SG183416A1 - Processes for the preparation of s1p1 receptor modulators and crystalline forms thereof - Google Patents

Info

Publication number

SG183416A1

SG183416A1 SG2012061685A SG2012061685A SG183416A1 SG 183416 A1 SG183416 A1 SG 183416A1 SG 2012061685 A SG2012061685 A SG 2012061685A SG 2012061685 A SG2012061685 A SG 2012061685A SG 183416 A1 SG183416 A1 SG 183416A1

Authority

SG

Singapore

Prior art keywords

salt

trifluoromethyl

isopropoxy

benzyloxy

pyrrolo

Prior art date

2010-03-03

Links

• Espacenet
• Global Dossier
• Discuss

• 238000000034 method Methods 0.000 title claims abstract description 202
• 230000008569 process Effects 0.000 title claims abstract description 97
• 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 title claims abstract description 96
• 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 title claims abstract description 95
• 238000002360 preparation method Methods 0.000 title abstract description 75
• 150000001875 compounds Chemical class 0.000 claims abstract description 371
• 150000003839 salts Chemical class 0.000 claims abstract description 277
• RLGFHVZCVPTTLP-OAHLLOKOSA-N 2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetic acid Chemical compound C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC(O)=O)CC2)=C2Cl)C2=C1 RLGFHVZCVPTTLP-OAHLLOKOSA-N 0.000 claims abstract description 81
• 238000011282 treatment Methods 0.000 claims abstract description 80
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 68
• 208000035475 disorder Diseases 0.000 claims abstract description 32
• 206010052779 Transplant rejections Diseases 0.000 claims abstract description 14
• 239000000203 mixture Substances 0.000 claims description 284
• 239000002253 acid Substances 0.000 claims description 171
• 239000002904 solvent Substances 0.000 claims description 159
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 126
• 239000008194 pharmaceutical composition Substances 0.000 claims description 92
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 82
• 238000000113 differential scanning calorimetry Methods 0.000 claims description 75
• 238000000634 powder X-ray diffraction Methods 0.000 claims description 70
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 66
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 65
• 229910052799 carbon Inorganic materials 0.000 claims description 63
• 238000001757 thermogravimetry curve Methods 0.000 claims description 63
• 238000002411 thermogravimetry Methods 0.000 claims description 60
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 60
• 125000000217 alkyl group Chemical group 0.000 claims description 58
• 239000003814 drug Substances 0.000 claims description 56
• 150000008545 L-lysines Chemical class 0.000 claims description 55
• 229910052739 hydrogen Inorganic materials 0.000 claims description 54
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 36
• 238000004519 manufacturing process Methods 0.000 claims description 36
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 35
• 230000004580 weight loss Effects 0.000 claims description 31
• 241001465754 Metazoa Species 0.000 claims description 28
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 25
• NGMORLNIWOFWIA-WZNJZOFCSA-N 2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetic acid;(2s)-2,6-diaminohexanoic acid Chemical compound NCCCC[C@H](N)C(O)=O.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC(O)=O)CC2)=C2Cl)C2=C1 NGMORLNIWOFWIA-WZNJZOFCSA-N 0.000 claims description 22
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 22
• SKOIWBPVBTURJZ-UHFFFAOYSA-N 4-(chloromethyl)-1-propan-2-yloxy-2-(trifluoromethyl)benzene Chemical compound CC(C)OC1=CC=C(CCl)C=C1C(F)(F)F SKOIWBPVBTURJZ-UHFFFAOYSA-N 0.000 claims description 21
• 238000002441 X-ray diffraction Methods 0.000 claims description 20
• 239000003937 drug carrier Substances 0.000 claims description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
• 230000003301 hydrolyzing effect Effects 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• FMRZLMJTOCTKPU-UHFFFAOYSA-N 4-propan-2-yloxy-3-(trifluoromethyl)benzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C=C1C(F)(F)F FMRZLMJTOCTKPU-UHFFFAOYSA-N 0.000 claims description 16
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 14
• 239000003795 chemical substances by application Substances 0.000 claims description 14
• 201000006417 multiple sclerosis Diseases 0.000 claims description 14
• FMYJSEMKYVIQCF-QCUBGVIVSA-N 2-[(3R)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl]acetic acid ethane-1,2-diamine hydrate Chemical compound O.NCCN.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC(O)=O)CC2)=C2Cl)C2=C1 FMYJSEMKYVIQCF-QCUBGVIVSA-N 0.000 claims description 13
• XLLSQMOGHKEOOC-XFULWGLBSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetic acid Chemical compound OCC(N)(CO)CO.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC(O)=O)CC2)=C2Cl)C2=C1 XLLSQMOGHKEOOC-XFULWGLBSA-N 0.000 claims description 13
• RNCVVXUSWKAGEL-UHFFFAOYSA-N 4-propan-2-yloxy-3-(trifluoromethyl)benzonitrile Chemical compound CC(C)OC1=CC=C(C#N)C=C1C(F)(F)F RNCVVXUSWKAGEL-UHFFFAOYSA-N 0.000 claims description 13
• 235000019766 L-Lysine Nutrition 0.000 claims description 12
• 239000004472 Lysine Substances 0.000 claims description 12
• MLNWUYROPZPMJD-QCUBGVIVSA-M sodium 2-[(3R)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1H-pyrrolo[1,2-a]indol-3-yl]acetate hydrate Chemical compound O.[Na+].CC(C)Oc1ccc(COc2ccc3n4CC[C@H](CC([O-])=O)c4c(Cl)c3c2)cc1C(F)(F)F MLNWUYROPZPMJD-QCUBGVIVSA-M 0.000 claims description 12
• BOYONATXSZSGEJ-UHFFFAOYSA-N [4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methanol Chemical compound CC(C)OC1=CC=C(CO)C=C1C(F)(F)F BOYONATXSZSGEJ-UHFFFAOYSA-N 0.000 claims description 9
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
• 208000002874 Acne Vulgaris Diseases 0.000 claims description 8
• 206010009900 Colitis ulcerative Diseases 0.000 claims description 8
• 208000011231 Crohn disease Diseases 0.000 claims description 8
• 201000004681 Psoriasis Diseases 0.000 claims description 8
• 206010063837 Reperfusion injury Diseases 0.000 claims description 8
• 101710155454 Sphingosine 1-phosphate receptor 1 Proteins 0.000 claims description 8
• 102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 claims description 8
• 201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
• 206010000496 acne Diseases 0.000 claims description 8
• 239000012320 chlorinating reagent Substances 0.000 claims description 8
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 7
• 206010004659 Biliary cirrhosis Diseases 0.000 claims description 7
• 208000007882 Gastritis Diseases 0.000 claims description 7
• 206010055171 Hypertensive nephropathy Diseases 0.000 claims description 7
• 206010047642 Vitiligo Diseases 0.000 claims description 7
• 206010061989 glomerulosclerosis Diseases 0.000 claims description 7
• 208000006454 hepatitis Diseases 0.000 claims description 7
• 231100000283 hepatitis Toxicity 0.000 claims description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 7
• 208000031225 myocardial ischemia Diseases 0.000 claims description 7
• 208000005987 polymyositis Diseases 0.000 claims description 7
• KLQBNXIJGAPZRO-XFULWGLBSA-M sodium;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound [Na+].C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1 KLQBNXIJGAPZRO-XFULWGLBSA-M 0.000 claims description 7
• 206010043778 thyroiditis Diseases 0.000 claims description 7
• ZSVAEAZGPVDZBP-QQPYHFHTSA-L zinc;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound [Zn+2].C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1 ZSVAEAZGPVDZBP-QQPYHFHTSA-L 0.000 claims description 7
• SYJXPQLYUYTYEH-XYYPWZPKSA-N (2s)-2-amino-5-(diaminomethylideneamino)pentanoic acid;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetic acid Chemical compound OC(=O)[C@@H](N)CCCNC(N)=N.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC(O)=O)CC2)=C2Cl)C2=C1 SYJXPQLYUYTYEH-XYYPWZPKSA-N 0.000 claims description 6
• PNIZRKMCXPNJFR-FRRIPSOJSA-N 2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetic acid;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC(O)=O)CC2)=C2Cl)C2=C1 PNIZRKMCXPNJFR-FRRIPSOJSA-N 0.000 claims description 6
• DCISGIJQKHOIEM-QQPYHFHTSA-L calcium;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound [Ca+2].C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1 DCISGIJQKHOIEM-QQPYHFHTSA-L 0.000 claims description 6
• MJTTXFOUOIHRKO-XFULWGLBSA-M potassium;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound [K+].C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1 MJTTXFOUOIHRKO-XFULWGLBSA-M 0.000 claims description 6
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
• CQZQCORFYSSCFY-UHFFFAOYSA-N 4-fluoro-3-(trifluoromethyl)benzonitrile Chemical compound FC1=CC=C(C#N)C=C1C(F)(F)F CQZQCORFYSSCFY-UHFFFAOYSA-N 0.000 claims description 5
• 238000002560 therapeutic procedure Methods 0.000 claims description 4
• 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims description 3
• UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 3
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 3
• 239000003638 chemical reducing agent Substances 0.000 claims description 2
• 208000033017 acquired idiopathic inflammatory myopathy Diseases 0.000 claims 2
• 125000001176 L-lysyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 claims 1
• 239000000543 intermediate Substances 0.000 abstract description 26
• 210000004698 lymphocyte Anatomy 0.000 abstract description 22
• 208000027866 inflammatory disease Diseases 0.000 abstract description 17
• 208000023275 Autoimmune disease Diseases 0.000 abstract description 13
• 230000004054 inflammatory process Effects 0.000 abstract description 13
• 206010061218 Inflammation Diseases 0.000 abstract description 12
• 206010028980 Neoplasm Diseases 0.000 abstract description 10
• 201000011510 cancer Diseases 0.000 abstract description 9
• 230000002792 vascular Effects 0.000 abstract description 8
• 230000001154 acute effect Effects 0.000 abstract description 7
• 230000001404 mediated effect Effects 0.000 abstract description 7
• 230000033115 angiogenesis Effects 0.000 abstract description 6
