SK3192000A3 - Pyrrolopyrrolone derivatives as inhibitors of neutrophil elastase - Google Patents

Info

Publication number

SK3192000A3

SK3192000A3 SK319-2000A SK3192000A SK3192000A3 SK 3192000 A3 SK3192000 A3 SK 3192000A3 SK 3192000 A SK3192000 A SK 3192000A SK 3192000 A3 SK3192000 A3 SK 3192000A3

Authority

SK

Slovakia

Prior art keywords

isopropyl

carbonyl

rel

pyrrol

methanesulfonyl

Prior art date

1997-09-09

Links

• Espacenet
• Global Dossier
• Discuss

• 108010028275 Leukocyte Elastase Proteins 0.000 title description 6
• 102000016799 Leukocyte elastase Human genes 0.000 title description 6
• 239000003112 inhibitor Substances 0.000 title description 5
• ACJSMQZKXAMMRA-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyrrol-5-one Chemical class N1C=CC2=NC(=O)C=C21 ACJSMQZKXAMMRA-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 213
• -1 4-phenyl-piperazin-1-ylmethyl Chemical group 0.000 claims description 90
• 239000002904 solvent Substances 0.000 claims description 84
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 83
• 239000000203 mixture Substances 0.000 claims description 70
• 238000006243 chemical reaction Methods 0.000 claims description 43
• 238000000034 method Methods 0.000 claims description 41
• VIXWGKYSYIBATJ-UHFFFAOYSA-N pyrrol-2-one Chemical compound O=C1C=CC=N1 VIXWGKYSYIBATJ-UHFFFAOYSA-N 0.000 claims description 30
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
• 150000003839 salts Chemical class 0.000 claims description 24
• 238000002360 preparation method Methods 0.000 claims description 23
• 125000004432 carbon atom Chemical group C* 0.000 claims description 19
• 229910052757 nitrogen Inorganic materials 0.000 claims description 18
• 239000002253 acid Substances 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 12
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 11
• 239000001257 hydrogen Substances 0.000 claims description 11
• 206010006451 bronchitis Diseases 0.000 claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims description 10
• 239000012453 solvate Substances 0.000 claims description 10
• 229910052717 sulfur Inorganic materials 0.000 claims description 10
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
• 239000004480 active ingredient Substances 0.000 claims description 9
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 229910052801 chlorine Inorganic materials 0.000 claims description 8
• 150000002148 esters Chemical class 0.000 claims description 8
• 229910052736 halogen Inorganic materials 0.000 claims description 8
• 125000005843 halogen group Chemical group 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 230000008569 process Effects 0.000 claims description 8
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
• 150000002367 halogens Chemical group 0.000 claims description 7
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
• 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 claims description 6
• 206010006458 Bronchitis chronic Diseases 0.000 claims description 6
• 229930040373 Paraformaldehyde Natural products 0.000 claims description 6
• 150000008064 anhydrides Chemical class 0.000 claims description 6
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
• 208000007451 chronic bronchitis Diseases 0.000 claims description 6
• 239000012458 free base Substances 0.000 claims description 6
• 229920002866 paraformaldehyde Polymers 0.000 claims description 6
• 125000003386 piperidinyl group Chemical group 0.000 claims description 6
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 125000002757 morpholinyl group Chemical group 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 125000004193 piperazinyl group Chemical group 0.000 claims description 5
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
• 230000002378 acidificating effect Effects 0.000 claims description 4
• 125000003118 aryl group Chemical group 0.000 claims description 4
• 125000005842 heteroatom Chemical group 0.000 claims description 4
• 125000002950 monocyclic group Chemical group 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000004434 sulfur atom Chemical group 0.000 claims description 4
• 125000000335 thiazolyl group Chemical group 0.000 claims description 4
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000001424 substituent group Chemical group 0.000 claims description 3
• 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 claims description 3
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
• 125000003342 alkenyl group Chemical group 0.000 claims description 2
• 208000006673 asthma Diseases 0.000 claims description 2
• 125000002785 azepinyl group Chemical group 0.000 claims description 2
• 125000002393 azetidinyl group Chemical group 0.000 claims description 2
• 150000001733 carboxylic acid esters Chemical class 0.000 claims description 2
• 239000007795 chemical reaction product Substances 0.000 claims description 2
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
• 125000002971 oxazolyl group Chemical group 0.000 claims description 2
• 230000001590 oxidative effect Effects 0.000 claims description 2
• DSILUGCORMLHPA-UHFFFAOYSA-N 2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,2-b]pyrrol-5-one Chemical compound N1CCC2NC(=O)CC21 DSILUGCORMLHPA-UHFFFAOYSA-N 0.000 claims 10
• 239000003208 petroleum Substances 0.000 claims 3
• MEDXAFZZWXHGBT-HYVNUMGLSA-N (3ar,6s,6as)-4-methylsulfonyl-6-propan-2-yl-1-[2-(pyrrolidin-1-ylmethyl)-1,3-oxazole-4-carbonyl]-3,3a,6,6a-tetrahydro-2h-pyrrolo[3,2-b]pyrrol-5-one Chemical compound C([C@@H]1[C@@H]2[C@@H](C(N1S(C)(=O)=O)=O)C(C)C)CN2C(=O)C(N=1)=COC=1CN1CCCC1 MEDXAFZZWXHGBT-HYVNUMGLSA-N 0.000 claims 1
