JPH09509651A - 心・血管の、炎症性の及び免疫の疾患を治療するための化合物及び方法 - Google Patents
心・血管の、炎症性の及び免疫の疾患を治療するための化合物及び方法Info
- Publication number
- JPH09509651A JPH09509651A JP7518563A JP51856395A JPH09509651A JP H09509651 A JPH09509651 A JP H09509651A JP 7518563 A JP7518563 A JP 7518563A JP 51856395 A JP51856395 A JP 51856395A JP H09509651 A JPH09509651 A JP H09509651A
- Authority
- JP
- Japan
- Prior art keywords
- trans
- propoxy
- trimethoxyphenyl
- tetrahydrofuran
- compound
- 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.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 168
- 238000000034 method Methods 0.000 title claims abstract description 36
- 230000002757 inflammatory effect Effects 0.000 title description 6
- 208000024172 Cardiovascular disease Diseases 0.000 title description 4
- 208000027866 inflammatory disease Diseases 0.000 title description 4
- 230000002526 effect on cardiovascular system Effects 0.000 title description 3
- 208000026278 immune system disease Diseases 0.000 title description 3
- 102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 claims abstract description 27
- 108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 claims abstract description 27
- 238000004519 manufacturing process Methods 0.000 claims abstract description 21
- 230000001404 mediated effect Effects 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 201000010099 disease Diseases 0.000 claims abstract description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 239000001301 oxygen Substances 0.000 claims abstract description 7
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 5
- 239000003937 drug carrier Substances 0.000 claims abstract 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 138
- -1 2-hydroxyethoxy Chemical group 0.000 claims description 67
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 34
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 27
- 125000004076 pyridyl group Chemical group 0.000 claims description 26
- 125000000304 alkynyl group Chemical group 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 18
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 13
- 241001465754 Metazoa Species 0.000 claims description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 12
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 108010003541 Platelet Activating Factor Proteins 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
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- 150000001768 cations Chemical class 0.000 claims description 6
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- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
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- 241000283690 Bos taurus Species 0.000 claims description 4
- ZQHOSYBLSYGUBK-UHFFFAOYSA-N C1(=CC=CC=C1)C1OC(CC1)C1=CC(=C(C(=C1)OC)OC)OC Chemical compound C1(=CC=CC=C1)C1OC(CC1)C1=CC(=C(C(=C1)OC)OC)OC ZQHOSYBLSYGUBK-UHFFFAOYSA-N 0.000 claims description 4
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
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- 230000006022 acute inflammation Effects 0.000 claims description 4
