CN1092409A - 用于治疗白三烯有关的疾病的化合物 - Google Patents

用于治疗白三烯有关的疾病的化合物 Download PDF

Info

Publication number: CN1092409A
Authority: CN; China
Prior art keywords: phenyl; pyridyl; sulfo; ethyl; octyloxy
Prior art date: 1991-09-19
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.): Pending

Application number

CN93103596A

Other languages

English (en)

Chinese (zh)

Inventor

P·A·钱伯斯

R·A·戴恩斯

D·R·扎卡斯

W·D·金斯伯里

I·彭德拉克

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.)

SmithKline Beecham Corp

Original Assignee

SmithKline Beecham Corp

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.)

1991-09-19

Filing date

1993-03-19

Publication date

1994-09-21

1992-09-01 Priority to JP5506069A priority Critical patent/JPH06510786A/ja

1992-09-01 Priority to CA002119467A priority patent/CA2119467A1/fr

1992-09-01 Priority to EP92920043A priority patent/EP0604529A1/fr

1992-09-01 Priority to AU25735/92A priority patent/AU2573592A/en

1992-09-01 Priority to PCT/US1992/007466 priority patent/WO1993006085A1/fr

1992-09-08 Priority to MA22940A priority patent/MA22649A1/fr

1992-09-17 Priority to IL103205A priority patent/IL103205A0/xx

1992-09-17 Priority to NZ244371A priority patent/NZ244371A/en

1992-09-17 Priority to APAP/P/1992/000428A priority patent/AP333A/en

1992-09-18 Priority to PT100881A priority patent/PT100881A/pt

1992-09-21 Priority to MX9205358A priority patent/MX9205358A/es

1993-03-19 Application filed by SmithKline Beecham Corp filed Critical SmithKline Beecham Corp

