BRPI0709579A2 - modificações de cristal - Google Patents

Info

Publication number

BRPI0709579A2

BRPI0709579A2 BRPI0709579-1A BRPI0709579A BRPI0709579A2 BR PI0709579 A2 BRPI0709579 A2 BR PI0709579A2 BR PI0709579 A BRPI0709579 A BR PI0709579A BR PI0709579 A2 BRPI0709579 A2 BR PI0709579A2

Authority

BR

Brazil

Prior art keywords

methyl

dione

imidazolidine

chloro

yloxy

Prior art date

2006-03-16

Links

• Espacenet
• Global Dossier
• Discuss

• 238000012986 modification Methods 0.000 title abstract description 48
• 230000004048 modification Effects 0.000 title abstract description 46
• 239000013078 crystal Substances 0.000 title abstract description 19
• 238000000034 method Methods 0.000 claims abstract description 89
• 230000008569 process Effects 0.000 claims abstract description 42
• 238000002360 preparation method Methods 0.000 claims abstract description 26
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
• 238000002560 therapeutic procedure Methods 0.000 claims abstract description 7
• 150000001875 compounds Chemical class 0.000 claims description 117
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 58
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 56
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 52
• SFJFBTPHDHUUPU-OAHLLOKOSA-N (5s)-5-[[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylmethyl]-5-methylimidazolidine-2,4-dione Chemical compound C1CC(OC=2N=CC(Cl)=CC=2)CCN1S(=O)(=O)C[C@@]1(C)NC(=O)NC1=O SFJFBTPHDHUUPU-OAHLLOKOSA-N 0.000 claims description 40
• -1 5-chloro-pyridin-2-yloxy Chemical group 0.000 claims description 39
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
• 201000010099 disease Diseases 0.000 claims description 27
• AMZYBOJPLHNYJD-UHFFFAOYSA-N 5-chloro-2-piperidin-4-yloxypyridine Chemical compound N1=CC(Cl)=CC=C1OC1CCNCC1 AMZYBOJPLHNYJD-UHFFFAOYSA-N 0.000 claims description 24
• 238000011282 treatment Methods 0.000 claims description 24
• 108700023418 Amidases Proteins 0.000 claims description 23
• 102000005922 amidase Human genes 0.000 claims description 23
• 230000015572 biosynthetic process Effects 0.000 claims description 22
• 238000003786 synthesis reaction Methods 0.000 claims description 18
• 238000002425 crystallisation Methods 0.000 claims description 16
• 230000008025 crystallization Effects 0.000 claims description 16
• 150000003839 salts Chemical class 0.000 claims description 16
• 230000000694 effects Effects 0.000 claims description 13
• QDXMWEMIYNOVGF-GFCCVEGCSA-N (5s)-5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1CSC[C@@]1(C)NC(=O)NC1=O QDXMWEMIYNOVGF-GFCCVEGCSA-N 0.000 claims description 11
• 238000011321 prophylaxis Methods 0.000 claims description 11
• 229910016523 CuKa Inorganic materials 0.000 claims description 10
• 102000004190 Enzymes Human genes 0.000 claims description 9
• 108090000790 Enzymes Proteins 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 230000005855 radiation Effects 0.000 claims description 9
• IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 claims description 8
• 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 8
• 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 8
• 108091022884 dihydropyrimidinase Proteins 0.000 claims description 8
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 7
• 239000012458 free base Substances 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 235000015096 spirit Nutrition 0.000 claims description 7
• YIKDNCZROZXWCF-UHFFFAOYSA-N 3-benzylsulfanyl-2-(carbamoylamino)-2-methylpropanoic acid Chemical compound NC(=O)NC(C(O)=O)(C)CSCC1=CC=CC=C1 YIKDNCZROZXWCF-UHFFFAOYSA-N 0.000 claims description 6
• 229940079593 drug Drugs 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 102100036238 Dihydropyrimidinase Human genes 0.000 claims description 5
• 241000316848 Rhodococcus <scale insect> Species 0.000 claims description 5
• 230000009286 beneficial effect Effects 0.000 claims description 5
• 230000002255 enzymatic effect Effects 0.000 claims description 5
• 230000005764 inhibitory process Effects 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 4
• 208000027866 inflammatory disease Diseases 0.000 claims description 4
• 102000005741 Metalloproteases Human genes 0.000 claims description 2
• 108010006035 Metalloproteases Proteins 0.000 claims description 2
• RHYBFKMFHLPQPH-UHFFFAOYSA-N N-methylhydantoin Chemical compound CN1CC(=O)NC1=O RHYBFKMFHLPQPH-UHFFFAOYSA-N 0.000 claims description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
• 238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
• SZFUWUOHDRMCKD-UHFFFAOYSA-N 5-chloro-1h-pyridin-2-one Chemical compound OC1=CC=C(Cl)C=N1 SZFUWUOHDRMCKD-UHFFFAOYSA-N 0.000 claims 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims 1
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 141
• 239000000203 mixture Substances 0.000 description 90
• 239000000243 solution Substances 0.000 description 88
• 238000006243 chemical reaction Methods 0.000 description 63
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 61
• 239000002904 solvent Substances 0.000 description 56
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
• 239000007787 solid Substances 0.000 description 51
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
• 239000000047 product Substances 0.000 description 44
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
• 238000005160 1H NMR spectroscopy Methods 0.000 description 39
• 239000000725 suspension Substances 0.000 description 29
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 27
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 27
• 239000000463 material Substances 0.000 description 27
• 239000002253 acid Substances 0.000 description 26
• 230000002829 reductive effect Effects 0.000 description 26
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
• 238000001914 filtration Methods 0.000 description 22
• WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 22
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
• 239000011541 reaction mixture Substances 0.000 description 21
• 238000010992 reflux Methods 0.000 description 20
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 19
• 239000000523 sample Substances 0.000 description 19
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 18
• WHVOJNLCZRPSOY-UHFFFAOYSA-N 2-amino-3-benzylsulfanyl-2-methylpropanamide Chemical compound NC(=O)C(N)(C)CSCC1=CC=CC=C1 WHVOJNLCZRPSOY-UHFFFAOYSA-N 0.000 description 18
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
• 229940024606 amino acid Drugs 0.000 description 18
• 238000004458 analytical method Methods 0.000 description 17
• 238000007792 addition Methods 0.000 description 16
• 239000012071 phase Substances 0.000 description 16
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 15
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 150000001408 amides Chemical class 0.000 description 14
