JP2001506574A - シクロオキシゲナーゼ―２阻害剤およびロイコトリエンａ４ヒドロラーゼ阻害剤を含有する免疫抑制効果をもつ配合物 - Google Patents
シクロオキシゲナーゼ―２阻害剤およびロイコトリエンａ４ヒドロラーゼ阻害剤を含有する免疫抑制効果をもつ配合物Info
- Publication number
- JP2001506574A JP2001506574A JP52935897A JP52935897A JP2001506574A JP 2001506574 A JP2001506574 A JP 2001506574A JP 52935897 A JP52935897 A JP 52935897A JP 52935897 A JP52935897 A JP 52935897A JP 2001506574 A JP2001506574 A JP 2001506574A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- methyl
- amino
- phenyl
- group
- 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
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 title claims abstract description 33
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 title claims description 22
- 229940126065 leukotriene A4 hydrolase inhibitor Drugs 0.000 title claims description 21
- 239000000203 mixture Substances 0.000 title description 28
- 238000009472 formulation Methods 0.000 title description 9
- 230000001506 immunosuppresive effect Effects 0.000 title description 6
- 238000000034 method Methods 0.000 claims abstract description 37
- 238000011282 treatment Methods 0.000 claims abstract description 25
- 210000000056 organ Anatomy 0.000 claims abstract description 22
- 102100022118 Leukotriene A-4 hydrolase Human genes 0.000 claims abstract description 15
- 108010072713 leukotriene A4 hydrolase Proteins 0.000 claims abstract description 14
- 239000004093 hydrolase inhibitor Substances 0.000 claims abstract description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 7
- -1 haloal Coxy Chemical group 0.000 claims description 251
- 125000000217 alkyl group Chemical group 0.000 claims description 125
- 150000001875 compounds Chemical class 0.000 claims description 86
- 125000003545 alkoxy group Chemical group 0.000 claims description 59
- 125000003118 aryl group Chemical group 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
- 150000003839 salts Chemical class 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 40
- 125000004432 carbon atom Chemical group C* 0.000 claims description 38
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 25
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
- 125000003282 alkyl amino group Chemical group 0.000 claims description 23
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 23
- 125000001188 haloalkyl group Chemical group 0.000 claims description 23
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 23
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 21
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 21
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 108010037462 Cyclooxygenase 2 Proteins 0.000 claims description 18
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 17
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 16
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 16
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000002252 acyl group Chemical group 0.000 claims description 15
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 15
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical group CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 14
- 108010036949 Cyclosporine Proteins 0.000 claims description 14
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 14
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 13
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 13
- 125000002971 oxazolyl group Chemical group 0.000 claims description 13
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 13
- 125000005466 alkylenyl group Chemical group 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 229960001265 ciclosporin Drugs 0.000 claims description 12
- 229930182912 cyclosporin Natural products 0.000 claims description 12
- 125000001153 fluoro group Chemical group F* 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 239000003018 immunosuppressive agent Substances 0.000 claims description 12
