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

Info

Publication number

NO323238B1

NO323238B1 NO20023363A NO20023363A NO323238B1 NO 323238 B1 NO323238 B1 NO 323238B1 NO 20023363 A NO20023363 A NO 20023363A NO 20023363 A NO20023363 A NO 20023363A NO 323238 B1 NO323238 B1 NO 323238B1

Authority

NO

Norway

Prior art keywords

alkyl

radicals

mmol

mixture

halogen

Prior art date

2000-01-13

Links

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• 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
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