• 230000001575 pathological effect Effects 0.000 abstract description 6
• 201000001320 Atherosclerosis Diseases 0.000 abstract description 5
• 230000007547 defect Effects 0.000 abstract description 5
• 230000005748 tumor development Effects 0.000 abstract description 5
• 230000001684 chronic effect Effects 0.000 abstract description 4
• 230000004968 inflammatory condition Effects 0.000 abstract description 4
• 208000037765 diseases and disorders Diseases 0.000 abstract description 3
• 229940075993 receptor modulator Drugs 0.000 abstract description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 107
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 102
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 98
• 239000007787 solid Substances 0.000 description 62
• 239000003446 ligand Substances 0.000 description 55
• -1 acetic acid L-arginine salt Chemical class 0.000 description 51
• 239000002585 base Substances 0.000 description 50
• 239000000243 solution Substances 0.000 description 50
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 48
• 241000699670 Mus sp. Species 0.000 description 47
• 238000012360 testing method Methods 0.000 description 40
• 235000019439 ethyl acetate Nutrition 0.000 description 37
• 201000010099 disease Diseases 0.000 description 36
• 241000700159 Rattus Species 0.000 description 35
• 230000000694 effects Effects 0.000 description 34
• 239000000523 sample Substances 0.000 description 33
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
• 238000005481 NMR spectroscopy Methods 0.000 description 32
• 238000006243 chemical reaction Methods 0.000 description 31
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
• 239000000047 product Substances 0.000 description 30
• 238000003556 assay Methods 0.000 description 29
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 29
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 28
• 230000001225 therapeutic effect Effects 0.000 description 28
• 208000016261 weight loss Diseases 0.000 description 28
• XZUAPPXGIFNDRA-UHFFFAOYSA-N ethane-1,2-diamine;hydrate Chemical compound O.NCCN XZUAPPXGIFNDRA-UHFFFAOYSA-N 0.000 description 27
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
• LENZDBCJOHFCAS-UHFFFAOYSA-O Htris Chemical compound OCC([NH3+])(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-O 0.000 description 26
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 26
• 239000011541 reaction mixture Substances 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
• 238000007792 addition Methods 0.000 description 25
• NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 25
• 229910000073 phosphorus hydride Inorganic materials 0.000 description 24
• 239000012298 atmosphere Substances 0.000 description 23
• 229940079593 drug Drugs 0.000 description 23
• 239000012453 solvate Substances 0.000 description 23
• 239000000725 suspension Substances 0.000 description 23
• 125000003545 alkoxy group Chemical group 0.000 description 22
• 239000003054 catalyst Substances 0.000 description 22
• 238000001914 filtration Methods 0.000 description 22
• 239000000843 powder Substances 0.000 description 22
• 238000001179 sorption measurement Methods 0.000 description 22
• 239000000706 filtrate Substances 0.000 description 21
• 239000003981 vehicle Substances 0.000 description 21
• 239000012267 brine Substances 0.000 description 20
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
• 238000003756 stirring Methods 0.000 description 20
• 239000000556 agonist Substances 0.000 description 19
• 229910052783 alkali metal Inorganic materials 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 19
• 206010009887 colitis Diseases 0.000 description 19
• MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 18
• 239000003153 chemical reaction reagent Substances 0.000 description 18
• 230000004083 survival effect Effects 0.000 description 18
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 17
• 239000004480 active ingredient Substances 0.000 description 17
• 229910052700 potassium Chemical group 0.000 description 17
• 239000011591 potassium Chemical group 0.000 description 17
• 230000002152 alkylating effect Effects 0.000 description 16
• 229910052757 nitrogen Inorganic materials 0.000 description 16
• 239000002244 precipitate Substances 0.000 description 16
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 230000000911 decarboxylating effect Effects 0.000 description 15
• 238000010438 heat treatment Methods 0.000 description 15
• 150000004677 hydrates Chemical class 0.000 description 15
• 239000007788 liquid Substances 0.000 description 15
• 239000003921 oil Substances 0.000 description 15
• 235000019198 oils Nutrition 0.000 description 15
• 125000005233 alkylalcohol group Chemical group 0.000 description 14
• 239000008346 aqueous phase Substances 0.000 description 14
• 239000012141 concentrate Substances 0.000 description 14
• 235000008504 concentrate Nutrition 0.000 description 14
• 201000002491 encephalomyelitis Diseases 0.000 description 14
• 125000001188 haloalkyl group Chemical group 0.000 description 14
• 238000010172 mouse model Methods 0.000 description 14
• 229960005235 piperonyl butoxide Drugs 0.000 description 14
• 239000003826 tablet Substances 0.000 description 14
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• 229910052736 halogen Inorganic materials 0.000 description 13
• 150000002367 halogens Chemical class 0.000 description 13
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 12
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
• 150000001340 alkali metals Chemical class 0.000 description 12
• 239000002775 capsule Substances 0.000 description 12
• 210000001072 colon Anatomy 0.000 description 12
• 238000001816 cooling Methods 0.000 description 12
• 239000012071 phase Substances 0.000 description 12
• 230000002829 reductive effect Effects 0.000 description 12
• 210000003491 skin Anatomy 0.000 description 12
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 11
• 230000008484 agonism Effects 0.000 description 11
• 238000004458 analytical method Methods 0.000 description 11
• 230000015572 biosynthetic process Effects 0.000 description 11
• 239000000460 chlorine Substances 0.000 description 11
• 230000008595 infiltration Effects 0.000 description 11
• 238000001764 infiltration Methods 0.000 description 11
• 238000002347 injection Methods 0.000 description 11
• 239000007924 injection Substances 0.000 description 11
• 229940044601 receptor agonist Drugs 0.000 description 11
• 239000000018 receptor agonist Substances 0.000 description 11
• 239000011734 sodium Substances 0.000 description 11
• DUYSYHSSBDVJSM-KRWOKUGFSA-N sphingosine 1-phosphate Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)COP(O)(O)=O DUYSYHSSBDVJSM-KRWOKUGFSA-N 0.000 description 11
• 208000024891 symptom Diseases 0.000 description 11
• 238000002054 transplantation Methods 0.000 description 11
• 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 10
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
• 241000283984 Rodentia Species 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 125000004438 haloalkoxy group Chemical group 0.000 description 10
• 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 10
• 239000010410 layer Substances 0.000 description 10
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 10
• 229910052708 sodium Inorganic materials 0.000 description 10
• 125000001424 substituent group Chemical group 0.000 description 10
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
• 229930105110 Cyclosporin A Natural products 0.000 description 9
• PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 9
• 108010036949 Cyclosporine Proteins 0.000 description 9
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 9
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
• 238000010171 animal model Methods 0.000 description 9
• 210000004369 blood Anatomy 0.000 description 9
• 239000008280 blood Substances 0.000 description 9
• 229960001265 ciclosporin Drugs 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 235000005911 diet Nutrition 0.000 description 9
• 230000037213 diet Effects 0.000 description 9
• 239000001257 hydrogen Substances 0.000 description 9
• 230000006698 induction Effects 0.000 description 9
• 231100000861 limb weakness Toxicity 0.000 description 9
• 208000027905 limb weakness Diseases 0.000 description 9
• 229910052744 lithium Inorganic materials 0.000 description 9
• 230000002093 peripheral effect Effects 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• 206010052804 Drug tolerance Diseases 0.000 description 8
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
• WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 8
• 241000699666 Mus <mouse, genus> Species 0.000 description 8
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 8
• 150000004703 alkoxides Chemical class 0.000 description 8
• 239000002552 dosage form Substances 0.000 description 8
• 210000003414 extremity Anatomy 0.000 description 8
• 235000013305 food Nutrition 0.000 description 8
• 230000026781 habituation Effects 0.000 description 8
• 239000003018 immunosuppressive agent Substances 0.000 description 8
• 238000005259 measurement Methods 0.000 description 8
• 229910052763 palladium Inorganic materials 0.000 description 8
• 210000005105 peripheral blood lymphocyte Anatomy 0.000 description 8
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 8
• 238000011552 rat model Methods 0.000 description 8
• 102000005962 receptors Human genes 0.000 description 8
• 108020003175 receptors Proteins 0.000 description 8
• 230000009467 reduction Effects 0.000 description 8
• 238000006722 reduction reaction Methods 0.000 description 8
• NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 7
• 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 7
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
• 229930194542 Keto Natural products 0.000 description 7
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
• 239000000010 aprotic solvent Substances 0.000 description 7
• 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 7
• 239000011575 calcium Substances 0.000 description 7