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 11
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 11
- 229930105110 Cyclosporin A Natural products 0.000 claims description 10
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 10
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 10
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 10
- 230000004044 response Effects 0.000 claims description 10
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 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 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 9
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 9
- 235000019260 propionic acid Nutrition 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 8
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 230000028993 immune response Effects 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 7
- 125000001769 aryl amino group Chemical group 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 7
- 235000010290 biphenyl Nutrition 0.000 claims description 7
- 239000004305 biphenyl Substances 0.000 claims description 7
- 125000002837 carbocyclic group Chemical group 0.000 claims description 7
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 7
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 7
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 7
- 230000005764 inhibitory process Effects 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 108010036941 Cyclosporins Proteins 0.000 claims description 6
- 230000004913 activation Effects 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
- 230000001028 anti-proliverative effect Effects 0.000 claims description 6
- 125000005099 aryl alkyl carbonyl group Chemical group 0.000 claims description 6
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 125000006003 dichloroethyl group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 6
- 229940124589 immunosuppressive drug Drugs 0.000 claims description 6
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 6
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 6
- 206010018691 Granuloma Diseases 0.000 claims description 5
- 206010020751 Hypersensitivity Diseases 0.000 claims description 5
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 claims description 5
- 201000009906 Meningitis Diseases 0.000 claims description 5
- KTDZCOWXCWUPEO-UHFFFAOYSA-N NS-398 Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1CCCCC1 KTDZCOWXCWUPEO-UHFFFAOYSA-N 0.000 claims description 5
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 5
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims description 5
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 5
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- 208000006673 asthma Diseases 0.000 claims description 5
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 5
- 125000004470 heterocyclooxy group Chemical group 0.000 claims description 5
- 210000000265 leukocyte Anatomy 0.000 claims description 5
- 229960001929 meloxicam Drugs 0.000 claims description 5
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 5
- 229940002612 prodrug Drugs 0.000 claims description 5
- 239000000651 prodrug Substances 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
- INRQTVDUZFESAO-UHFFFAOYSA-N 4-(3,4-difluorophenyl)-3-(4-methylsulfonylphenyl)-2h-furan-5-one Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=C(F)C(F)=CC=2)C(=O)OC1 INRQTVDUZFESAO-UHFFFAOYSA-N 0.000 claims description 4
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical compound [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 4
- CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 claims description 4
- 208000023328 Basedow disease Diseases 0.000 claims description 4