• HUXNOGURDDFLLU-UHFFFAOYSA-N 1-(1h-pyrrol-2-ylmethyl)piperidine Chemical compound C=1C=CNC=1CN1CCCCC1 HUXNOGURDDFLLU-UHFFFAOYSA-N 0.000 claims 1
• 239000013067 intermediate product Substances 0.000 claims 1
• 208000027866 inflammatory disease Diseases 0.000 abstract description 2
• 210000002345 respiratory system Anatomy 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 446
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 239
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 172
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 166
• 239000000543 intermediate Substances 0.000 description 155
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 148
• 239000000243 solution Substances 0.000 description 147
• 239000007787 solid Substances 0.000 description 132
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 99
• 238000004809 thin layer chromatography Methods 0.000 description 82
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 68
• 239000011541 reaction mixture Substances 0.000 description 65
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
• 235000019441 ethanol Nutrition 0.000 description 59
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 50
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 46
• 239000000843 powder Substances 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
• 239000000047 product Substances 0.000 description 38
• 229910021529 ammonia Inorganic materials 0.000 description 34
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 31
• 238000004949 mass spectrometry Methods 0.000 description 28
• 239000000377 silicon dioxide Substances 0.000 description 28
• 238000003756 stirring Methods 0.000 description 28
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 26
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 26
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 26
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 25
• 235000019341 magnesium sulphate Nutrition 0.000 description 25
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 24
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
• 239000002585 base Substances 0.000 description 21
• 238000003818 flash chromatography Methods 0.000 description 21
• 239000000284 extract Substances 0.000 description 20
• 239000000725 suspension Substances 0.000 description 20
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 19
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
• 125000006239 protecting group Chemical group 0.000 description 19
• 238000010992 reflux Methods 0.000 description 19
• 235000017557 sodium bicarbonate Nutrition 0.000 description 19
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 19
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• 102000016387 Pancreatic elastase Human genes 0.000 description 17
• 108010067372 Pancreatic elastase Proteins 0.000 description 17
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 16
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 229910052938 sodium sulfate Inorganic materials 0.000 description 16
• 235000011152 sodium sulphate Nutrition 0.000 description 16
• 239000007858 starting material Substances 0.000 description 16
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
• 239000000126 substance Substances 0.000 description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
• 201000010099 disease Diseases 0.000 description 13
• 229910000029 sodium carbonate Inorganic materials 0.000 description 13
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 12
• 238000001819 mass spectrum Methods 0.000 description 12
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
• YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 11
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 11
• 229910000027 potassium carbonate Inorganic materials 0.000 description 11
• 235000011181 potassium carbonates Nutrition 0.000 description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
• 210000001519 tissue Anatomy 0.000 description 9
• 102000004190 Enzymes Human genes 0.000 description 8
• 108090000790 Enzymes Proteins 0.000 description 8
• 239000006260 foam Substances 0.000 description 8
• 239000012442 inert solvent Substances 0.000 description 8
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 8
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
• 0 CN(CCC1*)C1=O Chemical compound CN(CCC1*)C1=O 0.000 description 7
• 229960000583 acetic acid Drugs 0.000 description 7
• 230000004968 inflammatory condition Effects 0.000 description 7
• 210000004072 lung Anatomy 0.000 description 7
• 210000000440 neutrophil Anatomy 0.000 description 7
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
• WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 6
• 239000008187 granular material Substances 0.000 description 6
• 239000011734 sodium Substances 0.000 description 6
• 229910052708 sodium Inorganic materials 0.000 description 6
• 239000011780 sodium chloride Substances 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 6
• 239000003981 vehicle Substances 0.000 description 6
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 5
• 239000006286 aqueous extract Substances 0.000 description 5
• 230000009286 beneficial effect Effects 0.000 description 5
• HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 230000004054 inflammatory process Effects 0.000 description 5
• 239000000463 material Substances 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
• 238000007363 ring formation reaction Methods 0.000 description 5
