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

NO20023363L (no

NO20023363D0 (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
DRTJEZPDASSXHH-UHFFFAOYSA-N 6-(4-fluorophenyl)-7-methyl-2,3-dihydro-1h-pyrrolizine Chemical compound CC1=C2CCCN2C=C1C1=CC=C(F)C=C1 DRTJEZPDASSXHH-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
238000002965 ELISA Methods 0.000 description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 3
108010029485 Protein Isoforms Proteins 0.000 description 3
102000001708 Protein Isoforms Human genes 0.000 description 3
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
235000011054 acetic acid Nutrition 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
125000002723 alicyclic group Chemical group 0.000 description 3
230000000172 allergic effect Effects 0.000 description 3
230000001754 anti-pyretic effect Effects 0.000 description 3
208000010668 atopic eczema Diseases 0.000 description 3
239000006227 byproduct Substances 0.000 description 3
210000004027 cell Anatomy 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
238000006114 decarboxylation reaction Methods 0.000 description 3
229960002986 dinoprostone Drugs 0.000 description 3
238000004821 distillation Methods 0.000 description 3
239000000839 emulsion Substances 0.000 description 3
238000006911 enzymatic reaction Methods 0.000 description 3
KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 description 3
229960001123 epoprostenol Drugs 0.000 description 3
NJQOQWYCTZWWOT-UHFFFAOYSA-N ethyl 1-acetylcyclohexane-1-carboxylate Chemical compound CCOC(=O)C1(C(C)=O)CCCCC1 NJQOQWYCTZWWOT-UHFFFAOYSA-N 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
239000006260 foam Substances 0.000 description 3
125000005843 halogen group Chemical group 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
239000011777 magnesium Substances 0.000 description 3
229910052749 magnesium Inorganic materials 0.000 description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
239000012188 paraffin wax Substances 0.000 description 3
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
238000004611 spectroscopical analysis Methods 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 3
HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
IVUHTLFKBDDICS-UHFFFAOYSA-N (4-methylsulfanylphenyl)boronic acid Chemical compound CSC1=CC=C(B(O)O)C=C1 IVUHTLFKBDDICS-UHFFFAOYSA-N 0.000 description 2
FMNQRUKVXAQEAZ-JNRFBPFXSA-N (5z,8s,9r,10e,12s)-9,12-dihydroxy-8-[(1s)-1-hydroxy-3-oxopropyl]heptadeca-5,10-dienoic acid Chemical compound CCCCC[C@H](O)\C=C\[C@@H](O)[C@H]([C@@H](O)CC=O)C\C=C/CCCC(O)=O FMNQRUKVXAQEAZ-JNRFBPFXSA-N 0.000 description 2
JLIDRDJNLAWIKT-UHFFFAOYSA-N 1,2-dimethyl-3h-benzo[e]indole Chemical compound C1=CC=CC2=C(C(=C(C)N3)C)C3=CC=C21 JLIDRDJNLAWIKT-UHFFFAOYSA-N 0.000 description 2
KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 description 2
IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 2
AZUYLZMQTIKGSC-UHFFFAOYSA-N 1-[6-[4-(5-chloro-6-methyl-1H-indazol-4-yl)-5-methyl-3-(1-methylindazol-5-yl)pyrazol-1-yl]-2-azaspiro[3.3]heptan-2-yl]prop-2-en-1-one Chemical compound ClC=1C(=C2C=NNC2=CC=1C)C=1C(=NN(C=1C)C1CC2(CN(C2)C(C=C)=O)C1)C=1C=C2C=NN(C2=CC=1)C AZUYLZMQTIKGSC-UHFFFAOYSA-N 0.000 description 2
JQZAEUFPPSRDOP-UHFFFAOYSA-N 1-chloro-4-(chloromethyl)benzene Chemical compound ClCC1=CC=C(Cl)C=C1 JQZAEUFPPSRDOP-UHFFFAOYSA-N 0.000 description 2
KLLUMCWTDJTFCM-UHFFFAOYSA-N 1-ethenyl-3-propanoylpyrrolidin-2-one Chemical compound CCC(=O)C1CCN(C=C)C1=O KLLUMCWTDJTFCM-UHFFFAOYSA-N 0.000 description 2
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 2
CCHNWURRBFGQCD-UHFFFAOYSA-N 2-chlorocyclohexan-1-one Chemical compound ClC1CCCCC1=O CCHNWURRBFGQCD-UHFFFAOYSA-N 0.000 description 2
PIAOLBVUVDXHHL-UHFFFAOYSA-N 2-nitroethenylbenzene Chemical class [O-][N+](=O)C=CC1=CC=CC=C1 PIAOLBVUVDXHHL-UHFFFAOYSA-N 0.000 description 2
MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
QRVYABWJVXXOTN-UHFFFAOYSA-N 4-methylsulfanylbenzaldehyde Chemical compound CSC1=CC=C(C=O)C=C1 QRVYABWJVXXOTN-UHFFFAOYSA-N 0.000 description 2
125000002373 5 membered heterocyclic group Chemical group 0.000 description 2
HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 2
RKBMKGLWKJEOEP-UHFFFAOYSA-N 5-[(4-methylsulfanylphenyl)methyl]-3,4-dihydro-2h-pyrrole Chemical compound C1=CC(SC)=CC=C1CC1=NCCC1 RKBMKGLWKJEOEP-UHFFFAOYSA-N 0.000 description 2
PZMVSPKZURPPAE-UHFFFAOYSA-N 5-benzyl-2,3-dihydro-1h-pyrrole Chemical compound C=1C=CC=CC=1CC1=CCCN1 PZMVSPKZURPPAE-UHFFFAOYSA-N 0.000 description 2
CGCMZVLJSARYKJ-UHFFFAOYSA-N 5-methyl-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C=12CCCN2C(C)=CC=1C1=CC=CC=C1 CGCMZVLJSARYKJ-UHFFFAOYSA-N 0.000 description 2
