CA1314654C - Antagonistes des leucotrienes - Google Patents

Antagonistes des leucotrienes

Info

Publication number: CA1314654C
Authority: CA; Canada
Prior art keywords: alkyl; phenyl; hydrogen; alkoxy; hydroxy
Prior art date: 1987-10-26
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 - Lifetime

Application number

CA000550194A

Other languages

English (en)

Inventor

John Gerald Gleason

Ralph Floyd Hall

Thomas Wen-Fu Ku Ku

Carl David Perchonock

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

GlaxoSmithKline Inc

Original Assignee

Smith Kline and French Canada Ltd

Priority date (The priority date 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 date listed.)

1987-10-26

Filing date

1987-10-26

Publication date

1993-03-16

1987-10-26 Application filed by Smith Kline and French Canada Ltd filed Critical Smith Kline and French Canada Ltd

1987-10-26 Priority to CA000550194A priority Critical patent/CA1314654C/fr

1993-03-16 Application granted granted Critical

1993-03-16 Publication of CA1314654C publication Critical patent/CA1314654C/fr

2010-03-16 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

239000003199 leukotriene receptor blocking agent Substances 0.000 title abstract description 25
150000001875 compounds Chemical class 0.000 claims abstract description 82
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
239000000203 mixture Substances 0.000 claims description 34
239000001257 hydrogen Substances 0.000 claims description 33
229910052739 hydrogen Inorganic materials 0.000 claims description 33
-1 10-undecynyloxy, 11-dodecynyl Chemical group 0.000 claims description 30
125000000217 alkyl group Chemical group 0.000 claims description 24
125000003545 alkoxy group Chemical group 0.000 claims description 20
150000002431 hydrogen Chemical group 0.000 claims description 20
238000000034 method Methods 0.000 claims description 14
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 13
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 11
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
239000003937 drug carrier Substances 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 7
150000003573 thiols Chemical class 0.000 claims description 7
125000006539 C12 alkyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000001246 bromo group Chemical group Br* 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000001309 chloro group Chemical group Cl* 0.000 claims description 6
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 6
230000003647 oxidation Effects 0.000 claims description 6
238000007254 oxidation reaction Methods 0.000 claims description 6
125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
235000019260 propionic acid Nutrition 0.000 claims description 5
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 4
101100295738 Gallus gallus COR3 gene Proteins 0.000 claims description 3
229910006069 SO3H Inorganic materials 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000005518 carboxamido group Chemical group 0.000 claims description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 3
229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 2
150000002148 esters Chemical group 0.000 claims description 2
LDTLDBDUBGAEDT-UHFFFAOYSA-N methyl 3-sulfanylpropanoate Chemical compound COC(=O)CCS LDTLDBDUBGAEDT-UHFFFAOYSA-N 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 4
238000010511 deprotection reaction Methods 0.000 claims 3
OHENAIYDQKASOE-UHFFFAOYSA-N 3-(2-carboxyethylsulfinyl)-2-hydroxy-3-[2-(8-phenyloctyl)phenyl]propanoic acid Chemical compound OC(=O)CCS(=O)C(C(O)C(O)=O)C1=CC=CC=C1CCCCCCCCC1=CC=CC=C1 OHENAIYDQKASOE-UHFFFAOYSA-N 0.000 claims 2
JOHPTDYYKFDKBX-UHFFFAOYSA-N 3-(2-carboxyethylsulfonyl)-2-hydroxy-3-[2-(8-phenyloctyl)phenyl]propanoic acid Chemical compound OC(=O)CCS(=O)(=O)C(C(O)C(O)=O)C1=CC=CC=C1CCCCCCCCC1=CC=CC=C1 JOHPTDYYKFDKBX-UHFFFAOYSA-N 0.000 claims 2
ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims 2
125000004185 ester group Chemical group 0.000 claims 2
SYSBOXNRHCEKRA-UHFFFAOYSA-N methyl 3-[2-(8-phenyloctyl)phenyl]oxirane-2-carboxylate Chemical compound COC(=O)C1OC1C1=CC=CC=C1CCCCCCCCC1=CC=CC=C1 SYSBOXNRHCEKRA-UHFFFAOYSA-N 0.000 claims 1
230000001590 oxidative effect Effects 0.000 claims 1
125000006239 protecting group Chemical group 0.000 claims 1
125000000101 thioether group Chemical group 0.000 claims 1
150000002617 leukotrienes Chemical class 0.000 abstract description 44
238000011282 treatment Methods 0.000 abstract description 18
239000002253 acid Substances 0.000 abstract description 10
239000008194 pharmaceutical composition Substances 0.000 abstract description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
201000010099 disease Diseases 0.000 abstract description 8
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 abstract 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
239000000243 solution Substances 0.000 description 25
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 16
239000002243 precursor Substances 0.000 description 16
239000000047 product Substances 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
230000000694 effects Effects 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
GWNVDXQDILPJIG-SHSCPDMUSA-N Leukotriene C4 Natural products CCCCCC=C/CC=C/C=C/C=C/C(SCC(NC(=O)CCC(N)C(=O)O)C(=O)NCC(=O)O)C(O)CCCC(=O)O GWNVDXQDILPJIG-SHSCPDMUSA-N 0.000 description 13
GWNVDXQDILPJIG-NXOLIXFESA-N leukotriene C4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O GWNVDXQDILPJIG-NXOLIXFESA-N 0.000 description 13
238000012360 testing method Methods 0.000 description 13
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
150000001299 aldehydes Chemical class 0.000 description 10
238000006243 chemical reaction Methods 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
229960001340 histamine Drugs 0.000 description 8
230000003389 potentiating effect Effects 0.000 description 8
210000001519 tissue Anatomy 0.000 description 8
239000003981 vehicle Substances 0.000 description 7
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
241000282414 Homo sapiens Species 0.000 description 6
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
208000010668 atopic eczema Diseases 0.000 description 6
125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
230000002685 pulmonary effect Effects 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
229940044551 receptor antagonist Drugs 0.000 description 6
239000002464 receptor antagonist Substances 0.000 description 6
239000007787 solid Substances 0.000 description 6
239000000725 suspension Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
206010002198 Anaphylactic reaction Diseases 0.000 description 5
OTZRAYGBFWZKMX-SHSCPDMUSA-N Leukotriene E4 Natural products CCCCCC=C/CC=C/C=C/C=C/C(SCC(N)C(=O)O)C(O)CCCC(=O)O OTZRAYGBFWZKMX-SHSCPDMUSA-N 0.000 description 5
241000700159 Rattus Species 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
230000009471 action Effects 0.000 description 5