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- 125000005055 alkyl alkoxy group Chemical group 0.000 claims description 4
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- 208000028867 ischemia Diseases 0.000 claims description 4
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- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 125000005425 toluyl group Chemical group 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 2
- BSLQJEXPGCYJPJ-NHCUHLMSSA-N BrCC=CCOC=1C=C(C=C(C1OCCC)S(=O)(=O)C)[C@@H]1O[C@H](CC1)C1=CC(=C(C(=C1)OC)OC)OC Chemical compound BrCC=CCOC=1C=C(C=C(C1OCCC)S(=O)(=O)C)[C@@H]1O[C@H](CC1)C1=CC(=C(C(=C1)OC)OC)OC BSLQJEXPGCYJPJ-NHCUHLMSSA-N 0.000 claims description 2
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 150000003457 sulfones Chemical class 0.000 claims description 2
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 claims 6
- 238000001727 in vivo Methods 0.000 claims 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- OTISLSMPVRENDE-DNQXCXABSA-N (2r,5r)-2-(3-methylsulfonyl-5-phenylmethoxy-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)oxolane Chemical compound C1=C([C@@H]2O[C@H](CC2)C=2C=C(OC)C(OC)=C(OC)C=2)C=C(S(C)(=O)=O)C(OCCC)=C1OCC1=CC=CC=C1 OTISLSMPVRENDE-DNQXCXABSA-N 0.000 claims 1
- IWUOADATEBCZIF-DHIUTWEWSA-N 2-[2-[2-methoxy-6-methylsulfonyl-4-[(2r,5r)-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]phenoxy]ethyl]isoindole-1,3-dione Chemical compound COC1=C(OC)C(OC)=CC([C@@H]2O[C@H](CC2)C=2C=C(C(OCCN3C(C4=CC=CC=C4C3=O)=O)=C(OC)C=2)S(C)(=O)=O)=C1 IWUOADATEBCZIF-DHIUTWEWSA-N 0.000 claims 1
- LVLOLDZMBZWPRP-DHIUTWEWSA-N 4-[2-propoxy-3-propylsulfonyl-5-[(2r,5r)-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]phenoxy]but-2-yn-1-amine Chemical compound C1=C(S(=O)(=O)CCC)C(OCCC)=C(OCC#CCN)C=C1[C@@H]1O[C@@H](C=2C=C(OC)C(OC)=C(OC)C=2)CC1 LVLOLDZMBZWPRP-DHIUTWEWSA-N 0.000 claims 1
- NSKRAPSLLJBUKZ-NHCUHLMSSA-N 4-[3-methylsulfonyl-2-propoxy-5-[(2R,5R)-5-(3,4,5-trimethoxyphenyl)oxolan-2-yl]phenoxy]but-2-en-1-amine Chemical compound NCC=CCOC=1C=C(C=C(C1OCCC)S(=O)(=O)C)[C@@H]1O[C@H](CC1)C1=CC(=C(C(=C1)OC)OC)OC NSKRAPSLLJBUKZ-NHCUHLMSSA-N 0.000 claims 1
- GDIHNGUSWGSKSU-UHFFFAOYSA-N ON(C(=O)N)C(C)CC Chemical compound ON(C(=O)N)C(C)CC GDIHNGUSWGSKSU-UHFFFAOYSA-N 0.000 claims 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 239000003848 thrombocyte activating factor antagonist Substances 0.000 abstract description 7
- 230000004071 biological effect Effects 0.000 abstract description 6
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 230000028709 inflammatory response Effects 0.000 abstract description 4
- 210000000224 granular leucocyte Anatomy 0.000 abstract description 3
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- 210000000265 leukocyte Anatomy 0.000 abstract 1
- 230000019254 respiratory burst Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 276
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
- 239000000243 solution Substances 0.000 description 156