1993-03-19 Priority to CN93103596A priority patent/CN1092409A/zh

1994-09-21 Publication of CN1092409A publication Critical patent/CN1092409A/zh

Status Pending legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 110
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 16
201000010099 disease Diseases 0.000 title description 14
150000002617 leukotrienes Chemical class 0.000 title description 14
238000011282 treatment Methods 0.000 title description 14
239000002253 acid Substances 0.000 claims abstract description 68
229920002554 vinyl polymer Polymers 0.000 claims description 184
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 151
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 151
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 129
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 116
-1 N-oxide compound Chemical class 0.000 claims description 111
229910052760 oxygen Inorganic materials 0.000 claims description 91
239000001301 oxygen Substances 0.000 claims description 87
150000003839 salts Chemical class 0.000 claims description 75
229910003002 lithium salt Inorganic materials 0.000 claims description 73
159000000002 lithium salts Chemical class 0.000 claims description 73
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 62
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 53
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 52
125000005447 octyloxy 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])O* 0.000 claims description 52
239000000203 mixture Substances 0.000 claims description 46
SMBQBQBNOXIFSF-UHFFFAOYSA-N dilithium Chemical class [Li][Li] SMBQBQBNOXIFSF-UHFFFAOYSA-N 0.000 claims description 40
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 34
125000003545 alkoxy group Chemical group 0.000 claims description 25
125000000217 alkyl group Chemical group 0.000 claims description 24
RAHZWNYVWXNFOC-UHFFFAOYSA-N sulfur dioxide Inorganic materials O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 21
239000004291 sulphur dioxide Substances 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 20
150000002148 esters Chemical group 0.000 claims description 19
229910052799 carbon Inorganic materials 0.000 claims description 17
CMEWLCATCRTSGF-UHFFFAOYSA-N N,N-dimethyl-4-nitrosoaniline Chemical compound CN(C)C1=CC=C(N=O)C=C1 CMEWLCATCRTSGF-UHFFFAOYSA-N 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
150000001721 carbon Chemical group 0.000 claims description 11
239000011737 fluorine Substances 0.000 claims description 11
229910052731 fluorine Inorganic materials 0.000 claims description 11
239000001257 hydrogen Substances 0.000 claims description 11
239000008194 pharmaceutical composition Substances 0.000 claims description 10
150000001408 amides Chemical class 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
KAKQVSNHTBLJCH-UHFFFAOYSA-N trifluoromethanesulfonimidic acid Chemical compound NS(=O)(=O)C(F)(F)F KAKQVSNHTBLJCH-UHFFFAOYSA-N 0.000 claims description 6
IMNDHOCGZLYMRO-UHFFFAOYSA-N n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC=C1 IMNDHOCGZLYMRO-UHFFFAOYSA-N 0.000 claims description 5
229940124530 sulfonamide Drugs 0.000 claims description 5
125000002252 acyl group Chemical group 0.000 claims description 4
125000003831 tetrazolyl group Chemical group 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 3
125000004953 trihalomethyl group Chemical group 0.000 claims description 3
125000003836 4-phenylbutoxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
150000002500 ions Chemical class 0.000 claims description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 10
LOTBYPQQWICYBB-UHFFFAOYSA-N methyl n-hexyl-n-[2-(hexylamino)ethyl]carbamate Chemical compound CCCCCCNCCN(C(=O)OC)CCCCCC LOTBYPQQWICYBB-UHFFFAOYSA-N 0.000 claims 5
239000002671 adjuvant Substances 0.000 claims 1
229960003424 phenylacetic acid Drugs 0.000 claims 1
239000003279 phenylacetic acid Substances 0.000 claims 1
150000001412 amines Chemical class 0.000 abstract description 5
239000003199 leukotriene receptor blocking agent Substances 0.000 abstract description 2
150000007513 acids Chemical class 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 232
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 148
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 139
150000001336 alkenes Chemical class 0.000 description 132
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 130
125000003118 aryl group Chemical group 0.000 description 112
239000000376 reactant Substances 0.000 description 112
238000005160 1H NMR spectroscopy Methods 0.000 description 101
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 98
235000019439 ethyl acetate Nutrition 0.000 description 95
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 89
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 87
125000001931 aliphatic group Chemical group 0.000 description 84
229910052786 argon Inorganic materials 0.000 description 74
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239000007787 solid Substances 0.000 description 66
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 64
239000000047 product Substances 0.000 description 64
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 61
239000000243 solution Substances 0.000 description 56
239000000460 chlorine Substances 0.000 description 55
238000005406 washing Methods 0.000 description 54
238000006243 chemical reaction Methods 0.000 description 50
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 50
239000002904 solvent Substances 0.000 description 49
238000004440 column chromatography Methods 0.000 description 47
239000000741 silica gel Substances 0.000 description 46
229910002027 silica gel Inorganic materials 0.000 description 46
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 43
125000004076 pyridyl group Chemical group 0.000 description 43
238000000034 method Methods 0.000 description 42
150000004702 methyl esters Chemical class 0.000 description 40
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 38
238000004364 calculation method Methods 0.000 description 37
229940095102 methyl benzoate Drugs 0.000 description 34
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238000003756 stirring Methods 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
238000001704 evaporation Methods 0.000 description 30
239000003921 oil Substances 0.000 description 29
235000019198 oils Nutrition 0.000 description 29
239000011734 sodium Substances 0.000 description 29
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000007789 gas Substances 0.000 description 25
239000012071 phase Substances 0.000 description 23
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 22
239000000284 extract Substances 0.000 description 22
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238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 21
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235000012239 silicon dioxide Nutrition 0.000 description 21
238000003820 Medium-pressure liquid chromatography Methods 0.000 description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
210000003205 muscle Anatomy 0.000 description 19
229910052708 sodium Inorganic materials 0.000 description 19
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
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238000002360 preparation method Methods 0.000 description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 16
239000002585 base Substances 0.000 description 15