MCEDQKSNRPGMRO-UHFFFAOYSA-N 6-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C=1N2CCCC2=CC=1C1=CC=CC=C1 MCEDQKSNRPGMRO-UHFFFAOYSA-N 0.000 description 2
MAOVDPMWJVIGRL-UHFFFAOYSA-N 7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C1=CN2CCCC2=C1C1=CC=CC=C1 MAOVDPMWJVIGRL-UHFFFAOYSA-N 0.000 description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
101000725401 Homo sapiens Cytochrome c oxidase subunit 2 Proteins 0.000 description 2
101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 2
206010061218 Inflammation Diseases 0.000 description 2
108010044467 Isoenzymes Proteins 0.000 description 2
239000002841 Lewis acid Substances 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
239000007832 Na2SO4 Substances 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
XNRNNGPBEPRNAR-UHFFFAOYSA-N Thromboxane B2 Natural products CCCCCC(O)C=CC1OC(O)CC(O)C1CC=CCCCC(O)=O XNRNNGPBEPRNAR-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
UGAPHEBNTGUMBB-UHFFFAOYSA-N acetic acid;ethyl acetate Chemical compound CC(O)=O.CCOC(C)=O UGAPHEBNTGUMBB-UHFFFAOYSA-N 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000000654 additive Substances 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
125000004450 alkenylene group Chemical group 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
125000004183 alkoxy alkyl group Chemical group 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
235000011114 ammonium hydroxide Nutrition 0.000 description 2
230000000202 analgesic effect Effects 0.000 description 2
239000002221 antipyretic Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
239000010953 base metal Substances 0.000 description 2
DULCUDSUACXJJC-UHFFFAOYSA-N benzeneacetic acid ethyl ester Natural products CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
230000031709 bromination Effects 0.000 description 2
238000005893 bromination reaction Methods 0.000 description 2
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
235000011148 calcium chloride Nutrition 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
238000006352 cycloaddition reaction Methods 0.000 description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
230000006378 damage Effects 0.000 description 2
229960001259 diclofenac Drugs 0.000 description 2
DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
230000004064 dysfunction Effects 0.000 description 2
239000003480 eluent Substances 0.000 description 2
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
ZLQPAONBGBXGFN-UHFFFAOYSA-N ethyl 2-(4-methylsulfanylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(SC)C=C1 ZLQPAONBGBXGFN-UHFFFAOYSA-N 0.000 description 2
PKEODRHQTYWNPA-UHFFFAOYSA-N ethyl 2-bromo-3-(4-methylsulfonylphenyl)prop-2-enoate Chemical compound CCOC(=O)C(Br)=CC1=CC=C(S(C)(=O)=O)C=C1 PKEODRHQTYWNPA-UHFFFAOYSA-N 0.000 description 2
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
150000002430 hydrocarbons Chemical group 0.000 description 2
239000012535 impurity Substances 0.000 description 2
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
229910052740 iodine Inorganic materials 0.000 description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
229910052742 iron Inorganic materials 0.000 description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
150000002596 lactones Chemical class 0.000 description 2
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 description 2
150000007517 lewis acids Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
238000005259 measurement Methods 0.000 description 2
125000002950 monocyclic group Chemical group 0.000 description 2
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
CPJSUEIXXCENMM-UHFFFAOYSA-N phenacetin Chemical compound CCOC1=CC=C(NC(C)=O)C=C1 CPJSUEIXXCENMM-UHFFFAOYSA-N 0.000 description 2
LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical class BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 2
229960002429 proline Drugs 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
SGUKUZOVHSFKPH-YNNPMVKQSA-N prostaglandin G2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](OO)CCCCC)[C@H]2C\C=C/CCCC(O)=O SGUKUZOVHSFKPH-YNNPMVKQSA-N 0.000 description 2
YIBNHAJFJUQSRA-YNNPMVKQSA-N prostaglandin H2 Chemical compound C1[C@@H]2OO[C@H]1[C@H](/C=C/[C@@H](O)CCCCC)[C@H]2C\C=C/CCCC(O)=O YIBNHAJFJUQSRA-YNNPMVKQSA-N 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
125000000168 pyrrolyl group Chemical group 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
235000010356 sorbitol Nutrition 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