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 117
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 110
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 106
- 239000011541 reaction mixture Substances 0.000 description 95
- 238000005160 1H NMR spectroscopy Methods 0.000 description 93
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 83
- 239000000047 product Substances 0.000 description 54
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/12—Radicals substituted by oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D307/10—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/14—Radicals substituted by nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/18—Radicals substituted by singly bound hetero atoms other than halogen by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 式、 〔式中、Ar1は、 であり、Ar2は、 であり、そしてここに、 Wは、独立して、−AN(OM)C(O)N(R3)R4、 −AN(R3)C(O)N(OM)R4、 −AN(OM)C(O)R4、 −AC(O)N(OM)R4、 −N(OM)C(O)N(R3)R4、 −N(R3)C(O)N(OM)R4、 −N(OM)C(O)R4、 −C(O)N(OM)R4、 −S(O)nR3、 −S(O)4−CH2C(O)A、 −S(O)4−CH2CH(OH)A、及び −C(O)NHA よりなる群より選ばれ、 Xは、O、S、S(O)、CR5であり、 Y1、Y2は独立して、 (a)水素、 (b)低級アルキル、低級アルコキシ、低級アルケニル、低級アルキニル 、アルキルアリール、 (c)−AN(OM)C(O)N(R3)R4、 −AN(R3)C(O)N(OM)R4、 −AN(OM)C(O)R4、 −AC(O)N(OM)R4、 −AN(R3)C(O)N(OM)R4、 −C(O)N(OM)R4、及び −C(O)NHR3 よりなる群より選ばれ、 ここにAは、置換された又は無置換の低級アルキル、低級アルキル−アルコ キシ、−低級アルキル−ヘテロ芳香族−低級アルキル−、低級アルケニル、低級 アルキニル、アルカリール又はアラルキルよりなる群より選ばれ; Mは、水素、薬剤学的に許容しうる陽イオン、及び代謝的に切断されうる脱 離基より選ばれ; R1及びR2は、独立して水素、低級アルキル、C3〜8のシクロアルキル、 ハロ低級アルキル、ハロ、−COOHより選ばれ; R3及びR4は、独立して水素、置換された又は無置換のアルキル、1個又は より多くの炭素原子がS、N又はOによって置き換えられた置換された又は無置 換のアルキル、3乃至8個の炭素原子よりなる置換された又は無置換のシクロア ルキル、1個又はより多くの炭素原子がS、N又はOによって置き換えられた3 乃至8個の炭素原子よりなる置換された又は無置換のシクロアルキル、及び、ア ルケニル、アルキニル、アリール、アラルキル、アルカリール、C1〜6−アル コキシ−C1〜10アルキル、C1〜6アルキルチオ−C1〜10アルキル、C1〜 6ヒドロキシ−C1〜6アルキル、C1〜6カルボニル−C1〜6アルキル、C 1〜6アミノ−C1〜6アルキルよりなる群より選ばれ; R5は、 (a)水素、 (b)低級アルキル、低級アルケニル、低級アルキニル、アルカリール、 (c)−AN(OM)C(O)N(R3)R4、 −AN(R3)C(O)N(OM)R4、 −AN(OM)C(O)R4、 −AC(O)N(OM)R4、 −AC(O)N(OM)R4、 −AS(O)nR3 −AS(O)nCH2C(O)R3、 −AS(O)nCH2CH(OH)R3、 −AC(O)NHR3、 よりなる群より選ばれ、 式中、各nは、独立して0、1又は2であり;Aは、置換された又は無置換の低 級アルキル、低級アルキル−アルコキシ、低級アルケニル、低級アルキニル、ア ルカリール及びアラルキルよりなる群より選ばれ、Mは、水素、薬剤学的に許容 しうる陽イオン、又は代謝的に切断され得る脱離基より選ばれる。〕の化合物。 2. 次の構造、 〔式中、Aは、置換された又は無置換の低級アルキル、低級アルキル−アルコキ シ、低級アルケニル、低級アルキニル、アルカリール及びアラルキルよりなる群 より選ばれ、 R3及びR4は、独立して、置換された又は無置換のアルキル、アルケニル、 アルキニル、アリール、アラルキル、アルカリール、水素、C1〜6アルコキシ −C1〜10アルキル及びC1〜6アルキルチオ−C1〜10アルキルよりなる群よ り選ばれ、そしてXは、N又はC−OCH3である。〕を有する化合物及び薬剤 学的に許容し得るその塩。 3. R3及びR4が、独立して、置換された又は無置換の低級アルキル、低級ア ルケニル、低級アルキニル、フェニル、ベンジル、トルイル、水素、C1〜6ア ルコキシC1〜6アルキル及びC1〜6アルキルチオ−C1〜6アルキルよりな る群より選ばれるものである、請求項2の化合物。 4. 次の構造、 〔式中、R3及びR4は、独立して、置換された又は無置換のアルキル、アルケニ ル、アルキニル、アリール、アラルキル、アルカリール、水素、C1〜6アルコ キシ−C1〜10アルキル及びC1〜6アルキルチオ−C1〜10アルキルよりなる 群より選ばれ、Xは、N又はC−OCH3であり、そしてmは2〜10である。〕 を有する化合物及び薬剤学的に許容し得るその塩。 5. R3及びR4が、独立して、置換された又は無置換の低級アルキル、低級ア ルケニル、低級アルキニル、フェニル、ベンジル、トルイル、水素、C1〜6ア ルコキシ−C1〜6アルキル及びC1〜6アルキルチオ−C1〜6アルキルより なる群より選ばれるものである、請求項4の化合物。 