238000001816 cooling Methods 0.000 description 15
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KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 13
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230000000171 quenching effect Effects 0.000 description 13
229920006395 saturated elastomer Polymers 0.000 description 13
CRZQGDNQQAALAY-UHFFFAOYSA-N Methyl benzeneacetate Chemical compound COC(=O)CC1=CC=CC=C1 CRZQGDNQQAALAY-UHFFFAOYSA-N 0.000 description 12
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UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 11
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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 10
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239000012895 dilution Substances 0.000 description 9
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238000010438 heat treatment Methods 0.000 description 8
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 8
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ZDQWVKDDJDIVAL-UHFFFAOYSA-N catecholborane Chemical compound C1=CC=C2O[B]OC2=C1 ZDQWVKDDJDIVAL-UHFFFAOYSA-N 0.000 description 1
238000004113 cell culture Methods 0.000 description 1
230000010261 cell growth Effects 0.000 description 1
229950009789 cetomacrogol 1000 Drugs 0.000 description 1
238000012875 competitive assay Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229960000265 cromoglicic acid Drugs 0.000 description 1
238000013461 design Methods 0.000 description 1
VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 1
229960000520 diphenhydramine Drugs 0.000 description 1
VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
RCFKEIREOSXLET-UHFFFAOYSA-N disulfamide Chemical compound CC1=CC(Cl)=C(S(N)(=O)=O)C=C1S(N)(=O)=O RCFKEIREOSXLET-UHFFFAOYSA-N 0.000 description 1
229940079593 drug Drugs 0.000 description 1
230000000857 drug effect Effects 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
238000004945 emulsification Methods 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
208000037902 enteropathy Diseases 0.000 description 1
230000003628 erosive effect Effects 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
150000002169 ethanolamines Chemical class 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
238000007421 fluorometric assay Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
230000008014 freezing Effects 0.000 description 1
238000007710 freezing Methods 0.000 description 1
230000004927 fusion Effects 0.000 description 1
210000005095 gastrointestinal system Anatomy 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
230000012010 growth Effects 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
238000009396 hybridization Methods 0.000 description 1
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
239000012535 impurity Substances 0.000 description 1
230000002779 inactivation Effects 0.000 description 1
229910052738 indium Inorganic materials 0.000 description 1
230000006698 induction Effects 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
208000028774 intestinal disease Diseases 0.000 description 1
150000002497 iodine compounds Chemical class 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
239000008101 lactose Substances 0.000 description 1
230000003902 lesion Effects 0.000 description 1
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 1
229940057995 liquid paraffin Drugs 0.000 description 1
239000007791 liquid phase Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000012280 lithium aluminium hydride Substances 0.000 description 1
GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical class [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
102000006240 membrane receptors Human genes 0.000 description 1
108020004084 membrane receptors Proteins 0.000 description 1
125000005358 mercaptoalkyl group Chemical group 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
OKHRRIGNGQFVEE-UHFFFAOYSA-N methyl(diphenyl)silicon Chemical compound C=1C=CC=CC=1[Si](C)C1=CC=CC=C1 OKHRRIGNGQFVEE-UHFFFAOYSA-N 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 1
AFFLGGQVNFXPEV-UHFFFAOYSA-N n-decene Natural products CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 0.000 description 1
238000010899 nucleation Methods 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
229940066842 petrolatum Drugs 0.000 description 1
235000019271 petrolatum Nutrition 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
150000002990 phenothiazines Chemical class 0.000 description 1
GRJHONXDTNBDTC-UHFFFAOYSA-N phenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CC=CC=C1 GRJHONXDTNBDTC-UHFFFAOYSA-N 0.000 description 1
125000003884 phenylalkyl group Chemical group 0.000 description 1
230000006461 physiological response Effects 0.000 description 1
150000004885 piperazines Chemical class 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000004033 plastic Substances 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000012264 purified product Substances 0.000 description 1
239000008213 purified water Substances 0.000 description 1
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
SHNUBALDGXWUJI-UHFFFAOYSA-N pyridin-2-ylmethanol Chemical compound OCC1=CC=CC=N1 SHNUBALDGXWUJI-UHFFFAOYSA-N 0.000 description 1
HEKUTLLFKJGUOD-UHFFFAOYSA-N pyridin-2-ylmethyl prop-2-enoate Chemical compound C=CC(=O)OCC1=CC=CC=N1 HEKUTLLFKJGUOD-UHFFFAOYSA-N 0.000 description 1
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
239000002516 radical scavenger Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000011084 recovery Methods 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000027425 release of sequestered calcium ion into cytosol Effects 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000452 restraining effect Effects 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
238000013390 scatchard method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000010703 silicon Substances 0.000 description 1
229910052710 silicon Inorganic materials 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
230000004936 stimulating effect Effects 0.000 description 1
238000003860 storage Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
125000000547 substituted alkyl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000001308 synthesis method Methods 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
NBRKLOOSMBRFMH-UHFFFAOYSA-N tert-butyl chloride Chemical compound CC(C)(C)Cl NBRKLOOSMBRFMH-UHFFFAOYSA-N 0.000 description 1
KJTULOVPMGUBJS-UHFFFAOYSA-N tert-butyl-[tert-butyl(diphenyl)silyl]oxy-diphenylsilane Chemical compound C=1C=CC=CC=1[Si](C=1C=CC=CC=1)(C(C)(C)C)O[Si](C(C)(C)C)(C=1C=CC=CC=1)C1=CC=CC=C1 KJTULOVPMGUBJS-UHFFFAOYSA-N 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical class OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
210000005090 tracheal smooth muscle Anatomy 0.000 description 1
238000012546 transfer Methods 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
229910052721 tungsten Inorganic materials 0.000 description 1
230000001982 uveitic effect Effects 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
229940099259 vaseline Drugs 0.000 description 1
239000004034 viscosity adjusting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Pulmonology (AREA)
Immunology (AREA)
Dermatology (AREA)
Pyridine Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Thiazole And Isothizaole Compounds (AREA)
Discharge Lamps And Accessories Thereof (AREA)
Cathode-Ray Tubes And Fluorescent Screens For Display (AREA)

