSA-N ethyl 2-[2-[di(propan-2-yl)carbamoyl]-5-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenoxy]pentoxy]phenoxy]-2-methylpropanoate Chemical compound C1=C(C(=O)N(C(C)C)C(C)C)C(OC(C)(C)C(=O)OCC)=CC(OCCCCCOC=2C=CC(=CC=2)C(N)=NO)=C1 VDUMSOCVLPXFHT-UHFFFAOYSA-N 0.000 claims description 2
- LXPWTGIOHCMLCC-UHFFFAOYSA-N ethyl 2-[2-[di(propan-2-yl)carbamoyl]-5-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenoxy]pentoxy]phenoxy]acetate Chemical compound C1=C(C(=O)N(C(C)C)C(C)C)C(OCC(=O)OCC)=CC(OCCCCCOC=2C=CC(=CC=2)C(N)=NO)=C1 LXPWTGIOHCMLCC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 7
- XPTVQEJPZNFBLF-UHFFFAOYSA-N 2-[2-[di(propan-2-yl)carbamoyl]-5-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenoxy]pentoxy]phenoxy]-2-methylpropanoic acid Chemical compound C1=C(OC(C)(C)C(O)=O)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C(N)=NO)C=C1 XPTVQEJPZNFBLF-UHFFFAOYSA-N 0.000 claims 1
- LZUFWEXLKGZWDB-UHFFFAOYSA-N 2-hydroxy-4-[5-[4-[(e)-n'-hydroxycarbamimidoyl]phenoxy]pentoxy]-n-phenyl-n-propan-2-ylbenzamide Chemical compound C=1C=CC=CC=1N(C(C)C)C(=O)C(C(=C1)O)=CC=C1OCCCCCOC1=CC=C(C(\N)=N\O)C=C1 LZUFWEXLKGZWDB-UHFFFAOYSA-N 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 239000002464 receptor antagonist Substances 0.000 abstract description 2
- 229940044551 receptor antagonist Drugs 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 48
- 238000006243 chemical reaction Methods 0.000 description 44
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
- 229910052757 nitrogen Inorganic materials 0.000 description 28
- 239000000463 material Substances 0.000 description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
- 239000002253 acid Substances 0.000 description 17
- 238000004587 chromatography analysis Methods 0.000 description 17
- 239000003480 eluent Substances 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 229910001868 water Inorganic materials 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 239000004480 active ingredient Substances 0.000 description 10
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 10
- 229910052938 sodium sulfate Inorganic materials 0.000 description 10
- 235000011152 sodium sulphate Nutrition 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 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 description 6
- 239000002953 phosphate buffered saline Substances 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 150000003254 radicals Chemical class 0.000 description 6
- 239000012312 sodium hydride Substances 0.000 description 6
- 229910000104 sodium hydride Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 150000008064 anhydrides Chemical class 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 210000000440 neutrophil Anatomy 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- ISBAUDHGTJFJEM-UHFFFAOYSA-N [5-[5-(4-cyanophenoxy)pentoxy]-2-[di(propan-2-yl)carbamoyl]phenyl] acetate Chemical compound C1=C(OC(C)=O)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 ISBAUDHGTJFJEM-UHFFFAOYSA-N 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 238000004220 aggregation Methods 0.000 description 4
- 239000006285 cell suspension Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 229940043279 diisopropylamine Drugs 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 210000003622 mature neutrocyte Anatomy 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JPPYKLFDTALDOD-UHFFFAOYSA-N 2-[5-[5-(4-cyanophenoxy)pentoxy]-2-[di(propan-2-yl)carbamoyl]phenoxy]-2-methylpropanoic acid Chemical compound C1=C(OC(C)(C)C(O)=O)C(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 JPPYKLFDTALDOD-UHFFFAOYSA-N 0.000 description 3