6. トランス−2−〔4−(2−(N’−ヒドロキシ−N’−置換ウレイジル )エトキシ)3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4, 5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔4−(2−(N’−ヒドロキシ−N’−置換ウレイジル) エトキシ)−3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4, 5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(2−(N’−ヒドロキシ−N’−置換ウレイジル) エトキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3, 4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(3−(N’−ヒドロキシ−N’−置換ウレイジル) プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−〔3−(2−(N’−ヒドロキシ−N’−置換ウレイジル) プロポキシ)−4−ブロポキシ−5−メチルスルホニルフェニル〕−5−(3, 4,5−トリメトキシフェニル)テトラヒドロフラン、 よりなる群より選ばれる、請求項1の化合物。 7. トランス−2−〔3−(2−(N−ヒドロキシ−N’−置換ウレイジル) プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(3−(N’−ヒドロキシ−N’−置換ウレイジル) エトキシ)−4−プロポキシ−5−メタンスルホニルフェニル〕−5−(3,4 ,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(4−(N’−ヒドロキシ−N’−置換ウレイジル) ブチルオキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−〔3−(4−(N’−ヒドロキシ−N’−置換ウレイジル )−2−ブテノキシ)−4−プロポキシ−5−メタンスルホニルフェニル〕−5 −(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 よりなる群より選ばれる、請求項1の化合物。 8. トランス−2−(3−メトキシ−4−ヒドロキシエトキシ−5−ヨードフ ェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−(3−メトキシ−4−メチルスルホキシエトキシ−5−ヨー ドフェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン 、 トランス−2−〔4−(2−ヒドロキシエトキシ)−3−メト キシ−5−メチルチオフェニル〕−5−(3,4,5−トリメトキシフェニル) テトラヒドロフラン、 トランス−2〔4−(2−ヒドロキシエトキシ)−3−メトキシ−5−メチ ルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒ ドロフラン、及び トランス−2−〔4−(2−メチルスルホキシエトキシ)−3−メトキシ− 5−メトキシスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル )テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 9. トランス−2−〔4−(2−フタルイミジルエトキシ)−3−メトキシ− 5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル) テトラヒドロフラン、 トランス−2−〔4−(2−アミノエトキシ)−3−メトキシ−5−メチル スルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒド ロフラン、 トランス−2−〔4−(2−(N’−メチル−N’−ヒドロキシウレイジル )エトキシ)−3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4 ,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔4−(2−(N’−ブチル−N’−ヒドロキシウレイジル )エトキシ)−3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4 ,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−〔4−(2−(N’−ブチル−N’−シクロヘキサニル−N ’−ヒドロキシ)ウレイジルエトキシ)−3−メトキ シ−5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニ ル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 10. トランス−2−〔4−(2−(N−ヒドロキシアミノエトキシ)−3− メトキシ−5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシ フェニル)テトラヒドロフラン、 トランス−2−〔4−(2−(N−ヒドロキシ−N’−ハイドロゲンウレイ ジル)−3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4,5− トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔4−(2−(N−ヒドロキシ−N’−メチルウレイジル) エトキシ)−3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4, 5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔4−(2−(N−ヒドロキシ−N’−プロピルウレイジル )エトキシ)−3−メトキシ−5−メチルスルホニルフェニル〕−5−(3,4 ,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−(3−ベンジルオキシ−4−プロポキシ−5−メチルスルホ ニルフェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラ ン よりなる群より選ばれる、請求項1の化合物。 