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
• 206010061218 Inflammation Diseases 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 229910004298 SiO 2 Inorganic materials 0.000 description 4
• 239000008346 aqueous phase Substances 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 229910052794 bromium Inorganic materials 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 239000003054 catalyst Substances 0.000 description 4
• 210000004027 cell Anatomy 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000013078 crystal Substances 0.000 description 4
• 239000002027 dichloromethane extract Substances 0.000 description 4
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 4
• 239000003480 eluent Substances 0.000 description 4
• 239000000839 emulsion Substances 0.000 description 4
• 208000015181 infectious disease Diseases 0.000 description 4
• 230000003834 intracellular effect Effects 0.000 description 4
• CQRPUKWAZPZXTO-UHFFFAOYSA-M magnesium;2-methylpropane;chloride Chemical compound [Mg+2].[Cl-].C[C-](C)C CQRPUKWAZPZXTO-UHFFFAOYSA-M 0.000 description 4
• 230000014759 maintenance of location Effects 0.000 description 4
• 229920001467 poly(styrenesulfonates) Polymers 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 229920006395 saturated elastomer Polymers 0.000 description 4
• 230000028327 secretion Effects 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 3
• 229910015900 BF3 Inorganic materials 0.000 description 3
• FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 description 3
• 241000400611 Eucalyptus deanei Species 0.000 description 3
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 239000012448 Lithium borohydride Substances 0.000 description 3
• 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 3
• 235000019502 Orange oil Nutrition 0.000 description 3
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
• 229920002472 Starch Polymers 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
• 239000000443 aerosol Substances 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• 239000007864 aqueous solution Substances 0.000 description 3
• 238000003556 assay Methods 0.000 description 3
• 239000012298 atmosphere Substances 0.000 description 3
• LAORHHSYLRWIMN-PWZMFNOBSA-N benzyl (2s,3r)-3-amino-2-(1-ethoxy-3-methyl-1-oxobutan-2-yl)pyrrolidine-1-carboxylate Chemical compound CCOC(=O)C(C(C)C)[C@H]1[C@H](N)CCN1C(=O)OCC1=CC=CC=C1 LAORHHSYLRWIMN-PWZMFNOBSA-N 0.000 description 3
• PCEHCHSVPXQJFP-UHFFFAOYSA-N benzyl pyrrole-1-carboxylate Chemical compound C1=CC=CN1C(=O)OCC1=CC=CC=C1 PCEHCHSVPXQJFP-UHFFFAOYSA-N 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 229910052799 carbon Inorganic materials 0.000 description 3
• 239000003638 chemical reducing agent Substances 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 238000004296 chiral HPLC Methods 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
• 239000012230 colorless oil Substances 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• WJYHCYBNUJVCEH-UHFFFAOYSA-N cyclohexane;ethoxyethane Chemical compound CCOCC.C1CCCCC1 WJYHCYBNUJVCEH-UHFFFAOYSA-N 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
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
• 238000010511 deprotection reaction Methods 0.000 description 3
• 230000001066 destructive effect Effects 0.000 description 3
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
• IQDGSYLLQPDQDV-UHFFFAOYSA-N dimethylazanium;chloride Chemical compound Cl.CNC IQDGSYLLQPDQDV-UHFFFAOYSA-N 0.000 description 3
• 239000003602 elastase inhibitor Substances 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 239000007789 gas Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 210000000265 leukocyte Anatomy 0.000 description 3
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
• VMVNZNXAVJHNDJ-UHFFFAOYSA-N methyl 2,2,2-trifluoroacetate Chemical compound COC(=O)C(F)(F)F VMVNZNXAVJHNDJ-UHFFFAOYSA-N 0.000 description 3
• 239000002674 ointment Substances 0.000 description 3
• 239000010502 orange oil Substances 0.000 description 3
• 239000003960 organic solvent Substances 0.000 description 3
• NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 3
• 239000008188 pellet Substances 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 3
• FFBJXAVQHJFYGV-UHFFFAOYSA-N pyrrol-2-one;hydrochloride Chemical compound Cl.O=C1C=CC=N1 FFBJXAVQHJFYGV-UHFFFAOYSA-N 0.000 description 3
• 230000002829 reductive effect Effects 0.000 description 3
• 239000011347 resin Substances 0.000 description 3
• 229920005989 resin Polymers 0.000 description 3
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 229940032147 starch Drugs 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 3
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 2
• IVSFBKFNMKSNJO-UHFFFAOYSA-N 2-(pyrrolidin-1-ylmethyl)-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(CN2CCCC2)=N1 IVSFBKFNMKSNJO-UHFFFAOYSA-N 0.000 description 2
• ABFPKTQEQNICFT-UHFFFAOYSA-M 2-chloro-1-methylpyridin-1-ium;iodide Chemical compound [I-].C[N+]1=CC=CC=C1Cl ABFPKTQEQNICFT-UHFFFAOYSA-M 0.000 description 2
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 2
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• BDCHCJSIJYFPJO-UHFFFAOYSA-N 4-methylsulfonyl-6-propan-2-yl-1,2,3,3a,6,6a-hexahydropyrrolo[3,2-b]pyrrol-5-one Chemical compound N1CCC2N(S(C)(=O)=O)C(=O)C(C(C)C)C21 BDCHCJSIJYFPJO-UHFFFAOYSA-N 0.000 description 2
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• 241000699800 Cricetinae Species 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 108090001007 Interleukin-8 Proteins 0.000 description 2