• 150000001413 amino acids Chemical class 0.000 description 14
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 13
• 238000004296 chiral HPLC Methods 0.000 description 13
• 229940091173 hydantoin Drugs 0.000 description 13
• 239000000843 powder Substances 0.000 description 13
• 238000003756 stirring Methods 0.000 description 13
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 12
• 238000004128 high performance liquid chromatography Methods 0.000 description 12
• 239000010410 layer Substances 0.000 description 12
• 239000003921 oil Substances 0.000 description 12
• 235000019198 oils Nutrition 0.000 description 12
• 239000012074 organic phase Substances 0.000 description 12
• 239000000126 substance Substances 0.000 description 12
• 235000001014 amino acid Nutrition 0.000 description 11
• 239000008346 aqueous phase Substances 0.000 description 11
• 239000000706 filtrate Substances 0.000 description 11
• 239000012044 organic layer Substances 0.000 description 11
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
• 238000012360 testing method Methods 0.000 description 11
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 10
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 10
• 238000001953 recrystallisation Methods 0.000 description 10
• 239000011734 sodium Substances 0.000 description 10
• WHVOJNLCZRPSOY-LLVKDONJSA-N (2s)-2-amino-3-benzylsulfanyl-2-methylpropanamide Chemical compound NC(=O)[C@@](N)(C)CSCC1=CC=CC=C1 WHVOJNLCZRPSOY-LLVKDONJSA-N 0.000 description 9
• 238000004821 distillation Methods 0.000 description 9
• 229940011051 isopropyl acetate Drugs 0.000 description 9
• GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 9
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
• 235000019341 magnesium sulphate Nutrition 0.000 description 9
• 239000003444 phase transfer catalyst Substances 0.000 description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 9
• VKQMFBKYDZYYOB-UHFFFAOYSA-N acetic acid;5-chloro-2-piperidin-4-yloxypyridine Chemical compound CC(O)=O.N1=CC(Cl)=CC=C1OC1CCNCC1 VKQMFBKYDZYYOB-UHFFFAOYSA-N 0.000 description 8
• 230000002210 biocatalytic effect Effects 0.000 description 8
• 239000003480 eluent Substances 0.000 description 8
• 229940088598 enzyme Drugs 0.000 description 8
• 238000010438 heat treatment Methods 0.000 description 8
• 206010039083 rhinitis Diseases 0.000 description 8
• YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 238000010586 diagram Methods 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 239000002243 precursor Substances 0.000 description 7
• GPRLUSIRSONVHX-LLVKDONJSA-N (2s)-2-amino-3-benzylsulfanyl-2-methylpropanoic acid Chemical compound OC(=O)[C@@](N)(C)CSCC1=CC=CC=C1 GPRLUSIRSONVHX-LLVKDONJSA-N 0.000 description 6
• QDXMWEMIYNOVGF-UHFFFAOYSA-N 5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1CSCC1(C)NC(=O)NC1=O QDXMWEMIYNOVGF-UHFFFAOYSA-N 0.000 description 6
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 6
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 229960000583 acetic acid Drugs 0.000 description 6
• HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
• PSTOVESVKXDXQX-UHFFFAOYSA-N bromomethylsulfanylmethylbenzene Chemical compound BrCSCC1=CC=CC=C1 PSTOVESVKXDXQX-UHFFFAOYSA-N 0.000 description 6
• 208000015181 infectious disease Diseases 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 239000003960 organic solvent Substances 0.000 description 6
• 238000000926 separation method Methods 0.000 description 6
• 125000000446 sulfanediyl group Chemical group *S* 0.000 description 6
• 230000009466 transformation Effects 0.000 description 6
• GXBXYLVXNQXXNV-RXMQYKEDSA-N [(4s)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulfonyl chloride Chemical compound ClS(=O)(=O)C[C@@]1(C)NC(=O)NC1=O GXBXYLVXNQXXNV-RXMQYKEDSA-N 0.000 description 5
• 150000001412 amines Chemical class 0.000 description 5
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 5
• 239000002131 composite material Substances 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 150000002148 esters Chemical class 0.000 description 5
• 238000001704 evaporation Methods 0.000 description 5
• 230000008020 evaporation Effects 0.000 description 5
• 239000007789 gas Substances 0.000 description 5
• XPXMKIXDFWLRAA-UHFFFAOYSA-N hydrazinide Chemical compound [NH-]N XPXMKIXDFWLRAA-UHFFFAOYSA-N 0.000 description 5
• 230000007062 hydrolysis Effects 0.000 description 5
• 238000006460 hydrolysis reaction Methods 0.000 description 5
• 150000002466 imines Chemical class 0.000 description 5
• 229960004592 isopropanol Drugs 0.000 description 5
• 239000008363 phosphate buffer Substances 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• 208000011580 syndromic disease Diseases 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• IXBZJPOQTSAQHW-UHFFFAOYSA-N 4-phenylbutane-2-thione Chemical compound CC(=S)CCC1=CC=CC=C1 IXBZJPOQTSAQHW-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
• 101000577881 Homo sapiens Macrophage metalloelastase Proteins 0.000 description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
• 208000012659 Joint disease Diseases 0.000 description 4
• 102100027998 Macrophage metalloelastase Human genes 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 238000005481 NMR spectroscopy Methods 0.000 description 4
• 206010047112 Vasculitides Diseases 0.000 description 4
• 206010047115 Vasculitis Diseases 0.000 description 4
• 159000000021 acetate salts Chemical class 0.000 description 4
• 208000006673 asthma Diseases 0.000 description 4
• 239000012455 biphasic mixture Substances 0.000 description 4
• 230000003197 catalytic effect Effects 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• 238000000113 differential scanning calorimetry Methods 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 239000007903 gelatin capsule Substances 0.000 description 4
• 230000001965 increasing effect Effects 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 239000000155 melt Substances 0.000 description 4
• YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 description 4
• 150000002825 nitriles Chemical class 0.000 description 4
• 201000008482 osteoarthritis Diseases 0.000 description 4
• HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
• 201000000306 sarcoidosis Diseases 0.000 description 4
• 239000011975 tartaric acid Substances 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• 201000008827 tuberculosis Diseases 0.000 description 4
• 238000005406 washing Methods 0.000 description 4
• WHVOJNLCZRPSOY-NSHDSACASA-N (2r)-2-amino-3-benzylsulfanyl-2-methylpropanamide Chemical compound NC(=O)[C@](N)(C)CSCC1=CC=CC=C1 WHVOJNLCZRPSOY-NSHDSACASA-N 0.000 description 3
• HUQKETMNDVHIDK-HKUYNNGSSA-N (3r,5r)-3-(benzylsulfanylmethyl)-3-methyl-5-phenylmorpholin-2-one Chemical compound C([C@@]1(C)C(OC[C@H](N1)C=1C=CC=CC=1)=O)SCC1=CC=CC=C1 HUQKETMNDVHIDK-HKUYNNGSSA-N 0.000 description 3
• SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 3
• IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 3
• DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 3
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
• IOYISRWOQOVKRF-UHFFFAOYSA-N 3-benzylsulfanyl-2-methyl-2-[(2,2,2-trifluoroacetyl)amino]propanoic acid Chemical compound FC(F)(F)C(=O)NC(C(O)=O)(C)CSCC1=CC=CC=C1 IOYISRWOQOVKRF-UHFFFAOYSA-N 0.000 description 3
• LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 3
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
• ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 3
• 241000228257 Aspergillus sp. Species 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
• 206010011224 Cough Diseases 0.000 description 3
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• 206010020751 Hypersensitivity Diseases 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
• 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 3
• 208000036142 Viral infection Diseases 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• QNAYBMKLOCPYGJ-UHFFFAOYSA-M alaninate Chemical compound CC(N)C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-M 0.000 description 3
• 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 3
• 235000008206 alpha-amino acids Nutrition 0.000 description 3
• 239000001099 ammonium carbonate Substances 0.000 description 3
• 235000012501 ammonium carbonate Nutrition 0.000 description 3
• 230000008901 benefit Effects 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 230000036983 biotransformation Effects 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 239000000460 chlorine Substances 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 239000002027 dichloromethane extract Substances 0.000 description 3
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 230000002458 infectious effect Effects 0.000 description 3
• 230000002757 inflammatory effect Effects 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 3
• 238000005259 measurement Methods 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
• 230000000704 physical effect Effects 0.000 description 3
• 230000004044 response Effects 0.000 description 3
• 206010039073 rheumatoid arthritis Diseases 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• 239000008107 starch Substances 0.000 description 3
• 235000019698 starch Nutrition 0.000 description 3
• 239000000758 substrate Substances 0.000 description 3
• 235000000346 sugar Nutrition 0.000 description 3
• 235000002906 tartaric acid Nutrition 0.000 description 3
• 238000000844 transformation Methods 0.000 description 3
• 238000000825 ultraviolet detection Methods 0.000 description 3
• 238000005292 vacuum distillation Methods 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• XQOAISAXGMMWET-FCHUYYIVSA-N (2r)-3-benzylsulfanyl-2-methyl-2-[[(1r)-1-phenyl-2-trimethylsilyloxyethyl]amino]propanenitrile Chemical compound C([C@](C)(N[C@@H](CO[Si](C)(C)C)C=1C=CC=CC=1)C#N)SCC1=CC=CC=C1 XQOAISAXGMMWET-FCHUYYIVSA-N 0.000 description 2
• IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 2
• WSHFLRJRPXSPCI-OLBMHGAYSA-N (5S)-5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione (1S)-1-phenylethanamine Chemical compound C[C@@H](C1=CC=CC=C1)N.C(C1=CC=CC=C1)SC[C@@]1(C(NC(N1)=O)=O)C WSHFLRJRPXSPCI-OLBMHGAYSA-N 0.000 description 2
• BDJMLYLTLRLXGL-PXNSSMCTSA-N (5r)-5-(benzylsulfanylmethyl)-1-[(1r)-2-hydroxy-1-phenylethyl]-5-methylimidazolidine-2,4-dione Chemical compound C([C@@]1(C)C(NC(=O)N1[C@@H](CO)C=1C=CC=CC=1)=O)SCC1=CC=CC=C1 BDJMLYLTLRLXGL-PXNSSMCTSA-N 0.000 description 2
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
• GCTFDMFLLBCLPF-UHFFFAOYSA-N 2,5-dichloropyridine Chemical compound ClC1=CC=C(Cl)N=C1 GCTFDMFLLBCLPF-UHFFFAOYSA-N 0.000 description 2
• MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 2
• OBYWDEOSSLOLHG-LREBCSMRSA-N 2-amino-3-benzylsulfanyl-2-methylpropanamide;(2r,3r)-2,3-dihydroxybutanedioic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.NC(=O)C(N)(C)CSCC1=CC=CC=C1 OBYWDEOSSLOLHG-LREBCSMRSA-N 0.000 description 2
• WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
• QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
• 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
• GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• 208000036487 Arthropathies Diseases 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 208000020084 Bone disease Diseases 0.000 description 2
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
• 208000002691 Choroiditis Diseases 0.000 description 2
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
• 201000003883 Cystic fibrosis Diseases 0.000 description 2
• 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 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• 206010014561 Emphysema Diseases 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 230000005526 G1 to G0 transition Effects 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• 101000990902 Homo sapiens Matrix metalloproteinase-9 Proteins 0.000 description 2
• NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
• 150000008575 L-amino acids Chemical class 0.000 description 2
• IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 description 2
• 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 2
• 229930195725 Mannitol Natural products 0.000 description 2
• 102100030412 Matrix metalloproteinase-9 Human genes 0.000 description 2
• 101710170181 Metalloproteinase inhibitor Proteins 0.000 description 2
• 201000002481 Myositis Diseases 0.000 description 2
• 102000035195 Peptidases Human genes 0.000 description 2
• 108091005804 Peptidases Proteins 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
• 208000003971 Posterior uveitis Diseases 0.000 description 2
• 239000004365 Protease Substances 0.000 description 2
• 241000589516 Pseudomonas Species 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 206010063837 Reperfusion injury Diseases 0.000 description 2
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 2
• 208000025747 Rheumatic disease Diseases 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• 208000006045 Spondylarthropathies Diseases 0.000 description 2
• CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 239000004809 Teflon Substances 0.000 description 2
• 229920006362 Teflon® Polymers 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• 208000007536 Thrombosis Diseases 0.000 description 2
• GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
• 208000027418 Wounds and injury Diseases 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 125000005219 aminonitrile group Chemical group 0.000 description 2
• 230000003466 anti-cipated effect Effects 0.000 description 2
• 238000013459 approach Methods 0.000 description 2
• 206010003246 arthritis Diseases 0.000 description 2
• 208000010668 atopic eczema Diseases 0.000 description 2