11. トランス−2−(3−ベンジルオキシ−4−プロポキシ−5−プロピル スルホニルフェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒド ロフラン、 トランス−2−(3−ヒドロキシ−4−プロポキシ−5−プロピルスルホニ ルフェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン 、 トランス−2−〔3−(2−(N−ベンジルオキシカルボニルアミノ)エト キシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3,4, 5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(2−アミノエトキシ)−4−プロポキシ−5−プロ ピルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラ ヒドロフラン、及び トランス−2−〔3−(2−(N’−N’−ヒドロキシウレイジル)エトキ シ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3,4,5 −トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 12. トランス−2−〔3−(2−(N’−(プロピン−2−イル)−N’− ヒドロキシウレイジル)エトキシ)−4−プロポキシ−5−プロピルスルホニル フェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(2−(N’−(1−メチルプロピル)−N’−ヒド ロキシウレイジル)エトキシ)−4−プロポキシ−5−プロピルスルホニルフェ ニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(2−(N’−(1−メチルプロピン−2−イル)− N’−ヒドロキシウレイジル)エトキシ)−4−プロ ポキシ−5−プロピルスルホニルフェニル)−5−(3,4,5−トリメトキシ フェニル)テトラヒドロフラン、及び トランス−2−〔3−(2−(N’−メチル−N’−ヒドロキシウレイジル )エトキシ)−4−プロポキシ−5−プロピルスルホニルフェニル)−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 13. トランス−2−〔3−(3−(N’−ベンジルオキシカルボニルアミノ )プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−( 3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(3−アミノプロポキシ)−4−プロポキシ−5−プ ロピルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テト ラヒドロフラン、 トランス−2−〔3−(3−N’−メチル−N’ヒドロキシウレイジル)プ ロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3, 4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(3−(N’−ブチル−N’−ヒドロキシウレイジル )プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−( 3,4,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−〔3−(3−(N’−1−メチルプロピン−2−イル)−N ’−ヒドロキシウレイジル)プロポキシ)−4−プロポキシ−5−プロピルスル ホニルフェニル〕−5−(3,4,5− トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 14. トランス−2−(3−ヒドロキシ−4−プロポキシ−5−メチルスルホ ニルフェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラ ン、 トランス−2−〔3−(4−フタルイミジル−2−ブテノキシ)−4−プロ ポキシ−5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフ ェニル)テトラヒドロフラン、 トランス−2−〔3−(4−アミノ−2−ブテノキシ)−4−プロポキシ− 5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル) テトラヒドロフラン、 トランス−2−〔3−(4−(N’−メチル−N’−ヒドロキシウレイジル )−2−ブテノキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5 −(3,4,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−〔3−(4−(N’−エチル−N’−ヒドロキシウレイジル )−2−ブテノキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5 −(3,4,5−トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 15. トランス−2−〔3−(4−(N’−ブチル−N’−ヒドロキシウレイ ジル)−2−ブテノキシ)−4−プロポキシ−5−メチルスルホニルフェニル) −5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(4−(N’−(プロピン−2−イル) −N’−ヒドロキシウレイジル)−2−ブテノキシ)−4−プロポキシ−5−メ チルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラ ヒドロフラン、 トランス−2−〔3−(4−(N’−(2,3−ジクロロベンジル)−N’ −ヒドロキシウレイジル)−2−ブテノキシ)−4−プロポキシ−5−メチルス ルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロ フラン、 トランス−2−〔3−(4−(N’−アミノ−N−ヒドロキシウレイジル)−2 −ブテノキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフエニル)テトラヒドロフラン、及び トランス−2−〔3−(4−ブロモ−2−ブテノキシ)−4−プロポキシ− 5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル) テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 16. トランス−2−〔3−(4−ヒドロキシアミノ−2−ブテノキシ)−4 −プロポキシ−5−メチルスルホニルフェニル〕−5−(3,4,5−トリメト キシフェニル)テトラヒドロフラン、 トランス−2−〔3−(4−(N’−アミノ−N−ヒドロキシウレイジル) −2−ブテノキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5− (3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(プロポキシ−2−オン)−4−プロポキシ−5−メ チルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラ ヒドロフラン、 トランス−2−〔3−(プロポキシ−2−オール)−4−プロポキシ−5− メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テト ラヒドロフラン、及び