- VUMGNEJAKHYWHJ-UHFFFAOYSA-N 4-(5-chloropentoxy)benzonitrile Chemical compound ClCCCCCOC1=CC=C(C#N)C=C1 VUMGNEJAKHYWHJ-UHFFFAOYSA-N 0.000 description 3
- AXESBPHKQIZJAS-UHFFFAOYSA-N 4-[5-(4-cyano-3-fluorophenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C#N)C(F)=C1 AXESBPHKQIZJAS-UHFFFAOYSA-N 0.000 description 3
- JEOPLXLAPYHMHY-UHFFFAOYSA-N 4-[5-(4-cyanophenoxy)pentoxy]-2-hydroxy-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#N)C=C1 JEOPLXLAPYHMHY-UHFFFAOYSA-N 0.000 description 3
- KSHYKAOOJUQFKX-UHFFFAOYSA-N 4-[5-(4-cyanophenoxy)pentoxy]-n,n-di(propan-2-yl)benzamide Chemical compound C1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCCOC1=CC=C(C#N)C=C1 KSHYKAOOJUQFKX-UHFFFAOYSA-N 0.000 description 3
- YIJWBPAOJXIYJY-UHFFFAOYSA-N 4-hydroxy-n,n-di(propan-2-yl)benzamide Chemical compound CC(C)N(C(C)C)C(=O)C1=CC=C(O)C=C1 YIJWBPAOJXIYJY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 125000003435 aroyl group Chemical group 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 125000001589 carboacyl group Chemical group 0.000 description 3
- 150000001735 carboxylic acids Chemical class 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- GOTTVYZERXLQLW-UHFFFAOYSA-N ethyl 2-[5-[5-(4-cyanophenoxy)pentoxy]-2-[di(propan-2-yl)carbamoyl]phenoxy]-2-methylpropanoate Chemical compound C1=C(C(=O)N(C(C)C)C(C)C)C(OC(C)(C)C(=O)OCC)=CC(OCCCCCOC=2C=CC(=CC=2)C#N)=C1 GOTTVYZERXLQLW-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 150000004820 halides Chemical class 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 208000004235 neutropenia Diseases 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229940127557 pharmaceutical product Drugs 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- UIAFKZKHHVMJGS-UHFFFAOYSA-N 2,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1O UIAFKZKHHVMJGS-UHFFFAOYSA-N 0.000 description 2
- REIVHYDACHXPNH-UHFFFAOYSA-N 2-fluoro-4-hydroxybenzonitrile Chemical compound OC1=CC=C(C#N)C(F)=C1 REIVHYDACHXPNH-UHFFFAOYSA-N 0.000 description 2
- HWKUZTFIZATJPM-UHFFFAOYSA-N 2-fluoro-4-methoxybenzonitrile Chemical compound COC1=CC=C(C#N)C(F)=C1 HWKUZTFIZATJPM-UHFFFAOYSA-N 0.000 description 2
- RCDXMZKGCHRNPS-UHFFFAOYSA-N 4-[4-(4-cyanophenoxy)butoxy]-3-methoxy-n,n-di(propan-2-yl)benzamide Chemical compound COC1=CC(C(=O)N(C(C)C)C(C)C)=CC=C1OCCCCOC1=CC=C(C#N)C=C1 RCDXMZKGCHRNPS-UHFFFAOYSA-N 0.000 description 2
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- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 description 1
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- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
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- 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
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- 238000003786 synthesis reaction Methods 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
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 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 description 1
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- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
- C07C259/18—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to carbon atoms of six-membered aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Lubricants (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/987,856 US5455274A (en) | 1992-12-09 | 1992-12-09 | Hydroxyamidine derivatives |