150000003462 sulfoxides Chemical class 0.000 description 2
208000024891 symptom Diseases 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
125000003396 thiol group Chemical class [H]S* 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 2
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000011701 zinc Substances 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
UAYWVJHJZHQCIE-UHFFFAOYSA-L zinc iodide Chemical compound I[Zn]I UAYWVJHJZHQCIE-UHFFFAOYSA-L 0.000 description 2
RQYKQWFHJOBBAO-JTQLQIEISA-N (2s)-1-benzoylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(=O)C1=CC=CC=C1 RQYKQWFHJOBBAO-JTQLQIEISA-N 0.000 description 1
TWFGIHLFQWPEJC-HFKSONKOSA-N (2s,3s)-2-[4-[4-(diaminomethylideneamino)butyl]triazol-1-yl]-n-[11-[4-[4-[4-[11-[[(2s,3s)-2-[4-[4-(diaminomethylideneamino)butyl]triazol-1-yl]-3-methylpentanoyl]amino]undecanoyl]piperazin-1-yl]-6-[2-[2-(2-prop-2-ynoxyethoxy)ethoxy]ethylamino]-1,3,5-triazi Chemical compound N1([C@@H]([C@@H](C)CC)C(=O)NCCCCCCCCCCC(=O)N2CCN(CC2)C=2N=C(NCCOCCOCCOCC#C)N=C(N=2)N2CCN(CC2)C(=O)CCCCCCCCCCNC(=O)[C@H]([C@@H](C)CC)N2N=NC(CCCCN=C(N)N)=C2)C=C(CCCCN=C(N)N)N=N1 TWFGIHLFQWPEJC-HFKSONKOSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
PCTZLSCYMRXUGW-UHFFFAOYSA-N 1,1,1,2,2-pentafluorobutane Chemical group [CH2]CC(F)(F)C(F)(F)F PCTZLSCYMRXUGW-UHFFFAOYSA-N 0.000 description 1
125000006098 1,1-dimethylethyl sulfinyl group Chemical group 0.000 description 1
IDCXLYCLPHRSAZ-UHFFFAOYSA-N 1,5-diphenylpyrazole Chemical class C=1C=CC=CC=1N1N=CC=C1C1=CC=CC=C1 IDCXLYCLPHRSAZ-UHFFFAOYSA-N 0.000 description 1
LTUZWGRJHXDJQU-UHFFFAOYSA-N 1-(4-fluorobenzoyl)pyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CCCN1C(=O)C1=CC=C(F)C=C1 LTUZWGRJHXDJQU-UHFFFAOYSA-N 0.000 description 1
QDLKMRTVELBKFE-UHFFFAOYSA-N 1-(bromomethyl)-4-methylsulfanylbenzene Chemical compound CSC1=CC=C(CBr)C=C1 QDLKMRTVELBKFE-UHFFFAOYSA-N 0.000 description 1
BPWDIXPFAHESAF-UHFFFAOYSA-N 1-[3,3-dimethyl-5-(4-methylsulfonylphenyl)cyclopenta-1,4-dien-1-yl]-4-fluorobenzene Chemical compound C=1C(C)(C)C=C(C=2C=CC(F)=CC=2)C=1C1=CC=C(S(C)(=O)=O)C=C1 BPWDIXPFAHESAF-UHFFFAOYSA-N 0.000 description 1
IGPKPXAYHDIMIS-UHFFFAOYSA-N 1-[3-(carboxymethyl)-1-phenyl-6,7-dihydro-5h-pyrrolizin-2-yl]cyclohexane-1-carboxylic acid Chemical compound C=12CCCN2C(CC(=O)O)=C(C2(CCCCC2)C(O)=O)C=1C1=CC=CC=C1 IGPKPXAYHDIMIS-UHFFFAOYSA-N 0.000 description 1
RIFKADJTWUGDOV-UHFFFAOYSA-N 1-cyclohexylethanone Chemical compound CC(=O)C1CCCCC1 RIFKADJTWUGDOV-UHFFFAOYSA-N 0.000 description 1
DHUHKGAJTMBKPF-UHFFFAOYSA-N 1-ethenyl-3-(2-phenylacetyl)pyrrolidin-2-one Chemical compound O=C1N(C=C)CCC1C(=O)CC1=CC=CC=C1 DHUHKGAJTMBKPF-UHFFFAOYSA-N 0.000 description 1
RIFJNEMVBUEXGR-UHFFFAOYSA-N 1-ethenyl-3-[2-(4-methylsulfanylphenyl)acetyl]pyrrolidin-2-one Chemical compound C1=CC(SC)=CC=C1CC(=O)C1C(=O)N(C=C)CC1 RIFJNEMVBUEXGR-UHFFFAOYSA-N 0.000 description 1
WRWPPGUCZBJXKX-UHFFFAOYSA-N 1-fluoro-4-methylbenzene Chemical compound CC1=CC=C(F)C=C1 WRWPPGUCZBJXKX-UHFFFAOYSA-N 0.000 description 1
125000006094 1-methylethyl sulfinyl group Chemical group 0.000 description 1
125000006096 1-methylpropyl sulfinyl group Chemical group 0.000 description 1
125000006127 1-methylpropyl sulfonyl group Chemical group 0.000 description 1
JEVLNYKVERCGQE-UHFFFAOYSA-N 1-methylsulfonyl-4-(2-nitroethenyl)benzene Chemical group CS(=O)(=O)C1=CC=C(C=C[N+]([O-])=O)C=C1 JEVLNYKVERCGQE-UHFFFAOYSA-N 0.000 description 1
KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
IELVZKKFWNCUAQ-UHFFFAOYSA-N 1h-pyrrolizine-1-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)C=CN21 IELVZKKFWNCUAQ-UHFFFAOYSA-N 0.000 description 1
YHZODXGIMHTEJV-UHFFFAOYSA-N 1h-pyrrolo[1,2-a]imidazole Chemical compound N1C=CN2C=CC=C21 YHZODXGIMHTEJV-UHFFFAOYSA-N 0.000 description 1
CYXQJHOJIQTXLE-UHFFFAOYSA-N 2,3-dihydro-1h-pyrrolizine Chemical class C1=CN2CCCC2=C1 CYXQJHOJIQTXLE-UHFFFAOYSA-N 0.000 description 1
QYABACHSSGCCOE-UHFFFAOYSA-N 2-(1-phenyl-6,7-dihydro-5h-pyrrolizin-3-yl)acetic acid Chemical compound C=12CCCN2C(CC(=O)O)=CC=1C1=CC=CC=C1 QYABACHSSGCCOE-UHFFFAOYSA-N 0.000 description 1
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
FLAYZKKEOIAALB-UHFFFAOYSA-N 2-bromo-1-(4-chlorophenyl)ethanone Chemical compound ClC1=CC=C(C(=O)CBr)C=C1 FLAYZKKEOIAALB-UHFFFAOYSA-N 0.000 description 1
QSKPIOLLBIHNAC-UHFFFAOYSA-N 2-chloro-acetaldehyde Chemical compound ClCC=O QSKPIOLLBIHNAC-UHFFFAOYSA-N 0.000 description 1
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 1
125000006097 2-methylpropyl sulfinyl group Chemical group 0.000 description 1
125000006128 2-methylpropyl sulfonyl group Chemical group 0.000 description 1