• 239000010949 copper Substances 0.000 description 7
• 229960004132 diethyl ether Drugs 0.000 description 7
• 238000001938 differential scanning calorimetry curve Methods 0.000 description 7
• 230000001747 exhibiting effect Effects 0.000 description 7
• 238000002474 experimental method Methods 0.000 description 7
• 230000001965 increasing effect Effects 0.000 description 7
• 208000015181 infectious disease Diseases 0.000 description 7
• 125000000468 ketone group Chemical group 0.000 description 7
• 210000001165 lymph node Anatomy 0.000 description 7
• 229920000609 methyl cellulose Polymers 0.000 description 7
• 239000001923 methylcellulose Substances 0.000 description 7
• 235000010981 methylcellulose Nutrition 0.000 description 7
• 229920001843 polymethylhydrosiloxane Polymers 0.000 description 7
• 229940002612 prodrug Drugs 0.000 description 7
• 239000000651 prodrug Substances 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 7
• KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 6
• 206010033799 Paralysis Diseases 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 6
• 238000010521 absorption reaction Methods 0.000 description 6
• 210000000436 anus Anatomy 0.000 description 6
• 229910052786 argon Inorganic materials 0.000 description 6
• 125000004429 atom Chemical group 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 230000000747 cardiac effect Effects 0.000 description 6
• PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 6
• 239000000839 emulsion Substances 0.000 description 6
• 239000008103 glucose Substances 0.000 description 6
• 230000001939 inductive effect Effects 0.000 description 6
• 230000003834 intracellular effect Effects 0.000 description 6
• 210000000265 leukocyte Anatomy 0.000 description 6
• PMAOQCBJCVYOSI-QQPYHFHTSA-L magnesium;2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound [Mg+2].C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1.C1=C(C(F)(F)F)C(OC(C)C)=CC=C1COC1=CC=C(N2C([C@@H](CC([O-])=O)CC2)=C2Cl)C2=C1 PMAOQCBJCVYOSI-QQPYHFHTSA-L 0.000 description 6
• 238000002844 melting Methods 0.000 description 6
• 230000008018 melting Effects 0.000 description 6
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
• 239000012074 organic phase Substances 0.000 description 6
• FVZVCSNXTFCBQU-UHFFFAOYSA-N phosphanyl Chemical group [PH2] FVZVCSNXTFCBQU-UHFFFAOYSA-N 0.000 description 6
• 230000000704 physical effect Effects 0.000 description 6
• 239000002243 precursor Substances 0.000 description 6
• 230000004044 response Effects 0.000 description 6
• 239000007921 spray Substances 0.000 description 6
• 239000000126 substance Substances 0.000 description 6
• 239000000375 suspending agent Substances 0.000 description 6
• 229910052722 tritium Inorganic materials 0.000 description 6
• 230000004584 weight gain Effects 0.000 description 6
• 235000019786 weight gain Nutrition 0.000 description 6
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 5
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• 102000047918 Myelin Basic Human genes 0.000 description 5
• 101710107068 Myelin basic protein Proteins 0.000 description 5
• ZNORAFJUESSLTM-UHFFFAOYSA-N [4-[5-bis(3,5-ditert-butyl-4-methoxyphenyl)phosphanyl-1,3-benzodioxol-4-yl]-1,3-benzodioxol-5-yl]-bis(3,5-ditert-butyl-4-methoxyphenyl)phosphane Chemical compound C1=C(C(C)(C)C)C(OC)=C(C(C)(C)C)C=C1P(C=1C(=C2OCOC2=CC=1)C=1C(=CC=C2OCOC2=1)P(C=1C=C(C(OC)=C(C=1)C(C)(C)C)C(C)(C)C)C=1C=C(C(OC)=C(C=1)C(C)(C)C)C(C)(C)C)C1=CC(C(C)(C)C)=C(OC)C(C(C)(C)C)=C1 ZNORAFJUESSLTM-UHFFFAOYSA-N 0.000 description 5
• 239000000443 aerosol Substances 0.000 description 5
• 230000008901 benefit Effects 0.000 description 5
• 239000000872 buffer Substances 0.000 description 5
• 229910052791 calcium Inorganic materials 0.000 description 5
• 239000000969 carrier Substances 0.000 description 5
• 125000003636 chemical group Chemical group 0.000 description 5
• 238000004296 chiral HPLC Methods 0.000 description 5
• 230000000875 corresponding effect Effects 0.000 description 5
• 239000013078 crystal Substances 0.000 description 5
• 239000002270 dispersing agent Substances 0.000 description 5
• 229960003444 immunosuppressant agent Drugs 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• PWBJWDKDPAPGED-UHFFFAOYSA-N n'-chlorobutanediamide Chemical compound NC(=O)CCC(=O)NCl PWBJWDKDPAPGED-UHFFFAOYSA-N 0.000 description 5
• 210000000056 organ Anatomy 0.000 description 5
• 230000007170 pathology Effects 0.000 description 5
• GYZZZILPVUYAFJ-UHFFFAOYSA-N phanephos Chemical compound C1CC(C(=C2)P(C=3C=CC=CC=3)C=3C=CC=CC=3)=CC=C2CCC2=CC=C1C=C2P(C=1C=CC=CC=1)C1=CC=CC=C1 GYZZZILPVUYAFJ-UHFFFAOYSA-N 0.000 description 5
• 230000000144 pharmacologic effect Effects 0.000 description 5
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
• 238000001144 powder X-ray diffraction data Methods 0.000 description 5
• 238000010898 silica gel chromatography Methods 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• 239000007858 starting material Substances 0.000 description 5
• TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 5
• 238000004809 thin layer chromatography Methods 0.000 description 5
• 210000001519 tissue Anatomy 0.000 description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
• 238000003828 vacuum filtration Methods 0.000 description 5
• WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 4
• WLSIHCGKTRVIKU-CQSZACIVSA-N (2r)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-(2-phenylmethoxyethyl)butanoic acid Chemical compound CC(C)(C)OC(=O)C[C@H](C(O)=O)CCOCC1=CC=CC=C1 WLSIHCGKTRVIKU-CQSZACIVSA-N 0.000 description 4
• YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 4
• DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 4
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 4
• FRDAATYAJDYRNW-UHFFFAOYSA-N 3-methyl-3-pentanol Chemical compound CCC(C)(O)CC FRDAATYAJDYRNW-UHFFFAOYSA-N 0.000 description 4
• LOCBLDCQGSSKFR-OAHLLOKOSA-N 4-o-tert-butyl 1-o-methyl (2r)-2-(2-phenylmethoxyethyl)butanedioate Chemical compound CC(C)(C)OC(=O)C[C@H](C(=O)OC)CCOCC1=CC=CC=C1 LOCBLDCQGSSKFR-OAHLLOKOSA-N 0.000 description 4
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
• 238000011725 BALB/c mouse Methods 0.000 description 4
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
• 238000011740 C57BL/6 mouse Methods 0.000 description 4
• 102000036530 EDG receptors Human genes 0.000 description 4
• 108091007263 EDG receptors Proteins 0.000 description 4
• 108010010803 Gelatin Proteins 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 206010025327 Lymphopenia Diseases 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
• 102100033979 Protein strawberry notch homolog 1 Human genes 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 4
• MXGXXBYVDMVJAO-UHFFFAOYSA-N [1-[2-bis(3,5-dimethylphenyl)phosphanylnaphthalen-1-yl]naphthalen-2-yl]-bis(3,5-dimethylphenyl)phosphane Chemical group CC1=CC(C)=CC(P(C=2C=C(C)C=C(C)C=2)C=2C(=C3C=CC=CC3=CC=2)C=2C3=CC=CC=C3C=CC=2P(C=2C=C(C)C=C(C)C=2)C=2C=C(C)C=C(C)C=2)=C1 MXGXXBYVDMVJAO-UHFFFAOYSA-N 0.000 description 4
• JZOSBBLJKXSBBN-UHFFFAOYSA-N [3-(4-diphenylphosphanyl-2,6-dimethoxypyridin-3-yl)-2,6-dimethoxypyridin-4-yl]-diphenylphosphane Chemical compound COC=1N=C(OC)C=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C=1C(OC)=NC(OC)=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 JZOSBBLJKXSBBN-UHFFFAOYSA-N 0.000 description 4
• 239000002671 adjuvant Substances 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 230000037396 body weight Effects 0.000 description 4
• 230000008859 change Effects 0.000 description 4
• 239000003086 colorant Substances 0.000 description 4
• 230000003511 endothelial effect Effects 0.000 description 4
• YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 4
• UGYBUUFBYIJHGI-SNVBAGLBSA-N ethyl 2-[(3r)-6-hydroxy-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound OC1=CC=C2N3CC[C@H](CC(=O)OCC)C3=CC2=C1 UGYBUUFBYIJHGI-SNVBAGLBSA-N 0.000 description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
• 239000012065 filter cake Substances 0.000 description 4
• 239000007789 gas Substances 0.000 description 4
• 229920000159 gelatin Polymers 0.000 description 4
• 235000019322 gelatine Nutrition 0.000 description 4
• 235000011852 gelatine desserts Nutrition 0.000 description 4
• 230000001506 immunosuppresive effect Effects 0.000 description 4
• 238000001727 in vivo Methods 0.000 description 4
• 239000007937 lozenge Substances 0.000 description 4
• 231100001023 lymphopenia Toxicity 0.000 description 4
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 229910052751 metal Inorganic materials 0.000 description 4
• 239000002184 metal Substances 0.000 description 4
• 229940098779 methanesulfonic acid Drugs 0.000 description 4
• NCDZICHZPSZWGO-SECBINFHSA-N methyl 2-[(3r)-6-hydroxy-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound OC1=CC=C2N3CC[C@H](CC(=O)OC)C3=CC2=C1 NCDZICHZPSZWGO-SECBINFHSA-N 0.000 description 4
• 239000012044 organic layer Substances 0.000 description 4
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000003755 preservative agent Substances 0.000 description 4
• 108090000765 processed proteins & peptides Proteins 0.000 description 4
• 238000011321 prophylaxis Methods 0.000 description 4
• 238000012552 review Methods 0.000 description 4
• 239000000741 silica gel Substances 0.000 description 4
• 229910002027 silica gel Inorganic materials 0.000 description 4
• WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 4
• 239000003381 stabilizer Substances 0.000 description 4
• 210000000130 stem cell Anatomy 0.000 description 4
• 238000010189 synthetic method Methods 0.000 description 4
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
• 230000008719 thickening Effects 0.000 description 4
• 239000002562 thickening agent Substances 0.000 description 4
• UHUUYVZLXJHWDV-UHFFFAOYSA-N trimethyl(methylsilyloxy)silane Chemical compound C[SiH2]O[Si](C)(C)C UHUUYVZLXJHWDV-UHFFFAOYSA-N 0.000 description 4
• 238000010792 warming Methods 0.000 description 4
• JRGCJXUFDLNQOT-XMMPIXPASA-N (3r)-5-phenylmethoxy-3-[5-tri(propan-2-yl)silyloxy-1h-indol-2-yl]pentanoic acid Chemical compound C([C@@H](C=1NC2=CC=C(C=C2C=1)O[Si](C(C)C)(C(C)C)C(C)C)CC(O)=O)COCC1=CC=CC=C1 JRGCJXUFDLNQOT-XMMPIXPASA-N 0.000 description 3
• PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
• MYIFLDFUXIHOCJ-UHFFFAOYSA-N 2-amino-2-[2-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]ethyl]propane-1,3-diol;hydrochloride Chemical compound Cl.C1=C(Cl)C(CCC(CO)(CO)N)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 MYIFLDFUXIHOCJ-UHFFFAOYSA-N 0.000 description 3
• FHFODVLFDCZXNM-UHFFFAOYSA-N 2-methyl-4-tri(propan-2-yl)silyloxyaniline Chemical compound CC(C)[Si](C(C)C)(C(C)C)OC1=CC=C(N)C(C)=C1 FHFODVLFDCZXNM-UHFFFAOYSA-N 0.000 description 3
• MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 3
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
• ADLVDYMTBOSDFE-UHFFFAOYSA-N 5-chloro-6-nitroisoindole-1,3-dione Chemical class C1=C(Cl)C([N+](=O)[O-])=CC2=C1C(=O)NC2=O ADLVDYMTBOSDFE-UHFFFAOYSA-N 0.000 description 3
• 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
• 229920002261 Corn starch Polymers 0.000 description 3
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
• CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
• XXRCUYVCPSWGCC-UHFFFAOYSA-N Ethyl pyruvate Chemical compound CCOC(=O)C(C)=O XXRCUYVCPSWGCC-UHFFFAOYSA-N 0.000 description 3
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
• 206010062016 Immunosuppression Diseases 0.000 description 3
• PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-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
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
• 240000007472 Leucaena leucocephala Species 0.000 description 3
• 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 102000002233 Myelin-Oligodendrocyte Glycoprotein Human genes 0.000 description 3
• 108010000123 Myelin-Oligodendrocyte Glycoprotein Proteins 0.000 description 3
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
• 210000001744 T-lymphocyte Anatomy 0.000 description 3
• 208000025865 Ulcer Diseases 0.000 description 3
• 208000036142 Viral infection Diseases 0.000 description 3
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 230000004913 activation Effects 0.000 description 3
• 239000000654 additive Substances 0.000 description 3
• 235000019270 ammonium chloride Nutrition 0.000 description 3
• 125000003118 aryl group Chemical group 0.000 description 3
• 210000003719 b-lymphocyte Anatomy 0.000 description 3
• 230000006399 behavior Effects 0.000 description 3
• BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 3
• 239000011230 binding agent Substances 0.000 description 3
• 230000036471 bradycardia Effects 0.000 description 3
• 208000006218 bradycardia Diseases 0.000 description 3
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
• 239000001768 carboxy methyl cellulose Substances 0.000 description 3
• 230000001413 cellular effect Effects 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 208000010247 contact dermatitis Diseases 0.000 description 3
• 239000008120 corn starch Substances 0.000 description 3
• 239000006071 cream Substances 0.000 description 3
• 239000013058 crude material Substances 0.000 description 3
• 229960004397 cyclophosphamide Drugs 0.000 description 3
• 230000034994 death Effects 0.000 description 3
• 230000006735 deficit Effects 0.000 description 3
• 238000003795 desorption Methods 0.000 description 3
• 229910052805 deuterium Inorganic materials 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 238000004821 distillation Methods 0.000 description 3
• 150000002148 esters Chemical group 0.000 description 3
• DCIFXYFKVKDOLL-UHFFFAOYSA-N ethyl 5-phenylmethoxy-1h-indole-2-carboxylate Chemical compound C=1C=C2NC(C(=O)OCC)=CC2=CC=1OCC1=CC=CC=C1 DCIFXYFKVKDOLL-UHFFFAOYSA-N 0.000 description 3
• 208000012997 experimental autoimmune encephalomyelitis Diseases 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 235000019253 formic acid Nutrition 0.000 description 3
• 239000000499 gel Substances 0.000 description 3
• 239000008273 gelatin Substances 0.000 description 3
• 238000003384 imaging method Methods 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 230000028993 immune response Effects 0.000 description 3
• 230000001861 immunosuppressant effect Effects 0.000 description 3
• 229940125721 immunosuppressive agent Drugs 0.000 description 3
• 238000000338 in vitro Methods 0.000 description 3
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 3
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 230000003993 interaction Effects 0.000 description 3
• 229960002725 isoflurane Drugs 0.000 description 3
• 238000002955 isolation Methods 0.000 description 3
• 210000002510 keratinocyte Anatomy 0.000 description 3
• 150000002576 ketones Chemical group 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000012280 lithium aluminium hydride Substances 0.000 description 3
• 210000003141 lower extremity Anatomy 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 210000003563 lymphoid tissue Anatomy 0.000 description 3
• 230000014759 maintenance of location Effects 0.000 description 3
• RLGONGIXQTVGGO-RUZDIDTESA-N methyl (3r)-5-phenylmethoxy-3-[5-tri(propan-2-yl)silyloxy-1h-indol-2-yl]pentanoate Chemical compound C([C@H](CC(=O)OC)C=1NC2=CC=C(O[Si](C(C)C)(C(C)C)C(C)C)C=C2C=1)COCC1=CC=CC=C1 RLGONGIXQTVGGO-RUZDIDTESA-N 0.000 description 3
• 230000000813 microbial effect Effects 0.000 description 3
• 230000005012 migration Effects 0.000 description 3
• 238000013508 migration Methods 0.000 description 3
• 231100000252 nontoxic Toxicity 0.000 description 3
• 230000003000 nontoxic effect Effects 0.000 description 3
• 210000004248 oligodendroglia Anatomy 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 239000006072 paste Substances 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• WQKGAJDYBZOFSR-UHFFFAOYSA-N potassium;propan-2-olate Chemical compound [K+].CC(C)[O-] WQKGAJDYBZOFSR-UHFFFAOYSA-N 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 238000009097 single-agent therapy Methods 0.000 description 3
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
• 235000019345 sodium thiosulphate Nutrition 0.000 description 3
• 238000013222 sprague-dawley male rat Methods 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• 230000009885 systemic effect Effects 0.000 description 3
• PAYQDIFQSGVMNY-SDXDJHTJSA-N tert-butyl (2z)-2-(6-phenylmethoxy-1,2-dihydropyrrolo[1,2-a]indol-3-ylidene)acetate Chemical compound CC(C)(C)OC(=O)\C=C1\CCN(C2=CC=3)C1=CC2=CC=3OCC1=CC=CC=C1 PAYQDIFQSGVMNY-SDXDJHTJSA-N 0.000 description 3
• 238000012546 transfer Methods 0.000 description 3
• 230000036269 ulceration Effects 0.000 description 3
• 230000009385 viral infection Effects 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
• UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
• RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 2
• IVSZLXZYQVIEFR-UHFFFAOYSA-N 1,3-Dimethylbenzene Natural products CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 description 2
• OKXVARYIKDXAEO-UHFFFAOYSA-N 2,3,3-trimethylbutan-2-ol Chemical compound CC(C)(C)C(C)(C)O OKXVARYIKDXAEO-UHFFFAOYSA-N 0.000 description 2
• IKECULIHBUCAKR-UHFFFAOYSA-N 2,3-dimethylbutan-2-ol Chemical compound CC(C)C(C)(C)O IKECULIHBUCAKR-UHFFFAOYSA-N 0.000 description 2
• XKIRHOWVQWCYBT-UHFFFAOYSA-N 3-ethylpentan-3-ol Chemical compound CCC(O)(CC)CC XKIRHOWVQWCYBT-UHFFFAOYSA-N 0.000 description 2
• OYMNPJXKQVTQTR-UHFFFAOYSA-N 5-[4-phenyl-5-(trifluoromethyl)-2-thiophenyl]-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C=1SC(C=2ON=C(N=2)C=2C=C(C=CC=2)C(F)(F)F)=CC=1C1=CC=CC=C1 OYMNPJXKQVTQTR-UHFFFAOYSA-N 0.000 description 2
• KGYXZUGVROUFOU-UHFFFAOYSA-N 6-phenylmethoxy-1,2-dihydropyrrolo[1,2-a]indol-3-one Chemical compound O=C1CCN(C2=CC=3)C1=CC2=CC=3OCC1=CC=CC=C1 KGYXZUGVROUFOU-UHFFFAOYSA-N 0.000 description 2
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
• 208000030090 Acute Disease Diseases 0.000 description 2
• 241000416162 Astragalus gummifer Species 0.000 description 2
• 208000034172 Autoimmune Experimental Myasthenia Gravis Diseases 0.000 description 2
• 206010064539 Autoimmune myocarditis Diseases 0.000 description 2
• 241000283690 Bos taurus Species 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• GATVIKZLVQHOMN-UHFFFAOYSA-N Chlorodibromomethane Chemical compound ClC(Br)Br GATVIKZLVQHOMN-UHFFFAOYSA-N 0.000 description 2
• 208000017667 Chronic Disease Diseases 0.000 description 2
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
• 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• 206010061818 Disease progression Diseases 0.000 description 2
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
• JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 2
• YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
• HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 2
• 241000282326 Felis catus Species 0.000 description 2
• XPDWGBQVDMORPB-UHFFFAOYSA-N Fluoroform Chemical compound FC(F)F XPDWGBQVDMORPB-UHFFFAOYSA-N 0.000 description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
• 241000589602 Francisella tularensis Species 0.000 description 2
• 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 2
• 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 2
• 208000009329 Graft vs Host Disease Diseases 0.000 description 2
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
• TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
• 241000187479 Mycobacterium tuberculosis Species 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 206010029260 Neuroblastoma Diseases 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• 235000019502 Orange oil Nutrition 0.000 description 2
• URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
• 108010081690 Pertussis Toxin Proteins 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
• 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
• 241000700157 Rattus norvegicus Species 0.000 description 2
• 208000007400 Relapsing-Remitting Multiple Sclerosis Diseases 0.000 description 2
• 206010040047 Sepsis Diseases 0.000 description 2
• 101710155457 Sphingosine 1-phosphate receptor 3 Proteins 0.000 description 2
• 102100025747 Sphingosine 1-phosphate receptor 3 Human genes 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 229930006000 Sucrose Natural products 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