• 102000004890 Interleukin-8 Human genes 0.000 description 2
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 2
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
• 240000007472 Leucaena leucocephala Species 0.000 description 2
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
• CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• YTAHJIFKAKIKAV-XNMGPUDCSA-N [(1R)-3-morpholin-4-yl-1-phenylpropyl] N-[(3S)-2-oxo-5-phenyl-1,3-dihydro-1,4-benzodiazepin-3-yl]carbamate Chemical compound O=C1[C@H](N=C(C2=C(N1)C=CC=C2)C1=CC=CC=C1)NC(O[C@H](CCN1CCOCC1)C1=CC=CC=C1)=O YTAHJIFKAKIKAV-XNMGPUDCSA-N 0.000 description 2
• 238000002835 absorbance Methods 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000000654 additive Substances 0.000 description 2
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
• 125000005907 alkyl ester group Chemical group 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 2
• 229940063655 aluminum stearate Drugs 0.000 description 2
• 235000019270 ammonium chloride Nutrition 0.000 description 2
• 239000004599 antimicrobial Substances 0.000 description 2
• 239000003963 antioxidant agent Substances 0.000 description 2
• 239000007900 aqueous suspension Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• 208000037976 chronic inflammation Diseases 0.000 description 2
• 230000006020 chronic inflammation Effects 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000012043 crude product Substances 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 229910001873 dinitrogen Inorganic materials 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 239000004744 fabric Substances 0.000 description 2
• 239000000945 filler Substances 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 239000012362 glacial acetic acid Substances 0.000 description 2
• 150000003840 hydrochlorides Chemical class 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 230000007062 hydrolysis Effects 0.000 description 2
• 238000006460 hydrolysis reaction Methods 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000002757 inflammatory effect Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
• 229910052740 iodine Inorganic materials 0.000 description 2
• 239000011630 iodine Substances 0.000 description 2
• 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 2
• 150000003951 lactams Chemical class 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 230000004199 lung function Effects 0.000 description 2
• 230000000813 microbial effect Effects 0.000 description 2
• 239000002808 molecular sieve Substances 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 239000012044 organic layer Substances 0.000 description 2
• 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 2
• 238000007254 oxidation reaction Methods 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 239000002504 physiological saline solution Substances 0.000 description 2
• 235000015497 potassium bicarbonate Nutrition 0.000 description 2
• 229910000028 potassium bicarbonate Inorganic materials 0.000 description 2
• 239000011736 potassium bicarbonate Substances 0.000 description 2
• IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
• 239000003755 preservative agent Substances 0.000 description 2
• SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 2
• KIDHWZJUCRJVML-UHFFFAOYSA-N putrescine Chemical compound NCCCCN KIDHWZJUCRJVML-UHFFFAOYSA-N 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 235000009518 sodium iodide Nutrition 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 239000000600 sorbitol Substances 0.000 description 2
• 235000010356 sorbitol Nutrition 0.000 description 2
• 238000005694 sulfonylation reaction Methods 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 150000003899 tartaric acid esters Chemical class 0.000 description 2
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 239000002562 thickening agent Substances 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 229950004288 tosilate Drugs 0.000 description 2
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-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
• 238000001665 trituration Methods 0.000 description 2
• 210000000689 upper leg Anatomy 0.000 description 2
• 239000003039 volatile agent Substances 0.000 description 2
• 238000005406 washing Methods 0.000 description 2
• IORHBIZYYBINFX-UHFFFAOYSA-N (1-ethoxy-3-methylbut-1-enoxy)-tri(propan-2-yl)silane Chemical compound CCOC(=CC(C)C)O[Si](C(C)C)(C(C)C)C(C)C IORHBIZYYBINFX-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
• PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 1
• YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
• DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
• DFPYXQYWILNVAU-UHFFFAOYSA-N 1-hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1.C1=CC=C2N(O)N=NC2=C1 DFPYXQYWILNVAU-UHFFFAOYSA-N 0.000 description 1
• ILAOVOOZLVGAJF-UHFFFAOYSA-N 1-methylpyrrole-2-carboxylic acid Chemical compound CN1C=CC=C1C(O)=O ILAOVOOZLVGAJF-UHFFFAOYSA-N 0.000 description 1
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
• ICFGFAUMBISMLR-UHFFFAOYSA-N 1h-pyrazole-5-carbaldehyde Chemical compound O=CC=1C=CNN=1 ICFGFAUMBISMLR-UHFFFAOYSA-N 0.000 description 1
• ORQZPZWDDRVGNI-UHFFFAOYSA-N 2,2,2-trifluoro-n-(2-oxopyrrolidin-3-yl)acetamide Chemical compound FC(F)(F)C(=O)NC1CCNC1=O ORQZPZWDDRVGNI-UHFFFAOYSA-N 0.000 description 1
• BLCJBICVQSYOIF-UHFFFAOYSA-N 2,2-diaminobutanoic acid Chemical compound CCC(N)(N)C(O)=O BLCJBICVQSYOIF-UHFFFAOYSA-N 0.000 description 1
• NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 description 1