GUGQQGROXHPINL-UHFFFAOYSA-N 2-oxobutanoyl chloride Chemical compound CCC(=O)C(Cl)=O GUGQQGROXHPINL-UHFFFAOYSA-N 0.000 description 1
DOTYXUNKIZCKPH-UHFFFAOYSA-N 2h-pyrrolo[2,1-b][1,3]oxazine Chemical class C1=CCOC2=CC=CN21 DOTYXUNKIZCKPH-UHFFFAOYSA-N 0.000 description 1
IZECWPMZUJMMLG-UHFFFAOYSA-N 2h-pyrrolo[2,1-b][1,3]thiazine Chemical class C1=CCSC2=CC=CN21 IZECWPMZUJMMLG-UHFFFAOYSA-N 0.000 description 1
IAYIROUIYOEEAO-UHFFFAOYSA-N 3,3-dimethyl-1-methylsulfanyl-4h-isoquinoline Chemical compound C1=CC=C2C(SC)=NC(C)(C)CC2=C1 IAYIROUIYOEEAO-UHFFFAOYSA-N 0.000 description 1
APTPOHBDWBGOML-UHFFFAOYSA-N 3-(4-fluorophenyl)-4-(4-methylsulfonylphenyl)thiophene Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=CSC=C1C1=CC=C(F)C=C1 APTPOHBDWBGOML-UHFFFAOYSA-N 0.000 description 1
IIOKDOJKJGCOEP-UHFFFAOYSA-N 3h-pyrrolo[1,2-a]imidazole Chemical class C1=CN2CC=NC2=C1 IIOKDOJKJGCOEP-UHFFFAOYSA-N 0.000 description 1
CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 1
LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
UFTHEDBYLPFRDP-UHFFFAOYSA-N 5,6-dihydro-2h-oxazine Chemical compound C1CC=CNO1 UFTHEDBYLPFRDP-UHFFFAOYSA-N 0.000 description 1
MSTFRUQNYRRUKZ-UHFFFAOYSA-N 5,6-dihydro-2h-thiazine Chemical compound C1CC=CNS1 MSTFRUQNYRRUKZ-UHFFFAOYSA-N 0.000 description 1
FQKOGTWNFJGTLT-UHFFFAOYSA-N 5,6-dihydroindolizine Chemical compound C1=CCCN2C=CC=C21 FQKOGTWNFJGTLT-UHFFFAOYSA-N 0.000 description 1
SGNZYJXNUURYCH-UHFFFAOYSA-N 5,6-dihydroxyindole Chemical compound C1=C(O)C(O)=CC2=C1NC=C2 SGNZYJXNUURYCH-UHFFFAOYSA-N 0.000 description 1
VZCIAZMKVAJRCL-UHFFFAOYSA-N 5-(4-fluorophenyl)-6-(4-methylsulfonylphenyl)spiro[2.4]hept-5-ene Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C(C1)=C(C=2C=CC(F)=CC=2)CC11CC1 VZCIAZMKVAJRCL-UHFFFAOYSA-N 0.000 description 1
LMFPZECRFHSNDT-UHFFFAOYSA-N 5-[(4-chlorophenyl)methyl]-3,4-dihydro-2h-pyrrole Chemical compound C1=CC(Cl)=CC=C1CC1=NCCC1 LMFPZECRFHSNDT-UHFFFAOYSA-N 0.000 description 1
BRVMXKDGQVEXMJ-UHFFFAOYSA-N 5-bromo-2,3-bis(4-fluorophenyl)thiophene Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CC(F)=CC=2)SC(Br)=C1 BRVMXKDGQVEXMJ-UHFFFAOYSA-N 0.000 description 1
YJPXMUSHLQHTMD-UHFFFAOYSA-N 5-bromo-6-(4-fluorophenyl)-7-methyl-2,3-dihydro-1h-pyrrolizine Chemical compound CC1=C2CCCN2C(Br)=C1C1=CC=C(F)C=C1 YJPXMUSHLQHTMD-UHFFFAOYSA-N 0.000 description 1
PCRAJUQPZZXDPT-UHFFFAOYSA-N 5-ethenyl-5-nitrocyclohexa-1,3-diene Chemical compound [O-][N+](=O)C1(C=C)CC=CC=C1 PCRAJUQPZZXDPT-UHFFFAOYSA-N 0.000 description 1
PEJRZQAZWLOTTN-UHFFFAOYSA-N 5-methyl-6-(2-methylpropyl)-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound CC(C)CC1=C(C)N2CCCC2=C1C1=CC=CC=C1 PEJRZQAZWLOTTN-UHFFFAOYSA-N 0.000 description 1
BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
XMDTVLDSPRGYRX-UHFFFAOYSA-N 6-(2,2,3,3,4,4,4-heptafluorobutyl)-5-methyl-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C=12CCCN2C(C)=C(CC(F)(F)C(F)(F)C(F)(F)F)C=1C1=CC=CC=C1 XMDTVLDSPRGYRX-UHFFFAOYSA-N 0.000 description 1
PBQUFSVICNEOTA-UHFFFAOYSA-N 6-(4-fluorophenyl)-7-methyl-5-(4-methylsulfonylphenyl)-2,3-dihydro-1h-pyrrolizine Chemical compound CC1=C2CCCN2C(C=2C=CC(=CC=2)S(C)(=O)=O)=C1C1=CC=C(F)C=C1 PBQUFSVICNEOTA-UHFFFAOYSA-N 0.000 description 1
KPMCIEZQJPGIFO-UHFFFAOYSA-N 6-cyclohexyl-5-methyl-7-phenyl-2,3-dihydro-1h-pyrrolizine Chemical compound C=1C=CC=CC=1C1=C2CCCN2C(C)=C1C1CCCCC1 KPMCIEZQJPGIFO-UHFFFAOYSA-N 0.000 description 1
WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
GYVVQGCGBQUCRH-UHFFFAOYSA-N 7-phenyl-5-(trifluoromethyl)-2,3-dihydro-1h-pyrrolizine Chemical compound C=12CCCN2C(C(F)(F)F)=CC=1C1=CC=CC=C1 GYVVQGCGBQUCRH-UHFFFAOYSA-N 0.000 description 1
OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 1
NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
206010002199 Anaphylactic shock Diseases 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
241000972773 Aulopiformes Species 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
101100328518 Caenorhabditis elegans cnt-1 gene Proteins 0.000 description 1
VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
208000010201 Exanthema Diseases 0.000 description 1
JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 1
238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
238000005863 Friedel-Crafts acylation reaction Methods 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
238000003747 Grignard reaction Methods 0.000 description 1
108010081348 HRT1 protein Hairy Proteins 0.000 description 1
102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 1
HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
238000006736 Huisgen cycloaddition reaction Methods 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
