ES2202560T3 - Triciclicos sustituidos. - Google Patents
Triciclicos sustituidos.Info
- Publication number
- ES2202560T3 ES2202560T3 ES97308645T ES97308645T ES2202560T3 ES 2202560 T3 ES2202560 T3 ES 2202560T3 ES 97308645 T ES97308645 T ES 97308645T ES 97308645 T ES97308645 T ES 97308645T ES 2202560 T3 ES2202560 T3 ES 2202560T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- arthritis
- phenyl
- acid
- alkoxy
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 193
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 77
- 238000011282 treatment Methods 0.000 claims abstract description 50
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 44
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 39
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 26
- 206010040070 Septic Shock Diseases 0.000 claims abstract description 14
- 230000036303 septic shock Effects 0.000 claims abstract description 13
- -1 carbocyclic radicals Chemical class 0.000 claims description 230
- 239000002253 acid Substances 0.000 claims description 179
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 117
- 206010003246 arthritis Diseases 0.000 claims description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- 239000001257 hydrogen Substances 0.000 claims description 51
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
- 125000005843 halogen group Chemical group 0.000 claims description 43
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 41
- 201000010099 disease Diseases 0.000 claims description 38
- 229910052760 oxygen Chemical group 0.000 claims description 29
- 239000001301 oxygen Chemical group 0.000 claims description 29
- 102000005473 Secretory Phospholipases A2 Human genes 0.000 claims description 27
- 108010031873 Secretory Phospholipases A2 Proteins 0.000 claims description 27
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 27
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 24
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- 239000011593 sulfur Substances 0.000 claims description 24
- 208000012659 Joint disease Diseases 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 23
- 208000014674 injury Diseases 0.000 claims description 21
- 208000011580 syndromic disease Diseases 0.000 claims description 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
- 206010006448 Bronchiolitis Diseases 0.000 claims description 18
- 208000015181 infectious disease Diseases 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 16
- 206010006451 bronchitis Diseases 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000000623 heterocyclic group Chemical group 0.000 claims description 15
- 208000036487 Arthropathies Diseases 0.000 claims description 14
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 14
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 230000000366 juvenile effect Effects 0.000 claims description 13
- 125000004076 pyridyl group Chemical group 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 206010033645 Pancreatitis Diseases 0.000 claims description 12
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 208000006673 asthma Diseases 0.000 claims description 12
- 239000004305 biphenyl Substances 0.000 claims description 12
- 235000010290 biphenyl Nutrition 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 12
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 12
- 230000008733 trauma Effects 0.000 claims description 12
- 125000002256 xylenyl group Chemical group C1(C(C=CC=C1)C)(C)* 0.000 claims description 12
- 230000001684 chronic effect Effects 0.000 claims description 11
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 11
- 230000035939 shock Effects 0.000 claims description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 10
- 208000004756 Respiratory Insufficiency Diseases 0.000 claims description 10
- 201000010105 allergic rhinitis Diseases 0.000 claims description 10