• 238000010533 azeotropic distillation Methods 0.000 description 2
• AKGGYBADQZYZPD-UHFFFAOYSA-N benzylacetone Chemical compound CC(=O)CCC1=CC=CC=C1 AKGGYBADQZYZPD-UHFFFAOYSA-N 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• 206010006451 bronchitis Diseases 0.000 description 2
• HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 150000005323 carbonate salts Chemical class 0.000 description 2
• 238000005119 centrifugation Methods 0.000 description 2
• WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 2
• KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 description 2
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
• 238000005859 coupling reaction Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• 229960001305 cysteine hydrochloride Drugs 0.000 description 2
• 230000006378 damage Effects 0.000 description 2
• 238000001514 detection method Methods 0.000 description 2
• WYURNTSHIVDZCO-SVYQBANQSA-N deuterated tetrahydrofuran Substances [2H]C1([2H])OC([2H])([2H])C([2H])([2H])C1([2H])[2H] WYURNTSHIVDZCO-SVYQBANQSA-N 0.000 description 2
• JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 2
• 239000002270 dispersing agent Substances 0.000 description 2
• 229940112141 dry powder inhaler Drugs 0.000 description 2
• 238000002474 experimental method Methods 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 2
• 230000004927 fusion Effects 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
• 239000008187 granular material Substances 0.000 description 2
• 150000001469 hydantoins Chemical class 0.000 description 2
• 229910052739 hydrogen Inorganic materials 0.000 description 2
• 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
• 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 2
• 230000006872 improvement Effects 0.000 description 2
• 239000012535 impurity Substances 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 229910052500 inorganic mineral Inorganic materials 0.000 description 2
• 229940030980 inova Drugs 0.000 description 2
• 230000000302 ischemic effect Effects 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• 210000004072 lung Anatomy 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000000594 mannitol Substances 0.000 description 2
• 235000010355 mannitol Nutrition 0.000 description 2
• 229940126170 metalloproteinase inhibitor Drugs 0.000 description 2
• 239000003475 metalloproteinase inhibitor Substances 0.000 description 2
• 235000010755 mineral Nutrition 0.000 description 2
• 239000011707 mineral Substances 0.000 description 2
• 201000009240 nasopharyngitis Diseases 0.000 description 2
• 229910052757 nitrogen Inorganic materials 0.000 description 2
• 239000008188 pellet Substances 0.000 description 2
• 201000001245 periodontitis Diseases 0.000 description 2
• 239000000546 pharmaceutical excipient Substances 0.000 description 2
• 238000003408 phase transfer catalysis Methods 0.000 description 2
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
• 230000003389 potentiating effect Effects 0.000 description 2
• YAQKNCSWDMGPOY-JEDNCBNOSA-N propan-2-yl (2s)-2-aminopropanoate;hydrochloride Chemical compound Cl.CC(C)OC(=O)[C@H](C)N YAQKNCSWDMGPOY-JEDNCBNOSA-N 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 235000018102 proteins Nutrition 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 108090000623 proteins and genes Proteins 0.000 description 2
• 208000002815 pulmonary hypertension Diseases 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 230000000552 rheumatic effect Effects 0.000 description 2
• CPRMKOQKXYSDML-UHFFFAOYSA-M rubidium hydroxide Chemical compound [OH-].[Rb+] CPRMKOQKXYSDML-UHFFFAOYSA-M 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 238000001179 sorption measurement Methods 0.000 description 2
• 201000005671 spondyloarthropathy Diseases 0.000 description 2
• 238000003860 storage Methods 0.000 description 2
• QMGVPVSNSZLJIA-FVWCLLPLSA-N strychnine Chemical compound O([C@H]1CC(N([C@H]2[C@H]1[C@H]1C3)C=4C5=CC=CC=4)=O)CC=C1CN1[C@@H]3[C@]25CC1 QMGVPVSNSZLJIA-FVWCLLPLSA-N 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229910052717 sulfur Inorganic materials 0.000 description 2
• 239000006228 supernatant Substances 0.000 description 2
• 239000006188 syrup Substances 0.000 description 2
• 235000020357 syrup Nutrition 0.000 description 2
• 229940095064 tartrate Drugs 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
• 238000012546 transfer Methods 0.000 description 2
• LEIMLDGFXIOXMT-UHFFFAOYSA-N trimethylsilyl cyanide Chemical compound C[Si](C)(C)C#N LEIMLDGFXIOXMT-UHFFFAOYSA-N 0.000 description 2
• 238000010792 warming Methods 0.000 description 2
• HDTRYLNUVZCQOY-UHFFFAOYSA-N &alpha;-D-glucopyranosyl-&alpha;-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
• RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
• SSJXIUAHEKJCMH-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-diamine Chemical compound N[C@@H]1CCCC[C@H]1N SSJXIUAHEKJCMH-PHDIDXHHSA-N 0.000 description 1
• GEJJWYZZKKKSEV-UONOGXRCSA-N (1r,2s)-2-amino-1,2-diphenylethanol Chemical compound C1([C@@H](O)[C@@H](N)C=2C=CC=CC=2)=CC=CC=C1 GEJJWYZZKKKSEV-UONOGXRCSA-N 0.000 description 1
• QXMBIHIWBRHUHS-GRHHLOCNSA-N (2S)-2-(phenylmethoxycarbonylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1.OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 QXMBIHIWBRHUHS-GRHHLOCNSA-N 0.000 description 1
• AQIHDXGKQHFBNW-ZCFIWIBFSA-N (2r)-2-(4-hydroxyphenoxy)propanoic acid Chemical compound OC(=O)[C@@H](C)OC1=CC=C(O)C=C1 AQIHDXGKQHFBNW-ZCFIWIBFSA-N 0.000 description 1
• QJQWACHPCNJIFW-QRWMCTBCSA-N (2r)-2-(benzylsulfanylmethyl)-2-methyl-4-phenyl-1,3-oxazolidine Chemical compound C([C@@]1(C)OCC(N1)C=1C=CC=CC=1)SCC1=CC=CC=C1 QJQWACHPCNJIFW-QRWMCTBCSA-N 0.000 description 1
• GPRLUSIRSONVHX-NSHDSACASA-N (2r)-2-amino-3-benzylsulfanyl-2-methylpropanoic acid Chemical compound OC(=O)[C@](N)(C)CSCC1=CC=CC=C1 GPRLUSIRSONVHX-NSHDSACASA-N 0.000 description 1
• JCBPETKZIGVZRE-SCSAIBSYSA-N (2r)-2-aminobutan-1-ol Chemical compound CC[C@@H](N)CO JCBPETKZIGVZRE-SCSAIBSYSA-N 0.000 description 1
• GGTYBZJRPHEQDG-WCCKRBBISA-N (2s)-2,5-diaminopentanoic acid hydrochloride Chemical compound Cl.NCCC[C@H](N)C(O)=O GGTYBZJRPHEQDG-WCCKRBBISA-N 0.000 description 1
• IOYISRWOQOVKRF-GFCCVEGCSA-N (2s)-3-benzylsulfanyl-2-methyl-2-[(2,2,2-trifluoroacetyl)amino]propanoic acid Chemical compound FC(F)(F)C(=O)N[C@](C(O)=O)(C)CSCC1=CC=CC=C1 IOYISRWOQOVKRF-GFCCVEGCSA-N 0.000 description 1
• MJGBOFOZSAEULI-RUCXOUQFSA-N (2s)-5-oxopyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCC(=O)N1.OC(=O)[C@@H]1CCC(=O)N1 MJGBOFOZSAEULI-RUCXOUQFSA-N 0.000 description 1
• QDXMWEMIYNOVGF-LBPRGKRZSA-N (5r)-5-(benzylsulfanylmethyl)-5-methylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1CSC[C@]1(C)NC(=O)NC1=O QDXMWEMIYNOVGF-LBPRGKRZSA-N 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• ROIFLZSXJWPESS-UHFFFAOYSA-N 1-[4-(5-chloropyridin-2-yl)oxypiperidin-1-yl]sulfonylpropan-2-one Chemical compound C1CN(S(=O)(=O)CC(=O)C)CCC1OC1=CC=C(Cl)C=N1 ROIFLZSXJWPESS-UHFFFAOYSA-N 0.000 description 1