トランス−2−〔3−(2−フタルイミジル)プロポキシ)−4−プロポキ シ−5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニ ル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 17. トランス−2−〔3−(2−アミノプロポキシ)−4−プロポキシ−5 −メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テ トラヒドロフラン、 トランス−2−〔3−(2−(N’−メチル−N’−ヒドロキシウレイジル )−プロポキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−( 3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(2−(N’−ブチル−N’−ヒドロキシウレイジル )プロポキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(プロポキシ−2−オン)−4−プロポキシ−5−プ ロピルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テト ラヒドロフラン、及び トランス−2−〔3−(プロポキシ−2−オール)−4−プロポキシ−5− プロピルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テ トラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 18. トランス−2−〔3−(2−メチルスルホニルフェニル〕−4−プロポ キシ−5−プロピルスルホニルフェニル〕−5−(3,4,5−トリメトキシフ ェニル)テトラヒドロフラン、 トランス−2−〔3−(2−ヒドロキシアミノプロポキシ)−4−プロポキ シ−5−プロピルスルホニルフェニル−5−(3,4,5−トリメトキシフェニ ル)テトラヒドロフラン、 トランス−2−〔3−(2−(N’−アミノ−N−ヒドロキシウレイジル) −プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−( 3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(2−(N’−メチル−N−ヒドロキシウレイジル) プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、及び トランス−2−〔3−(3−(N−ベンジルオキシカルボニルアミノ)プロ ポキシ)−4−エトキシ−5−メタンスルホニルフェニル〕−5−(3,4,5 −トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 19. トランス−2−〔3−(3−アミノエトキシ)−4−プロポキシ−5− メタンスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テト ラヒドロフラン、 トランス−2−〔3−(3−(N’−メチル−N’ヒドロキシウレイジル) プロポキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テト ラヒドロフラン、 トランス−2−〔3−(4−フタルイミジルブチルオキシ)−4−プロポキ シ−5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニ ル)テトラヒドロフラン、 トランス−2−〔3−(4−アミノブチルオキシ)−4−プロポキシ−5− メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テト ラヒドロフラン、及び トランス−2−〔3−(4−(N’−メチル−N’−ヒドロキシウレイジル )ブチルオキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−( 3,4,5−トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 20. トランス−2−(3−メチルスルホニル−5−(4−フタルイミド−ブ ト−2−イニルオキシ)−4−プロピルオキシフェニル)−5−(3,4,5− トリメトキシフェニル)テトラヒドロフラン、 トランス−2−(3−ヒドロキシ−5−メチルスルホニル−4−プロピルオ キシフェニル)−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラ ン、 トランス−2−〔3−(4−アミノーブト−2−イニルオキシ)−5−メチ ルスルホニル−4−プロピルオキシフェニル〕−5−(3,4,5−トリメトキ シフェニル)テトラヒドロフラン、 トランス−2−〔3−(4−(N’−メチル−N’−ヒドロキシウレイジル )−ブト−2−イニルオキシ〕−5−メチルスルホニル−4−プロピルオキシフ ェニル〕−5−(3,4,5−トリメト キシフェニル)テトラヒドロフラン、及び トランス−2−〔3−プロピルスルホニル−5−(4−フタルイミド−ブト −2−イニルオキシ)−4−プロピルオキシフェニル〕−5−(3,4,5−ト リメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 21. トランス−2−〔3−(4−アミノ−ブト−2−イニルオキシ)−5− プロピルスルホニル−4−プロピルオキシフェニル〕−5−(3,4,5−トリ メトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(4−(N’−ブチル−N’−ヒドロキシウレイジル )−ブト−2−イニルオキシ〕−5−プロピルスルホニル−4−プロピルオキシ フェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔3−メチルスルホニル−5−(4−ヒドロキシ−ブト−2 −イニルオキシ)−4−プロピルオキシフェニル〕−5−(3,4,5−トリメ トキシフェニル)テトラヒドロフラン、 トランス−2−〔3−(4−(N−フェノキシカルボニルオキシ−N−フェ ノキシカルボニルアミノ)−ブト−2−イニルオキシ)−5−メチルスルホニル −4−プロピルオキシフェニル〕−5−(3,4,5−トリメトキシフェニル) テトラヒドロフラン、及び、 トランス−2−〔3−〔4−(N−ヒドロキシウレイジル)−ブト−2−イ ニルオキシ〕−5−メチルスルホニル−4−プロピルオキシフェニル〕−5−( 3,4,5−トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 22. トランス−2−〔3−(2−(N’−ヒドロキシ−N’−メチルウレイ ジル)エトキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−〔 5−(2,3−ジメトキシ)ピリジル〕テトラヒドロフラン、 トランス−2−〔3−(2−(N’−ヒドロキシ−N’−ブチルウレイジル )エトキシ)−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−〔5 −(2,3−ジメトキシ)ピリジル〕テトラヒドロフラン、 トランス−2−(3−ベンジルオキシ−4−プロポキシ−5−プロピルスル ホニルフェニル)−5−〔5−(2,3−ジメトキシ)ピリジル〕テトラヒドロ フラン、 トランス−2−(3−ヒドロキシ−4−プロポキシ−5−メチルスルホニル フェニル)−5−〔5−(2,3−ジメトキシ)ピリジル〕テトラヒドロフラン 、及び トランス−2−(3−ヒドロキシ−4−プロポキシ−5−プロピルスルホニ ルフェニル)−5−〔5−(2,3−ジメトキシ)ピリジル〕テトラヒドロフラ ン よりなる群より選ばれる、請求項1の化合物。 