- 239000011575 calcium Substances 0.000 claims description 10
- 229910052791 calcium Inorganic materials 0.000 claims description 10
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 10
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 10
- 230000001575 pathological effect Effects 0.000 claims description 10
- 239000000651 prodrug Substances 0.000 claims description 10
- 229940002612 prodrug Drugs 0.000 claims description 10
- 201000004193 respiratory failure Diseases 0.000 claims description 10
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 claims description 10
- 206010000599 Acromegaly Diseases 0.000 claims description 9
- 206010003256 Arthritis gonococcal Diseases 0.000 claims description 9
- 206010003274 Arthritis viral Diseases 0.000 claims description 9
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 9
- 206010006811 Bursitis Diseases 0.000 claims description 9
- 206010008690 Chondrocalcinosis pyrophosphate Diseases 0.000 claims description 9
- 201000011275 Epicondylitis Diseases 0.000 claims description 9
- 201000005569 Gout Diseases 0.000 claims description 9
- 206010019617 Henoch-Schonlein purpura Diseases 0.000 claims description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 9
- 201000002980 Hyperparathyroidism Diseases 0.000 claims description 9
- 206010020751 Hypersensitivity Diseases 0.000 claims description 9
- 208000016604 Lyme disease Diseases 0.000 claims description 9
- 206010036030 Polyarthritis Diseases 0.000 claims description 9
- 206010065159 Polychondritis Diseases 0.000 claims description 9
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 9
- 206010037660 Pyrexia Diseases 0.000 claims description 9
- 208000033464 Reiter syndrome Diseases 0.000 claims description 9
- 229910006069 SO3H Inorganic materials 0.000 claims description 9
- 201000002661 Spondylitis Diseases 0.000 claims description 9
- 208000006011 Stroke Diseases 0.000 claims description 9
- 206010047115 Vasculitis Diseases 0.000 claims description 9
- 208000027418 Wounds and injury Diseases 0.000 claims description 9
- 208000002849 chondrocalcinosis Diseases 0.000 claims description 9
- 239000013078 crystal Substances 0.000 claims description 9
- 230000006378 damage Effects 0.000 claims description 9
- 230000008021 deposition Effects 0.000 claims description 9
- 230000002538 fungal effect Effects 0.000 claims description 9
- 208000020346 hyperlipoproteinemia Diseases 0.000 claims description 9
- 230000002981 neuropathic effect Effects 0.000 claims description 9
- 201000008482 osteoarthritis Diseases 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 208000030428 polyarticular arthritis Diseases 0.000 claims description 9
- 208000002574 reactive arthritis Diseases 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 9
- 239000012453 solvate Substances 0.000 claims description 9
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 9
- 150000003555 thioacetals Chemical class 0.000 claims description 9
- 230000002792 vascular Effects 0.000 claims description 9
- 208000021240 acute bronchiolitis Diseases 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 7
- 230000003287 optical effect Effects 0.000 claims description 7
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
- 208000008190 Agammaglobulinemia Diseases 0.000 claims description 6
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 6
- 206010020983 Hypogammaglobulinaemia Diseases 0.000 claims description 6
- 208000007451 chronic bronchitis Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 150000002431 hydrogen Chemical class 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 201000004990 juvenile ankylosing spondylitis Diseases 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- 125000006553 (C3-C8) cycloalkenyl group Chemical group 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 4
- 208000002240 Tennis Elbow Diseases 0.000 claims description 3
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 3
- 238000006356 dehydrogenation reaction Methods 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000003367 polycyclic group Chemical group 0.000 claims description 3
- 125000006413 ring segment Chemical group 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- PHLMLOIEAYWBBX-UHFFFAOYSA-N 4-[[9-benzyl-5-carbamoyl-2-(2-cyanoethyl)-5,6,7,8-tetrahydrocarbazol-3-yl]oxy]butanoic acid Chemical compound NC(=O)C1CCCC2=C1C1=CC(OCCCC(O)=O)=C(CCC#N)C=C1N2CC1=CC=CC=C1 PHLMLOIEAYWBBX-UHFFFAOYSA-N 0.000 claims description 2
- CGZZUCYZEGYRAT-UHFFFAOYSA-N 9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=CC(OC)=CC(OC)=C2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 CGZZUCYZEGYRAT-UHFFFAOYSA-N 0.000 claims description 2
- JPNCLCUFHSHYHS-UHFFFAOYSA-N 9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydrocarbazole-4-carboxylic acid Chemical compound C12=CC(OC)=CC(OC)=C2C=2C(C(O)=O)CCCC=2N1CC1=CC=CC=C1 JPNCLCUFHSHYHS-UHFFFAOYSA-N 0.000 claims description 2
- PTOFERBJZMNRQD-UHFFFAOYSA-N 9-benzyl-5-(cyanomethoxy)-7-methoxy-1,2,3,4-tetrahydrocarbazole-4-carboxamide Chemical compound C12=CC(OC)=CC(OCC#N)=C2C=2C(C(N)=O)CCCC=2N1CC1=CC=CC=C1 PTOFERBJZMNRQD-UHFFFAOYSA-N 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 208000004575 Infectious Arthritis Diseases 0.000 claims 8
- 206010057178 Osteoarthropathies Diseases 0.000 claims 8
- 206010037549 Purpura Diseases 0.000 claims 8
- 241001672981 Purpura Species 0.000 claims 8
- 208000003295 carpal tunnel syndrome Diseases 0.000 claims 8
- 230000001969 hypertrophic effect Effects 0.000 claims 8
- 201000011201 multicentric reticulohistiocytosis Diseases 0.000 claims 8
- 208000007056 sickle cell anemia Diseases 0.000 claims 8
- 230000000306 recurrent effect Effects 0.000 claims 7
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 6
- 206010003267 Arthritis reactive Diseases 0.000 claims 4
- 206010016654 Fibrosis Diseases 0.000 claims 3
- 125000002877 alkyl aryl group Chemical group 0.000 claims 3
- 230000004761 fibrosis Effects 0.000 claims 3
- 239000003937 drug carrier Substances 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims 1
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
- SFDXDSDKMGTHOJ-UHFFFAOYSA-N 4-[(9-benzyl-5-carbamoyl-2-ethyl-5,6,7,8-tetrahydrocarbazol-3-yl)oxy]butanoic acid Chemical compound C1=2CCCC(C(N)=O)C=2C=2C=C(OCCCC(O)=O)C(CC)=CC=2N1CC1=CC=CC=C1 SFDXDSDKMGTHOJ-UHFFFAOYSA-N 0.000 claims 1
- XLBVLTAWSGYKMP-UHFFFAOYSA-N 4-[[9-benzyl-5-carbamoyl-3-(2-cyanoethyl)-5,6,7,8-tetrahydro-4h-carbazol-3-yl]oxy]butanoic acid Chemical compound NC(=O)C1CCCC2=C1C=1CC(CCC#N)(OCCCC(O)=O)C=CC=1N2CC1=CC=CC=C1 XLBVLTAWSGYKMP-UHFFFAOYSA-N 0.000 claims 1
- 125000005121 aminocarbonylalkoxy group Chemical group 0.000 claims 1
- 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 abstract description 16
- 235000014113 dietary fatty acids Nutrition 0.000 abstract description 10
- 239000000194 fatty acid Substances 0.000 abstract description 10
- 229930195729 fatty acid Natural products 0.000 abstract description 10
- 150000004665 fatty acids Chemical class 0.000 abstract description 10
- 229940114079 arachidonic acid Drugs 0.000 abstract description 8
- 235000021342 arachidonic acid Nutrition 0.000 abstract description 8
- 238000012261 overproduction Methods 0.000 abstract description 2
- WZSDNEJJUSYNSG-UHFFFAOYSA-N azocan-1-yl-(3,4,5-trimethoxyphenyl)methanone Chemical compound COC1=C(OC)C(OC)=CC(C(=O)N2CCCCCCC2)=C1 WZSDNEJJUSYNSG-UHFFFAOYSA-N 0.000 abstract 1
- 208000035475 disorder Diseases 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 143
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 141
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 116
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
- 239000000243 solution Substances 0.000 description 87
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 76
- 238000002360 preparation method Methods 0.000 description 72
- 239000000203 mixture Substances 0.000 description 71
- 239000000047 product Substances 0.000 description 69
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 60
- 239000012267 brine Substances 0.000 description 59
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 59
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 57
- 238000000921 elemental analysis Methods 0.000 description 54
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 50
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- 229910052938 sodium sulfate Inorganic materials 0.000 description 46
- 235000011152 sodium sulphate Nutrition 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 38
- 150000001408 amides Chemical class 0.000 description 37
- 239000000741 silica gel Substances 0.000 description 36
- 229910002027 silica gel Inorganic materials 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 35
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 33
- 150000002148 esters Chemical class 0.000 description 31
- 238000010992 reflux Methods 0.000 description 28
- 239000002585 base Substances 0.000 description 26
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 25
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 24
- 239000012312 sodium hydride Substances 0.000 description 24
- 229910000104 sodium hydride Inorganic materials 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical class N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 20
- 150000001412 amines Chemical class 0.000 description 18
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 18
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 17
- 239000000543 intermediate Substances 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 16
- 239000004480 active ingredient Substances 0.000 description 16
- 239000012442 inert solvent Substances 0.000 description 16
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
- 238000005804 alkylation reaction Methods 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 15
- 230000029936 alkylation Effects 0.000 description 14
- 230000004044 response Effects 0.000 description 14
- 238000012360 testing method Methods 0.000 description 14
- 238000010438 heat treatment Methods 0.000 description 13
- 239000002480 mineral oil Substances 0.000 description 13
- 235000010446 mineral oil Nutrition 0.000 description 13
- 229910052763 palladium Inorganic materials 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- 239000003981 vehicle Substances 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 239000011592 zinc chloride Substances 0.000 description 11
- 235000005074 zinc chloride Nutrition 0.000 description 11
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 10
- 229920002472 Starch Polymers 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 230000002452 interceptive effect Effects 0.000 description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 10
- 239000008107 starch Substances 0.000 description 10
- 235000019698 starch Nutrition 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 150000002576 ketones Chemical class 0.000 description 9
- 230000001404 mediated effect Effects 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 150000001241 acetals Chemical class 0.000 description 8
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- 150000004702 methyl esters Chemical class 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 7
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
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- 239000003054 catalyst Substances 0.000 description 7
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- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- WEAXQUBYRSEBJD-UHFFFAOYSA-N methyl 1h-indole-4-carboxylate Chemical compound COC(=O)C1=CC=CC2=C1C=CN2 WEAXQUBYRSEBJD-UHFFFAOYSA-N 0.000 description 1
- WBFLFLNAZDXPFD-UHFFFAOYSA-N methyl 2-[[5-carbamoyl-2-(5-cyanopentyl)-8-methyl-9-tridecyl-5,6,7,8-tetrahydrocarbazol-3-yl]oxy]acetate Chemical compound C12=CC(OCC(=O)OC)=C(CCCCCC#N)C=C2N(CCCCCCCCCCCCC)C2=C1C(C(N)=O)CCC2C WBFLFLNAZDXPFD-UHFFFAOYSA-N 0.000 description 1
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- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FTQWRYSLUYAIRQ-UHFFFAOYSA-N n-[(octadecanoylamino)methyl]octadecanamide Chemical compound CCCCCCCCCCCCCCCCCC(=O)NCNC(=O)CCCCCCCCCCCCCCCCC FTQWRYSLUYAIRQ-UHFFFAOYSA-N 0.000 description 1
- NPKYYJGDHWBTSU-UHFFFAOYSA-N n-benzyl-3,5-dimethoxyaniline Chemical compound COC1=CC(OC)=CC(NCC=2C=CC=CC=2)=C1 NPKYYJGDHWBTSU-UHFFFAOYSA-N 0.000 description 1
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- IRPSFTAPNYCTEJ-UHFFFAOYSA-N n-benzyl-6-methoxy-7-(2-phenylethyl)-2,3,4,9-tetrahydro-1h-carbazole-4-carboxamide Chemical compound COC1=CC=2C=3C(C(=O)NCC=4C=CC=CC=4)CCCC=3NC=2C=C1CCC1=CC=CC=C1 IRPSFTAPNYCTEJ-UHFFFAOYSA-N 0.000 description 1
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- CATWEXRJGNBIJD-UHFFFAOYSA-N n-tert-butyl-2-methylpropan-2-amine Chemical group CC(C)(C)NC(C)(C)C CATWEXRJGNBIJD-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
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- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
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- OJMIONKXNSYLSR-UHFFFAOYSA-N phosphorous acid Chemical compound OP(O)O OJMIONKXNSYLSR-UHFFFAOYSA-N 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- ISYUCUGTDNJIHV-UHFFFAOYSA-N propyl 2-bromoacetate Chemical compound CCCOC(=O)CBr ISYUCUGTDNJIHV-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- ABPJREHLAYHTHW-UHFFFAOYSA-N pyrano[2,3-g]indole Chemical compound O1C=CC=C2C3=NC=CC3=CC=C21 ABPJREHLAYHTHW-UHFFFAOYSA-N 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- FHHPUSMSKHSNKW-SMOYURAASA-M sodium deoxycholate Chemical compound [Na+].C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 FHHPUSMSKHSNKW-SMOYURAASA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
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- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
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- 239000008117 stearic acid Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
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- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
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- 238000010189 synthetic method Methods 0.000 description 1
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
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- WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 125000002889 tridecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000011686 zinc sulphate Substances 0.000 description 1
- 235000009529 zinc sulphate Nutrition 0.000 description 1
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- 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
- C07D409/04—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 directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/572—Five-membered rings
- C07F9/5728—Five-membered rings condensed with carbocyclic rings or carbocyclic ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Diabetes (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
- Fats And Perfumes (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US2984996P | 1996-10-30 | 1996-10-30 | |
| US29849P | 1996-10-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2202560T3 true ES2202560T3 (es) | 2004-04-01 |
Family
ID=21851210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES97308645T Expired - Lifetime ES2202560T3 (es) | 1996-10-30 | 1997-10-29 | Triciclicos sustituidos. |
Country Status (26)
| Country | Link |
|---|---|
| EP (1) | EP0839806B1 (enExample) |
| JP (1) | JP2001503055A (enExample) |
| KR (1) | KR20000049210A (enExample) |
| CN (1) | CN1233176A (enExample) |
| AR (1) | AR010050A1 (enExample) |
| AT (1) | ATE244703T1 (enExample) |
| AU (1) | AU734096B2 (enExample) |
| BR (1) | BR9713261A (enExample) |
| CA (1) | CA2269203A1 (enExample) |
| CO (1) | CO4920250A1 (enExample) |
| CZ (1) | CZ136899A3 (enExample) |
| DE (1) | DE69723393T2 (enExample) |
| DK (1) | DK0839806T3 (enExample) |
| EA (1) | EA003992B1 (enExample) |
| ES (1) | ES2202560T3 (enExample) |
| ID (1) | ID18685A (enExample) |
| IL (1) | IL129481A0 (enExample) |
| NO (1) | NO314899B1 (enExample) |
| NZ (1) | NZ335246A (enExample) |
| PE (1) | PE10999A1 (enExample) |
| PL (1) | PL332896A1 (enExample) |
| PT (1) | PT839806E (enExample) |
| TR (1) | TR199900956T2 (enExample) |
| TW (1) | TW513428B (enExample) |
| WO (1) | WO1998018464A1 (enExample) |
| YU (1) | YU19299A (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2301586A1 (en) * | 1997-08-28 | 1999-03-04 | William Louis Macias | Method for treatment of non-rheumatoid arthritis |
| HUP0102981A3 (en) | 1998-03-31 | 2002-10-28 | Shionogi & Co | Pyrrolo[1,2-a]pyrazine derivatives and pharmaceutical compositions thereof |
| IL129484A0 (en) * | 1998-04-17 | 2000-02-29 | Lilly Co Eli | Substituted tricyclics |
| DZ2769A1 (fr) * | 1998-04-17 | 2003-12-01 | Lilly Co Eli | Composés tricycliques substitués. |
| TR200003194T2 (tr) | 1998-05-01 | 2001-03-21 | Eli Lilly And Company | Hastalık tedavisine mahsus sPLA2 önleyici bileşikler |
| KR20010034881A (ko) | 1998-05-21 | 2001-04-25 | 시오노 요시히코 | ｓＰＬＡ2 억제 효과를 갖는 피롤로[1,2-ｂ]피리다진 유도체 |
| ATE329619T1 (de) | 1998-10-14 | 2006-07-15 | Shionogi & Co | Spla2-inhibitoren zur behandlung von ischämischen reperfusionsschäden |
| US6448284B1 (en) * | 1998-12-22 | 2002-09-10 | Eli Lilly And Company | Substituted tricyclics |
| AU6015600A (en) | 1999-07-19 | 2001-02-05 | Shionogi & Co., Ltd. | Tricyclic compounds having spla2-inhibitory activities |
| US6673781B1 (en) | 1999-08-02 | 2004-01-06 | Shionogi & Co., Ltd. | Tricyclic compounds having sPLA2-inhibitory activities |
| US6787545B1 (en) | 1999-08-23 | 2004-09-07 | Shiongi & Co., Ltd. | Pyrrolotriazine derivatives having spla2-inhibitory activities |
| MY125942A (en) | 1999-09-07 | 2006-09-29 | Upjohn Co | Aminoalkoxy carbazoles for the treatment of cns diseases |
| US6756376B1 (en) | 1999-11-15 | 2004-06-29 | Shionogi & Co., Ltd. | Tricyclic azaindolizine derivatives having an sPLA2-inhibitory activities |
| WO2001049323A1 (en) * | 2000-01-06 | 2001-07-12 | Eli Lilly And Company | Combination therapy for the treatment of inflammatory and respiratory diseases |
| JPWO2002000621A1 (ja) | 2000-06-29 | 2004-04-22 | 塩野義製薬株式会社 | Ｘ型ｓＰＬＡ２阻害作用を有する化合物 |
| WO2002000256A1 (fr) | 2000-06-29 | 2002-01-03 | Shionogi & Co., Ltd. | Remedes contre la cirrhose |
| US6872743B2 (en) | 2000-12-18 | 2005-03-29 | Eli Lilly And Company | sPLA2 inhibitors |
| TWI314457B (enExample) | 2001-03-19 | 2009-09-11 | Shionogi & Co | |
| AUPS282602A0 (en) | 2002-06-07 | 2002-06-27 | Garvan Institute Of Medical Research | Method of inhibiting cell proliferation |
| US8329913B2 (en) | 2004-10-29 | 2012-12-11 | Zeria Pharmaceutical Co., Ltd. | Carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof |
| ES2924728T3 (es) | 2015-06-15 | 2022-10-10 | Raziel Therapeutics Ltd | Derivados de carbazol para el tratamiento de enfermedades fibróticas, así como de síntomas y afecciones relacionados con las mismas |
| CN112409493B (zh) * | 2020-08-12 | 2022-09-30 | 浙江工业大学 | 一种重组融合酶及其在乙醛酸甲酯合成中的应用 |
| US12440370B2 (en) | 2020-10-21 | 2025-10-14 | Purewick Corporation | Apparatus with compressible casing for receiving discharged urine |
| US12208031B2 (en) | 2020-10-21 | 2025-01-28 | Purewick Corporation | Adapters for fluid collection devices |