• 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 1
• OIEDQMIEPJIRFT-UHFFFAOYSA-N 1-benzylsulfanylpropan-2-one Chemical compound CC(=O)CSCC1=CC=CC=C1 OIEDQMIEPJIRFT-UHFFFAOYSA-N 0.000 description 1
• 229940044613 1-propanol Drugs 0.000 description 1
• NRKYWOKHZRQRJR-UHFFFAOYSA-N 2,2,2-trifluoroacetamide Chemical compound NC(=O)C(F)(F)F NRKYWOKHZRQRJR-UHFFFAOYSA-N 0.000 description 1
• DLNKOYKMWOXYQA-UHFFFAOYSA-N 2-amino-1-phenylpropan-1-ol Chemical compound CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
• OBYWDEOSSLOLHG-UHFFFAOYSA-N 2-amino-3-benzylsulfanyl-2-methylpropanamide;2,3-dihydroxybutanedioic acid Chemical compound OC(=O)C(O)C(O)C(O)=O.NC(=O)C(N)(C)CSCC1=CC=CC=C1 OBYWDEOSSLOLHG-UHFFFAOYSA-N 0.000 description 1
• YUSCZPWCIWNVSV-UHFFFAOYSA-N 2-bromoethylsulfanylmethylbenzene Chemical compound BrCCSCC1=CC=CC=C1 YUSCZPWCIWNVSV-UHFFFAOYSA-N 0.000 description 1
• CWUGIPSBHFLNTE-UHFFFAOYSA-N 2-hydroxy-2-methylbutanedinitrile Chemical compound N#CC(O)(C)CC#N CWUGIPSBHFLNTE-UHFFFAOYSA-N 0.000 description 1
• VQEDENJDYAWVOH-UHFFFAOYSA-N 2-methoxy-2-methylpropane;toluene Chemical compound COC(C)(C)C.CC1=CC=CC=C1 VQEDENJDYAWVOH-UHFFFAOYSA-N 0.000 description 1
• PJKVFARRVXDXAD-UHFFFAOYSA-N 2-naphthaldehyde Chemical compound C1=CC=CC2=CC(C=O)=CC=C21 PJKVFARRVXDXAD-UHFFFAOYSA-N 0.000 description 1
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
• XORIOVHPKOZEMR-UHFFFAOYSA-N 2-piperidin-4-yloxypyridine Chemical compound C1CNCCC1OC1=CC=CC=N1 XORIOVHPKOZEMR-UHFFFAOYSA-N 0.000 description 1
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
• ITPRPWLFGDOUAI-UHFFFAOYSA-N 5-(benzylsulfanylmethyl)-1-methylimidazolidine-2,4-dione Chemical compound O=C1NC(=O)N(C)C1CSCC1=CC=CC=C1 ITPRPWLFGDOUAI-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 244000215068 Acacia senegal Species 0.000 description 1
• 206010067484 Adverse reaction Diseases 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 206010001889 Alveolitis Diseases 0.000 description 1
• 208000035939 Alveolitis allergic Diseases 0.000 description 1
• 102000004092 Amidohydrolases Human genes 0.000 description 1
• 108090000531 Amidohydrolases Proteins 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 102000013142 Amylases Human genes 0.000 description 1
• 108010065511 Amylases Proteins 0.000 description 1
• 206010002921 Aortitis Diseases 0.000 description 1
• 206010053555 Arthritis bacterial Diseases 0.000 description 1
• 206010003267 Arthritis reactive Diseases 0.000 description 1
• 201000002909 Aspergillosis Diseases 0.000 description 1
• 208000036641 Aspergillus infections Diseases 0.000 description 1
• BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
• 208000025978 Athletic injury Diseases 0.000 description 1
• 241000193830 Bacillus <bacterium> Species 0.000 description 1
• 208000009137 Behcet syndrome Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 241001260012 Bursa Species 0.000 description 1
• OBYWDEOSSLOLHG-RFVHGSKJSA-N C(=O)(O)C(O)C(O)C(=O)O.N[C@@](C(=O)N)(CSCC1=CC=CC=C1)C Chemical compound C(=O)(O)C(O)C(O)C(=O)O.N[C@@](C(=O)N)(CSCC1=CC=CC=C1)C OBYWDEOSSLOLHG-RFVHGSKJSA-N 0.000 description 1
• NVUPTIBWWSABOG-UHFFFAOYSA-N C(C1=CC=CC=C1)=O.[Cl] Chemical compound C(C1=CC=CC=C1)=O.[Cl] NVUPTIBWWSABOG-UHFFFAOYSA-N 0.000 description 1
• JJIFEURZOYTXAG-NRYLJRBGSA-N C[C@@H](N)CO.C[C@@H](O)CN Chemical compound C[C@@H](N)CO.C[C@@H](O)CN JJIFEURZOYTXAG-NRYLJRBGSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-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
• 206010007882 Cellulitis Diseases 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 102100027995 Collagenase 3 Human genes 0.000 description 1
• 208000009248 Congenital Hip Dislocation Diseases 0.000 description 1
• 206010010741 Conjunctivitis Diseases 0.000 description 1
• 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 241000711573 Coronaviridae Species 0.000 description 1
• 108010091326 Cryoglobulins Proteins 0.000 description 1
• 238000006969 Curtius rearrangement reaction Methods 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
• 150000008574 D-amino acids Chemical class 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• QWIZNVHXZXRPDR-UHFFFAOYSA-N D-melezitose Natural products O1C(CO)C(O)C(O)C(O)C1OC1C(O)C(CO)OC1(CO)OC1OC(CO)C(O)C(O)C1O QWIZNVHXZXRPDR-UHFFFAOYSA-N 0.000 description 1
• 206010051055 Deep vein thrombosis Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• 206010012735 Diarrhoea Diseases 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 208000006926 Discoid Lupus Erythematosus Diseases 0.000 description 1
• 206010015150 Erythema Diseases 0.000 description 1
• 206010015218 Erythema multiforme Diseases 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 241000400611 Eucalyptus deanei Species 0.000 description 1
• 206010016207 Familial Mediterranean fever Diseases 0.000 description 1
• 208000027445 Farmer Lung Diseases 0.000 description 1
• 206010016741 Fixed eruption Diseases 0.000 description 1
• 206010017533 Fungal infection Diseases 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 208000005577 Gastroenteritis 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
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 229920000084 Gum arabic Polymers 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 208000003695 Histiocytic Necrotizing Lymphadenitis Diseases 0.000 description 1
• 206010069070 Histiocytic necrotising lymphadenitis Diseases 0.000 description 1
• 101000577887 Homo sapiens Collagenase 3 Proteins 0.000 description 1
• 101000990915 Homo sapiens Stromelysin-1 Proteins 0.000 description 1
• 201000003838 Idiopathic interstitial pneumonia Diseases 0.000 description 1
• 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 1
• 208000004575 Infectious Arthritis Diseases 0.000 description 1
• 206010061246 Intervertebral disc degeneration Diseases 0.000 description 1
• 206010022941 Iridocyclitis Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• 208000015282 Kikuchi-Fujimoto disease Diseases 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
• PQFMNVGMJJMLAE-QMMMGPOBSA-N L-tyrosinamide Chemical compound NC(=O)[C@@H](N)CC1=CC=C(O)C=C1 PQFMNVGMJJMLAE-QMMMGPOBSA-N 0.000 description 1
• 208000008930 Low Back Pain Diseases 0.000 description 1
• 206010025323 Lymphomas Diseases 0.000 description 1
• 208000019695 Migraine disease Diseases 0.000 description 1
• 208000003250 Mixed connective tissue disease Diseases 0.000 description 1
• 201000002795 Muckle-Wells syndrome Diseases 0.000 description 1
• 208000021642 Muscular disease Diseases 0.000 description 1
• 208000023178 Musculoskeletal disease Diseases 0.000 description 1
• 241000186359 Mycobacterium Species 0.000 description 1
• 241000187469 Mycobacterium neoaurum Species 0.000 description 1
