IL98090A - Dihydrobenzofiran-2-carboxylic acids converted by alkoxy and their history and pharmaceutical preparations containing them - Google Patents
Dihydrobenzofiran-2-carboxylic acids converted by alkoxy and their history and pharmaceutical preparations containing themInfo
- Publication number
- IL98090A IL98090A IL9809091A IL9809091A IL98090A IL 98090 A IL98090 A IL 98090A IL 9809091 A IL9809091 A IL 9809091A IL 9809091 A IL9809091 A IL 9809091A IL 98090 A IL98090 A IL 98090A
- Authority
- IL
- Israel
- Prior art keywords
- propyl
- carbon atoms
- compound
- dihydro
- benzopyran
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 82
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
- 239000001257 hydrogen Substances 0.000 claims abstract description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 7
- 239000001301 oxygen Substances 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 239000011593 sulfur Substances 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 230000001404 mediated effect Effects 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 125000004432 carbon atom Chemical group C* 0.000 claims description 38
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 24
- VNYSSYRCGWBHLG-AMOLWHMGSA-N leukotriene B4 Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC(O)=O VNYSSYRCGWBHLG-AMOLWHMGSA-N 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- -1 2-amino-4-thiazolyl Chemical group 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 claims description 4
- 201000005569 Gout Diseases 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
- NKRDPYYEABXMKT-UHFFFAOYSA-N 7-[3-[3-methoxy-2-prop-2-enyl-4-(1,3-thiazol-4-yl)phenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC=2CCC(C(O)=O)OC=2C(CCC)=C1OCCCOC(C(=C1OC)CC=C)=CC=C1C1=CSC=N1 NKRDPYYEABXMKT-UHFFFAOYSA-N 0.000 claims description 2
- PKXKEQQNXAOFDZ-UHFFFAOYSA-N 7-[3-[3-methoxy-4-(2-methoxy-1,3-thiazol-4-yl)-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(O)=O)CCC)C=CC=1C1=CSC(OC)=N1 PKXKEQQNXAOFDZ-UHFFFAOYSA-N 0.000 claims description 2
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims 13
- 239000003937 drug carrier Substances 0.000 claims 8
- PUGSQEGOAXWGCW-UHFFFAOYSA-N 7-[3-[3-methoxy-2-propyl-4-(2-sulfanylidene-3h-1,3-thiazol-4-yl)phenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(O)=O)CCC)C=CC=1C1=CSC(=S)N1 PUGSQEGOAXWGCW-UHFFFAOYSA-N 0.000 claims 1
- PDNAXMNHGWAVAV-UHFFFAOYSA-N 7-[3-[4-(2-benzylsulfanyl-1,3-thiazol-4-yl)-3-methoxy-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(O)=O)CCC)C=CC=1C(N=1)=CSC=1SCC1=CC=CC=C1 PDNAXMNHGWAVAV-UHFFFAOYSA-N 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 10
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 4
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 4
- OFDNQWIFNXBECV-VFSYNPLYSA-N dolastatin 10 Chemical compound CC(C)[C@H](N(C)C)C(=O)N[C@@H](C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)[C@H](OC)CC(=O)N1CCC[C@H]1[C@H](OC)[C@@H](C)C(=O)N[C@H](C=1SC=CN=1)CC1=CC=CC=C1 OFDNQWIFNXBECV-VFSYNPLYSA-N 0.000 abstract description 4
- 150000002431 hydrogen Chemical class 0.000 abstract 2
- VNYSSYRCGWBHLG-AMOLWHMGSA-M leukotriene B4(1-) Chemical compound CCCCC\C=C/C[C@@H](O)\C=C\C=C\C=C/[C@@H](O)CCCC([O-])=O VNYSSYRCGWBHLG-AMOLWHMGSA-M 0.000 abstract 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 162
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 52
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 52