RRHGJUQNOFWUDK-UHFFFAOYSA-N Isoprene Chemical compound CC(=C)C=C RRHGJUQNOFWUDK-UHFFFAOYSA-N 0.000 description 1
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
229930182821 L-proline Natural products 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
241001494479 Pecora Species 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
JHBIMJKLBUMNAU-UHFFFAOYSA-N SC-58125 Chemical compound C1=CC(S(=O)(=O)C)=CC=C1N1C(C=2C=CC(F)=CC=2)=CC(C(F)(F)F)=N1 JHBIMJKLBUMNAU-UHFFFAOYSA-N 0.000 description 1
229910006074 SO2NH2 Inorganic materials 0.000 description 1
229910006069 SO3H Inorganic materials 0.000 description 1
101100355633 Salmo salar ran gene Proteins 0.000 description 1
229940124639 Selective inhibitor Drugs 0.000 description 1
206010040070 Septic Shock Diseases 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
239000004141 Sodium laurylsulphate Substances 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
208000007536 Thrombosis Diseases 0.000 description 1
229940111979 Thromboxane synthase inhibitor Drugs 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
238000005672 Willgerodt-Kindler rearrangement reaction Methods 0.000 description 1
238000006856 Wolf-Kishner-Huang Minlon reduction reaction Methods 0.000 description 1
238000005644 Wolff-Kishner reduction reaction Methods 0.000 description 1
239000006096 absorbing agent Substances 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
230000009471 action Effects 0.000 description 1
230000001154 acute effect Effects 0.000 description 1
238000006136 alcoholysis reaction Methods 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
150000001351 alkyl iodides Chemical class 0.000 description 1
125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
229940035676 analgesics Drugs 0.000 description 1
230000002052 anaphylactic effect Effects 0.000 description 1
208000003455 anaphylaxis Diseases 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
239000000730 antalgic agent Substances 0.000 description 1
230000003266 anti-allergic effect Effects 0.000 description 1
230000003361 anti-bronchoconstrictory effect Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
239000002260 anti-inflammatory agent Substances 0.000 description 1
239000000043 antiallergic agent Substances 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
238000006254 arylation reaction Methods 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
229940092714 benzenesulfonic acid Drugs 0.000 description 1
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
CCDWGDHTPAJHOA-UHFFFAOYSA-N benzylsilicon Chemical compound [Si]CC1=CC=CC=C1 CCDWGDHTPAJHOA-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000000601 blood cell Anatomy 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
239000011449 brick Substances 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
AOJDZKCUAATBGE-UHFFFAOYSA-N bromomethane Chemical compound Br[CH2] AOJDZKCUAATBGE-UHFFFAOYSA-N 0.000 description 1
210000000621 bronchi Anatomy 0.000 description 1
239000000168 bronchodilator agent Substances 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
229960001948 caffeine Drugs 0.000 description 1
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000003710 calcium ionophore Substances 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
239000002775 capsule Substances 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
150000001733 carboxylic acid esters Chemical group 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
NVRSPIKUPKOSIY-UHFFFAOYSA-N chembl1743348 Chemical compound CC=1N=NOC=1O NVRSPIKUPKOSIY-UHFFFAOYSA-N 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000012320 chlorinating reagent Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
235000013985 cinnamic acid Nutrition 0.000 description 1
WBYWAXJHAXSJNI-UHFFFAOYSA-N cinnamic acid group Chemical class C(C=CC1=CC=CC=C1)(=O)O WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 1
230000035602 clotting Effects 0.000 description 1
229940125810 compound 20 Drugs 0.000 description 1
229940125898 compound 5 Drugs 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
230000001120 cytoprotective effect Effects 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000011903 deuterated solvents‎ Substances 0.000 description 1
238000003745 diagnosis Methods 0.000 description 1
238000010586 diagram Methods 0.000 description 1
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
OAGOUCJGXNLJNL-UHFFFAOYSA-N dimethylcyanamide Chemical compound CN(C)C#N OAGOUCJGXNLJNL-UHFFFAOYSA-N 0.000 description 1