| US12257174B2 (en) | 2020-10-21 | 2025-03-25 | Purewick Corporation | Fluid collection assemblies including at least one of a protrusion or at least one expandable material |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3479391A (en) * | 1966-10-03 | 1969-11-18 | Squibb & Sons Inc | Delta**3,14-17alpha-hydroxy-norprogesterone and esters |
| US3939177A (en) * | 1972-11-22 | 1976-02-17 | Sterling Drug Inc. | 4-Aminomethyl-9-benzyl-1,2,3,4-tetrahydrocarbazoles |
| US3979391A (en) * | 1972-11-22 | 1976-09-07 | Sterling Drug Inc. | 1,2,3,4-Tetrahydrocarbazoles |
| US5420289A (en) * | 1989-10-27 | 1995-05-30 | American Home Products Corporation | Substituted indole-, indene-, pyranoindole- and tetrahydrocarbazole-alkanoic acid derivatives as inhibitors of PLA2 and lipoxygenase |
| IL109309A (en) * | 1993-04-16 | 2000-06-29 | Lilly Co Eli | 1-H-indole-3-acetic acid hydrazide SPLA2 inhibitors and pharmaceutical compositions containing them |
| IL109311A0 (en) * | 1993-04-16 | 1994-07-31 | Lilly Co Eli | 1H-indole-3-acetamide sPla2 inhibitors |
-
1997
- 1997-10-23 KR KR1019990703309A patent/KR20000049210A/ko not_active Ceased
- 1997-10-23 CZ CZ991368A patent/CZ136899A3/cs unknown
- 1997-10-23 CN CN97198834A patent/CN1233176A/zh active Pending
- 1997-10-23 IL IL12948197A patent/IL129481A0/xx unknown
- 1997-10-23 BR BR9713261-6A patent/BR9713261A/pt unknown
- 1997-10-23 TR TR1999/00956T patent/TR199900956T2/xx unknown
- 1997-10-23 NZ NZ335246A patent/NZ335246A/en unknown
- 1997-10-23 JP JP10520585A patent/JP2001503055A/ja active Pending
- 1997-10-23 CA CA002269203A patent/CA2269203A1/en not_active Abandoned
- 1997-10-23 EA EA199900305A patent/EA003992B1/ru not_active IP Right Cessation
- 1997-10-23 PL PL97332896A patent/PL332896A1/xx unknown
- 1997-10-23 YU YU19299A patent/YU19299A/sh unknown
- 1997-10-23 AU AU51494/98A patent/AU734096B2/en not_active Ceased
- 1997-10-23 WO PCT/US1997/019183 patent/WO1998018464A1/en not_active Ceased
- 1997-10-24 PE PE1997000950A patent/PE10999A1/es not_active Application Discontinuation
- 1997-10-27 ID IDP973534A patent/ID18685A/id unknown
- 1997-10-28 AR ARP970104997A patent/AR010050A1/es active IP Right Grant
- 1997-10-28 CO CO97063171A patent/CO4920250A1/es unknown
- 1997-10-29 EP EP97308645A patent/EP0839806B1/en not_active Expired - Lifetime
- 1997-10-29 PT PT97308645T patent/PT839806E/pt unknown
- 1997-10-29 AT AT97308645T patent/ATE244703T1/de active
- 1997-10-29 ES ES97308645T patent/ES2202560T3/es not_active Expired - Lifetime
- 1997-10-29 DE DE69723393T patent/DE69723393T2/de not_active Expired - Lifetime
- 1997-10-29 DK DK97308645T patent/DK0839806T3/da active
- 1997-10-30 TW TW086116217A patent/TW513428B/zh not_active IP Right Cessation
-
1999
- 1999-04-16 NO NO19991831A patent/NO314899B1/no not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| PT839806E (pt) | 2003-11-28 |
| NO991831L (no) | 1999-06-21 |
| PE10999A1 (es) | 1999-02-10 |
| DE69723393T2 (de) | 2004-06-09 |
| EP0839806B1 (en) | 2003-07-09 |
| KR20000049210A (ko) | 2000-07-25 |
| EA199900305A1 (ru) | 1999-12-29 |
| NO991831D0 (no) | 1999-04-16 |
| NZ335246A (en) | 2001-09-28 |
| ATE244703T1 (de) | 2003-07-15 |
| CO4920250A1 (es) | 2000-05-29 |
| AR010050A1 (es) | 2000-05-17 |
| NO314899B1 (no) | 2003-06-10 |
| TR199900956T2 (xx) | 1999-07-21 |
| DK0839806T3 (da) | 2003-10-27 |
| CA2269203A1 (en) | 1998-05-07 |
| AU5149498A (en) | 1998-05-22 |
| EP0839806A1 (en) | 1998-05-06 |
| EA003992B1 (ru) | 2003-12-25 |
| BR9713261A (pt) | 2000-03-28 |
| YU19299A (sh) | 2000-03-21 |
| WO1998018464A1 (en) | 1998-05-07 |
| TW513428B (en) | 2002-12-11 |
| IL129481A0 (en) | 2000-02-29 |
| CN1233176A (zh) | 1999-10-27 |
| ID18685A (id) | 1998-04-30 |
| JP2001503055A (ja) | 2001-03-06 |
| PL332896A1 (en) | 1999-10-25 |
| AU734096B2 (en) | 2001-06-07 |
| CZ136899A3 (cs) | 1999-09-15 |
| DE69723393D1 (de) | 2003-08-14 |
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