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- 239000012267 brine Substances 0.000 description 28
- 239000011541 reaction mixture Substances 0.000 description 28
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 27
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 27
- 229910052938 sodium sulfate Inorganic materials 0.000 description 27
- 235000011152 sodium sulphate Nutrition 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- 239000010410 layer Substances 0.000 description 25
- 238000003818 flash chromatography Methods 0.000 description 19
- 238000001819 mass spectrum Methods 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- YEESKJGWJFYOOK-IJHYULJSSA-N leukotriene D4 Chemical compound CCCCC\C=C/C\C=C/C=C/C=C/[C@H]([C@@H](O)CCCC(O)=O)SC[C@H](N)C(=O)NCC(O)=O YEESKJGWJFYOOK-IJHYULJSSA-N 0.000 description 7
- 210000000440 neutrophil Anatomy 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 6
- 239000012981 Hank's balanced salt solution Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000008485 antagonism Effects 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 4
- 239000001095 magnesium carbonate Substances 0.000 description 4
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 4
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 3
- WJAASTDRAAMYNK-UHFFFAOYSA-N benzyl carbamimidothioate;hydron;chloride Chemical compound Cl.NC(=N)SCC1=CC=CC=C1 WJAASTDRAAMYNK-UHFFFAOYSA-N 0.000 description 3
- 230000035605 chemotaxis Effects 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 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 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 3
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- 101100545004 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YSP2 gene Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000002975 chemoattractant Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000009089 cytolysis Effects 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- 150000002084 enol ethers Chemical group 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000012997 ficoll-paque Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- HCZKYJDFEPMADG-TXEJJXNPSA-N masoprocol Chemical compound C([C@H](C)[C@H](C)CC=1C=C(O)C(O)=CC=1)C1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-TXEJJXNPSA-N 0.000 description 2
- VPWUEPFRXJWMRV-UHFFFAOYSA-N methyl 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC(C(C)=O)=C(OC)C(CCC)=C1OCCCOC1=CC=C(CCC(O2)C(=O)OC)C2=C1CCC VPWUEPFRXJWMRV-UHFFFAOYSA-N 0.000 description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000004062 sedimentation Methods 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
- 150000003557 thiazoles Chemical class 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 239000003039 volatile agent Substances 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- UHAYGLCGMYKNGL-UHFFFAOYSA-N 3-[7-[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propoxy]-8-propyl-3,4-dihydro-2h-chromen-2-yl]propanoic acid Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1OCCCOC1=CC=C(CCC(CCC(O)=O)O2)C2=C1CCC UHAYGLCGMYKNGL-UHFFFAOYSA-N 0.000 description 1
- DFGKGUXTPFWHIX-UHFFFAOYSA-N 6-[2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]acetyl]-3H-1,3-benzoxazol-2-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)C1=CC2=C(NC(O2)=O)C=C1 DFGKGUXTPFWHIX-UHFFFAOYSA-N 0.000 description 1
- ZVVCSBSDFGYRCB-UHFFFAOYSA-N 7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound C1=CC(C(C)=O)=C(OC)C(CCC)=C1OCCCOC1=CC=C(CCC(O2)C(O)=O)C2=C1CCC ZVVCSBSDFGYRCB-UHFFFAOYSA-N 0.000 description 1