• 208000031888 Mycoses Diseases 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• 201000009623 Myopathy Diseases 0.000 description 1
• 125000003047 N-acetyl group Chemical group 0.000 description 1
• WXNXCEHXYPACJF-ZETCQYMHSA-N N-acetyl-L-leucine Chemical compound CC(C)C[C@@H](C(O)=O)NC(C)=O WXNXCEHXYPACJF-ZETCQYMHSA-N 0.000 description 1
• CBQJSKKFNMDLON-JTQLQIEISA-N N-acetyl-L-phenylalanine Chemical compound CC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 CBQJSKKFNMDLON-JTQLQIEISA-N 0.000 description 1
• CAHKINHBCWCHCF-JTQLQIEISA-N N-acetyl-L-tyrosine Chemical compound CC(=O)N[C@H](C(O)=O)CC1=CC=C(O)C=C1 CAHKINHBCWCHCF-JTQLQIEISA-N 0.000 description 1
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 108010024026 Nitrile hydratase Proteins 0.000 description 1
• QMGVPVSNSZLJIA-UHFFFAOYSA-N Nux Vomica Natural products C1C2C3C4N(C=5C6=CC=CC=5)C(=O)CC3OCC=C2CN2C1C46CC2 QMGVPVSNSZLJIA-UHFFFAOYSA-N 0.000 description 1
• ORNHHCBFFGPZJU-ODIXNEOGSA-N OC(=O)[C@H](O)C1=CC=CC=C1.NC(=O)[C@@](N)(C)CSCC1=CC=CC=C1 Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1.NC(=O)[C@@](N)(C)CSCC1=CC=CC=C1 ORNHHCBFFGPZJU-ODIXNEOGSA-N 0.000 description 1
• 206010030216 Oesophagitis Diseases 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 241001420836 Ophthalmitis Species 0.000 description 1
• 208000010191 Osteitis Deformans Diseases 0.000 description 1
• 206010031264 Osteonecrosis Diseases 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 208000027868 Paget disease Diseases 0.000 description 1
• 208000002193 Pain Diseases 0.000 description 1
• 206010034277 Pemphigoid Diseases 0.000 description 1
• 241000721454 Pemphigus Species 0.000 description 1
• 241000228168 Penicillium sp. Species 0.000 description 1
• 208000037581 Persistent Infection Diseases 0.000 description 1
• 206010036030 Polyarthritis Diseases 0.000 description 1
• 206010065159 Polychondritis Diseases 0.000 description 1
• 206010036774 Proctitis Diseases 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• 208000003251 Pruritus Diseases 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 208000006311 Pyoderma Diseases 0.000 description 1
• 206010037660 Pyrexia Diseases 0.000 description 1
• LOUPRKONTZGTKE-LHHVKLHASA-N Quinidine Natural products C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 1
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 1
• MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 description 1
• 208000018569 Respiratory Tract disease Diseases 0.000 description 1
• 206010039094 Rhinitis perennial Diseases 0.000 description 1
• 208000036284 Rhinitis seasonal Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 208000034189 Sclerosis Diseases 0.000 description 1
• 206010039793 Seborrhoeic dermatitis Diseases 0.000 description 1
• 201000002661 Spondylitis Diseases 0.000 description 1
• 102100030416 Stromelysin-1 Human genes 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• 206010042742 Sympathetic ophthalmia Diseases 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 206010042953 Systemic sclerosis Diseases 0.000 description 1
• 208000001106 Takayasu Arteritis Diseases 0.000 description 1
• HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
• MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
• 208000024780 Urticaria Diseases 0.000 description 1
• 206010046996 Varicose vein Diseases 0.000 description 1
• 206010047249 Venous thrombosis Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• 208000035222 X-linked skeletal dysplasia-intellectual disability syndrome Diseases 0.000 description 1
• 238000002441 X-ray diffraction Methods 0.000 description 1
• WIQIWPPQGWGVHD-JEDNCBNOSA-N [(2s)-1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]azanium;chloride Chemical compound Cl.C[C@H](N)C(=O)OC(C)(C)C WIQIWPPQGWGVHD-JEDNCBNOSA-N 0.000 description 1
• WIQIWPPQGWGVHD-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]azanium;chloride Chemical compound Cl.CC(N)C(=O)OC(C)(C)C WIQIWPPQGWGVHD-UHFFFAOYSA-N 0.000 description 1
• 239000000205 acacia gum Substances 0.000 description 1
• 235000010489 acacia gum Nutrition 0.000 description 1
• ORIVJJGKYBVFIY-UHFFFAOYSA-N acetic acid;1-piperidin-1-yloxypiperidine Chemical compound CC(O)=O.C1CCCCN1ON1CCCCC1 ORIVJJGKYBVFIY-UHFFFAOYSA-N 0.000 description 1
• 229940022682 acetone Drugs 0.000 description 1
• WEVYAHXRMPXWCK-FIBGUPNXSA-N acetonitrile-d3 Chemical compound [2H]C([2H])([2H])C#N WEVYAHXRMPXWCK-FIBGUPNXSA-N 0.000 description 1
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
• 229960001138 acetylsalicylic acid Drugs 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 230000006838 adverse reaction Effects 0.000 description 1
• 150000001299 aldehydes Chemical class 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 230000029936 alkylation Effects 0.000 description 1
• 238000005804 alkylation reaction Methods 0.000 description 1
• 208000002205 allergic conjunctivitis Diseases 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 201000010105 allergic rhinitis Diseases 0.000 description 1
• 230000007815 allergy Effects 0.000 description 1
• HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 229910021529 ammonia Inorganic materials 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 235000019418 amylase Nutrition 0.000 description 1
• 229940025131 amylases Drugs 0.000 description 1
• 206010068168 androgenetic alopecia Diseases 0.000 description 1
• 201000004612 anterior uveitis Diseases 0.000 description 1
• 230000000118 anti-neoplastic effect Effects 0.000 description 1
• 229940053195 antiepileptics hydantoin derivative Drugs 0.000 description 1
• 229940034982 antineoplastic agent Drugs 0.000 description 1
• 238000010936 aqueous wash Methods 0.000 description 1
• 238000011914 asymmetric synthesis Methods 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 201000004984 autoimmune cardiomyopathy Diseases 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 230000001580 bacterial effect Effects 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000003833 bile salt Substances 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 208000010217 blepharitis Diseases 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 208000024883 bone remodeling disease Diseases 0.000 description 1
• RRKTZKIUPZVBMF-UHFFFAOYSA-N brucine Natural products C1=2C=C(OC)C(OC)=CC=2N(C(C2)=O)C3C(C4C5)C2OCC=C4CN2C5C31CC2 RRKTZKIUPZVBMF-UHFFFAOYSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
• 239000008116 calcium stearate Substances 0.000 description 1
• 235000013539 calcium stearate Nutrition 0.000 description 1
• 238000007707 calorimetry Methods 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• 229940041514 candida albicans extract Drugs 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
• 125000002915 carbonyl group Chemical group [*: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