| US07/987,856 | 1992-12-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2110838A1 true CA2110838A1 (en) | 1994-06-10 |
Family
ID=25533631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002110838A Abandoned CA2110838A1 (en) | 1992-12-09 | 1993-12-07 | Hyrdroxyamidine derivatives |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US5455274A (enExample) |
| EP (1) | EP0601977B1 (enExample) |
| JP (1) | JPH06263710A (enExample) |
| KR (1) | KR940014313A (enExample) |
| AT (1) | ATE148103T1 (enExample) |
| AU (1) | AU671683B2 (enExample) |
| CA (1) | CA2110838A1 (enExample) |
| DE (1) | DE69307669T2 (enExample) |
| DK (1) | DK0601977T3 (enExample) |
| ES (1) | ES2096265T3 (enExample) |
| FI (1) | FI935452A7 (enExample) |
| GR (1) | GR3022367T3 (enExample) |
| HU (1) | HUT65778A (enExample) |
| IL (1) | IL107842A (enExample) |
| NO (2) | NO180300C (enExample) |
| NZ (1) | NZ250379A (enExample) |
| PH (1) | PH29931A (enExample) |
| TW (2) | TW267999B (enExample) |
| ZA (1) | ZA939193B (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5821267A (en) * | 1993-10-21 | 1998-10-13 | G.D. Searle & Co. | Amidino derivatives useful as nitric oxide synthase inhibitors |
| DE4424713A1 (de) * | 1994-07-13 | 1996-01-18 | Boehringer Ingelheim Kg | Substituierte Benzamidine, ihre Herstellung und Verwendung als Arnzneistoffe |
| JP2770769B2 (ja) * | 1995-02-16 | 1998-07-02 | 日本メクトロン株式会社 | ビスアミドキシム化合物、その製造法およびそれを含有する含フッ素エラストマー組成物 |
| ID24720A (id) * | 1997-12-12 | 2000-08-03 | Novartis Ag | Senyawa amidino tersubstitusi dalam perawatan penyakit gangguan paru-paru kronis |
| WO2000027199A1 (en) * | 1998-11-12 | 2000-05-18 | Eli Lilly And Company | Aminobenzisoxazole compounds and libraries thereof |
| US7262223B2 (en) | 2004-01-23 | 2007-08-28 | Neurochem (International) Limited | Amidine derivatives for treating amyloidosis |
| CA2554696C (en) | 2004-02-13 | 2009-06-30 | Warner-Lambert Company Llc | Androgen receptor modulators |
| WO2005100305A1 (en) | 2004-04-13 | 2005-10-27 | Warner-Lambert Company Llc | Androgen modulators |
| BRPI0509980A (pt) | 2004-04-22 | 2007-10-16 | Warner Lambert Co | moduladores de androgênio |
| US8338648B2 (en) * | 2004-06-12 | 2012-12-25 | Signum Biosciences, Inc. | Topical compositions and methods for epithelial-related conditions |
| CA2572898C (en) * | 2004-07-05 | 2010-04-20 | Dong Wha Pharmaceutical Ind. Co., Ltd. | Composition for the prevention and treatment of allergic inflammatory disease |
| MXPA06015169A (es) | 2004-07-08 | 2007-08-21 | Warner Lambert Co | Moduladores de androgenos. |
| KR20060017929A (ko) | 2004-08-04 | 2006-02-28 | 동화약품공업주식회사 | 티아졸 유도체가 치환된 신규한 벤즈아미딘 유도체, 그의제조방법 및 이를 유효성분으로 하는 약학 조성물 |
| TW200724139A (en) | 2005-05-05 | 2007-07-01 | Warner Lambert Co | Androgen modulators |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5922697B2 (ja) * | 1976-01-13 | 1984-05-28 | エーザイ株式会社 | ビス−（メタ−アミジノフエノキシ）−化合物 |
| NL7908922A (nl) * | 1979-12-12 | 1981-07-16 | Akzo Nv | Carboximidamide derivaten. |
| US4324794A (en) * | 1980-08-26 | 1982-04-13 | Research Triangle Institute | Inhibition of respiratory syncytial virus-induced cell fusion by amidino compounds |
| US4661505A (en) * | 1982-11-03 | 1987-04-28 | Eli Lilly And Company | Leukotriene antagonists |
| CA1243322A (en) * | 1984-01-23 | 1988-10-18 | Joshua Rokach | Antagonists of slow reacting substances of anaphylaxis |