- PWBIFHFPTKIDON-UHFFFAOYSA-N 7-[3-[3-methoxy-2-propyl-4-(1,3-thiazol-4-yl)phenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(O)=O)CCC)C=CC=1C1=CSC=N1 PWBIFHFPTKIDON-UHFFFAOYSA-N 0.000 description 1
- KZQNDFFVZLIJCF-UHFFFAOYSA-N 7-[3-[3-methoxy-4-(2-methyl-1,3-oxazol-4-yl)-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(O)=O)CCC)C=CC=1C1=COC(C)=N1 KZQNDFFVZLIJCF-UHFFFAOYSA-N 0.000 description 1
- MUCFSURAOMWHPO-UHFFFAOYSA-N 7-[3-[3-methoxy-4-(2-methylsulfanyl-1,3-thiazol-4-yl)-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylic acid Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(O)=O)CCC)C=CC=1C1=CSC(SC)=N1 MUCFSURAOMWHPO-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- QKUVJKMCSNBTNR-UHFFFAOYSA-N C(=O)N.COC=1C(=C(OCCCOC2=C(C3=C(CCC(O3)C(=O)OC)C=C2)CCC)C=CC1C=1N=CSC1)CC=C Chemical compound C(=O)N.COC=1C(=C(OCCCOC2=C(C3=C(CCC(O3)C(=O)OC)C=C2)CCC)C=CC1C=1N=CSC1)CC=C QKUVJKMCSNBTNR-UHFFFAOYSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 239000012998 Hepes-buffered hanks’ balanced salt solution Substances 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000003680 Leukotriene B4 receptors Human genes 0.000 description 1
- 108090000093 Leukotriene B4 receptors Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- PRQROPMIIGLWRP-UHFFFAOYSA-N N-formyl-methionyl-leucyl-phenylalanin Chemical compound CSCCC(NC=O)C(=O)NC(CC(C)C)C(=O)NC(C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- YNNGZCVDIREDDK-UHFFFAOYSA-N aminocarbamodithioic acid Chemical compound NNC(S)=S YNNGZCVDIREDDK-UHFFFAOYSA-N 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- HCZKYJDFEPMADG-UHFFFAOYSA-N erythro-nordihydroguaiaretic acid Natural products C=1C=C(O)C(O)=CC=1CC(C)C(C)CC1=CC=C(O)C(O)=C1 HCZKYJDFEPMADG-UHFFFAOYSA-N 0.000 description 1
- AEOCXXJPGCBFJA-UHFFFAOYSA-N ethionamide Chemical compound CCC1=CC(C(N)=S)=CC=N1 AEOCXXJPGCBFJA-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 229960003951 masoprocol Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- OBFUZLNWLLSHRO-UHFFFAOYSA-N methyl 3-[7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxy]-8-propyl-3,4-dihydro-2h-chromen-2-yl]propanoate Chemical compound C1=CC(C(C)=O)=C(OC)C(CCC)=C1OCCCOC1=CC=C(CCC(CCC(=O)OC)O2)C2=C1CCC OBFUZLNWLLSHRO-UHFFFAOYSA-N 0.000 description 1
- NNCXYAUSDRHUDR-UHFFFAOYSA-N methyl 7-[3-[3-methoxy-2-propyl-4-(2-sulfanylidene-3h-1,3-thiazol-4-yl)phenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(=O)OC)CCC)C=CC=1C1=CSC(=S)N1 NNCXYAUSDRHUDR-UHFFFAOYSA-N 0.000 description 1
- DBYNPZWTSKPKPS-UHFFFAOYSA-N methyl 7-[3-[3-methoxy-2-propyl-4-(2-thiocyanatoacetyl)phenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC(C(=O)CSC#N)=C(OC)C(CCC)=C1OCCCOC1=CC=C(CCC(O2)C(=O)OC)C2=C1CCC DBYNPZWTSKPKPS-UHFFFAOYSA-N 0.000 description 1
- NVOOLMSHQKCKKY-UHFFFAOYSA-N methyl 7-[3-[3-methoxy-2-propyl-4-[2-(trifluoromethylsulfonyloxy)acetyl]phenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC(C(=O)COS(=O)(=O)C(F)(F)F)=C(OC)C(CCC)=C1OCCCOC1=CC=C(CCC(O2)C(=O)OC)C2=C1CCC NVOOLMSHQKCKKY-UHFFFAOYSA-N 0.000 description 1
- HZMRDMDSXDDPMR-UHFFFAOYSA-N methyl 7-[3-[3-methoxy-4-(1,3-oxazol-4-yl)-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(=O)OC)CCC)C=CC=1C1=COC=N1 HZMRDMDSXDDPMR-UHFFFAOYSA-N 0.000 description 1
- IOGOKPUTVZGUHQ-UHFFFAOYSA-N methyl 7-[3-[3-methoxy-4-(2-methoxy-1,3-thiazol-4-yl)-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(=O)OC)CCC)C=CC=1C1=CSC(OC)=N1 IOGOKPUTVZGUHQ-UHFFFAOYSA-N 0.000 description 1