CN93103596A 1991-09-19 1993-03-19 用于治疗白三烯有关的疾病的化合物 Pending CN1092409A (zh)

Priority Applications (12)

Application Number	Priority Date	Filing Date	Title
CA002119467A CA2119467A1 (fr)	1991-09-19	1992-09-01	Composes pyridiniques pour le traitement des maladies associees aux leucotrienes
EP92920043A EP0604529A1 (fr)	1991-09-19	1992-09-01	Composes de pyridine utilises dans le traitement des maladies apparentees aux leucotrienes
AU25735/92A AU2573592A (en)	1991-09-19	1992-09-01	Pyridine compounds for treating leukotriene-related diseases
PCT/US1992/007466 WO1993006085A1 (fr)	1991-09-19	1992-09-01	Composes de pyridine utilises dans le traitement des maladies apparentees aux leucotrienes
JP5506069A JPH06510786A (ja)	1991-09-19	1992-09-01	ロイコトリエン関連疾患治療用ピリジン化合物
MA22940A MA22649A1 (fr)	1991-09-19	1992-09-08	Procede de preparation de composes pour le traitement des maladies en rapport avec le leucotriene .
IL103205A IL103205A0 (en)	1991-09-19	1992-09-17	Compounds for treating leukotriene-related diseases
NZ244371A NZ244371A (en)	1991-09-19	1992-09-17	Pyridyl-substituted benzylsulphides and analogues and pharmaceutical compositions
APAP/P/1992/000428A AP333A (en)	1991-09-19	1992-09-17	Phenyl-substituted pyridyl aliphatic compounds for treating leukotriene-related diseases.
PT100881A PT100881A (pt)	1991-09-19	1992-09-18	Compostos possuindo um grupo piridilo substituido ligado a um grupo fenilo substituido por um alquilo ou eter contendo um heteroatomo e seu uso
MX9205358A MX9205358A (es)	1991-09-19	1992-09-21	Compuestos para tratar enfermedades relacionadas con leucotrieno.
CN93103596A CN1092409A (zh)	1991-09-19	1993-03-19	用于治疗白三烯有关的疾病的化合物

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US76271091A	1991-09-19	1991-09-19
US79093191A	1991-11-12	1991-11-12
US80959391A	1991-12-18	1991-12-18
US93286992A	1992-08-20	1992-08-20
CN93103596A CN1092409A (zh)	1991-09-19	1993-03-19	用于治疗白三烯有关的疾病的化合物

Publications (1)

Publication Number	Publication Date
CN1092409A true CN1092409A (zh)	1994-09-21

Family

ID=36809157

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CN93103596A Pending CN1092409A (zh)	1991-09-19	1993-03-19	用于治疗白三烯有关的疾病的化合物

Country Status (12)