• 230000006044 T cell activation Effects 0.000 description 2
• ZWZUFQPXYVYAFO-UHFFFAOYSA-N Tert-butyl (triphenylphosphoranylidene)acetate Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OC(C)(C)C)C1=CC=CC=C1 ZWZUFQPXYVYAFO-UHFFFAOYSA-N 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 208000030886 Traumatic Brain injury Diseases 0.000 description 2
• IOPQYDKQISFMJI-UHFFFAOYSA-N [1-[2-bis(4-methylphenyl)phosphanylnaphthalen-1-yl]naphthalen-2-yl]-bis(4-methylphenyl)phosphane Chemical group C1=CC(C)=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC(C)=CC=1)C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 IOPQYDKQISFMJI-UHFFFAOYSA-N 0.000 description 2
• JSFGZPUFCTXDJY-UHFFFAOYSA-N [2-[4-[bis(4-fluorophenyl)methyl]piperazin-1-yl]phenyl]methanol Chemical compound OCC1=CC=CC=C1N1CCN(C(C=2C=CC(F)=CC=2)C=2C=CC(F)=CC=2)CC1 JSFGZPUFCTXDJY-UHFFFAOYSA-N 0.000 description 2
• RZZDRSHFIVOQAF-UHFFFAOYSA-N [4-(5-diphenylphosphanyl-1,3-benzodioxol-4-yl)-1,3-benzodioxol-5-yl]-diphenylphosphane Chemical compound C=12OCOC2=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1C1=C2OCOC2=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RZZDRSHFIVOQAF-UHFFFAOYSA-N 0.000 description 2
• KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 2
• 239000013543 active substance Substances 0.000 description 2
• 150000001299 aldehydes Chemical group 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 150000004982 aromatic amines Chemical class 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 230000004888 barrier function Effects 0.000 description 2
• 238000009835 boiling Methods 0.000 description 2
• 210000000988 bone and bone Anatomy 0.000 description 2
• JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 2
• DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 2
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
• 229910000024 caesium carbonate Inorganic materials 0.000 description 2
• VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 229910002091 carbon monoxide Inorganic materials 0.000 description 2
• 238000006555 catalytic reaction Methods 0.000 description 2
• 210000004534 cecum Anatomy 0.000 description 2
• 229920002678 cellulose Polymers 0.000 description 2
• 239000001913 cellulose Substances 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• KQIADDMXRMTWHZ-UHFFFAOYSA-N chloro-tri(propan-2-yl)silane Chemical compound CC(C)[Si](Cl)(C(C)C)C(C)C KQIADDMXRMTWHZ-UHFFFAOYSA-N 0.000 description 2
• MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
• 238000004587 chromatography analysis Methods 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 229910052802 copper Inorganic materials 0.000 description 2
• OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
• 239000010779 crude oil Substances 0.000 description 2
• DMEGYFMYUHOHGS-UHFFFAOYSA-N cycloheptane Chemical compound C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
• 230000003247 decreasing effect Effects 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• 239000012954 diazonium Substances 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 230000005750 disease progression Effects 0.000 description 2
• 239000006185 dispersion Substances 0.000 description 2
• 239000003995 emulsifying agent Substances 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• XGSPICCWSLPBOA-SAPNQHFASA-N ethyl (2e)-2-(6-phenylmethoxy-1,2-dihydropyrrolo[1,2-a]indol-3-ylidene)acetate Chemical compound CCOC(=O)\C=C1/CCN(C2=CC=3)C1=CC2=CC=3OCC1=CC=CC=C1 XGSPICCWSLPBOA-SAPNQHFASA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 229960005167 everolimus Drugs 0.000 description 2
• 238000013213 extrapolation Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 2
• 229960000556 fingolimod Drugs 0.000 description 2
• KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 2
• 235000019634 flavors Nutrition 0.000 description 2
• 238000000684 flow cytometry Methods 0.000 description 2
• 238000002866 fluorescence resonance energy transfer Methods 0.000 description 2
• 238000011010 flushing procedure Methods 0.000 description 2
• 238000010575 fractional recrystallization Methods 0.000 description 2
• 229940118764 francisella tularensis Drugs 0.000 description 2
• 230000006870 function Effects 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 208000024908 graft versus host disease Diseases 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• ZQBFAOFFOQMSGJ-UHFFFAOYSA-N hexafluorobenzene Chemical compound FC1=C(F)C(F)=C(F)C(F)=C1F ZQBFAOFFOQMSGJ-UHFFFAOYSA-N 0.000 description 2
• 238000004128 high performance liquid chromatography Methods 0.000 description 2
• 230000036571 hydration Effects 0.000 description 2
• 238000006703 hydration reaction Methods 0.000 description 2
• 150000002431 hydrogen Chemical class 0.000 description 2
• 238000002649 immunization Methods 0.000 description 2
• 230000003053 immunization Effects 0.000 description 2
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
• 125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 239000003112 inhibitor Substances 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 230000000977 initiatory effect Effects 0.000 description 2
• 238000007689 inspection Methods 0.000 description 2
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
• 238000002372 labelling Methods 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 150000002596 lactones Chemical group 0.000 description 2
• 230000003902 lesion Effects 0.000 description 2
• 230000000670 limiting effect Effects 0.000 description 2
• HAUKUGBTJXWQMF-UHFFFAOYSA-N lithium;propan-2-olate Chemical compound [Li+].CC(C)[O-] HAUKUGBTJXWQMF-UHFFFAOYSA-N 0.000 description 2
• 208000020442 loss of weight Diseases 0.000 description 2
• 239000006210 lotion Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 239000012139 lysis buffer Substances 0.000 description 2
• 229940124302 mTOR inhibitor Drugs 0.000 description 2
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 2
• 229910052987 metal hydride Inorganic materials 0.000 description 2
• 150000004681 metal hydrides Chemical class 0.000 description 2
• 206010061289 metastatic neoplasm Diseases 0.000 description 2
• DZEGAPVTLIWRND-GOSISDBHSA-N methyl (3r)-5-hydroxy-3-[5-tri(propan-2-yl)silyloxy-1h-indol-2-yl]pentanoate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OC1=CC=C2NC([C@H](CCO)CC(=O)OC)=CC2=C1 DZEGAPVTLIWRND-GOSISDBHSA-N 0.000 description 2
• UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 210000001616 monocyte Anatomy 0.000 description 2
• RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 2
• HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 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
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 210000003928 nasal cavity Anatomy 0.000 description 2
• 239000006199 nebulizer Substances 0.000 description 2
• KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 2
• 230000007935 neutral effect Effects 0.000 description 2
• LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
• FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 230000001019 normoglycemic effect Effects 0.000 description 2
• CTQNGGLPUBDAKN-UHFFFAOYSA-N o-dimethylbenzene Natural products CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 238000006772 olefination reaction Methods 0.000 description 2
• 239000010502 orange oil Substances 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 210000002997 osteoclast Anatomy 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 239000012188 paraffin wax Substances 0.000 description 2
• 239000006201 parenteral dosage form Substances 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• AQIXEPGDORPWBJ-UHFFFAOYSA-N pentan-3-ol Chemical compound CCC(O)CC AQIXEPGDORPWBJ-UHFFFAOYSA-N 0.000 description 2
• PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 2
• 210000005259 peripheral blood Anatomy 0.000 description 2
• 239000011886 peripheral blood Substances 0.000 description 2
• 210000001986 peyer's patch Anatomy 0.000 description 2
• 230000026731 phosphorylation Effects 0.000 description 2
• 238000006366 phosphorylation reaction Methods 0.000 description 2
• 239000006187 pill Substances 0.000 description 2
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
• 229910000027 potassium carbonate Inorganic materials 0.000 description 2
• 159000000001 potassium salts Chemical class 0.000 description 2
• BWXCFVVJEFYDOI-UHFFFAOYSA-M potassium;2-ethoxycarbonyl-6-phenylmethoxy-1h-pyrrolo[1,2-a]indol-3-olate Chemical compound [K+].C=1C=C2N3CC(C(=O)OCC)=C([O-])C3=CC2=CC=1OCC1=CC=CC=C1 BWXCFVVJEFYDOI-UHFFFAOYSA-M 0.000 description 2
• 229920001592 potato starch Polymers 0.000 description 2
• 230000001376 precipitating effect Effects 0.000 description 2
• 230000035755 proliferation Effects 0.000 description 2
• 239000003380 propellant Substances 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• 230000001681 protective effect Effects 0.000 description 2
• 239000003586 protic polar solvent Substances 0.000 description 2
• 238000010791 quenching Methods 0.000 description 2
• 230000000171 quenching effect Effects 0.000 description 2
• 150000003254 radicals Chemical class 0.000 description 2
• 239000000700 radioactive tracer Substances 0.000 description 2
• 210000002345 respiratory system Anatomy 0.000 description 2
• 239000004576 sand Substances 0.000 description 2
• 230000009919 sequestration Effects 0.000 description 2
• 229910000029 sodium carbonate Inorganic materials 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
• WBQTXTBONIWRGK-UHFFFAOYSA-N sodium;propan-2-olate Chemical compound [Na+].CC(C)[O-] WBQTXTBONIWRGK-UHFFFAOYSA-N 0.000 description 2
• 239000012265 solid product Substances 0.000 description 2
• 230000000087 stabilizing effect Effects 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 230000000707 stereoselective effect Effects 0.000 description 2
• 238000006467 substitution reaction Methods 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 239000011885 synergistic combination Substances 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 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 2