- LZRRDNTVVKIKAS-UHFFFAOYSA-N methyl 7-[3-[3-methoxy-4-(2-methylsulfanyl-1,3-thiazol-4-yl)-2-propylphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound COC=1C(CCC)=C(OCCCOC=2C(=C3OC(CCC3=CC=2)C(=O)OC)CCC)C=CC=1C1=CSC(SC)=N1 LZRRDNTVVKIKAS-UHFFFAOYSA-N 0.000 description 1
- ZIDISROCWJFTOG-UHFFFAOYSA-N methyl 7-[3-[4-(2-bromoacetyl)-2-(cyclopropylmethyl)-3-methoxyphenoxy]propoxy]-8-propyl-3,4-dihydro-2h-chromene-2-carboxylate Chemical compound C1=CC=2CCC(C(=O)OC)OC=2C(CCC)=C1OCCCOC1=CC=C(C(=O)CBr)C(OC)=C1CC1CC1 ZIDISROCWJFTOG-UHFFFAOYSA-N 0.000 description 1
- 238000004452 microanalysis Methods 0.000 description 1
- 230000030505 negative regulation of chemotaxis Effects 0.000 description 1
- SPIFDSWFDKNERT-UHFFFAOYSA-N nickel;hydrate Chemical compound O.[Ni] SPIFDSWFDKNERT-UHFFFAOYSA-N 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- ZNNZYHKDIALBAK-UHFFFAOYSA-M potassium thiocyanate Chemical compound [K+].[S-]C#N ZNNZYHKDIALBAK-UHFFFAOYSA-M 0.000 description 1
- 229940116357 potassium thiocyanate Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 210000003492 pulmonary vein Anatomy 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000010567 reverse phase preparative liquid chromatography Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 230000016160 smooth muscle contraction Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000005207 tetraalkylammonium group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/521,777 US5073562A (en) | 1990-05-10 | 1990-05-10 | Alkoxy-substituted dihydrobenzopyran-2-carboxylic acids and derivatives thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL98090A0 IL98090A0 (en) | 1992-06-21 |
| IL98090A true IL98090A (en) | 1995-07-31 |
Family
ID=24078110
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL9809091A IL98090A (en) | 1990-05-10 | 1991-05-09 | Dihydrobenzofiran-2-carboxylic acids converted by alkoxy and their history and pharmaceutical preparations containing them |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5073562A (es) |
| EP (1) | EP0527922B1 (es) |
| JP (1) | JPH05507084A (es) |
| AT (1) | ATE119528T1 (es) |
| AU (1) | AU647487B2 (es) |
| CA (1) | CA2082500A1 (es) |
| DE (1) | DE69108025T2 (es) |
| DK (1) | DK0527922T3 (es) |
| ES (1) | ES2069295T3 (es) |
| GR (1) | GR3015349T3 (es) |
| IE (1) | IE62719B1 (es) |
| IL (1) | IL98090A (es) |
| NZ (1) | NZ238092A (es) |
| PT (1) | PT97614A (es) |
| WO (1) | WO1991017160A1 (es) |
| ZA (1) | ZA913546B (es) |
Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2677021B1 (fr) * | 1991-05-31 | 1993-10-01 | Upsa Laboratoires | Nouveaux derives de thiazole antagonistes des recepteurs a l'angiotensine ii; leurs procedes de preparation, compositions pharmaceutiques les contenant. |
| US5352690A (en) * | 1992-07-01 | 1994-10-04 | Eli Lilly And Company | 1,2,4-trioxygenated benzene derivatives useful as leukotriene antagonists |
| WO1995032201A1 (en) * | 1994-05-25 | 1995-11-30 | G.D. Searle & Co. | Alkoxy-substituted dihydrobenzopyran-2-sulfonimides derivatives, their preparation and their use as leukotriene b4 antagonists |
| US5516917A (en) * | 1994-06-08 | 1996-05-14 | G. D. Searle & Co. | Leukotriene B4 antagonists |
| CN1160399A (zh) * | 1994-10-13 | 1997-09-24 | 美国辉瑞有限公司 | 苯并吡喃和苯并稠合化合物、其制备方法和它们作为白三烯b4(ltb4)拮抗剂的用途 |
| KR100232340B1 (ko) * | 1994-10-13 | 1999-12-01 | 디. 제이. 우드, 스피겔 알렌 제이 | 류코트리엔 b4(ltb4) 길항물질로서의 벤조피란 및 벤조-축합된 화합물 |
| JP2002528533A (ja) | 1998-10-29 | 2002-09-03 | ブリストル−マイヤーズ スクイブ カンパニー | 酵素ｉｍｐｄｈの新規なインヒビター |