Country	Link
EP (1)	EP0604529A1 (fr)
JP (1)	JPH06510786A (fr)
CN (1)	CN1092409A (fr)
AP (1)	AP333A (fr)
AU (1)	AU2573592A (fr)
CA (1)	CA2119467A1 (fr)
IL (1)	IL103205A0 (fr)
MA (1)	MA22649A1 (fr)
MX (1)	MX9205358A (fr)
NZ (1)	NZ244371A (fr)
PT (1)	PT100881A (fr)
WO (1)	WO1993006085A1 (fr)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NZ254473A (en) *	1992-06-30	1996-11-26	Smithkline Beecham Corp	Preparation of phenylthiomethylpyridinylalkenoates
GB9313145D0 (en) *	1993-06-25	1993-08-11	Smithkline Beecham Plc	Process
IL115420A0 (en)	1994-09-26	1995-12-31	Zeneca Ltd	Aminoheterocyclic derivatives
DK0812194T3 (da) *	1995-03-02	2000-12-18	Smithkline Beecham Corp	Fremgangsmåde til behandling af atopisk dermatitis og kontaktdermatitis
GB9508137D0 (en) *	1995-04-21	1995-06-07	Smithkline Beecham Plc	Formulation
GB9602166D0 (en)	1996-02-02	1996-04-03	Zeneca Ltd	Aminoheterocyclic derivatives
US6313127B1 (en)	1996-02-02	2001-11-06	Zeneca Limited	Heterocyclic compounds useful as pharmaceutical agents
US5929096A (en) *	1996-02-29	1999-07-27	Smithkline Beecham Corporation	Method for treating atopic dermatitis and contact dermatitis
CN1228087A (zh) *	1996-08-14	1999-09-08	曾尼卡有限公司	取代的嘧啶衍生物和它们的药物用途
AU4557397A (en) *	1996-09-26	1998-04-17	Novartis Ag	Aryl-substituted acrylamides with leukotriene b4 (ltb-4) receptor antagonist activity
UA56197C2 (uk)	1996-11-08	2003-05-15	Зенека Лімітед	Гетероциклічні похідні
JP2001511798A (ja)	1997-02-13	2001-08-14	ゼネカ・リミテッド	オキシド−スクアレンシクラーゼ抑制剤として有用な複素環化合物
DE69815509T2 (de)	1997-02-13	2004-05-13	Astrazeneca Ab	Heterozyklische verbindungen die als oxido-squalen-zyklase-inhibitoren anwendung finden
GB9715895D0 (en)	1997-07-29	1997-10-01	Zeneca Ltd	Heterocyclic compounds
GB9902989D0 (en)	1999-02-11	1999-03-31	Zeneca Ltd	Heterocyclic derivatives

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4056619A (en) *	1975-09-08	1977-11-01	Warner-Lambert Company	1-Substituted-2-(2-pyridinyl)ethanone N-oxides
US5004743A (en) *	1987-11-25	1991-04-02	Merck Frosst Canada, Inc.	Pyridyl styrene dialkanoic acids as anti-leukotriene agents
JPH07116150B2 (ja) *	1990-06-07	1995-12-13	スミスクライン・ビーチャム・コーポレイション	安息香酸誘導体

1992
- 1992-09-01 JP JP5506069A patent/JPH06510786A/ja active Pending
- 1992-09-01 AU AU25735/92A patent/AU2573592A/en not_active Abandoned
- 1992-09-01 WO PCT/US1992/007466 patent/WO1993006085A1/fr not_active Ceased
- 1992-09-01 CA CA002119467A patent/CA2119467A1/fr not_active Abandoned
- 1992-09-01 EP EP92920043A patent/EP0604529A1/fr not_active Withdrawn
- 1992-09-08 MA MA22940A patent/MA22649A1/fr unknown
- 1992-09-17 AP APAP/P/1992/000428A patent/AP333A/en active
- 1992-09-17 NZ NZ244371A patent/NZ244371A/en unknown
- 1992-09-17 IL IL103205A patent/IL103205A0/xx unknown
- 1992-09-18 PT PT100881A patent/PT100881A/pt not_active Application Discontinuation
- 1992-09-21 MX MX9205358A patent/MX9205358A/es unknown
1993
- 1993-03-19 CN CN93103596A patent/CN1092409A/zh active Pending

Also Published As

Publication number	Publication date
IL103205A0 (en)	1993-02-21
AU2573592A (en)	1993-04-27
MX9205358A (es)	1993-07-01
EP0604529A1 (fr)	1994-07-06
MA22649A1 (fr)	1993-04-01
AP333A (en)	1994-04-25
AP9200428A0 (en)	1992-10-31
CA2119467A1 (fr)	1993-04-01
JPH06510786A (ja)	1994-12-01
PT100881A (pt)	1993-10-29
WO1993006085A1 (fr)	1993-04-01
NZ244371A (en)	1995-11-27

Legal Events

Date	Code	Title
1994-09-21	C06	Publication
1994-09-21	PB01	Publication
1996-12-11	C01	Deemed withdrawal of patent application (patent law 1993)
1996-12-11	WD01	Invention patent application deemed withdrawn after publication

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