230000000172 allergic effect Effects 0.000 description 5
230000036783 anaphylactic response Effects 0.000 description 5
208000003455 anaphylaxis Diseases 0.000 description 5
239000005557 antagonist Substances 0.000 description 5
239000012267 brine Substances 0.000 description 5
230000008602 contraction Effects 0.000 description 5
230000000875 corresponding effect Effects 0.000 description 5
239000012530 fluid Substances 0.000 description 5
OTZRAYGBFWZKMX-JUDRUQEKSA-N leukotriene E4 Chemical compound CCCCCC=CCC=C\C=C\C=C\[C@@H](SC[C@H](N)C(O)=O)[C@@H](O)CCCC(O)=O OTZRAYGBFWZKMX-JUDRUQEKSA-N 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
239000008024 pharmaceutical diluent Substances 0.000 description 5
239000000741 silica gel Substances 0.000 description 5
229910002027 silica gel Inorganic materials 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
238000003756 stirring Methods 0.000 description 5
229940086542 triethylamine Drugs 0.000 description 5
241000700199 Cavia porcellus Species 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000001154 acute effect Effects 0.000 description 4
229910052783 alkali metal Inorganic materials 0.000 description 4
239000002585 base Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
230000000747 cardiac effect Effects 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000012442 inert solvent Substances 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
108090000765 processed proteins & peptides Proteins 0.000 description 4
210000003491 skin Anatomy 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 4
JRXDMDTWEUAEFE-UHFFFAOYSA-N 2-(8-phenyloctyl)benzaldehyde Chemical compound O=CC1=CC=CC=C1CCCCCCCCC1=CC=CC=C1 JRXDMDTWEUAEFE-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
206010030113 Oedema Diseases 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
206010037423 Pulmonary oedema Diseases 0.000 description 3
208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
239000000556 agonist Substances 0.000 description 3
239000000427 antigen Substances 0.000 description 3
102000036639 antigens Human genes 0.000 description 3
108091007433 antigens Proteins 0.000 description 3
208000006673 asthma Diseases 0.000 description 3
230000003435 bronchoconstrictive effect Effects 0.000 description 3
230000000711 cancerogenic effect Effects 0.000 description 3
AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 3
229960004484 carbachol Drugs 0.000 description 3
229910002092 carbon dioxide Inorganic materials 0.000 description 3
231100000315 carcinogenic Toxicity 0.000 description 3
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
230000002757 inflammatory effect Effects 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
208000014674 injury Diseases 0.000 description 3
210000003734 kidney Anatomy 0.000 description 3
239000007788 liquid Substances 0.000 description 3
150000002924 oxiranes Chemical class 0.000 description 3
125000003884 phenylalkyl group Chemical group 0.000 description 3
208000005333 pulmonary edema Diseases 0.000 description 3
230000000241 respiratory effect Effects 0.000 description 3
230000004044 response Effects 0.000 description 3
230000035939 shock Effects 0.000 description 3
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
150000003568 thioethers Chemical class 0.000 description 3
239000003039 volatile agent Substances 0.000 description 3
KBPLFHHGFOOTCA-UHFFFAOYSA-N 1-Octanol Chemical compound CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
ALRHLSYJTWAHJZ-UHFFFAOYSA-N 3-hydroxypropionic acid Chemical class OCCC(O)=O ALRHLSYJTWAHJZ-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 2
XGBMCFCZEKCCDJ-UHFFFAOYSA-N 8-bromooctylbenzene Chemical compound BrCCCCCCCCC1=CC=CC=C1 XGBMCFCZEKCCDJ-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
101150041968 CDC13 gene Proteins 0.000 description 2
241000700198 Cavia Species 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
101100285518 Drosophila melanogaster how gene Proteins 0.000 description 2
206010014824 Endotoxic shock Diseases 0.000 description 2
UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
101100455054 Homo sapiens LTA4H gene Proteins 0.000 description 2
206010020751 Hypersensitivity Diseases 0.000 description 2
102100022118 Leukotriene A-4 hydrolase Human genes 0.000 description 2
208000019693 Lung disease Diseases 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
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101100075025 Scheffersomyces stipitis (strain ATCC 58785 / CBS 6054 / NBRC 10063 / NRRL Y-11545) LTA4 gene Proteins 0.000 description 2
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PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
208000007107 Stomach Ulcer Diseases 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
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HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
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GOQJMMHTSOQIEI-UHFFFAOYSA-N hex-5-yn-1-ol Chemical compound OCCCCC#C GOQJMMHTSOQIEI-UHFFFAOYSA-N 0.000 description 2
CKJWLEMTYAEICI-UHFFFAOYSA-N hex-5-ynyl 4-methylbenzenesulfonate Chemical compound CC1=CC=C(S(=O)(=O)OCCCCC#C)C=C1 CKJWLEMTYAEICI-UHFFFAOYSA-N 0.000 description 2
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 2
210000003630 histaminocyte Anatomy 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
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201000006370 kidney failure Diseases 0.000 description 2
230000023404 leukocyte cell-cell adhesion Effects 0.000 description 2
UFPQIRYSPUYQHK-WAQVJNLQSA-N leukotriene A4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(O)=O UFPQIRYSPUYQHK-WAQVJNLQSA-N 0.000 description 2
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 2
238000004519 manufacturing process Methods 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
210000001616 monocyte Anatomy 0.000 description 2
208000031225 myocardial ischemia Diseases 0.000 description 2
239000006199 nebulizer Substances 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
230000035699 permeability Effects 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
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150000003462 sulfoxides Chemical class 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 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
230000001225 therapeutic effect Effects 0.000 description 1
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
210000003437 trachea Anatomy 0.000 description 1
210000005092 tracheal tissue Anatomy 0.000 description 1
WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
230000002861 ventricular Effects 0.000 description 1
239000004034 viscosity adjusting agent Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000550194A 1987-10-26 1987-10-26 Antagonistes des leucotrienes Expired - Lifetime CA1314654C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000550194A CA1314654C (fr)	1987-10-26	1987-10-26	Antagonistes des leucotrienes