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• 108010062049 chirobiotic T Proteins 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical class NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 1
• 208000002849 chondrocalcinosis Diseases 0.000 description 1
• 208000013116 chronic cough Diseases 0.000 description 1
• 201000009151 chronic rhinitis Diseases 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 230000000295 complement effect Effects 0.000 description 1
• 239000002361 compost Substances 0.000 description 1
• 235000008504 concentrate Nutrition 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 239000004020 conductor Substances 0.000 description 1
• 210000002808 connective tissue Anatomy 0.000 description 1
• 208000018631 connective tissue disease Diseases 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 208000010247 contact dermatitis Diseases 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 208000022993 cryopyrin-associated periodic syndrome Diseases 0.000 description 1
• 208000004921 cutaneous lupus erythematosus Diseases 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-L cysteinate(2-) Chemical compound [S-]CC(N)C([O-])=O XUJNEKJLAYXESH-UHFFFAOYSA-L 0.000 description 1
• KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 238000004042 decolorization Methods 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 208000018180 degenerative disc disease Diseases 0.000 description 1
• 239000007857 degradation product Substances 0.000 description 1
• 239000008367 deionised water Substances 0.000 description 1
• 229910021641 deionized water Inorganic materials 0.000 description 1
• 230000017858 demethylation Effects 0.000 description 1
• 238000010520 demethylation reaction Methods 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 208000014906 developmental dysplasia of the hip Diseases 0.000 description 1
• 150000005690 diesters Chemical class 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• FAYZKENLPWLOJW-UHFFFAOYSA-N diethyl 2-(benzylsulfanylmethyl)-2-methylpropanedioate Chemical compound CCOC(=O)C(C)(C(=O)OCC)CSCC1=CC=CC=C1 FAYZKENLPWLOJW-UHFFFAOYSA-N 0.000 description 1
• UPQZOUHVTJNGFK-UHFFFAOYSA-N diethyl 2-methylpropanedioate Chemical compound CCOC(=O)C(C)C(=O)OCC UPQZOUHVTJNGFK-UHFFFAOYSA-N 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
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• 230000008034 disappearance Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 238000009826 distribution Methods 0.000 description 1
• 150000002019 disulfides Chemical class 0.000 description 1
• 229950010030 dl-alanine Drugs 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 239000003937 drug carrier Substances 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 239000000428 dust Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 206010014665 endocarditis Diseases 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 231100000321 erythema Toxicity 0.000 description 1
• 208000006881 esophagitis Diseases 0.000 description 1
• 238000010931 ester hydrolysis Methods 0.000 description 1
• 229940093499 ethyl acetate Drugs 0.000 description 1
• JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
• 230000001747 exhibiting effect Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 208000030533 eye disease Diseases 0.000 description 1
• 208000022195 farmer lung disease Diseases 0.000 description 1
• 239000000194 fatty acid Substances 0.000 description 1
• 229930195729 fatty acid Natural products 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000013305 food Nutrition 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 230000002068 genetic effect Effects 0.000 description 1
• 208000007565 gingivitis Diseases 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 150000004676 glycans Chemical class 0.000 description 1
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
• 239000010931 gold Substances 0.000 description 1
• 229910052737 gold Inorganic materials 0.000 description 1
• 230000005484 gravity Effects 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 239000004615 ingredient Substances 0.000 description 1
• 238000009413 insulation Methods 0.000 description 1
• 230000003993 interaction Effects 0.000 description 1
• 208000021600 intervertebral disc degenerative disease Diseases 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 238000010255 intramuscular injection Methods 0.000 description 1
• 239000007927 intramuscular injection Substances 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• 201000004614 iritis Diseases 0.000 description 1
• 208000002551 irritable bowel syndrome Diseases 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• SXQFCVDSOLSHOQ-UHFFFAOYSA-N lactamide Chemical compound CC(O)C(N)=O SXQFCVDSOLSHOQ-UHFFFAOYSA-N 0.000 description 1
• 239000000832 lactitol Substances 0.000 description 1
• VQHSOMBJVWLPSR-JVCRWLNRSA-N lactitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-JVCRWLNRSA-N 0.000 description 1
• 235000010448 lactitol Nutrition 0.000 description 1
• 229960003451 lactitol Drugs 0.000 description 1
• 150000002596 lactones Chemical class 0.000 description 1
• 230000003902 lesion Effects 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• JGZKUKYUQJUUNE-UHFFFAOYSA-L magnesium;ethoxyethane;dibromide Chemical compound [Mg+2].[Br-].[Br-].CCOCC JGZKUKYUQJUUNE-UHFFFAOYSA-L 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
• 239000000845 maltitol Substances 0.000 description 1
• 235000010449 maltitol Nutrition 0.000 description 1
• 229940035436 maltitol Drugs 0.000 description 1
• 208000027202 mammary Paget disease Diseases 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 229960001855 mannitol Drugs 0.000 description 1
• 208000008585 mastocytosis Diseases 0.000 description 1
• 229960001913 mecysteine Drugs 0.000 description 1
• QWIZNVHXZXRPDR-WSCXOGSTSA-N melezitose Chemical compound O([C@@]1(O[C@@H]([C@H]([C@@H]1O[C@@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O)CO)CO)[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QWIZNVHXZXRPDR-WSCXOGSTSA-N 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 description 1
• MCYHPZGUONZRGO-VKHMYHEASA-N methyl L-cysteinate Chemical compound COC(=O)[C@@H](N)CS MCYHPZGUONZRGO-VKHMYHEASA-N 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 206010027599 migraine Diseases 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 239000002808 molecular sieve Substances 0.000 description 1
• 239000012768 molten material Substances 0.000 description 1
• 230000002107 myocardial effect Effects 0.000 description 1
• IPZJNJPAVPZHJM-UHFFFAOYSA-N n-[(2,2-dimethylchromen-6-yl)methyl]-3,4-dimethoxy-n-phenylbenzenesulfonamide Chemical compound C1=C(OC)C(OC)=CC=C1S(=O)(=O)N(C=1C=CC=CC=1)CC1=CC=C(OC(C)(C)C=C2)C2=C1 IPZJNJPAVPZHJM-UHFFFAOYSA-N 0.000 description 1