• PQNCLOJYIDOBOK-PKTZIBPZSA-N tert-butyl (3r)-3-[(4s)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]-5-phenylmethoxypentanoate Chemical compound C([C@H](CC(=O)OC(C)(C)C)C(=O)N1C(OC[C@@H]1CC=1C=CC=CC=1)=O)COCC1=CC=CC=C1 PQNCLOJYIDOBOK-PKTZIBPZSA-N 0.000 description 2
• BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 2
• ZHMWFORNIXVHNI-UHFFFAOYSA-N tert-butyl n-[2-methyl-4-tri(propan-2-yl)silyloxyphenyl]carbamate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OC1=CC=C(NC(=O)OC(C)(C)C)C(C)=C1 ZHMWFORNIXVHNI-UHFFFAOYSA-N 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 238000002627 tracheal intubation Methods 0.000 description 2
• 235000010487 tragacanth Nutrition 0.000 description 2
• 239000000196 tragacanth Substances 0.000 description 2
• 229940116362 tragacanth Drugs 0.000 description 2
• 230000001052 transient effect Effects 0.000 description 2
• 230000009529 traumatic brain injury Effects 0.000 description 2
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 2
• GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 2
• CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
• 230000004614 tumor growth Effects 0.000 description 2
• NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• 230000003442 weekly effect Effects 0.000 description 2
• 239000000080 wetting agent Substances 0.000 description 2
• FMCGSUUBYTWNDP-ONGXEEELSA-N (1R,2S)-2-(dimethylamino)-1-phenyl-1-propanol Chemical compound CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 FMCGSUUBYTWNDP-ONGXEEELSA-N 0.000 description 1
• QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
• ZZMYWYZPNZRYPX-SANMLTNESA-N (2r)-2-amino-2-[5-[4-[2-(4-phenylphenyl)ethoxy]-3-(trifluoromethyl)phenyl]-1h-imidazol-2-yl]propan-1-ol Chemical compound N1C([C@@](N)(CO)C)=NC=C1C(C=C1C(F)(F)F)=CC=C1OCCC1=CC=C(C=2C=CC=CC=2)C=C1 ZZMYWYZPNZRYPX-SANMLTNESA-N 0.000 description 1
• DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
• RBVGOQHQBUPSGX-MOUTVQLLSA-N (2r,5r)-1-[2-[(2r,5r)-2,5-di(propan-2-yl)phospholan-1-yl]phenyl]-2,5-di(propan-2-yl)phospholane Chemical compound CC(C)[C@H]1CC[C@H](C(C)C)P1C1=CC=CC=C1P1[C@@H](C(C)C)CC[C@@H]1C(C)C RBVGOQHQBUPSGX-MOUTVQLLSA-N 0.000 description 1
• IRCDUOCGSIGEAI-AAVRWANBSA-N (2r,5r)-1-[2-[(2r,5r)-2,5-dimethylphospholan-1-yl]ethyl]-2,5-dimethylphospholane Chemical compound C[C@@H]1CC[C@@H](C)P1CCP1[C@H](C)CC[C@H]1C IRCDUOCGSIGEAI-AAVRWANBSA-N 0.000 description 1
• VHHAZLMVLLIMHT-CUPIEXAXSA-N (2s,5s)-1-[2-[(2s,5s)-2,5-diphenylphospholan-1-yl]ethyl]-2,5-diphenylphospholane Chemical compound C1([C@@H]2CC[C@H](P2CCP2[C@@H](CC[C@H]2C=2C=CC=CC=2)C=2C=CC=CC=2)C=2C=CC=CC=2)=CC=CC=C1 VHHAZLMVLLIMHT-CUPIEXAXSA-N 0.000 description 1
• RGXUCUWVGKLACF-UHFFFAOYSA-N (3-methylphenyl)methanamine Chemical compound CC1=CC=CC(CN)=C1 RGXUCUWVGKLACF-UHFFFAOYSA-N 0.000 description 1
• UFZKWTITXBRSPK-UHFFFAOYSA-N (4-phenylmethoxyphenyl)hydrazine Chemical compound C1=CC(NN)=CC=C1OCC1=CC=CC=C1 UFZKWTITXBRSPK-UHFFFAOYSA-N 0.000 description 1
• PPWAXELJUXMDJA-IBGZPJMESA-N (4s)-4-benzyl-3-(4-phenylmethoxybutanoyl)-1,3-oxazolidin-2-one Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CCCOCC1=CC=CC=C1 PPWAXELJUXMDJA-IBGZPJMESA-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
• BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
• LYHOBZAADXPPNW-UHFFFAOYSA-N (r)-xylyl-phanephos Chemical compound CC1=CC(C)=CC(P(C=2C=C(C)C=C(C)C=2)C=2C=3CCC4=CC=C(C(=C4)P(C=4C=C(C)C=C(C)C=4)C=4C=C(C)C=C(C)C=4)CCC(=CC=3)C=2)=C1 LYHOBZAADXPPNW-UHFFFAOYSA-N 0.000 description 1
• FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
• AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-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
• LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
• CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 description 1
• VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
• GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-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
• NSDBTDWOGVSEGV-UHFFFAOYSA-N 1-propan-2-yloxy-2-(trifluoromethyl)benzene Chemical compound CC(C)OC1=CC=CC=C1C(F)(F)F NSDBTDWOGVSEGV-UHFFFAOYSA-N 0.000 description 1
• 229940044613 1-propanol Drugs 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• SBASXUCJHJRPEV-UHFFFAOYSA-N 2-(2-methoxyethoxy)ethanol Chemical compound COCCOCCO SBASXUCJHJRPEV-UHFFFAOYSA-N 0.000 description 1
• UZYQSNQJLWTICD-UHFFFAOYSA-N 2-(n-benzoylanilino)-2,2-dinitroacetic acid Chemical compound C=1C=CC=CC=1N(C(C(=O)O)([N+]([O-])=O)[N+]([O-])=O)C(=O)C1=CC=CC=C1 UZYQSNQJLWTICD-UHFFFAOYSA-N 0.000 description 1
• XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
• IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 description 1
• IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 description 1
• KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
• ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
• ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
• 229940093475 2-ethoxyethanol Drugs 0.000 description 1
• GGDYAKVUZMZKRV-UHFFFAOYSA-N 2-fluoroethanol Chemical compound OCCF GGDYAKVUZMZKRV-UHFFFAOYSA-N 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• KIPMDPDAFINLIV-UHFFFAOYSA-N 2-nitroethanol Chemical compound OCC[N+]([O-])=O KIPMDPDAFINLIV-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
• XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 1
• SKYYWSWIUKISCX-UHFFFAOYSA-N 3-[[2-[4-phenyl-3-(trifluoromethyl)phenyl]-1-benzothiophen-5-yl]methylamino]propanoic acid Chemical compound C=1C2=CC(CNCCC(=O)O)=CC=C2SC=1C(C=C1C(F)(F)F)=CC=C1C1=CC=CC=C1 SKYYWSWIUKISCX-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• QGNGOGOOPUYKMC-UHFFFAOYSA-N 4-hydroxy-6-methylaniline Chemical compound CC1=CC(O)=CC=C1N QGNGOGOOPUYKMC-UHFFFAOYSA-N 0.000 description 1
• AWQSAIIDOMEEOD-UHFFFAOYSA-N 5,5-Dimethyl-4-(3-oxobutyl)dihydro-2(3H)-furanone Chemical compound CC(=O)CCC1CC(=O)OC1(C)C AWQSAIIDOMEEOD-UHFFFAOYSA-N 0.000 description 1
• HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 1
• 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 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• 241000251468 Actinopterygii Species 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 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 1
• 229910000809 Alumel Inorganic materials 0.000 description 1
• 208000024827 Alzheimer disease Diseases 0.000 description 1
• 206010002388 Angina unstable Diseases 0.000 description 1
• 208000034309 Bacterial disease carrier Diseases 0.000 description 1
• 101100191238 Caenorhabditis elegans pph-5 gene Proteins 0.000 description 1
• UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 206010007558 Cardiac failure chronic Diseases 0.000 description 1
• 206010007559 Cardiac failure congestive Diseases 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
• VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 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
• GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
• 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
• 241000283086 Equidae Species 0.000 description 1
• PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
• 241000287828 Gallus gallus Species 0.000 description 1
• 206010019280 Heart failures Diseases 0.000 description 1
• DOJXGHGHTWFZHK-UHFFFAOYSA-N Hexachloroacetone Chemical compound ClC(Cl)(Cl)C(=O)C(Cl)(Cl)Cl DOJXGHGHTWFZHK-UHFFFAOYSA-N 0.000 description 1
• 101000693265 Homo sapiens Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 0.000 description 1
• 206010065042 Immune reconstitution inflammatory syndrome Diseases 0.000 description 1
• 208000022559 Inflammatory bowel 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
• 229930064664 L-arginine Natural products 0.000 description 1
• 235000014852 L-arginine Nutrition 0.000 description 1
• 150000008535 L-arginines Chemical class 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 206010066453 Mesangioproliferative glomerulonephritis Diseases 0.000 description 1
• 229920000881 Modified starch Polymers 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 241000699667 Mus spretus Species 0.000 description 1
• HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
• FMCGSUUBYTWNDP-UHFFFAOYSA-N N-Methylephedrine Natural products CN(C)C(C)C(O)C1=CC=CC=C1 FMCGSUUBYTWNDP-UHFFFAOYSA-N 0.000 description 1
• AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
• OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-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
• 206010029155 Nephropathy toxic Diseases 0.000 description 1
• 208000028389 Nerve injury Diseases 0.000 description 1
• 206010029350 Neurotoxicity Diseases 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 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
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 208000001132 Osteoporosis Diseases 0.000 description 1
• 229920006975 PPE-P Polymers 0.000 description 1
• 208000034038 Pathologic Neovascularization Diseases 0.000 description 1
• 241001494479 Pecora Species 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 239000004820 Pressure-sensitive adhesive Substances 0.000 description 1
• 241000288906 Primates Species 0.000 description 1
• 102000016202 Proteolipids Human genes 0.000 description 1
• 108010010974 Proteolipids Proteins 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 206010057190 Respiratory tract infections Diseases 0.000 description 1
• 206010057430 Retinal injury Diseases 0.000 description 1
• 238000011803 SJL/J (JAX™ mice strain) Methods 0.000 description 1
• 244000272264 Saussurea lappa Species 0.000 description 1
• 235000006784 Saussurea lappa Nutrition 0.000 description 1
• 206010070834 Sensitisation Diseases 0.000 description 1
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
• DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
• 101710155458 Sphingosine 1-phosphate receptor 4 Proteins 0.000 description 1
• 102100029803 Sphingosine 1-phosphate receptor 4 Human genes 0.000 description 1
• 102100029802 Sphingosine 1-phosphate receptor 5 Human genes 0.000 description 1
• 101710155451 Sphingosine 1-phosphate receptor 5 Proteins 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 108700012920 TNF Proteins 0.000 description 1