KZTYYGOKRVBIMI-UHFFFAOYSA-N diphenyl sulfone Chemical compound C=1C=CC=CC=1S(=O)(=O)C1=CC=CC=C1 KZTYYGOKRVBIMI-UHFFFAOYSA-N 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
229940125436 dual inhibitor Drugs 0.000 description 1
150000002066 eicosanoids Chemical class 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000002158 endotoxin Substances 0.000 description 1
210000003743 erythrocyte Anatomy 0.000 description 1
IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
CHDFNIZLAAFFPX-UHFFFAOYSA-N ethoxyethane;oxolane Chemical compound CCOCC.C1CCOC1 CHDFNIZLAAFFPX-UHFFFAOYSA-N 0.000 description 1
WVADRPHNJPENSF-UHFFFAOYSA-N ethyl 1-(4-chlorophenyl)-2-phenyl-6,7-dihydro-5h-pyrrolizine-3-carboxylate Chemical compound C=12CCCN2C(C(=O)OCC)=C(C=2C=CC=CC=2)C=1C1=CC=C(Cl)C=C1 WVADRPHNJPENSF-UHFFFAOYSA-N 0.000 description 1
CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 1
JCBABJXRZWZNKS-UHFFFAOYSA-N ethyl 2-oxo-2-(1-phenyl-6,7-dihydro-5h-pyrrolizin-3-yl)acetate Chemical compound C=12CCCN2C(C(=O)C(=O)OCC)=CC=1C1=CC=CC=C1 JCBABJXRZWZNKS-UHFFFAOYSA-N 0.000 description 1
KGBQHQAJTDBHIE-UHFFFAOYSA-N ethyl 3-(4-fluorophenyl)-1-(4-methylsulfanylphenyl)-6,7-dihydro-5h-pyrrolizine-2-carboxylate Chemical compound CCOC(=O)C=1C(C=2C=CC(SC)=CC=2)=C2CCCN2C=1C1=CC=C(F)C=C1 KGBQHQAJTDBHIE-UHFFFAOYSA-N 0.000 description 1
HXJYZWLQNWXXTQ-UHFFFAOYSA-N ethyl 3-(4-fluorophenyl)-2-(4-methylsulfanylphenyl)-6,7-dihydro-5h-pyrrolizine-1-carboxylate Chemical compound CCOC(=O)C1=C2CCCN2C(C=2C=CC(F)=CC=2)=C1C1=CC=C(SC)C=C1 HXJYZWLQNWXXTQ-UHFFFAOYSA-N 0.000 description 1
AZWSNIDXFQIBEJ-UHFFFAOYSA-N ethyl 3-(4-fluorophenyl)-2-phenyl-6,7-dihydro-5h-pyrrolizine-1-carboxylate Chemical compound CCOC(=O)C1=C2CCCN2C(C=2C=CC(F)=CC=2)=C1C1=CC=CC=C1 AZWSNIDXFQIBEJ-UHFFFAOYSA-N 0.000 description 1
239000002024 ethyl acetate extract Substances 0.000 description 1
WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 1
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
JJOYCHKVKWDMEA-UHFFFAOYSA-N ethyl cyclohexanecarboxylate Chemical compound CCOC(=O)C1CCCCC1 JJOYCHKVKWDMEA-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
201000005884 exanthem Diseases 0.000 description 1
230000005284 excitation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000945 filler Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
239000011888 foil Substances 0.000 description 1
238000004508 fractional distillation Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
210000001156 gastric mucosa Anatomy 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
125000004438 haloalkoxy group Chemical group 0.000 description 1
239000001307 helium Substances 0.000 description 1
229910052734 helium Inorganic materials 0.000 description 1
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
229960002897 heparin Drugs 0.000 description 1
229920000669 heparin Polymers 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
MOTRZVVGCFFABN-UHFFFAOYSA-N hexane;2-propan-2-yloxypropane Chemical compound CCCCCC.CC(C)OC(C)C MOTRZVVGCFFABN-UHFFFAOYSA-N 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
229960000905 indomethacin Drugs 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000000893 inhibin Substances 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
239000011630 iodine Substances 0.000 description 1
208000028867 ischemia Diseases 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
239000008101 lactose Substances 0.000 description 1
230000003902 lesion Effects 0.000 description 1
150000002617 leukotrienes Chemical class 0.000 description 1
229920006008 lipopolysaccharide Polymers 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
239000000155 melt Substances 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000002207 metabolite Substances 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
ASVBZKXWHGILGE-UHFFFAOYSA-N methyl 1-(4-chlorosulfonylphenyl)-2-(4-fluorophenyl)-6,7-dihydro-5h-pyrrolizine-3-carboxylate Chemical compound C=12CCCN2C(C(=O)OC)=C(C=2C=CC(F)=CC=2)C=1C1=CC=C(S(Cl)(=O)=O)C=C1 ASVBZKXWHGILGE-UHFFFAOYSA-N 0.000 description 1
DSVDXLNMHRXLTE-UHFFFAOYSA-N methyl 2-(4-fluorophenyl)-1-phenyl-6,7-dihydro-5h-pyrrolizine-3-carboxylate Chemical compound C=12CCCN2C(C(=O)OC)=C(C=2C=CC(F)=CC=2)C=1C1=CC=CC=C1 DSVDXLNMHRXLTE-UHFFFAOYSA-N 0.000 description 1
HGGUOMMWTVBBBH-UHFFFAOYSA-N methyl 2-(4-methylsulfanylphenyl)acetate Chemical compound COC(=O)CC1=CC=C(SC)C=C1 HGGUOMMWTVBBBH-UHFFFAOYSA-N 0.000 description 1
JFGWPXKGINUNDH-UHFFFAOYSA-N methyl 3-phenylprop-2-ynoate Chemical compound COC(=O)C#CC1=CC=CC=C1 JFGWPXKGINUNDH-UHFFFAOYSA-N 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