| US4717736A (en) * | 1984-01-23 | 1988-01-05 | Merck Frosst Canada, Inc. | Antagonists of slow reacting substances of anaphylaxis |
| DE3830054A1 (de) * | 1988-09-03 | 1990-03-15 | Boehringer Mannheim Gmbh | Phenylamide - verfahren zu ihrer herstellung sowie diese verbindungen enthaltende arzneimittel |
| US4933347A (en) * | 1988-10-25 | 1990-06-12 | University Of North Carolina At Chapel Hill | Diamidines and bis(imidazolines) for the treatment of and prophylaxis against pneumocystis carinii pneumonia |
| US4963589A (en) * | 1988-10-25 | 1990-10-16 | The University Of North Carolina At Chapel Hill | Methods for treating Giardia lamblia |
| US5162361A (en) * | 1990-04-10 | 1992-11-10 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Method of treating diseases associated with elevated levels of interleukin 1 |
| US5124350A (en) * | 1990-06-28 | 1992-06-23 | G. D. Searle & Co. | Leukotriene b4 antagonists |
| CA2129526A1 (en) * | 1992-02-05 | 1993-08-06 | Franz Birke | Novel amidine derivatives, their preparation and their use as medicaments with ltb4 antagonistic effect |
-
1992
- 1992-12-09 US US07/987,856 patent/US5455274A/en not_active Expired - Fee Related
-
1993
- 1993-11-24 PH PH47320A patent/PH29931A/en unknown
- 1993-11-26 JP JP5296853A patent/JPH06263710A/ja active Pending
- 1993-11-30 DK DK93810841.2T patent/DK0601977T3/da active
- 1993-11-30 AT AT93810841T patent/ATE148103T1/de not_active IP Right Cessation
- 1993-11-30 EP EP93810841A patent/EP0601977B1/en not_active Expired - Lifetime
- 1993-11-30 DE DE69307669T patent/DE69307669T2/de not_active Expired - Fee Related
- 1993-11-30 ES ES93810841T patent/ES2096265T3/es not_active Expired - Lifetime
- 1993-12-02 IL IL10784293A patent/IL107842A/en not_active IP Right Cessation
- 1993-12-03 FI FI935452A patent/FI935452A7/fi unknown
- 1993-12-03 AU AU52180/93A patent/AU671683B2/en not_active Ceased
- 1993-12-07 NZ NZ250379A patent/NZ250379A/en unknown
- 1993-12-07 CA CA002110838A patent/CA2110838A1/en not_active Abandoned
- 1993-12-08 KR KR1019930026826A patent/KR940014313A/ko not_active Withdrawn
- 1993-12-08 ZA ZA939193A patent/ZA939193B/xx unknown
- 1993-12-08 HU HU9303501A patent/HUT65778A/hu unknown
- 1993-12-08 NO NO934483A patent/NO180300C/no unknown
- 1993-12-08 NO NO934483D patent/NO934483D0/no unknown
- 1993-12-22 TW TW082110864A patent/TW267999B/zh active
-
1994
- 1994-01-19 TW TW083100416A patent/TW294651B/zh not_active IP Right Cessation
-
1997
- 1997-01-23 GR GR970400016T patent/GR3022367T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| TW267999B (enExample) | 1996-01-11 |
| FI935452A7 (fi) | 1994-06-10 |
| HUT65778A (en) | 1994-07-28 |
| EP0601977A1 (en) | 1994-06-15 |
| DE69307669D1 (de) | 1997-03-06 |
| NO180300C (no) | 1997-03-26 |
| IL107842A (en) | 1998-08-16 |
| PH29931A (en) | 1996-09-16 |
| TW294651B (enExample) | 1997-01-01 |
| US5455274A (en) | 1995-10-03 |
| DK0601977T3 (da) | 1997-02-10 |
| JPH06263710A (ja) | 1994-09-20 |
| HU9303501D0 (en) | 1994-04-28 |
| GR3022367T3 (en) | 1997-04-30 |
| AU5218093A (en) | 1994-06-23 |
| DE69307669T2 (de) | 1997-11-13 |
| EP0601977B1 (en) | 1997-01-22 |
| ATE148103T1 (de) | 1997-02-15 |
| ES2096265T3 (es) | 1997-03-01 |
| IL107842A0 (en) | 1994-04-12 |
| KR940014313A (ko) | 1994-07-18 |
| NZ250379A (en) | 1995-12-21 |
| NO934483D0 (no) | 1993-12-08 |
| ZA939193B (en) | 1994-06-09 |
| FI935452A0 (fi) | 1993-12-03 |
| NO934483L (no) | 1994-06-10 |
| NO180300B (no) | 1996-12-16 |
| AU671683B2 (en) | 1996-09-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |