NO323238B1 - Kondenserte pyrrolforbindelser, farmasoytiske omfattende disse, og anvendelse av disse. - Google Patents

Kondenserte pyrrolforbindelser, farmasoytiske omfattende disse, og anvendelse av disse. Download PDF

Info

Publication number: NO323238B1
Authority: NO; Norway
Prior art keywords: alkyl; radicals; mmol; mixture; halogen
Prior art date: 2000-01-13

Application number

NO20023363A

Other languages

English (en)

Norwegian (no)

Other versions

NO20023363D0 (no

NO20023363L (no

Inventor

Stefan Laufer

Hans-Guenter Striegel

Karola Tollmann

Susanne Tries

Original Assignee

Merckle Gmbh

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-01-13

Filing date

2002-07-12

Publication date

2007-02-05

2002-07-12 Application filed by Merckle Gmbh filed Critical Merckle Gmbh

2002-07-12 Publication of NO20023363D0 publication Critical patent/NO20023363D0/no

2002-09-10 Publication of NO20023363L publication Critical patent/NO20023363L/no

2007-02-05 Publication of NO323238B1 publication Critical patent/NO323238B1/no

Links

150000003233 pyrroles Chemical class 0.000 title claims abstract description 15
239000003814 drug Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 85
125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
208000035475 disorder Diseases 0.000 claims abstract description 9
238000011282 treatment Methods 0.000 claims abstract description 9
208000025747 Rheumatic disease Diseases 0.000 claims abstract description 5
230000000552 rheumatic effect Effects 0.000 claims abstract description 5
-1 4-substituted phenyl Chemical group 0.000 claims description 87
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
229910052739 hydrogen Inorganic materials 0.000 claims description 41
125000000217 alkyl group Chemical group 0.000 claims description 36
229910052736 halogen Inorganic materials 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
150000002367 halogens Chemical class 0.000 claims description 24
229920006395 saturated elastomer Polymers 0.000 claims description 20
125000001424 substituent group Chemical group 0.000 claims description 19
125000003118 aryl group Chemical group 0.000 claims description 16
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 15
239000001257 hydrogen Substances 0.000 claims description 14
125000004432 carbon atom Chemical group C* 0.000 claims description 13
150000002148 esters Chemical class 0.000 claims description 12
150000003839 salts Chemical class 0.000 claims description 12
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
229910052731 fluorine Inorganic materials 0.000 claims description 10
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 9
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
125000004429 atom Chemical group 0.000 claims description 8
125000000753 cycloalkyl group Chemical group 0.000 claims description 8
239000011737 fluorine Substances 0.000 claims description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
239000000825 pharmaceutical preparation Substances 0.000 claims description 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
125000001153 fluoro group Chemical group F* 0.000 claims description 5
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000005422 alkyl sulfonamido group Chemical group 0.000 claims description 4
125000002619 bicyclic group Chemical group 0.000 claims description 4
125000005842 heteroatom Chemical group 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
230000003287 optical effect Effects 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
125000005153 alkyl sulfamoyl group Chemical group 0.000 claims 1
125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 abstract description 12
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 abstract description 10
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 abstract description 10
150000002478 indolizines Chemical class 0.000 abstract description 4
230000002401 inhibitory effect Effects 0.000 abstract description 4
108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 abstract description 3
239000008194 pharmaceutical composition Substances 0.000 abstract 1
150000003238 pyrrolizines Chemical class 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 190
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 187
239000000203 mixture Substances 0.000 description 159
239000000243 solution Substances 0.000 description 158
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 108
238000005160 1H NMR spectroscopy Methods 0.000 description 89
239000012071 phase Substances 0.000 description 88
239000011780 sodium chloride Substances 0.000 description 88
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 86
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
239000011734 sodium Substances 0.000 description 80
238000006243 chemical reaction Methods 0.000 description 74
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 65
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 61
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 58
239000000047 product Substances 0.000 description 56
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 53
150000003254 radicals Chemical class 0.000 description 50
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 49
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 42
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 41
239000000460 chlorine Chemical group 0.000 description 40
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
238000007792 addition Methods 0.000 description 34
239000003921 oil Substances 0.000 description 34
238000001816 cooling Methods 0.000 description 33
229910004298 SiO 2 Inorganic materials 0.000 description 32
238000004809 thin layer chromatography Methods 0.000 description 31
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 30
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 29
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 28
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
239000007858 starting material Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
239000002253 acid Substances 0.000 description 26
239000007787 solid Substances 0.000 description 26
239000005457 ice water Substances 0.000 description 22
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
239000012074 organic phase Substances 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 21
239000002904 solvent Substances 0.000 description 21
239000008346 aqueous phase Substances 0.000 description 20
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 19
230000015572 biosynthetic process Effects 0.000 description 19
ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 19
239000000706 filtrate Substances 0.000 description 19
238000000034 method Methods 0.000 description 19
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 18
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 18
238000002290 gas chromatography-mass spectrometry Methods 0.000 description 17
125000002152 1H-pyrrolizinyl group Chemical class C1(C=CN2C=CC=C12)* 0.000 description 16
101150041968 CDC13 gene Proteins 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
239000007789 gas Substances 0.000 description 16
239000000725 suspension Substances 0.000 description 16
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
239000013078 crystal Substances 0.000 description 15
238000004817 gas chromatography Methods 0.000 description 15
238000003756 stirring Methods 0.000 description 15
RSOADCLKZJGKCE-UHFFFAOYSA-N 5-benzyl-3,4-dihydro-2h-pyrrole Chemical compound C=1C=CC=CC=1CC1=NCCC1 RSOADCLKZJGKCE-UHFFFAOYSA-N 0.000 description 14
239000000284 extract Substances 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
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 12
MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 12
239000000543 intermediate Substances 0.000 description 12
238000010992 reflux Methods 0.000 description 12
238000004128 high performance liquid chromatography Methods 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 10
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 10
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
125000003545 alkoxy group Chemical group 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
230000008018 melting Effects 0.000 description 10
238000002844 melting Methods 0.000 description 10
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
230000009467 reduction Effects 0.000 description 10
238000006722 reduction reaction Methods 0.000 description 10
239000000126 substance Substances 0.000 description 10
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
238000001035 drying Methods 0.000 description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 9
238000000746 purification Methods 0.000 description 9
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 8
229910052794 bromium Inorganic materials 0.000 description 8
HCUYBXPSSCRKRF-UHFFFAOYSA-N diphosgene Chemical compound ClC(=O)OC(Cl)(Cl)Cl HCUYBXPSSCRKRF-UHFFFAOYSA-N 0.000 description 8
125000002768 hydroxyalkyl group Chemical group 0.000 description 8
230000005764 inhibitory process Effects 0.000 description 8
239000000463 material Substances 0.000 description 8
229910000104 sodium hydride Inorganic materials 0.000 description 8
229940124530 sulfonamide Drugs 0.000 description 8
150000003456 sulfonamides Chemical class 0.000 description 8
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 8
ODMMNALOCMNQJZ-UHFFFAOYSA-N 1H-pyrrolizine Chemical compound C1=CC=C2CC=CN21 ODMMNALOCMNQJZ-UHFFFAOYSA-N 0.000 description 7
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 7
229910018072 Al 2 O 3 Inorganic materials 0.000 description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
108010037462 Cyclooxygenase 2 Proteins 0.000 description 7
102100022364 Polyunsaturated fatty acid 5-lipoxygenase Human genes 0.000 description 7
125000002947 alkylene group Chemical group 0.000 description 7
239000002026 chloroform extract Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
230000007717 exclusion Effects 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
230000007935 neutral effect Effects 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 7
238000006467 substitution reaction Methods 0.000 description 7
150000003457 sulfones Chemical class 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 6
108010037464 Cyclooxygenase 1 Proteins 0.000 description 6
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
102000004190 Enzymes Human genes 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
229940114079 arachidonic acid Drugs 0.000 description 6
235000021342 arachidonic acid Nutrition 0.000 description 6
229910052786 argon Inorganic materials 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
239000012043 crude product Substances 0.000 description 6
238000005187 foaming Methods 0.000 description 6
125000001188 haloalkyl group Chemical group 0.000 description 6
125000000623 heterocyclic group Chemical group 0.000 description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
235000012239 silicon dioxide Nutrition 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
LTUZWGRJHXDJQU-JTQLQIEISA-N (2s)-1-(4-fluorobenzoyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)C1=CC=C(F)C=C1 LTUZWGRJHXDJQU-JTQLQIEISA-N 0.000 description 5
ZJFWCELATJMDNO-UHFFFAOYSA-N 2-bromo-1-(4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CBr)C=C1 ZJFWCELATJMDNO-UHFFFAOYSA-N 0.000 description 5
JOCMYOUZIDSYFO-UHFFFAOYSA-N 2-bromo-1-(4-methylsulfonylphenyl)ethanone Chemical compound CS(=O)(=O)C1=CC=C(C(=O)CBr)C=C1 JOCMYOUZIDSYFO-UHFFFAOYSA-N 0.000 description 5
MEPINLVYDXPOSN-UHFFFAOYSA-N 5-ethyl-3,4-dihydro-2h-pyrrole Chemical compound CCC1=NCCC1 MEPINLVYDXPOSN-UHFFFAOYSA-N 0.000 description 5
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 5
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 5
229960000583 acetic acid Drugs 0.000 description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 description 5
125000004414 alkyl thio group Chemical group 0.000 description 5
229910021529 ammonia Inorganic materials 0.000 description 5
238000009835 boiling Methods 0.000 description 5
150000007942 carboxylates Chemical class 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
210000003714 granulocyte Anatomy 0.000 description 5
239000012452 mother liquor Substances 0.000 description 5
229910000069 nitrogen hydride Inorganic materials 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
238000000926 separation method Methods 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
YSSYIJBAPDTSAY-UHFFFAOYSA-N 2-bromo-1-(4-methylsulfanylphenyl)ethanone Chemical compound CSC1=CC=C(C(=O)CBr)C=C1 YSSYIJBAPDTSAY-UHFFFAOYSA-N 0.000 description 4
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
PSVPUHBSBYJSMQ-UHFFFAOYSA-N 4-methylsulfonylbenzaldehyde Chemical compound CS(=O)(=O)C1=CC=C(C=O)C=C1 PSVPUHBSBYJSMQ-UHFFFAOYSA-N 0.000 description 4
NSQSVHNXEMBQCY-UHFFFAOYSA-N 6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C1=CC(Cl)=CC=C1C1=CN(CCC2)C2=C1C1=CC=CC=C1 NSQSVHNXEMBQCY-UHFFFAOYSA-N 0.000 description 4
KMNCYYWJHOOIFR-UHFFFAOYSA-N 6-(4-fluorophenyl)-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C1=CC(F)=CC=C1C1=CN(CCC2)C2=C1C1=CC=CC=C1 KMNCYYWJHOOIFR-UHFFFAOYSA-N 0.000 description 4
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
235000019270 ammonium chloride Nutrition 0.000 description 4
150000003863 ammonium salts Chemical class 0.000 description 4
230000003110 anti-inflammatory effect Effects 0.000 description 4
MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 4
238000003776 cleavage reaction Methods 0.000 description 4
229910052681 coesite Inorganic materials 0.000 description 4
229910052593 corundum Inorganic materials 0.000 description 4
229910052906 cristobalite Inorganic materials 0.000 description 4
CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 4
PBZBNXKPHQFJIC-UHFFFAOYSA-N ethyl 2-bromo-3-(4-methylsulfanylphenyl)prop-2-enoate Chemical compound CCOC(=O)C(Br)=CC1=CC=C(SC)C=C1 PBZBNXKPHQFJIC-UHFFFAOYSA-N 0.000 description 4
125000000524 functional group Chemical group 0.000 description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
150000003180 prostaglandins Chemical class 0.000 description 4
239000012047 saturated solution Substances 0.000 description 4
230000007017 scission Effects 0.000 description 4
235000010265 sodium sulphite Nutrition 0.000 description 4
229910052682 stishovite Inorganic materials 0.000 description 4
239000011593 sulfur Substances 0.000 description 4
229910052905 tridymite Inorganic materials 0.000 description 4
229910001845 yogo sapphire Inorganic materials 0.000 description 4
NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 3
RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 3
ZFCFBWSVQWGOJJ-UHFFFAOYSA-N 4-chlorobutanenitrile Chemical compound ClCCCC#N ZFCFBWSVQWGOJJ-UHFFFAOYSA-N 0.000 description 3
UWUCQSWOBYQGOX-UHFFFAOYSA-N 5-[(4-fluorophenyl)methyl]-3,4-dihydro-2h-pyrrole Chemical compound C1=CC(F)=CC=C1CC1=NCCC1 UWUCQSWOBYQGOX-UHFFFAOYSA-N 0.000 description 3
ALYCWOPERSWJOY-UHFFFAOYSA-N 6-(4-fluorophenyl)-5-methyl-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C=12CCCN2C(C)=C(C=2C=CC(F)=CC=2)C=1C1=CC=CC=C1 ALYCWOPERSWJOY-UHFFFAOYSA-N 0.000 description 3
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MOVFAUAADQBPRE-UHFFFAOYSA-N pyrrolo[2,1-b][1,3]thiazole Chemical compound S1C=CN2C=CC=C21 MOVFAUAADQBPRE-UHFFFAOYSA-N 0.000 description 1
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125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
206010037844 rash Diseases 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
230000008327 renal blood flow Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
235000019515 salmon Nutrition 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000036303 septic shock Effects 0.000 description 1
229910000077 silane Inorganic materials 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
125000003003 spiro group Chemical group 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
210000002437 synoviocyte Anatomy 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
ZZIZZTHXZRDOFM-XFULWGLBSA-N tamsulosin hydrochloride Chemical compound [H+].[Cl-].CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 ZZIZZTHXZRDOFM-XFULWGLBSA-N 0.000 description 1
239000013076 target substance Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
KIFUHOUSLBRPQP-UHFFFAOYSA-N tert-butyl 1-(4-chlorophenyl)-2-phenyl-6,7-dihydro-5h-pyrrolizine-3-carboxylate Chemical compound C=12CCCN2C(C(=O)OC(C)(C)C)=C(C=2C=CC=CC=2)C=1C1=CC=C(Cl)C=C1 KIFUHOUSLBRPQP-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
239000003768 thromboxane synthase inhibitor Substances 0.000 description 1
230000000451 tissue damage Effects 0.000 description 1
231100000827 tissue damage Toxicity 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 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
UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
230000007306 turnover Effects 0.000 description 1
230000036269 ulceration Effects 0.000 description 1
238000002211 ultraviolet spectrum Methods 0.000 description 1
235000012141 vanillin Nutrition 0.000 description 1
MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
229940124549 vasodilator Drugs 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pyrrole Compounds (AREA)

NO20023363A 2000-01-13 2002-07-12 Kondenserte pyrrolforbindelser, farmasoytiske omfattende disse, og anvendelse av disse. NO323238B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE10001166A DE10001166A1 (de)	2000-01-13	2000-01-13	Anellierte Pyrrolverbindungen, diese enthaltende pharmazeutische Mittel und deren Verwendung
PCT/EP2001/000332 WO2001051491A1 (fr)	2000-01-13	2001-01-12	Composes de pyrrole anneles, agents pharmaceutiques les contenant et leur utilisation

Publications (3)

Publication Number	Publication Date
NO20023363D0 NO20023363D0 (no)	2002-07-12
NO20023363L NO20023363L (no)	2002-09-10
NO323238B1 true NO323238B1 (no)	2007-02-05

Family

ID=7627401

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20023363A NO323238B1 (no)	2000-01-13	2002-07-12	Kondenserte pyrrolforbindelser, farmasoytiske omfattende disse, og anvendelse av disse.

Country Status (16)

Country	Link
US (1)	US6936632B2 (fr)
EP (1)	EP1246825B1 (fr)
JP (1)	JP2003525875A (fr)
KR (1)	KR20020081254A (fr)
CN (1)	CN1191254C (fr)
AT (1)	ATE256685T1 (fr)
AU (1)	AU2001230180A1 (fr)
CA (1)	CA2396413A1 (fr)
DE (2)	DE10001166A1 (fr)
DK (1)	DK1246825T3 (fr)
ES (1)	ES2213102T3 (fr)
MX (1)	MXPA02006863A (fr)
NO (1)	NO323238B1 (fr)
PT (1)	PT1246825E (fr)
TR (1)	TR200400270T4 (fr)
WO (1)	WO2001051491A1 (fr)

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DE10004157A1 (de)	2000-02-01	2001-08-02	Merckle Gmbh Chem Pharm Fabrik	4-Pyridyl-und 2,4-Pyrimidinyl-substituierte Pyrrolderivate und ihre Anwendung in der Pharmazie
CN1549711A (zh)	2001-08-30	2004-11-24	��Ĭ��	稠合的吡咯化合物在治疗关节软骨或软骨下骨组织退化中的用途
US20070077297A1 (en)	2004-09-30	2007-04-05	Scolr Pharma, Inc.	Modified release ibuprofen dosage form
US20060068009A1 (en) *	2004-09-30	2006-03-30	Scolr Pharma, Inc.	Modified release ibuprofen dosage form
US7749537B2 (en) *	2006-12-04	2010-07-06	Scolr Pharma, Inc.	Method of forming a tablet
US20190060286A1 (en)	2016-02-29	2019-02-28	University Of Florida Research Foundation, Incorpo	Chemotherapeutic Methods
CN117756811A (zh) *	2023-12-29	2024-03-26	贵州民族大学	一种合成多取代基吡咯化合物的方法

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DE10004157A1 (de)	2000-02-01	2001-08-02	Merckle Gmbh Chem Pharm Fabrik	4-Pyridyl-und 2,4-Pyrimidinyl-substituierte Pyrrolderivate und ihre Anwendung in der Pharmazie

2000
- 2000-01-13 DE DE10001166A patent/DE10001166A1/de not_active Withdrawn
2001
- 2001-01-12 CN CNB018065279A patent/CN1191254C/zh not_active Expired - Fee Related
- 2001-01-12 TR TR2004/00270T patent/TR200400270T4/xx unknown
- 2001-01-12 DE DE50101187T patent/DE50101187D1/de not_active Expired - Fee Related
- 2001-01-12 PT PT01902310T patent/PT1246825E/pt unknown
- 2001-01-12 AT AT01902310T patent/ATE256685T1/de not_active IP Right Cessation
- 2001-01-12 WO PCT/EP2001/000332 patent/WO2001051491A1/fr not_active Ceased
- 2001-01-12 KR KR1020027009012A patent/KR20020081254A/ko not_active Withdrawn
- 2001-01-12 JP JP2001551075A patent/JP2003525875A/ja active Pending
- 2001-01-12 ES ES01902310T patent/ES2213102T3/es not_active Expired - Lifetime
- 2001-01-12 MX MXPA02006863A patent/MXPA02006863A/es active IP Right Grant
- 2001-01-12 EP EP01902310A patent/EP1246825B1/fr not_active Expired - Lifetime
- 2001-01-12 CA CA002396413A patent/CA2396413A1/fr not_active Abandoned
- 2001-01-12 DK DK01902310T patent/DK1246825T3/da active
- 2001-01-12 US US10/169,988 patent/US6936632B2/en not_active Expired - Fee Related
- 2001-01-12 AU AU2001230180A patent/AU2001230180A1/en not_active Abandoned
2002
- 2002-07-12 NO NO20023363A patent/NO323238B1/no unknown

Also Published As

Publication number	Publication date
EP1246825B1 (fr)	2003-12-17
CN1418217A (zh)	2003-05-14
AU2001230180A1 (en)	2001-07-24
DE50101187D1 (de)	2004-01-29
EP1246825A1 (fr)	2002-10-09
DK1246825T3 (da)	2004-04-13
ES2213102T3 (es)	2004-08-16
ATE256685T1 (de)	2004-01-15
PT1246825E (pt)	2004-04-30
US20040122002A1 (en)	2004-06-24
US6936632B2 (en)	2005-08-30
WO2001051491A1 (fr)	2001-07-19
JP2003525875A (ja)	2003-09-02
KR20020081254A (ko)	2002-10-26
NO20023363D0 (no)	2002-07-12
MXPA02006863A (es)	2004-04-05
DE10001166A1 (de)	2001-07-19
CA2396413A1 (fr)	2001-07-19
CN1191254C (zh)	2005-03-02
NO20023363L (no)	2002-09-10
TR200400270T4 (tr)	2004-03-22

Publication	Publication Date	Title
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NO321042B1 (no)	2006-03-06	(Metylsulfonyl)fenyl-2-(5H)-furanoner, farmasoytiske preparater som omfatter forbindelsene, samt anvendelse av forbindelsene for fremstilling av medikamenter som COX-2 inhibitorer
WO1999047497A2 (fr)	1999-09-23	Acides carboxyliques et acylsulfonamides, compositions contenant ces composes et methodes de traitement
JP2019524652A (ja)	2019-09-05	新規［１，２，３］トリアゾロ［４，５−ｄ］ピリミジン誘導体
FI88713C (fi)	1993-06-28	Foerfarande foer framstaellning av terapeutiskt aktiva nitrometaner
KR100715918B1 (ko)	2007-05-08	항-염증 활성을 갖는 신규 이미다졸
HU185430B (en)	1985-02-28	Process for producing 6-chloro- or 6-bromol-1,2-dyhidro-3h-pyrrolo-bracket-1,2-a-bracket closed-pyrrole-1-cerboxylic acid derivatives
IE61731B1 (en)	1994-11-30	Aralkylaminoalkoxyphenyl derivatives, process of preparation and compositions containing the same
AU2009302375B2 (en)	2015-03-26	1-phenylpyrrole compounds
US6936632B2 (en)	2005-08-30	Fused pyrrole compounds, pharmaceutical agents containing the same, and the use thereof
CA2398111C (fr)	2008-08-12	Derives de pyrrole 4-pyridyl- et 2,4-pyrimidinyl-substitues et leur utilisation en pharmacie
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