• 206010049447 Tachyarrhythmia Diseases 0.000 description 1
• 208000001871 Tachycardia 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
• 206010044221 Toxic encephalopathy Diseases 0.000 description 1
• RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
• 208000034784 Tularaemia Diseases 0.000 description 1
• 208000007814 Unstable Angina Diseases 0.000 description 1
• 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
• 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
• GYKMEKRMASHMIH-VSJLXWSYSA-N [(3r,4r)-1-benzyl-4-diphenylphosphanylpyrrolidin-3-yl]-diphenylphosphane Chemical compound C=1C=CC=CC=1P([C@H]1[C@@H](CN(C1)CC=1C=CC=CC=1)P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 GYKMEKRMASHMIH-VSJLXWSYSA-N 0.000 description 1
• DTMVLPFJTUJZAY-UHFFFAOYSA-N [2-[2-bis(4-methylphenyl)phosphanyl-6-methoxyphenyl]-3-methoxyphenyl]-bis(4-methylphenyl)phosphane Chemical group COC=1C=CC=C(P(C=2C=CC(C)=CC=2)C=2C=CC(C)=CC=2)C=1C=1C(OC)=CC=CC=1P(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 DTMVLPFJTUJZAY-UHFFFAOYSA-N 0.000 description 1
• PCBOWMZAEDDKNH-HOTGVXAUSA-N [4-(trifluoromethoxy)phenyl]methyl (3as,6as)-2-(3-fluoro-4-sulfamoylbenzoyl)-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxylate Chemical compound C1=C(F)C(S(=O)(=O)N)=CC=C1C(=O)N1C[C@H]2CN(C(=O)OCC=3C=CC(OC(F)(F)F)=CC=3)C[C@@H]2C1 PCBOWMZAEDDKNH-HOTGVXAUSA-N 0.000 description 1
• XJJVPYMFHXMROQ-UHFFFAOYSA-N [4-[5-bis(3,5-dimethylphenyl)phosphanyl-1,3-benzodioxol-4-yl]-1,3-benzodioxol-5-yl]-bis(3,5-dimethylphenyl)phosphane Chemical compound CC1=CC(C)=CC(P(C=2C=C(C)C=C(C)C=2)C=2C(=C3OCOC3=CC=2)C=2C(=CC=C3OCOC3=2)P(C=2C=C(C)C=C(C)C=2)C=2C=C(C)C=C(C)C=2)=C1 XJJVPYMFHXMROQ-UHFFFAOYSA-N 0.000 description 1
• 206010000059 abdominal discomfort Diseases 0.000 description 1
• 230000003187 abdominal effect Effects 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 239000008186 active pharmaceutical agent Substances 0.000 description 1
• 206010069351 acute lung injury Diseases 0.000 description 1
• 206010000891 acute myocardial infarction Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 208000037883 airway inflammation Diseases 0.000 description 1
• 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
• OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-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
• VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
• 239000003708 ampul Substances 0.000 description 1
• 230000008485 antagonism Effects 0.000 description 1
• 230000003110 anti-inflammatory effect Effects 0.000 description 1
• 230000000840 anti-viral effect Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000013011 aqueous formulation Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 239000008135 aqueous vehicle Substances 0.000 description 1
• 206010003119 arrhythmia Diseases 0.000 description 1
• 230000006793 arrhythmia Effects 0.000 description 1
• 235000021311 artificial sweeteners Nutrition 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 201000004982 autoimmune uveitis Diseases 0.000 description 1
• 210000001142 back Anatomy 0.000 description 1
• LFYJSSARVMHQJB-QIXNEVBVSA-N bakuchiol Chemical compound CC(C)=CCC[C@@](C)(C=C)\C=C\C1=CC=C(O)C=C1 LFYJSSARVMHQJB-QIXNEVBVSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 229940092714 benzenesulfonic acid Drugs 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 1
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000036983 biotransformation Effects 0.000 description 1
• 239000004305 biphenyl Substances 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• 125000001246 bromo group Chemical group Br* 0.000 description 1
• FMWLUWPQPKEARP-UHFFFAOYSA-N bromodichloromethane Chemical compound ClC(Cl)Br FMWLUWPQPKEARP-UHFFFAOYSA-N 0.000 description 1
• 229950005228 bromoform Drugs 0.000 description 1
• RJCQBQGAPKAMLL-UHFFFAOYSA-N bromotrifluoromethane Chemical compound FC(F)(F)Br RJCQBQGAPKAMLL-UHFFFAOYSA-N 0.000 description 1
• 230000010083 bronchial hyperresponsiveness Effects 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 244000309464 bull Species 0.000 description 1
• LUEHNHVFDCZTGL-UHFFFAOYSA-N but-2-ynoic acid Chemical compound CC#CC(O)=O LUEHNHVFDCZTGL-UHFFFAOYSA-N 0.000 description 1
• PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 1
• 229940046731 calcineurin inhibitors Drugs 0.000 description 1
• 239000001110 calcium chloride Substances 0.000 description 1
• 229910001628 calcium chloride Inorganic materials 0.000 description 1
• HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 125000004432 carbon atom Chemical group C* 0.000 description 1
• 235000011089 carbon dioxide Nutrition 0.000 description 1
• 150000001723 carbon free-radicals Chemical class 0.000 description 1
• 150000007942 carboxylates Chemical group 0.000 description 1
• 238000012754 cardiac puncture Methods 0.000 description 1
• 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
• 238000007675 cardiac surgery Methods 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000010531 catalytic reduction reaction Methods 0.000 description 1
• 235000013330 chicken meat Nutrition 0.000 description 1
• 239000012069 chiral reagent Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 0.000 description 1
• 125000004775 chlorodifluoromethyl group Chemical group FC(F)(Cl)* 0.000 description 1
• AFYPFACVUDMOHA-UHFFFAOYSA-N chlorotrifluoromethane Chemical compound FC(F)(F)Cl AFYPFACVUDMOHA-UHFFFAOYSA-N 0.000 description 1
• VIRRLEDAYYYTOD-YHEOSNBFSA-N colforsin daropate hydrochloride Chemical compound Cl.O[C@H]([C@@]12C)CCC(C)(C)[C@@H]1[C@H](OC(=O)CCN(C)C)[C@H](OC(C)=O)[C@]1(C)[C@]2(O)C(=O)C[C@](C)(C=C)O1 VIRRLEDAYYYTOD-YHEOSNBFSA-N 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 239000012230 colorless oil Substances 0.000 description 1
• 238000002967 competitive immunoassay Methods 0.000 description 1
• 239000000306 component Substances 0.000 description 1
• 230000001010 compromised effect Effects 0.000 description 1
• NWFNSTOSIVLCJA-UHFFFAOYSA-L copper;diacetate;hydrate Chemical compound O.[Cu+2].CC([O-])=O.CC([O-])=O NWFNSTOSIVLCJA-UHFFFAOYSA-L 0.000 description 1
• KVBHFBAACGHMKE-UHFFFAOYSA-N copper;triphenylphosphane Chemical compound [Cu].[Cu].[Cu].[Cu].[Cu].[Cu].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 KVBHFBAACGHMKE-UHFFFAOYSA-N 0.000 description 1
• 208000029078 coronary artery disease Diseases 0.000 description 1
• 238000002447 crystallographic data Methods 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
• HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 150000003946 cyclohexylamines Chemical class 0.000 description 1
• HGTBZFMPHBAUCQ-KHZPMNTOSA-N cyclopentane;dicyclohexyl-[(1r)-1-(2-diphenylphosphanylcyclopentyl)ethyl]phosphane;iron Chemical compound [Fe].[CH]1[CH][CH][CH][CH]1.[C]1([C@@H](C)P(C2CCCCC2)C2CCCCC2)[CH][CH][CH][C]1P(C=1C=CC=CC=1)C1=CC=CC=C1 HGTBZFMPHBAUCQ-KHZPMNTOSA-N 0.000 description 1
• PWOQRKCAHTVFLB-UHFFFAOYSA-N cyclophosphamide hydrate Chemical compound O.ClCCN(CCCl)P1(=O)NCCCO1 PWOQRKCAHTVFLB-UHFFFAOYSA-N 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
• 238000006731 degradation reaction Methods 0.000 description 1
• 230000018044 dehydration Effects 0.000 description 1
• 238000006297 dehydration reaction Methods 0.000 description 1
• 230000002939 deleterious effect Effects 0.000 description 1
• 210000004443 dendritic cell Anatomy 0.000 description 1
• 238000004807 desolvation Methods 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 150000001989 diazonium salts Chemical class 0.000 description 1
• FJBFPHVGVWTDIP-UHFFFAOYSA-N dibromomethane Chemical compound BrCBr FJBFPHVGVWTDIP-UHFFFAOYSA-N 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
• UMNKXPULIDJLSU-UHFFFAOYSA-N dichlorofluoromethane Chemical compound FC(Cl)Cl UMNKXPULIDJLSU-UHFFFAOYSA-N 0.000 description 1
• 229940099364 dichlorofluoromethane Drugs 0.000 description 1
• 229940019778 diethylene glycol diethyl ether Drugs 0.000 description 1
• XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
• 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
• NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 description 1
• LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
• 230000009266 disease activity Effects 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
• GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 description 1
• 239000000890 drug combination Substances 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 229940112141 dry powder inhaler Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000005293 duran Substances 0.000 description 1
• 239000008157 edible vegetable oil Substances 0.000 description 1
• 238000010828 elution Methods 0.000 description 1
• 239000012156 elution solvent Substances 0.000 description 1
• 210000003038 endothelium Anatomy 0.000 description 1
• 210000003989 endothelium vascular Anatomy 0.000 description 1
• 239000003623 enhancer Substances 0.000 description 1
• 230000002708 enhancing effect Effects 0.000 description 1
• 229960002179 ephedrine Drugs 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 239000004210 ether based solvent Substances 0.000 description 1
• PJXAKKBUQNISBA-QGZVFWFLSA-N ethyl 2-[(3r)-4-chloro-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound C([C@@H]1CC(=O)OCC)CN(C2=CC=3)C1=C(Cl)C2=CC=3OCC1=CC=C(OC(C)C)C(C(F)(F)F)=C1 PJXAKKBUQNISBA-QGZVFWFLSA-N 0.000 description 1
• VAXORWFYUXIOSD-GOSISDBHSA-N ethyl 2-[(3r)-6-[[4-propan-2-yloxy-3-(trifluoromethyl)phenyl]methoxy]-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound C([C@@H]1CC(=O)OCC)CN(C2=CC=3)C1=CC2=CC=3OCC1=CC=C(OC(C)C)C(C(F)(F)F)=C1 VAXORWFYUXIOSD-GOSISDBHSA-N 0.000 description 1
• DUTGBYUBOSRSDQ-QGZVFWFLSA-N ethyl 2-[(3r)-6-phenylmethoxy-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound C([C@@H]1CC(=O)OCC)CN(C2=CC=3)C1=CC2=CC=3OCC1=CC=CC=C1 DUTGBYUBOSRSDQ-QGZVFWFLSA-N 0.000 description 1
• PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 1
• 229940117360 ethyl pyruvate Drugs 0.000 description 1
• 230000008020 evaporation Effects 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 150000004665 fatty acids Chemical class 0.000 description 1