23. トランス−2−〔3−(2−N−ベンジルオキシカルボニルアミノエト キシ)−4−プロポキシ−5−メチルスルホニルフェニル)〕−5−〔5−(2 ,3−ジメトキシ)ピリジル〕テトラヒドロフラン、 トランス−2−〔3−(2−N−ベンジルオキシカルボニルアミノエトキシ )−4−プロポキシ−5−プロピルスルホニルフェニル〕−5−〔5−(2,3 −ジメトキシ)ピリジル〕テトラヒドロ フラン、 トランス−2−〔3−(2−アミノエトキシ)−4−プロポキシ−5−メチ ルスルホニルフェニル〕−5−〔5−(2,3−ジメトキシ)ピリジル〕テトラ ヒドロフラン、 トランス−2−〔3−(2−アミノエトキシ)−4−プロポキシ−5−プロ ピルスルホニルフェニル〕−5−〔5−(2,3−ジメトキシ)ピリジル〕テト ラヒドロフラン、及び トランス−2−〔3−(2−(N’−ヒドロキシ−N−メチルウレイジル) エトキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−〔5−( 2,3−ジメトキシ)ピリジル〕テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 24. トランス−2−〔3−(2−(N’−ヒドロキシ−N’−ブチルウレイ ジル)エトキシ)−4−プロポキシ−5−プロピル−スルホニルフェニル〕−5 −〔5−(2,3−ジメトキシ)ピリジル〕テトラヒドロフラン、及び トランス−2−〔3−(2−(N’−ヒドロキシ−N’−エチルウレイジル )エトキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−〔5− (2,3−ジメトキシ)ピリジル〕テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 25. トランス−2−〔2−(N’−sec−ブチル−N’−ヒドロキシウレ イジルメチルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスル ホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフ ラン、 トランス−2−〔2−(N’−メチル−N’−ヒドロキシウレイジルメチル フラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスルホニルフェニ ル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−n−ブチル−N’−ヒドロキシウレイジルメ チルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスルホニルフ ェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−sec−ブチル−N’−ヒドロキシウレイジ ルメチルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスルホニ ルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン 、 トランス−2−〔2−(N’−ヒドロキシウレイジルメチルフラン−5−メ チレンオキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−(3−メチルブチル)−N’−ヒドロキシウ レイジルメチルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルス ルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロ フラン、 トランス−2−〔2−(N’−(イソプロピル−N’−ヒドロキシウレイジ ルメチルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスルホニ ルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン 、 トランス−2−〔2−(N’−シクロプロピルメチル−N’− ヒドロキシウレイジルメチルフラン−5−メチレンオキシ)−4−プロポキシ− 5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル) テトラヒドロフラン、 トランス−2−〔2−(N’−シクロブチル−N’−ヒドロキシウレイジル メチルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスルホニル フェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−ヒドロキシウレイジルメチルフラン−5−メ チレンオキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−(3−メチルプロピル)−N’−ヒドロキシ ウレイジルメチルピリジン−6−メチレンオキシ)−4−プロポキシ−5−メチ ルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒ ドロフラン、 トランス−2−〔2−N’−シクロプロピルメチル−N’−ヒドロキシウレ イジルメチルピリジン−6−メチレンオキシ)−4−プロポキシ−5−メチルス ルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロ フラン、 トランス−2−〔2−N’−n−ブチル−N’−ヒドロキシウレイジルメチ ルピリジン−6−メチレンオキシ)−4−プロポキシ−5−メチルスルホニルフ ェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−N’−n−ブチル−N’−ヒドロキシウレイジルメチ ルピリジン−6−メチレンオキシ)−4−プロポキシ −5−メチルスルホニルフェニル〕−5−(3,4,5−トリメトキシフェニル )テトラヒドロフラン塩酸塩、 トランス−2−〔2−(N’−ベンジル)−N’−ヒドロキシウレイジルメ チルピリジン−6−メチレンオキシ)−4−プロポキシ−5−メチルスルホニル フェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−アルキル−N’−ヒドロキシウレイジルメチ ルフラン−5−メチレンオキシ)−4−プロポキシ−5−メチルスルホニルフェ ニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフラン、 トランス−2−〔2−(N’−(3−アルキル)−N’−ヒドロキシウレイ ジルメチルピリジン−6−メチレンオキシ)−4−プロポキシ−5−メチルスル ホニルフェニル〕−5−(3,4,5−トリメトキシフェニル)テトラヒドロフ ラン、及び トランス−2−〔2−(N’−ヒドロキシウレイジルメチルフラン−5−メ チレンオキシ)−4−プロポキシ−5−メチルスルホニルフェニル〕−5−(3 ,4,5−トリメトキシフェニル)テトラヒドロフラン よりなる群より選ばれる、請求項1の化合物。 