• UFIUMDMAMPMTQG-UHFFFAOYSA-N 2-(2,2-dimethylpropanoyloxymethyl)-1,3-thiazole-4-carboxylic acid Chemical compound CC(C)(C)C(=O)OCC1=NC(C(O)=O)=CS1 UFIUMDMAMPMTQG-UHFFFAOYSA-N 0.000 description 1
• YCWNCBVSNHZJMF-UHFFFAOYSA-N 2-(hydroxymethyl)-1,3-thiazole-4-carboxylic acid Chemical compound OCC1=NC(C(O)=O)=CS1 YCWNCBVSNHZJMF-UHFFFAOYSA-N 0.000 description 1
• WSTCURFANPYLFZ-UHFFFAOYSA-N 2-(piperidin-1-ylmethyl)-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(CN2CCCCC2)=N1 WSTCURFANPYLFZ-UHFFFAOYSA-N 0.000 description 1
• IJMMZOUOWMJBHW-UHFFFAOYSA-N 2-[(4-phenylpiperazin-1-yl)methyl]-1,3-oxazole-4-carboxylic acid Chemical compound OC(=O)C1=COC(CN2CCN(CC2)C=2C=CC=CC=2)=N1 IJMMZOUOWMJBHW-UHFFFAOYSA-N 0.000 description 1
• FPCLPTIVHLELIP-UHFFFAOYSA-N 2-[(dibutylamino)methyl]-1,3-oxazole-4-carboxylic acid Chemical compound CCCCN(CCCC)CC1=NC(C(O)=O)=CO1 FPCLPTIVHLELIP-UHFFFAOYSA-N 0.000 description 1
• AKNVFSITWXYYRP-UHFFFAOYSA-N 2-[(dimethylazaniumyl)methyl]-1,3-thiazole-4-carboxylate Chemical compound CN(C)CC1=NC(C(O)=O)=CS1 AKNVFSITWXYYRP-UHFFFAOYSA-N 0.000 description 1
• JOPTYRBQYCIAFR-UHFFFAOYSA-N 2-formylfuran-3-carboxylic acid Chemical compound OC(=O)C=1C=COC=1C=O JOPTYRBQYCIAFR-UHFFFAOYSA-N 0.000 description 1
• YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
• FABVMBDCVAJXMB-UHFFFAOYSA-N 3,5-dichloro-2-hydroxybenzaldehyde Chemical compound OC1=C(Cl)C=C(Cl)C=C1C=O FABVMBDCVAJXMB-UHFFFAOYSA-N 0.000 description 1
• GNFTZDOKVXKIBK-UHFFFAOYSA-N 3-(2-methoxyethoxy)benzohydrazide Chemical compound COCCOC1=CC=CC(C(=O)NN)=C1 GNFTZDOKVXKIBK-UHFFFAOYSA-N 0.000 description 1
• YNDAMDVOGKACTP-UHFFFAOYSA-N 3-aminopyrrolidin-2-one Chemical compound NC1CCNC1=O YNDAMDVOGKACTP-UHFFFAOYSA-N 0.000 description 1
• PRRZDZJYSJLDBS-UHFFFAOYSA-N 3-bromo-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CBr PRRZDZJYSJLDBS-UHFFFAOYSA-N 0.000 description 1
• YAYDKIYXCYNSCG-UHFFFAOYSA-N 5-(bromomethyl)pyrazine-2-carboxylic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CN=C(CBr)C=N1 YAYDKIYXCYNSCG-UHFFFAOYSA-N 0.000 description 1
• YRULCWXBUVVDKA-UHFFFAOYSA-N 5-[[cyclopropyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]pyrazine-2-carboxylic acid Chemical compound C1CC1N(C(=O)OC(C)(C)C)CC1=CN=C(C(O)=O)C=N1 YRULCWXBUVVDKA-UHFFFAOYSA-N 0.000 description 1
• OKWIVAGIAIZCSZ-UHFFFAOYSA-N 5-formyl-1,2-oxazole-3-carboxylic acid Chemical compound OC(=O)C=1C=C(C=O)ON=1 OKWIVAGIAIZCSZ-UHFFFAOYSA-N 0.000 description 1
• ODPLFSCTCVMBMZ-UHFFFAOYSA-N 5-formyl-1-methylpyrazole-3-carboxylic acid Chemical compound CN1N=C(C(O)=O)C=C1C=O ODPLFSCTCVMBMZ-UHFFFAOYSA-N 0.000 description 1
• SHNRXUWGUKDPMA-UHFFFAOYSA-N 5-formyl-2-furoic acid Chemical compound OC(=O)C1=CC=C(C=O)O1 SHNRXUWGUKDPMA-UHFFFAOYSA-N 0.000 description 1
• UUKTVALKHIMMHN-UHFFFAOYSA-N 5-formyl-2-methylpyrazole-3-carboxylic acid Chemical compound CN1N=C(C=O)C=C1C(O)=O UUKTVALKHIMMHN-UHFFFAOYSA-N 0.000 description 1
• VFEAMMGYJFFXKV-UHFFFAOYSA-N 5-formylthiophene-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(C=O)S1 VFEAMMGYJFFXKV-UHFFFAOYSA-N 0.000 description 1
• RBYJWCRKFLGNDB-UHFFFAOYSA-N 5-methylpyrazine-2-carboxylic acid Chemical compound CC1=CN=C(C(O)=O)C=N1 RBYJWCRKFLGNDB-UHFFFAOYSA-N 0.000 description 1
• XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
• ISQLGKBALHPSQC-UHFFFAOYSA-N 6-(bromomethyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=C(CBr)N=C1 ISQLGKBALHPSQC-UHFFFAOYSA-N 0.000 description 1
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
• 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 description 1
• 235000019489 Almond oil Nutrition 0.000 description 1
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
• 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 101710081722 Antitrypsin Proteins 0.000 description 1
• 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 239000004342 Benzoyl peroxide Substances 0.000 description 1
• OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
• 206010006187 Breast cancer Diseases 0.000 description 1
• NKNCLMAQFNFXFQ-ZGTCLIOFSA-N C(C1=CC=CC=C1)OC(=O)N1[C@@H](C(CC1)NC(C(F)(F)F)=O)OCC Chemical compound C(C1=CC=CC=C1)OC(=O)N1[C@@H](C(CC1)NC(C(F)(F)F)=O)OCC NKNCLMAQFNFXFQ-ZGTCLIOFSA-N 0.000 description 1
• UZRUKLJLGXLGDM-UHFFFAOYSA-N CCCC(C(N)=O)N Chemical compound CCCC(C(N)=O)N UZRUKLJLGXLGDM-UHFFFAOYSA-N 0.000 description 1
• USQOVYLRWBOSQC-HNNXBMFYSA-N CCCCCCNC(=O)Oc1cccc(c1)-c1ccc(cc1F)[C@H](C)C(O)=O Chemical compound CCCCCCNC(=O)Oc1cccc(c1)-c1ccc(cc1F)[C@H](C)C(O)=O USQOVYLRWBOSQC-HNNXBMFYSA-N 0.000 description 1
• NJFICXWSMVNZRL-UHFFFAOYSA-N COC(=O)C=1N=C(OC1C)CBr Chemical compound COC(=O)C=1N=C(OC1C)CBr NJFICXWSMVNZRL-UHFFFAOYSA-N 0.000 description 1
• FFEARJCKVFRZRR-UHFFFAOYSA-N CSCCC(C(O)=O)N Chemical compound CSCCC(C(O)=O)N FFEARJCKVFRZRR-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• FWAMBLXIVRHIBI-WKLLBTDKSA-N Cl.C1(CC1)C=1N=C(C(=NC1)C(=O)N1CC[C@H]2N(C([C@H]([C@@H]21)C(C)C)=O)S(=O)(=O)C)CN Chemical compound Cl.C1(CC1)C=1N=C(C(=NC1)C(=O)N1CC[C@H]2N(C([C@H]([C@@H]21)C(C)C)=O)S(=O)(=O)C)CN FWAMBLXIVRHIBI-WKLLBTDKSA-N 0.000 description 1
• BZGDZNAYKIZCMK-UHFFFAOYSA-N Cl.N1CCC2NC(=O)CC21 Chemical compound Cl.N1CCC2NC(=O)CC21 BZGDZNAYKIZCMK-UHFFFAOYSA-N 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• 201000003883 Cystic fibrosis Diseases 0.000 description 1
• 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 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 206010061968 Gastric neoplasm Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 101001055222 Homo sapiens Interleukin-8 Proteins 0.000 description 1
• 101000851058 Homo sapiens Neutrophil elastase Proteins 0.000 description 1
• 238000006043 Intramolecular Michael addition reaction Methods 0.000 description 1
• OGNSCSPNOLGXSM-VKHMYHEASA-N L-2,4-diaminobutyric acid Chemical compound NCC[C@H](N)C(O)=O OGNSCSPNOLGXSM-VKHMYHEASA-N 0.000 description 1
• PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
• 239000002841 Lewis acid Substances 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010027476 Metastases Diseases 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 238000006957 Michael reaction Methods 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
• 208000033835 Myelomonocytic Acute Leukemia Diseases 0.000 description 1
• 108090000235 Myeloperoxidases Proteins 0.000 description 1
• 102000003896 Myeloperoxidases Human genes 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• 208000018262 Peripheral vascular disease Diseases 0.000 description 1
• 206010036790 Productive cough Diseases 0.000 description 1
• 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 1
• 208000029464 Pulmonary infiltrates Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• 206010040070 Septic Shock Diseases 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• 201000002661 Spondylitis Diseases 0.000 description 1
• 208000006011 Stroke Diseases 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
• 229920001615 Tragacanth Polymers 0.000 description 1
• APQHKWPGGHMYKJ-UHFFFAOYSA-N Tributyltin oxide Chemical compound CCCC[Sn](CCCC)(CCCC)O[Sn](CCCC)(CCCC)CCCC APQHKWPGGHMYKJ-UHFFFAOYSA-N 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• IORHBIZYYBINFX-WJDWOHSUSA-N [(z)-1-ethoxy-3-methylbut-1-enoxy]-tri(propan-2-yl)silane Chemical compound CCO\C(=C\C(C)C)O[Si](C(C)C)(C(C)C)C(C)C IORHBIZYYBINFX-WJDWOHSUSA-N 0.000 description 1
• KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 229960004308 acetylcysteine Drugs 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 208000011912 acute myelomonocytic leukemia M4 Diseases 0.000 description 1
• 239000000464 adrenergic agent Substances 0.000 description 1
• 125000003545 alkoxy group Chemical group 0.000 description 1
• 125000005233 alkylalcohol group Chemical group 0.000 description 1
• 239000008168 almond oil Substances 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
• 239000001099 ammonium carbonate Substances 0.000 description 1
• 235000011114 ammonium hydroxide Nutrition 0.000 description 1
• 239000003957 anion exchange resin Substances 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 230000002590 anti-leukotriene effect Effects 0.000 description 1
• 230000001475 anti-trypsic effect Effects 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 208000021328 arterial occlusion Diseases 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 210000003651 basophil Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• 229940092738 beeswax Drugs 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 235000019400 benzoyl peroxide Nutrition 0.000 description 1
• MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 1
• LEFNDSATCIPOAL-PWZMFNOBSA-N benzyl (2s,3r)-2-(1-ethoxy-3-methyl-1-oxobutan-2-yl)-3-[(2,2,2-trifluoroacetyl)amino]pyrrolidine-1-carboxylate Chemical compound CCOC(=O)C(C(C)C)[C@H]1[C@H](NC(=O)C(F)(F)F)CCN1C(=O)OCC1=CC=CC=C1 LEFNDSATCIPOAL-PWZMFNOBSA-N 0.000 description 1
• HDFLQKONEOEYPZ-OWCLPIDISA-N benzyl (3ar,6s,6as)-4-methylsulfonyl-5-oxo-6-propan-2-yl-3,3a,6,6a-tetrahydro-2h-pyrrolo[3,2-b]pyrrole-1-carboxylate Chemical compound C([C@@H]1[C@@H]2[C@@H](C(N1S(C)(=O)=O)=O)C(C)C)CN2C(=O)OCC1=CC=CC=C1 HDFLQKONEOEYPZ-OWCLPIDISA-N 0.000 description 1
• RUHBHKYDFXKLSF-SNVBAGLBSA-N benzyl (3r)-2-oxo-3-[(2,2,2-trifluoroacetyl)amino]pyrrolidine-1-carboxylate Chemical compound O=C1[C@H](NC(=O)C(F)(F)F)CCN1C(=O)OCC1=CC=CC=C1 RUHBHKYDFXKLSF-SNVBAGLBSA-N 0.000 description 1
• RUYVBCRRGKAIIB-UHFFFAOYSA-N benzyl 2,2-diaminobutanoate Chemical compound CCC(N)(N)C(=O)OCC1=CC=CC=C1 RUYVBCRRGKAIIB-UHFFFAOYSA-N 0.000 description 1
• NKNCLMAQFNFXFQ-UHFFFAOYSA-N benzyl 2-ethoxy-3-[(2,2,2-trifluoroacetyl)amino]pyrrolidine-1-carboxylate Chemical compound CCOC1C(NC(=O)C(F)(F)F)CCN1C(=O)OCC1=CC=CC=C1 NKNCLMAQFNFXFQ-UHFFFAOYSA-N 0.000 description 1
• RUHBHKYDFXKLSF-UHFFFAOYSA-N benzyl 2-oxo-3-[(2,2,2-trifluoroacetyl)amino]pyrrolidine-1-carboxylate Chemical compound O=C1C(NC(=O)C(F)(F)F)CCN1C(=O)OCC1=CC=CC=C1 RUHBHKYDFXKLSF-UHFFFAOYSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 210000000621 bronchi Anatomy 0.000 description 1
• 201000009267 bronchiectasis Diseases 0.000 description 1
• 229940124630 bronchodilator Drugs 0.000 description 1
• 239000000168 bronchodilator agent Substances 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 239000001569 carbon dioxide Substances 0.000 description 1
• 229910002092 carbon dioxide Inorganic materials 0.000 description 1
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
• 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
• 229940105329 carboxymethylcellulose Drugs 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000021164 cell adhesion Effects 0.000 description 1
• 229940082500 cetostearyl alcohol Drugs 0.000 description 1
• IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 201000006778 chronic monocytic leukemia Diseases 0.000 description 1
• 201000010902 chronic myelomonocytic leukemia Diseases 0.000 description 1
• 238000002983 circular dichroism Methods 0.000 description 1
• 238000003776 cleavage reaction Methods 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000009838 combustion analysis Methods 0.000 description 1