• KDFFXYVOTKKBDI-UHFFFAOYSA-N n-ethylnaphthalen-1-amine Chemical compound C1=CC=C2C(NCC)=CC=CC2=C1 KDFFXYVOTKKBDI-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 238000010899 nucleation Methods 0.000 description 1
• 230000000414 obstructive effect Effects 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 206010033675 panniculitis Diseases 0.000 description 1
• 208000010403 panophthalmitis Diseases 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000003182 parenteral nutrition solution Substances 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 239000013618 particulate matter Substances 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 208000022719 perennial allergic rhinitis Diseases 0.000 description 1
• 208000008494 pericarditis Diseases 0.000 description 1
• 208000028169 periodontal disease Diseases 0.000 description 1
• 230000003836 peripheral circulation Effects 0.000 description 1
• 230000002093 peripheral effect Effects 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 208000001297 phlebitis Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 150000003904 phospholipids Chemical class 0.000 description 1
• 208000017983 photosensitivity disease Diseases 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 201000006292 polyarteritis nodosa Diseases 0.000 description 1
• 208000030428 polyarticular arthritis Diseases 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 229920005862 polyol Polymers 0.000 description 1
• 150000003077 polyols Chemical class 0.000 description 1
• 208000015768 polyposis Diseases 0.000 description 1
• 229920001282 polysaccharide Polymers 0.000 description 1
• 239000005017 polysaccharide Substances 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
• 235000015277 pork Nutrition 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
• 239000008057 potassium phosphate buffer Substances 0.000 description 1
• CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
• 229920001592 potato starch Polymers 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
• XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
• VHWJSJBTUWUEAL-UHFFFAOYSA-N propanamide;hydrochloride Chemical compound Cl.CCC(N)=O VHWJSJBTUWUEAL-UHFFFAOYSA-N 0.000 description 1
• 229960005335 propanol Drugs 0.000 description 1
• 239000003380 propellant Substances 0.000 description 1
• 229940090181 propyl acetate Drugs 0.000 description 1
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 208000005069 pulmonary fibrosis Diseases 0.000 description 1
• 239000008213 purified water Substances 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 239000010453 quartz Substances 0.000 description 1
• 238000010791 quenching Methods 0.000 description 1
• 230000000171 quenching effect Effects 0.000 description 1
• 229960001404 quinidine Drugs 0.000 description 1
• MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000000241 respiratory effect Effects 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 230000000717 retained effect Effects 0.000 description 1
• 210000001525 retina Anatomy 0.000 description 1
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
• 230000002441 reversible effect Effects 0.000 description 1
• CHAWVFWLJTUJNI-UHFFFAOYSA-M rubidium(1+);hydroxide;hydrate Chemical compound O.[OH-].[Rb+] CHAWVFWLJTUJNI-UHFFFAOYSA-M 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• 238000012216 screening Methods 0.000 description 1
• 208000017022 seasonal allergic rhinitis Diseases 0.000 description 1
• 208000008742 seborrheic dermatitis Diseases 0.000 description 1
• 230000003248 secreting effect Effects 0.000 description 1
• 201000001223 septic arthritis Diseases 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 238000004467 single crystal X-ray diffraction Methods 0.000 description 1
• 208000025869 skeletal dysplasia-intellectual disability syndrome Diseases 0.000 description 1
• 201000008261 skin carcinoma Diseases 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
• WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
• 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
• 239000012265 solid product Substances 0.000 description 1
• 239000000600 sorbitol Substances 0.000 description 1
• 238000009331 sowing Methods 0.000 description 1
• 239000007921 spray Substances 0.000 description 1
• 229910001220 stainless steel Inorganic materials 0.000 description 1
• 239000010935 stainless steel Substances 0.000 description 1
• 229960005453 strychnine Drugs 0.000 description 1
• 238000010254 subcutaneous injection Methods 0.000 description 1
• 239000007929 subcutaneous injection Substances 0.000 description 1
• 229960004793 sucrose Drugs 0.000 description 1
• 150000005846 sugar alcohols Chemical class 0.000 description 1
• 150000008163 sugars Chemical class 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 238000004441 surface measurement Methods 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 230000008409 synovial inflammation Effects 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 230000002194 synthesizing effect Effects 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 235000012222 talc Nutrition 0.000 description 1
• 210000001738 temporomandibular joint Anatomy 0.000 description 1
• 210000002435 tendon Anatomy 0.000 description 1
• VVPYFSHBKMTJNL-QFIPXVFZSA-N tert-butyl (2r)-2-(benzylideneamino)-3-benzylsulfanyl-2-methylpropanoate Chemical compound C([C@@](C)(C(=O)OC(C)(C)C)N=CC=1C=CC=CC=1)SCC1=CC=CC=C1 VVPYFSHBKMTJNL-QFIPXVFZSA-N 0.000 description 1
• AMONUZJWIRBZBA-NSHDSACASA-N tert-butyl (2s)-2-(benzylideneamino)propanoate Chemical compound CC(C)(C)OC(=O)[C@H](C)N=CC1=CC=CC=C1 AMONUZJWIRBZBA-NSHDSACASA-N 0.000 description 1
• JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
• 238000010257 thawing Methods 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 150000003573 thiols Chemical class 0.000 description 1
• 230000007838 tissue remodeling Effects 0.000 description 1
• 239000004408 titanium dioxide Substances 0.000 description 1
• 235000010215 titanium dioxide Nutrition 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 230000007704 transition Effects 0.000 description 1
• 229940074410 trehalose Drugs 0.000 description 1
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 208000027930 type IV hypersensitivity disease Diseases 0.000 description 1
• 241000701161 unidentified adenovirus Species 0.000 description 1
• 150000003673 urethanes Chemical class 0.000 description 1
• 238000001291 vacuum drying Methods 0.000 description 1
• 230000003156 vasculitic effect Effects 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1
• 208000020854 vein disease Diseases 0.000 description 1
• 201000005539 vernal conjunctivitis Diseases 0.000 description 1
• 239000003643 water by type Substances 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 229940045860 white wax Drugs 0.000 description 1
• 239000012138 yeast extract Substances 0.000 description 1