239000011259 mixed solution Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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
125000006093 n-propyl sulfinyl group Chemical group 0.000 description 1
125000006124 n-propyl sulfonyl group Chemical group 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000006186 oral dosage form Substances 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
125000003431 oxalo group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
238000012856 packing Methods 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
125000005003 perfluorobutyl group Chemical group FC(F)(F)C(F)(F)C(F)(F)C(F)(F)* 0.000 description 1
125000005004 perfluoroethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
125000005009 perfluoropropyl group Chemical group FC(C(C(F)(F)F)(F)F)(F)* 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
229960003893 phenacetin Drugs 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
150000004633 phorbol derivatives Chemical class 0.000 description 1
239000002644 phorbol ester Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
125000005633 phthalidyl group Chemical group 0.000 description 1
HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
210000002826 placenta Anatomy 0.000 description 1
229920001921 poly-methyl-phenyl-siloxane Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
230000008569 process Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000000770 proinflammatory effect Effects 0.000 description 1
UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical class OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical class OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 1
150000003236 pyrrolines Chemical class 0.000 description 1
DXGJVAZNKXKXQR-UHFFFAOYSA-N pyrrolo[2,1-b][1,3]oxazole Chemical class O1C=CN2C=CC=C21 DXGJVAZNKXKXQR-UHFFFAOYSA-N 0.000 description 1
MOVFAUAADQBPRE-UHFFFAOYSA-N pyrrolo[2,1-b][1,3]thiazole Chemical compound S1C=CN2C=CC=C21 MOVFAUAADQBPRE-UHFFFAOYSA-N 0.000 description 1
239000010453 quartz Substances 0.000 description 1
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)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (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)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
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
JP2005504781A (ja) *	2001-08-30	2005-02-17	メルクル・ゲーエムベーハー	環付加したピロール化合物の関節軟骨または軟骨下骨変性の治療における使用
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

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4232038A (en) *	1979-08-31	1980-11-04	Syntex (U.S.A.) Inc.	5-Alkylsulfinylbenzoyl- and 5-alkylsulfonylbenzoyl-1,2-dihydro-3H-pyrrolo[1,]pyrrole-1-carboxylic acids
CA1242725A (fr)	1982-03-03	1988-10-04	E. I. Du Pont De Nemours And Company	2,3-diaryl-5-halo thiophenes antiinflammatoires et (ou) analgesiques
DE3915450A1 (de) *	1989-05-11	1990-11-15	Gerd Prof Dr Dannhardt	Substituierte pyrrolverbindungen und deren anwendung in der pharmazie
US5260451A (en)	1989-05-11	1993-11-09	Merckle Gmbh	Substituted pyrrole compounds and use thereof in pharmaceutical compositions
EP0679157B1 (fr)	1993-01-15	1997-11-19	G.D. Searle & Co.	Nouveaux thiophenes 3,4-diaryle et leurs analogues utilises comme agents anti-inflammatoires
US5380738A (en)	1993-05-21	1995-01-10	Monsanto Company	2-substituted oxazoles further substituted by 4-fluorophenyl and 4-methylsulfonylphenyl as antiinflammatory agents
US5474995A (en)	1993-06-24	1995-12-12	Merck Frosst Canada, Inc.	Phenyl heterocycles as cox-2 inhibitors
US5344991A (en)	1993-10-29	1994-09-06	G.D. Searle & Co.	1,2 diarylcyclopentenyl compounds for the treatment of inflammation
US5475018A (en)	1993-11-30	1995-12-12	G. D. Searle & Co.	1,5-diphenyl pyrazole compounds for treatment of inflammation
DK0743938T3 (da)	1994-02-10	1999-10-25	Searle & Co	Substituerede spiroforbindelser til behandling af inflammation
US5418254A (en)	1994-05-04	1995-05-23	G. D. Searle & Co.	Substituted cyclopentadienyl compounds for the treatment of inflammation
DE4419315A1 (de) *	1994-06-01	1995-12-07	Merckle Gmbh	Heteropyrrolizinverbindungen und deren Anwendung in der Pharmazie
DE4419247A1 (de) *	1994-06-01	1995-12-07	Merckle Gmbh	Sulfonylierte Pyrrolizincarbonsäureamide und deren Anwendung in der Pharmazie
DE4419246A1 (de) *	1994-06-01	1995-12-07	Merckle Gmbh	Heteroarylsubstituierte Pyrrolizinverbindungen und deren Anwendung in der Pharmazie
US5593994A (en)	1994-09-29	1997-01-14	The Dupont Merck Pharmaceutical Company	Prostaglandin synthase inhibitors
ES2247604T3 (es) *	1995-06-12	2006-03-01	G.D. SEARLE & CO.	Composiciones que comprenden un inhibidor de ciclooxigenasa-2 y un inhibidor de 5-lipoxigenasa.