• 239000008139 complexing agent Substances 0.000 description 1
• 238000004590 computer program Methods 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 238000006482 condensation reaction Methods 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 208000018631 connective tissue disease Diseases 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 239000007822 coupling agent Substances 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000000753 cycloalkyl group Chemical group 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000003247 decreasing effect Effects 0.000 description 1
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
• 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
• 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
• 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
• 239000012470 diluted sample Substances 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 238000000921 elemental analysis Methods 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• IXZGURYSCDHAIH-UHFFFAOYSA-N ethane;heptane Chemical compound CC.CCCCCCC IXZGURYSCDHAIH-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• ZYTPZSVMXSYIFE-CMDGGOBGSA-N ethyl (e)-2,4-dioxo-6-phenylhex-5-enoate Chemical compound CCOC(=O)C(=O)CC(=O)\C=C\C1=CC=CC=C1 ZYTPZSVMXSYIFE-CMDGGOBGSA-N 0.000 description 1
• ZGVZJEWTHZKKHY-UHFFFAOYSA-N ethyl 1-methyl-5-(2-phenylethenyl)pyrazole-3-carboxylate Chemical compound CN1N=C(C(=O)OCC)C=C1C=CC1=CC=CC=C1 ZGVZJEWTHZKKHY-UHFFFAOYSA-N 0.000 description 1
• UIZIBTYIZFDYCC-UHFFFAOYSA-N ethyl 2-(bromomethyl)-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(CBr)=N1 UIZIBTYIZFDYCC-UHFFFAOYSA-N 0.000 description 1
• NBCJEXKZJGNLIW-UHFFFAOYSA-N ethyl 2-(pyrrolidin-1-ylmethyl)-1,3-oxazole-4-carboxylate Chemical compound CCOC(=O)C1=COC(CN2CCCC2)=N1 NBCJEXKZJGNLIW-UHFFFAOYSA-N 0.000 description 1
• ZCTPQIAQHSPLTH-UHFFFAOYSA-N ethyl 2-methyl-5-(2-phenylethenyl)pyrazole-3-carboxylate Chemical compound CN1C(C(=O)OCC)=CC(C=CC=2C=CC=CC=2)=N1 ZCTPQIAQHSPLTH-UHFFFAOYSA-N 0.000 description 1
• AGGPRSBKBRLUMV-UHFFFAOYSA-N ethyl 5-formyl-1,2-oxazole-3-carboxylate Chemical compound CCOC(=O)C=1C=C(C=O)ON=1 AGGPRSBKBRLUMV-UHFFFAOYSA-N 0.000 description 1
• HXXLCBOXHRPRMJ-UHFFFAOYSA-N ethyl 5-formyl-1-methylpyrazole-3-carboxylate Chemical compound CCOC(=O)C=1C=C(C=O)N(C)N=1 HXXLCBOXHRPRMJ-UHFFFAOYSA-N 0.000 description 1
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
• 125000004494 ethyl ester group Chemical group 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• 238000001704 evaporation Methods 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 239000003172 expectorant agent Substances 0.000 description 1
• 239000000835 fiber Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 239000007903 gelatin capsule Substances 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000024693 gingival disease Diseases 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000001727 glucose Nutrition 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 102000052502 human ELANE Human genes 0.000 description 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
• 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
• 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
• 208000013403 hyperactivity Diseases 0.000 description 1
• 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 description 1
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
• MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 238000002329 infrared spectrum Methods 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 150000002560 ketene acetals Chemical class 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 150000007517 lewis acids Chemical class 0.000 description 1
• 229940057995 liquid paraffin Drugs 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 231100000516 lung damage Toxicity 0.000 description 1
• 208000037841 lung tumor Diseases 0.000 description 1
• 206010025135 lupus erythematosus Diseases 0.000 description 1
• 210000004698 lymphocyte Anatomy 0.000 description 1
• GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
• 239000004137 magnesium phosphate Substances 0.000 description 1
• 229960002261 magnesium phosphate Drugs 0.000 description 1
• 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
• 235000010994 magnesium phosphates Nutrition 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 229950002475 mesilate Drugs 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• 229960004452 methionine Drugs 0.000 description 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
• BGFZBYKHHGUPSG-UHFFFAOYSA-N methyl 2,4-diaminobutanoate;dihydrochloride Chemical compound Cl.Cl.COC(=O)C(N)CCN BGFZBYKHHGUPSG-UHFFFAOYSA-N 0.000 description 1
• NXXLIQGNOSXXHB-UHFFFAOYSA-N methyl 2-(bromomethyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CBr)=N1 NXXLIQGNOSXXHB-UHFFFAOYSA-N 0.000 description 1
• HLKQXQWARLHUBP-UHFFFAOYSA-N methyl 2-(piperidin-1-ylmethyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CN2CCCCC2)=N1 HLKQXQWARLHUBP-UHFFFAOYSA-N 0.000 description 1
• HPRCDTCZLUPVTP-UHFFFAOYSA-N methyl 2-(pyrrolidin-1-ylmethyl)-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CN2CCCC2)=N1 HPRCDTCZLUPVTP-UHFFFAOYSA-N 0.000 description 1
• PFLRSNJAUVPRAW-UHFFFAOYSA-N methyl 2-[(4-phenylpiperazin-1-yl)methyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CN2CCN(CC2)C=2C=CC=CC=2)=N1 PFLRSNJAUVPRAW-UHFFFAOYSA-N 0.000 description 1
• RGYWBCLGCBPHBP-UHFFFAOYSA-N methyl 2-[(cyclopropylmethylamino)methyl]-1,3-oxazole-4-carboxylate hydrochloride Chemical compound Cl.COC(=O)C1=COC(CNCC2CC2)=N1 RGYWBCLGCBPHBP-UHFFFAOYSA-N 0.000 description 1