26. 薬剤学的に許容し得る担体中の、請求項1の化合物の有効なPAF受容 体拮抗及び/又は5−リポキシゲナーゼ阻害量を含む、薬剤組成物。 27. 薬剤学的に許容し得る担体中の、請求項2の化合物の有効なPAF受容 体拮抗及び/又は5−リポキシゲナーゼ阻害量を含む、薬剤組成物。 28. 薬剤学的に許容し得る担体中の、請求項3の化合物の有効なPAF受容 体拮抗及び/又は5−リポキシゲナーゼ阻害量を含む、薬剤組成物。 29. 動物における、血小板活性化因子によって又は5−リポキシゲナーゼの 産物によって媒介される疾病の治療のための方法であって、そのような治療を必 要とする動物に、請求項1の化合物の、生体内における酸素ラジカルの生成を減 少させるのに有効な量を薬剤学的に許容し得る担体に入れて投与することを含む 方法。 30. 該動物がヒト、ウマ、イヌ及びウシよりなる群より選ばれるものである 、請求項29の方法。 31. 血小板活性化因子によって又は5−リポキシゲナーゼの産物によって媒 介される該疾病が、関節炎、急性炎症、喘息、内毒素ショック、疼痛、乾癬、眼 科炎症、虚血、胃腸潰瘍、心筋梗塞、炎症性大腸疾患、及び急性呼吸窮迫症候群 よりなる群より選ばれるものである、請求項29の方法。 32. 動物における、血小板活性化因子によって又は5−リポキシゲナーゼの 産物によって媒介される疾病の治療のための方法であって、そのような治療を必 要とする動物に、請求項2の化合物の、生体内における酸素ラジカルの生成を減 少させるのに有効な量を薬剤学的に許容し得る担体に入れて投与することを含む 方法。 33. 該動物がヒト、ウマ、イヌ及びウシよりなる群より選ばれるものである 、請求項32の方法。 34. 血小板活性化因子によって又は5−リポキシゲナーゼの産物によって媒 介される該疾病が、関節炎、急性炎症、喘息、内毒素ショック、疼痛、乾癬、眼 科炎症、虚血、胃腸潰瘍、心筋梗塞、炎 症性大腸疾患、及び急性呼吸窮迫症候群よりなる群より選ばれるものである、請 求項32の方法。 35. 動物における、血小板活性化因子によって又は5−リポキシゲナーゼの 産物によって媒介される疾病の治療のための方法であって、そのような治療を必 要とする動物に、請求項3の化合物の、生体内における酸素ラジカルの生成を減 少させるのに有効な量を薬剤学的に許容し得る担体に入れて投与することを含む 方法。 36. 該動物がヒト、ウマ、イヌ及びウシよりなる群より選ばれるものである 、請求項35の方法。 37. 血小板活性化因子によって又は5−リポキシゲナーゼの産物によって媒 介される該疾病が、関節炎、急性炎症、喘息、内毒素ショック、疼痛、乾癬、眼 科炎症、虚血、胃腸潰瘍、心筋梗塞、炎症性大腸疾患、及び急性呼吸窮迫症候群 よりなる群より選ばれるものである、請求項35の方法。 38. Wがメチルスルホニルである、請求項1の化合物。 39. 該ヘテロ芳香族置換基がフランである、請求項1の化合物。 40. 該ヘテロ芳香族置換基がピリジンである、請求項1の化合物。 41. 構造、 を有する、請求項1の化合物。 42. 構造、 を有する、請求項41の化合物。 43. 構造、 を有する、請求項41の化合物。
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-
1994
- 1994-01-06 US US08/178,222 patent/US5463083A/en not_active Expired - Fee Related
-
1995
- 1995-01-06 AU AU15974/95A patent/AU696227B2/en not_active Ceased
- 1995-01-06 JP JP7518563A patent/JPH09509651A/ja not_active Ceased
- 1995-01-06 CA CA002180123A patent/CA2180123A1/en not_active Abandoned
- 1995-01-06 EP EP95907972A patent/EP0749306A4/en not_active Ceased
- 1995-01-06 US US08/669,371 patent/US6420392B1/en not_active Expired - Fee Related
- 1995-01-06 WO PCT/US1995/000060 patent/WO1995018610A1/en not_active Application Discontinuation
- 1995-01-06 HU HU9601854A patent/HUT74982A/hu unknown
- 1995-01-06 CN CN95191813A patent/CN1143319A/zh active Pending
- 1995-06-06 US US08/466,332 patent/US5741809A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
AU696227B2 (en) | 1998-09-03 |
HU9601854D0 (en) | 1996-09-30 |
AU1597495A (en) | 1995-08-01 |
US6420392B1 (en) | 2002-07-16 |
CN1143319A (zh) | 1997-02-19 |
US5463083A (en) | 1995-10-31 |
WO1995018610A1 (en) | 1995-07-13 |
HUT74982A (en) | 1997-03-28 |
EP0749306A1 (en) | 1996-12-27 |
EP0749306A4 (en) | 1997-04-16 |
CA2180123A1 (en) | 1995-07-13 |
US5741809A (en) | 1998-04-21 |
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