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
CA000550194A CA1314654C (fr)	1987-10-26	1987-10-26	Antagonistes des leucotrienes

Publications (1)

Publication Number	Publication Date
CA1314654C true CA1314654C (fr)	1993-03-16

Family

ID=4136717

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000550194A Expired - Lifetime CA1314654C (fr)	1987-10-26	1987-10-26	Antagonistes des leucotrienes

Country Status (1)

Country	Link
CA (1)	CA1314654C (fr)

1987
- 1987-10-26 CA CA000550194A patent/CA1314654C/fr not_active Expired - Lifetime

Legal Events

Date	Code	Title	Description
2010-03-16	MKEX	Expiry

Publication	Publication Date	Title
US4820719A (en)	1989-04-11	Leukotriene antagonists
EP0296732B1 (fr)	1991-10-09	Antagonistes de leukotriène
EP0313697B1 (fr)	1992-03-04	Antagonistes de leukotriène
US4937253A (en)	1990-06-26	Ester prodrugs
EP0375348B1 (fr)	1993-06-23	Antagonistes de leukotriène
CA1314654C (fr)	1993-03-16	Antagonistes des leucotrienes
US4996214A (en)	1991-02-26	Quinolinyl substituted phenyl/thioalkanoic acid substituted propionic acids and leucotriene antagonist use thereof
EP0296731B1 (fr)	1992-08-26	Antagonistes de leukotriène
EP0403249B1 (fr)	1994-04-27	Antagonistes de leucotriène
US5314918A (en)	1994-05-24	Leukotriene antagonists
IE60494B1 (en)	1994-07-27	Leukotriene antagonists
US5143931A (en)	1992-09-01	Leukotriene antagonists containing tetrazolyl groups
US4939279A (en)	1990-07-03	Leukotriene antagonists
US5034537A (en)	1991-07-23	Leukotriene antagonists
US5189226A (en)	1993-02-23	Ortho-substituted benzaldehydes
AU7769491A (en)	1991-11-27	3-naphthyl-3-carboxyalkylthio or oxy substituted alkanoic acid leukotriene antagonists
EP0528957A1 (fr)	1993-03-03	Antagonistes de leucotriene sous forme d'acide alcanoique a anneau de cinq membres
PT86027B (pt)	1992-11-30	Processo de preparacao de acidos alcanoicos com substituintes fenil e sulfinil ou sulfonil
IE912180A1 (en)	1992-01-01	Chemical compounds
CZ396991A3 (cs)	1993-08-11	Deriváty alifatických kyselin a farmaceutické prostředky s jejich obsahem