| AU2001292874B2 (en) | 2000-09-27 | 2006-06-15 | Merck & Co., Inc. | Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders |
| CA2427610A1 (en) * | 2000-10-31 | 2002-08-08 | Merck & Co., Inc. | Benzopyrancarboxylic acid derivatives for the treatment of diabetes and lipid disorders |
| US7446127B2 (en) * | 2003-08-27 | 2008-11-04 | Sk Holdings Co, Ltd. | Chroman carboxylic acid derivatives for the treatment of diabetes and lipid disorders |
| AU2006259565B2 (en) | 2005-06-15 | 2011-01-06 | Complete Genomics, Inc. | Single molecule arrays for genetic and chemical analysis |
| EP1951900B1 (en) | 2005-10-07 | 2016-06-15 | Callida Genomics, Inc. | Self-assembled single molecule arrays and uses thereof |
| WO2007133831A2 (en) | 2006-02-24 | 2007-11-22 | Callida Genomics, Inc. | High throughput genome sequencing on dna arrays |
| EP3604555B1 (en) | 2011-10-14 | 2024-12-25 | President and Fellows of Harvard College | Sequencing by structure assembly |
| US9914967B2 (en) | 2012-06-05 | 2018-03-13 | President And Fellows Of Harvard College | Spatial sequencing of nucleic acids using DNA origami probes |
| US9476089B2 (en) | 2012-10-18 | 2016-10-25 | President And Fellows Of Harvard College | Methods of making oligonucleotide probes |
| US9540685B2 (en) | 2013-03-15 | 2017-01-10 | President And Fellows Of Harvard College | Methods of identifying homologous genes using FISH |
| US20180320226A1 (en) | 2014-08-19 | 2018-11-08 | President And Fellows Of Harvard College | RNA-Guided Systems For Probing And Mapping Of Nucleic Acids |
| US20230109070A1 (en) | 2019-10-18 | 2023-04-06 | The Board of Trustees og the Leland Standford Junior University | Clinical- and industrial-scale intact-tissue sequencing |
| US12071667B2 (en) | 2020-11-04 | 2024-08-27 | 10X Genomics, Inc. | Sequence analysis using meta-stable nucleic acid molecules |
| US12060603B2 (en) | 2021-01-19 | 2024-08-13 | 10X Genomics, Inc. | Methods for internally controlled in situ assays using padlock probes |
| EP4347877A1 (en) | 2021-06-01 | 2024-04-10 | 10X Genomics, Inc. | Methods and compositions for analyte detection and probe resolution |
| EP4347880B1 (en) | 2021-06-02 | 2026-02-04 | 10X Genomics, Inc. | Sample analysis using asymmetric circularizable probes |
| US20230026886A1 (en) | 2021-07-13 | 2023-01-26 | 10X Genomics, Inc. | Methods for preparing polymerized matrix with controllable thickness |
| CA3224093A1 (en) | 2021-07-30 | 2023-02-02 | Jorge Ivan Hernandez Neuta | Methods and compositions for synchronizing reactions in situ |
| US12139751B2 (en) | 2021-07-30 | 2024-11-12 | 10X Genomics, Inc. | Circularizable probes for in situ analysis |
| US12391984B2 (en) | 2021-08-03 | 2025-08-19 | 10X Genomics, Inc. | Compositions and methods for rolling circle amplification |
| US12460251B2 (en) | 2021-08-03 | 2025-11-04 | 10X Genomics, Inc. | Stabilization and/or compaction of nucleic acid molecules |
| WO2023015192A1 (en) | 2021-08-03 | 2023-02-09 | 10X Genomics, Inc. | Nucleic acid concatemers and methods for stabilizing and/or compacting the same |
| US12529096B2 (en) | 2021-08-03 | 2026-01-20 | 10X Genomics, Inc. | Stabilization and/or compaction of nucleic acid structures |
| WO2023023484A1 (en) | 2021-08-16 | 2023-02-23 | 10X Genomics, Inc. | Probes comprising a split barcode region and methods of use |
| US20230242974A1 (en) | 2021-12-27 | 2023-08-03 | 10X Genomics, Inc. | Methods and compositions for rolling circle amplification |