- AJFTZWGGHJXZOB-UHFFFAOYSA-N DuP 697 Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC(F)=CC=2)SC(Br)=C1 AJFTZWGGHJXZOB-UHFFFAOYSA-N 0.000 claims description 4
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 4
- 208000015023 Graves' disease Diseases 0.000 claims description 4
- UFPQIRYSPUYQHK-VRKJBCFNSA-N Leukotriene A4 Natural products CCCCCC=C/CC=C/C=C/C=C/[C@@H]1O[C@H]1CCCC(=O)O UFPQIRYSPUYQHK-VRKJBCFNSA-N 0.000 claims description 4
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- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 4
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 claims description 4
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
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- OUHAMHSISQCVQY-UHFFFAOYSA-N 1-[2-(4-benzylphenoxy)ethyl]-2-methyl-4-(2h-tetrazol-5-yl)piperidine Chemical compound CC1CC(C=2NN=NN=2)CCN1CCOC(C=C1)=CC=C1CC1=CC=CC=C1 OUHAMHSISQCVQY-UHFFFAOYSA-N 0.000 claims description 3
- IMGGKNXDSXRLHK-UHFFFAOYSA-N 2-[4-[4-(2-pyrrolidin-1-ylethoxy)phenoxy]phenyl]-1,3-oxazole Chemical compound C=1C=C(OC=2C=CC(=CC=2)C=2OC=CN=2)C=CC=1OCCN1CCCC1 IMGGKNXDSXRLHK-UHFFFAOYSA-N 0.000 claims description 3
- ZJOUYQCSZYKGKU-UHFFFAOYSA-N 3-[1-(4-methylsulfonylphenyl)-4-(trifluoromethyl)imidazol-2-yl]pyridine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1N1C(C=2C=NC=CC=2)=NC(C(F)(F)F)=C1 ZJOUYQCSZYKGKU-UHFFFAOYSA-N 0.000 claims description 3
- SBBJJLDNKNNWFJ-UHFFFAOYSA-N 3-[3-(4-benzylphenoxy)propyl-methylamino]propanoic acid;hydrochloride Chemical compound Cl.C1=CC(OCCCN(C)CCC(O)=O)=CC=C1CC1=CC=CC=C1 SBBJJLDNKNNWFJ-UHFFFAOYSA-N 0.000 claims description 3
- IUWJOVIQIJRTOX-UHFFFAOYSA-N 3-[3-[4-(4-fluorophenoxy)phenoxy]propyl-methylamino]propanoic acid Chemical compound C1=CC(OCCCN(C)CCC(O)=O)=CC=C1OC1=CC=C(F)C=C1 IUWJOVIQIJRTOX-UHFFFAOYSA-N 0.000 claims description 3
- NSRMOHFGSWCCFK-UHFFFAOYSA-N 4-[2-(5-methylpyridin-3-yl)-4-(trifluoromethyl)imidazol-1-yl]benzenesulfonamide Chemical compound CC1=CN=CC(C=2N(C=C(N=2)C(F)(F)F)C=2C=CC(=CC=2)S(N)(=O)=O)=C1 NSRMOHFGSWCCFK-UHFFFAOYSA-N 0.000 claims description 3
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Landscapes
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- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
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- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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| AU1952597A (en) * | 1996-02-13 | 1997-09-02 | G.D. Searle & Co. | Combinations, having immunosuppressive effects, containing cyclooxygenase-2 inhibitor and a leukotriene a4 hydrolase inhibitor |
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| AR038957A1 (es) | 2001-08-15 | 2005-02-02 | Pharmacia Corp | Terapia de combinacion para el tratamiento del cancer |
| KR20050034603A (ko) | 2001-10-09 | 2005-04-14 | 3-디멘져널 파마슈티칼즈 인코오포레이티드 | 치환된 디페닐옥사졸, 이의 합성 및 이의 형광프로브로서의 용도 |
| US20040146503A1 (en) * | 2002-08-28 | 2004-07-29 | Tesi Raymond J. | Methods and compositions for inducing stable immune tolerance |
| US7851486B2 (en) | 2002-10-17 | 2010-12-14 | Decode Genetics Ehf. | Susceptibility gene for myocardial infarction, stroke, and PAOD; methods of treatment |
| US7507531B2 (en) | 2002-10-17 | 2009-03-24 | Decode Genetics Chf. | Use of 5-lipoxygenase activating protein (FLAP) gene to assess susceptibility for myocardial infarction |
| EP1879875A1 (en) * | 2005-04-22 | 2008-01-23 | Wyeth | Crystal forms opf {[(2r)-7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-1-benzofuran-2-yl]methyl}amine hydrochloride |
| AT502258B1 (de) * | 2005-07-22 | 2007-09-15 | Univ Wien | Cox-i-inhibitorverbindungen |
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| PE20091017A1 (es) * | 2007-10-31 | 2009-07-16 | Janssen Pharmaceutica Nv | Diaminas en puente o fusionadas sustituidas con arilo como moduladores de leucotrieno a4 hidrolasa |