• FWTQVMVXUWMQHM-UHFFFAOYSA-N methyl 2-[(dibutylamino)methyl]-1,3-oxazole-4-carboxylate Chemical compound CCCCN(CCCC)CC1=NC(C(=O)OC)=CO1 FWTQVMVXUWMQHM-UHFFFAOYSA-N 0.000 description 1
• VOSCNOGVWUXDMU-UHFFFAOYSA-N methyl 2-[(dicyclohexylamino)methyl]-1,3-oxazole-4-carboxylate Chemical compound COC(=O)C1=COC(CN(C2CCCCC2)C2CCCCC2)=N1 VOSCNOGVWUXDMU-UHFFFAOYSA-N 0.000 description 1
• OIGRHUBIDWZLHR-UHFFFAOYSA-N methyl 5-(bromomethyl)pyrazine-2-carboxylate Chemical compound COC(=O)C1=CN=C(CBr)C=N1 OIGRHUBIDWZLHR-UHFFFAOYSA-N 0.000 description 1
• IRQSKJQDKUAART-UHFFFAOYSA-N methyl 6-(bromomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CBr)N=C1 IRQSKJQDKUAART-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 229940016286 microcrystalline cellulose Drugs 0.000 description 1
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
• 239000008108 microcrystalline cellulose Substances 0.000 description 1
• 239000004200 microcrystalline wax Substances 0.000 description 1
• 235000019808 microcrystalline wax Nutrition 0.000 description 1
• 229940114937 microcrystalline wax Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 210000001616 monocyte Anatomy 0.000 description 1
• HDZGCSFEDULWCS-UHFFFAOYSA-N monomethylhydrazine Chemical compound CNN HDZGCSFEDULWCS-UHFFFAOYSA-N 0.000 description 1
• 210000002200 mouth mucosa Anatomy 0.000 description 1
• 229940066491 mucolytics Drugs 0.000 description 1
• 230000003843 mucus production Effects 0.000 description 1
• 239000003149 muscarinic antagonist Substances 0.000 description 1
• 208000025113 myeloid leukemia Diseases 0.000 description 1
• 208000010125 myocardial infarction Diseases 0.000 description 1
• FGNGTWFJQFTFGN-UHFFFAOYSA-N n,n,n',n'-tetramethylethane-1,2-diamine Chemical compound CN(C)CCN(C)C.CN(C)CCN(C)C FGNGTWFJQFTFGN-UHFFFAOYSA-N 0.000 description 1
• PEECTLLHENGOKU-UHFFFAOYSA-N n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=NC=C1 PEECTLLHENGOKU-UHFFFAOYSA-N 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
• 239000012299 nitrogen atmosphere Substances 0.000 description 1
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• 230000000269 nucleophilic effect Effects 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
• 150000004965 peroxy acids Chemical class 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 230000003285 pharmacodynamic effect Effects 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical compound C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 1
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• 125000005544 phthalimido group Chemical group 0.000 description 1
• 239000002798 polar solvent Substances 0.000 description 1
• 229940068917 polyethylene glycols Drugs 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
• 229910052700 potassium Inorganic materials 0.000 description 1
• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 208000023958 prostate neoplasm Diseases 0.000 description 1
• 230000001681 protective effect Effects 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 239000003586 protic polar solvent Substances 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• NIPZZXUFJPQHNH-UHFFFAOYSA-M pyrazine-2-carboxylate Chemical compound [O-]C(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-M 0.000 description 1
• 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
• 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 description 1
• ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
• DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 229940107700 pyruvic acid Drugs 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000010410 reperfusion Effects 0.000 description 1
• 230000029058 respiratory gaseous exchange Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 230000007017 scission Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 125000005353 silylalkyl group Chemical group 0.000 description 1
• 229940023144 sodium glycolate Drugs 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 229940079832 sodium starch glycolate Drugs 0.000 description 1
• 239000008109 sodium starch glycolate Substances 0.000 description 1
• 229920003109 sodium starch glycolate Polymers 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 238000000527 sonication Methods 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000001593 sorbitan monooleate Substances 0.000 description 1
• 235000011069 sorbitan monooleate Nutrition 0.000 description 1
• 229940035049 sorbitan monooleate Drugs 0.000 description 1
• 229960002920 sorbitol Drugs 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008174 sterile solution Substances 0.000 description 1
• 239000012258 stirred mixture Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 description 1
• 230000006103 sulfonylation Effects 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000002511 suppository base Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
• 229960000278 theophylline Drugs 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 230000008719 thickening Effects 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 230000000451 tissue damage Effects 0.000 description 1
• 231100000827 tissue damage Toxicity 0.000 description 1
• 208000037816 tissue injury Diseases 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 239000002753 trypsin inhibitor Substances 0.000 description 1
• WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 239000010937 tungsten Substances 0.000 description 1
• 238000002604 ultrasonography Methods 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1