| WO2023141588A1 (en) | 2022-01-21 | 2023-07-27 | 10X Genomics, Inc. | Multiple readout signals for analyzing a sample |
| AU2023223467A1 (en) | 2022-02-23 | 2024-08-08 | Insitro, Inc. | Pooled optical screening and transcriptional measurements of cells comprising barcoded genetic perturbations |
| US12559791B2 (en) | 2022-05-06 | 2026-02-24 | 10X Genomics, Inc. | Methods and compositions for in situ analysis of V(D)J sequences |
| EP4540607A1 (en) | 2022-06-17 | 2025-04-23 | 10X Genomics, Inc. | Catalytic de-crosslinking of samples for in situ analysis |
| CN120129825A (zh) | 2022-10-14 | 2025-06-10 | 10X基因组学有限公司 | 用于评估生物样品质量的方法、组合物和系统 |
| WO2024102736A1 (en) | 2022-11-08 | 2024-05-16 | 10X Genomics, Inc. | Immobilization methods and compositions for in situ detection |
| EP4573210B1 (en) | 2022-11-16 | 2026-05-06 | 10X Genomics, Inc. | Method for analysing gene expression in cells in a pellet |
| US20240218437A1 (en) | 2022-12-16 | 2024-07-04 | 10X Genomics, Inc. | Methods and compositions for assessing performance |
| EP4646492A1 (en) | 2023-01-06 | 2025-11-12 | 10X Genomics, Inc. | Methods and compositions for in situ analysis of variant sequences |
| WO2024163948A2 (en) | 2023-02-03 | 2024-08-08 | 10X Genomics, Inc. | In situ analysis of variant sequences in biological samples |
| WO2025029831A1 (en) | 2023-07-31 | 2025-02-06 | 10X Genomics, Inc. | Methods and systems for targeted rna cleavage and target rna-primed rolling circle amplification |
| US20250207203A1 (en) | 2023-12-20 | 2025-06-26 | 10X Genomics, Inc. | In situ detection of copy number variations in biological samples |
| WO2025264702A1 (en) | 2024-06-18 | 2025-12-26 | 10X Genomics, Inc. | 3d hydrogels for nucleic acid sequencing |
| WO2026030369A1 (en) | 2024-07-31 | 2026-02-05 | 10X Genomics, Inc. | Methods and compositions for in situ analyte detection |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1384530A (en) * | 1971-07-29 | 1975-02-19 | Fisons Ltd | Chromone derivatives |
| ATE14579T1 (de) * | 1979-03-20 | 1985-08-15 | Fisons Plc | Pharmazeutische heterocyclische verbindungen, verfahren zu ihrer herstellung und sie enthaltende zusammensetzungen. |
| US4474788A (en) * | 1981-11-12 | 1984-10-02 | Fisons Plc | Anti-SRSA quinoline carboxylic acid derivatives |
| ZA844519B (en) * | 1983-06-24 | 1985-02-27 | Hoffmann La Roche | Dihydrobenzopyran derivatives |
| US4788214A (en) * | 1983-06-24 | 1988-11-29 | Hoffman-La Roche Inc. | 3,4-dihydro-2H-1-benzopyran derivatives |
| US4778903A (en) * | 1983-12-12 | 1988-10-18 | G. D. Searle & Co. | Substituted dihydrobenzopyrans |
| US4665203A (en) * | 1983-08-08 | 1987-05-12 | G. D. Searle & Co. | Substituted dihydrobenzopyrans useful as leukotriene D4 inhibitors |
| ZA84345B (en) * | 1983-08-08 | 1985-02-27 | Searle & Co | Substituted dihydrobenzopyrans |
| US4565882A (en) * | 1984-01-06 | 1986-01-21 | G. D. Searle & Co. | Substituted dihydrobenzopyran-2-carboxylates |
| US4546194A (en) * | 1984-05-29 | 1985-10-08 | G. D. Searle & Co. | Substituted chromanon-2-yl alkanols and derivatives thereof |
| US4889871A (en) * | 1987-05-29 | 1989-12-26 | G. D. Searle & Co. | Alkoxy-substituted dihydrobenzopyran-2-carboxylate derivatives |
| MX13485A (es) * | 1987-10-19 | 1993-05-01 | Pfizer | Procedimiento para obtener tetralinas, cromados y compuestos relacionados, sustituidos |
-
1990
- 1990-05-10 US US07/521,777 patent/US5073562A/en not_active Expired - Fee Related
-
1991
- 1991-05-01 AT AT91910026T patent/ATE119528T1/de not_active IP Right Cessation