DE19624290A1 (de)	1996-06-18	1998-01-02	Merckle Gmbh	Verwendungen von Pyrrolizin-Verbindungen in der Pharmazie
DE19624289A1 (de)	1996-06-18	1998-01-02	Merckle Gmbh	Pyrrolizin-Verbindungen und deren Verwendung
AU3953899A (en) *	1998-05-27	1999-12-13	Nippon Shinyaku Co. Ltd.	Cyclooxygenase-2 inhibitors
DE19845446A1 (de)	1998-10-02	2000-04-06	Merckle Gmbh	Antiinflammatorische Oxo- und Hydroxyderivate von Pyrrolizinen und deren Verwendung in der Pharmazie
HUP0204336A3 (en)	1999-11-23	2006-01-30	Merckle Gmbh	Anti-inflammatory oxo derivatives and hydroxy derivatives of pyrrolizines, and their pharmaceutical use and pharmaceutical compositions containing them their
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 WO PCT/EP2001/000332 patent/WO2001051491A1/fr not_active Ceased
- 2001-01-12 DE DE50101187T patent/DE50101187D1/de not_active Expired - Fee Related
- 2001-01-12 ES ES01902310T patent/ES2213102T3/es not_active Expired - Lifetime
- 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 CA CA002396413A patent/CA2396413A1/fr not_active Abandoned
- 2001-01-12 TR TR2004/00270T patent/TR200400270T4/xx unknown
- 2001-01-12 EP EP01902310A patent/EP1246825B1/fr not_active Expired - Lifetime
- 2001-01-12 MX MXPA02006863A patent/MXPA02006863A/es active IP Right Grant
- 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
- 2001-01-12 DK DK01902310T patent/DK1246825T3/da active
- 2001-01-12 KR KR1020027009012A patent/KR20020081254A/ko not_active Withdrawn
- 2001-01-12 JP JP2001551075A patent/JP2003525875A/ja active Pending
2002
- 2002-07-12 NO NO20023363A patent/NO323238B1/no unknown

Also Published As

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

Publication	Publication Date	Title
CN100486573C (zh)	2009-05-13	硝基化的和亚硝基化的环加氧酶-2抑制剂、组合物及其用途
FI113966B (fi)	2004-07-15	Pyrrolo [2,1-b] imidatsoli-, ja -tiatsoli- ja pyrrolo [2,1-b] -1,3-tiatsiinijohdannaiset ja niiden käyttö farmasiassa ja välituotteina
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
KR970011396B1 (ko)	1997-07-10	티아졸로 [5, 4-b] 아제핀 화합물
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
NO323238B1 (no)	2007-02-05	Kondenserte pyrrolforbindelser, farmasoytiske omfattende disse, og anvendelse av disse.
KR100715918B1 (ko)	2007-05-08	항-염증 활성을 갖는 신규 이미다졸
KR20010079602A (ko)	2001-08-22	선택적인 ｃｏｘ-2 저해제인 치환된 이미다조[1,2ａ]아진
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
AU2009302375B2 (en)	2015-03-26	1-phenylpyrrole compounds
CA2398111C (fr)	2008-08-12	Derives de pyrrole 4-pyridyl- et 2,4-pyrimidinyl-substitues et leur utilisation en pharmacie
US4347186A (en)	1982-08-31	Process for preparing 5-aroyl 1,2-dihydro-3-H pyrrolo[1,2-a]pyrrole-1-carboxylic acids and novel intermediates therein
NO874892L (no)	1988-06-17	Analogifremgangsmaate for fremstilling av terapeutisk aktive 3-(omega-(3,5-di-t-butyl-4-hydroxyfenyl)-alkanoyl)-pyrroler og deres deoxy-analoger.
RU2189979C2 (ru)	2002-09-27	Диарилметилиденфурановые производные, способ их получения и фармацевтическая композиция на их основе
CA2320829A1 (fr)	1999-09-02	Derives de diarylmethylene heterocyclique, leurs procedes de preparation et leurs utilisations therapeutiques
US4458081A (en)	1984-07-03	5-Aroyl 1,2-dihydro-3H-pyrrolo[1,2-a]pyrrole-1,1-decarboxylates
JP2002506851A (ja)	2002-03-05	カルボン酸類およびアシルスルホンアミド類、そのような化合物を含む組成物ならびに治療方法
Pelkey et al.	2006	Novel electrophilic ipso acylation-detosylation reaction of pyrroles
FR2692578A1 (fr)	1993-12-24	Dérivés d'indolizines, procédé de préparation et utilisation pour la préparation de composés aminoalkoxybenzènesulfonyl-indolizines à activité pharmaceutique.
GB2319772A (en)	1998-06-03	2-Phenylazulene derivatives and a process for their synthesis
Chen	2015	STUDY OF NOVEL SYNTHETIC METHODOLOGIES FOR INDOLYL DERIVATIVES AND BETA-FLUOROENALS
HUT58071A (en)	1992-01-28	Process for producing 2,3,4,5-tetrahydro-1-benzoxepines and pharmaceutical compositions comprising same as active ingredient
ZA200205707B (en)	2003-11-11	Nitrosated and nitrosylated cyclooxygenase-2 inhibitors, compositions and methods of use.