| PT2268646E (pt) | 2008-04-11 | 2013-12-10 | Janssen Pharmaceutica Nv | Aminas de tiazolopiridina-2-iloxi-fenil e de tiazolopirazina-2-iloxi-fenilo como moduladores da hidrolase de leucotrieno a4 |
| MX2011012190A (es) | 2009-05-14 | 2011-12-08 | Janssen Pharmaceutica Nv | Compuestos con dos porciones de heteroarilo biciclico fusionado como moduladores de la leucotrieno a4 hidrolasa. |
| EP2545964A1 (en) | 2011-07-13 | 2013-01-16 | Phenex Pharmaceuticals AG | Novel FXR (NR1H4) binding and activity modulating compounds |
| AU2014249168B2 (en) | 2013-03-12 | 2018-07-12 | Celltaxis, Llc | Methods of inhibiting leukotriene A4 hydrolase |
| EP2968265A4 (en) | 2013-03-14 | 2016-12-28 | Celtaxsys Inc | INHIBITORS OF THE LEUKOTRIEN A4 HYDROLASE |
| AU2014240042C1 (en) | 2013-03-14 | 2019-09-05 | Celltaxis, Llc | Inhibitors of leukotriene A4 hydrolase |
| MX2015011678A (es) | 2013-03-14 | 2016-07-08 | Celtaxsys Inc | Inhibidores de leucotrieno a4 hidrolasa. |
| NZ748641A (en) | 2016-06-13 | 2020-04-24 | Gilead Sciences Inc | Fxr (nr1h4) modulating compounds |
| CA2968836C (en) | 2016-06-13 | 2025-09-02 | Gilead Sciences, Inc. | FXR MODULATING COMPOUNDS (NR1H4) |
| ES2982801T3 (es) | 2017-03-28 | 2024-10-17 | Gilead Sciences Inc | Combinaciones terapéuticas para el tratamiento de las enfermedades hepáticas |
| EP3801559B1 (en) | 2018-05-31 | 2025-01-01 | Celltaxis, LLC | Method of reducing pulmonary exacerbations in respiratory disease patients |
| KR102692309B1 (ko) | 2019-01-15 | 2024-08-07 | 길리애드 사이언시즈, 인코포레이티드 | Fxr (nr1h4) 조정 화합물 |
| WO2020172075A1 (en) | 2019-02-19 | 2020-08-27 | Gilead Sciences, Inc. | Solid forms of fxr agonists |
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| US4873259A (en) | 1987-06-10 | 1989-10-10 | Abbott Laboratories | Indole, benzofuran, benzothiophene containing lipoxygenase inhibiting compounds |
| US5242940A (en) | 1987-05-29 | 1993-09-07 | Ortho Pharmaceutical Corporation | Pharmacologically active N-1 and C-5 heterocyclic pyrazoles and method for synthesizing the same |
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| ES2243978T3 (es) * | 1996-02-13 | 2005-12-01 | G.D. SEARLE & CO. | Composiciones que comprenden un inhibidor de la ciclooxigenasa-2 y un antagonista del receptor de leucotrieno b4. |
-
1997
- 1997-02-11 AU AU19525/97A patent/AU1952597A/en not_active Abandoned
- 1997-02-11 DK DK97907545T patent/DK0880363T3/da active
- 1997-02-11 ES ES97907545T patent/ES2183140T3/es not_active Expired - Lifetime
- 1997-02-11 JP JP52935897A patent/JP2001506574A/ja not_active Ceased
- 1997-02-11 PT PT97907545T patent/PT880363E/pt unknown
- 1997-02-11 WO PCT/US1997/001421 patent/WO1997029774A1/en not_active Ceased
- 1997-02-11 CA CA002246336A patent/CA2246336A1/en not_active Abandoned
- 1997-02-11 EP EP97907545A patent/EP0880363B1/en not_active Expired - Lifetime
- 1997-02-11 AT AT97907545T patent/ATE223732T1/de not_active IP Right Cessation
- 1997-02-11 DE DE69715382T patent/DE69715382T2/de not_active Expired - Fee Related
-
2000
- 2000-01-21 US US09/489,311 patent/US6407140B1/en not_active Expired - Fee Related
-
2002
- 2002-05-02 US US10/137,231 patent/US20030004191A1/en not_active Abandoned
-
2004
- 2004-08-27 US US10/928,835 patent/US20050043355A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0880363B1 (en) | 2002-09-11 |
| DK0880363T3 (da) | 2003-01-20 |
| AU1952597A (en) | 1997-09-02 |
| DE69715382D1 (de) | 2002-10-17 |
| ATE223732T1 (de) | 2002-09-15 |
| US20030004191A1 (en) | 2003-01-02 |
| WO1997029774A1 (en) | 1997-08-21 |
| US6407140B1 (en) | 2002-06-18 |
| DE69715382T2 (de) | 2003-04-30 |
| US20050043355A1 (en) | 2005-02-24 |
| PT880363E (pt) | 2002-12-31 |
| ES2183140T3 (es) | 2003-03-16 |
| EP0880363A1 (en) | 1998-12-02 |
| CA2246336A1 (en) | 1997-08-21 |
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