- 1991-05-01 ES ES91910026T patent/ES2069295T3/es not_active Expired - Lifetime
- 1991-05-01 DE DE69108025T patent/DE69108025T2/de not_active Expired - Fee Related
- 1991-05-01 AU AU79020/91A patent/AU647487B2/en not_active Ceased
- 1991-05-01 CA CA002082500A patent/CA2082500A1/en not_active Abandoned
- 1991-05-01 EP EP91910026A patent/EP0527922B1/en not_active Expired - Lifetime
- 1991-05-01 DK DK91910026.3T patent/DK0527922T3/da active
- 1991-05-01 WO PCT/US1991/002981 patent/WO1991017160A1/en not_active Ceased
- 1991-05-01 JP JP91509388A patent/JPH05507084A/ja active Pending
- 1991-05-09 NZ NZ238092A patent/NZ238092A/xx unknown
- 1991-05-09 PT PT97614A patent/PT97614A/pt not_active Application Discontinuation
- 1991-05-09 IE IE158391A patent/IE62719B1/en not_active IP Right Cessation
- 1991-05-09 IL IL9809091A patent/IL98090A/en not_active IP Right Cessation
- 1991-05-10 ZA ZA913546A patent/ZA913546B/xx unknown
-
1995
- 1995-03-09 GR GR950400438T patent/GR3015349T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DK0527922T3 (da) | 1995-05-22 |
| ZA913546B (en) | 1992-07-29 |
| CA2082500A1 (en) | 1991-11-11 |
| GR3015349T3 (en) | 1995-06-30 |
| IE911583A1 (en) | 1991-11-20 |
| IL98090A0 (en) | 1992-06-21 |
| WO1991017160A1 (en) | 1991-11-14 |
| ATE119528T1 (de) | 1995-03-15 |
| IE62719B1 (en) | 1995-02-22 |
| EP0527922B1 (en) | 1995-03-08 |
| DE69108025D1 (de) | 1995-04-13 |
| JPH05507084A (ja) | 1993-10-14 |
| AU647487B2 (en) | 1994-03-24 |
| US5073562A (en) | 1991-12-17 |
| NZ238092A (en) | 1993-10-26 |
| PT97614A (pt) | 1992-01-31 |
| DE69108025T2 (de) | 1995-08-10 |
| EP0527922A1 (en) | 1993-02-24 |
| AU7902091A (en) | 1991-11-27 |
| ES2069295T3 (es) | 1995-05-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU647487B2 (en) | Alkoxy-substituted dihydrobenzopyran-2-carboxylic acids and derivatives thereof | |
| EP0593478B1 (en) | Leukotriene b 4 antagonists | |
| EP0605729B1 (en) | Oxazolidine derivative and pharmaceutically acceptable salt thereof | |
| JP4276074B2 (ja) | ペルオキシソーム増殖剤応答性受容体δの活性化剤 | |
| EP0243018B1 (en) | Thiolactam-n-acetic acid derivatives, their production and use | |
| EP0456835A1 (en) | Quinazoline-3-alkanoic acid derivative, salt thereof, and production thereof | |
| KR20000016412A (ko) | 신규한 치환 2,4-티아졸리디네디온 유도체, 이의제조 방법 및이를 함유하는 약제학적 조성물 | |
| US4746669A (en) | Substituted thiazoles as immunoregulants | |
| EP0528935B1 (en) | Alkoxy-substituted dihydrobenzopyran-2-carboxylic acids and derivatives thereof | |
| US5516917A (en) | Leukotriene B4 antagonists | |
| US5212198A (en) | Alkoxy-substituted dihydrobenzopyran-2-carboxylic acids and derivatives thereof | |
| US5192782A (en) | Alkoxy-substituted dihydrobenzopyran-2-carboxylic acids and derivatives thereof | |
| US5578619A (en) | Alkoxy-substituted dihydrobenzopyran-2-sulfonimides | |
| US5380740A (en) | Anti-inflammatory compounds, compositions and method of use thereof | |
| JPH04270273A (ja) | チアゾリジン−２，４−ジオン誘導体とその塩及びその製造法 | |
| RO113856B1 (ro) | Derivati ai sulfonamidei, procedee de preparare a acestora si preparate farmaceutice pentru terapia diabetului | |
| US4855426A (en) | Process of preparing 1,5-epoxy-2,3,4,5-tetrahydro-1H-3-benzazepins | |
| US4761413A (en) | 1,5-epoxy-2,3,4,5-tetrahydro-1H-3-benzazepins and use in treatment of ulcers | |
| IE914409A1 (en) | Anti-inflammatory compounds | |
| US4910198A (en) | 1,5-epoxy-2,3,4,5-tetrahydro-1H-3-benzazepins | |
| CA1193197A (en) | Anti-inflammatory composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RH | Patent void |