• 239000012997 ficoll-paque Substances 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
• 239000006260 foam Substances 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
• 150000004160 forskolin derivatives Chemical class 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 238000007710 freezing Methods 0.000 description 1
• 230000008014 freezing Effects 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 239000003349 gelling agent Substances 0.000 description 1
• 210000003780 hair follicle Anatomy 0.000 description 1
• 125000005843 halogen group Chemical group 0.000 description 1
• 230000002439 hemostatic effect Effects 0.000 description 1
• 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
• 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
• 125000005241 heteroarylamino group Chemical group 0.000 description 1
• WMIYKQLTONQJES-UHFFFAOYSA-N hexafluoroethane Chemical compound FC(F)(F)C(F)(F)F WMIYKQLTONQJES-UHFFFAOYSA-N 0.000 description 1
• GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
• 238000002017 high-resolution X-ray diffraction Methods 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• 239000012456 homogeneous solution Substances 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• OVNUPJXMCMTQCN-UHFFFAOYSA-N hydron;(4-phenylmethoxyphenyl)hydrazine;chloride Chemical compound Cl.C1=CC(NN)=CC=C1OCC1=CC=CC=C1 OVNUPJXMCMTQCN-UHFFFAOYSA-N 0.000 description 1
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 239000005457 ice water Substances 0.000 description 1
• 210000000987 immune system Anatomy 0.000 description 1
• 239000012535 impurity Substances 0.000 description 1
• 239000005414 inactive ingredient Substances 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 229910052738 indium Inorganic materials 0.000 description 1
• APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 208000014674 injury Diseases 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 201000004332 intermediate coronary syndrome Diseases 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000011835 investigation Methods 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
• 210000004153 islets of langerhan Anatomy 0.000 description 1
• ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
• 229940011051 isopropyl acetate Drugs 0.000 description 1
• ULYZAYCEDJDHCC-UHFFFAOYSA-N isopropyl chloride Chemical compound CC(C)Cl ULYZAYCEDJDHCC-UHFFFAOYSA-N 0.000 description 1
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
• 239000004310 lactic acid Substances 0.000 description 1
• 235000014655 lactic acid Nutrition 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
• 238000011694 lewis rat Methods 0.000 description 1
• AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
• 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 1
• XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
• 229910052808 lithium carbonate Inorganic materials 0.000 description 1
• 229910000103 lithium hydride Inorganic materials 0.000 description 1
• 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
• LZWQNOHZMQIFBX-UHFFFAOYSA-N lithium;2-methylpropan-2-olate Chemical compound [Li+].CC(C)(C)[O-] LZWQNOHZMQIFBX-UHFFFAOYSA-N 0.000 description 1
• WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 229910001629 magnesium chloride Inorganic materials 0.000 description 1
• 238000002595 magnetic resonance imaging Methods 0.000 description 1
• 239000001630 malic acid Substances 0.000 description 1
• 235000011090 malic acid Nutrition 0.000 description 1
• 229960002510 mandelic acid Drugs 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 210000005015 mediastinal lymph node Anatomy 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 108020004999 messenger RNA Proteins 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• 239000002207 metabolite Substances 0.000 description 1
• 230000001394 metastastic effect Effects 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 description 1
• 238000007069 methylation reaction Methods 0.000 description 1
• HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
• 238000002406 microsurgery Methods 0.000 description 1
• 230000001617 migratory effect Effects 0.000 description 1
• 230000004079 mineral homeostasis Effects 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 238000002156 mixing Methods 0.000 description 1
• 235000019426 modified starch Nutrition 0.000 description 1
• PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 229960004866 mycophenolate mofetil Drugs 0.000 description 1
• 229960000951 mycophenolic acid Drugs 0.000 description 1
• HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical group OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
• MBHINSULENHCMF-UHFFFAOYSA-N n,n-dimethylpropanamide Chemical compound CCC(=O)N(C)C MBHINSULENHCMF-UHFFFAOYSA-N 0.000 description 1
• AGVKXDPPPSLISR-UHFFFAOYSA-N n-ethylcyclohexanamine Chemical compound CCNC1CCCCC1 AGVKXDPPPSLISR-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 229940073569 n-methylephedrine Drugs 0.000 description 1
• 235000021096 natural sweeteners Nutrition 0.000 description 1
• 230000001338 necrotic effect Effects 0.000 description 1
• 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 231100000417 nephrotoxicity Toxicity 0.000 description 1
• 230000007694 nephrotoxicity Effects 0.000 description 1
• 230000008764 nerve damage Effects 0.000 description 1
• 210000001178 neural stem cell Anatomy 0.000 description 1
• 208000004296 neuralgia Diseases 0.000 description 1
• 210000004498 neuroglial cell Anatomy 0.000 description 1
• 208000021722 neuropathic pain Diseases 0.000 description 1
• 231100000228 neurotoxicity Toxicity 0.000 description 1
• 230000007135 neurotoxicity Effects 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
• 230000003040 nociceptive effect Effects 0.000 description 1
• ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 1
• 239000002687 nonaqueous vehicle Substances 0.000 description 1
• BKIMMITUMNQMOS-UHFFFAOYSA-N normal nonane Natural products CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 1
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-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
• 238000009806 oophorectomy Methods 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 150000002894 organic compounds Chemical class 0.000 description 1
• 239000001301 oxygen Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 238000005192 partition Methods 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000009963 pathologic angiogenesis Effects 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
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• JYVLIDXNZAXMDK-UHFFFAOYSA-N pentan-2-ol Chemical compound CCCC(C)O JYVLIDXNZAXMDK-UHFFFAOYSA-N 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 230000002085 persistent effect Effects 0.000 description 1
• 239000008177 pharmaceutical agent Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 238000009521 phase II clinical trial Methods 0.000 description 1
• 238000005191 phase separation Methods 0.000 description 1
• 150000002989 phenols Chemical class 0.000 description 1
• BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
• 229960000395 phenylpropanolamine Drugs 0.000 description 1
• 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 239000013641 positive control Substances 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
• NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
• 229910000105 potassium hydride Inorganic materials 0.000 description 1
• GFHWKFUEQXUQSH-UHFFFAOYSA-N potassium;2,3,3-trimethylbutan-2-olate Chemical compound [K+].CC(C)(C)C(C)(C)[O-] GFHWKFUEQXUQSH-UHFFFAOYSA-N 0.000 description 1
• JKRFRMNOJLUTIG-UHFFFAOYSA-N potassium;2,3-dimethylbutan-2-olate Chemical compound [K+].CC(C)C(C)(C)[O-] JKRFRMNOJLUTIG-UHFFFAOYSA-N 0.000 description 1
• ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical compound [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 description 1
• LZDGSLFCXXQIQC-UHFFFAOYSA-N potassium;3-ethylpentan-3-olate Chemical compound [K+].CCC([O-])(CC)CC LZDGSLFCXXQIQC-UHFFFAOYSA-N 0.000 description 1
• IFHDBUXKDXSYNU-UHFFFAOYSA-N potassium;3-methylpentan-3-olate Chemical compound [K+].CCC(C)([O-])CC IFHDBUXKDXSYNU-UHFFFAOYSA-N 0.000 description 1
• CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
• 230000002335 preservative effect Effects 0.000 description 1
• 230000003449 preventive effect Effects 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 239000011241 protective layer Substances 0.000 description 1
• 238000011403 purification operation Methods 0.000 description 1
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
• 230000005855 radiation Effects 0.000 description 1
• 239000000376 reactant Substances 0.000 description 1
• 238000011084 recovery Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000013557 residual solvent Substances 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
• 229950005741 rolipram Drugs 0.000 description 1
• 238000007423 screening assay Methods 0.000 description 1
• 238000007789 sealing Methods 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 230000008313 sensitization Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000000377 silicon dioxide Substances 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012312 sodium hydride Substances 0.000 description 1
• 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
• 159000000000 sodium salts Chemical class 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 235000010265 sodium sulphite Nutrition 0.000 description 1
• DGPIGKCOQYBCJH-UHFFFAOYSA-M sodium;acetic acid;hydroxide Chemical compound O.[Na+].CC([O-])=O DGPIGKCOQYBCJH-UHFFFAOYSA-M 0.000 description 1
• SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
• 238000003836 solid-state method Methods 0.000 description 1
• 238000002798 spectrophotometry method Methods 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 208000020431 spinal cord injury Diseases 0.000 description 1
• 238000009987 spinning Methods 0.000 description 1
• 210000000952 spleen Anatomy 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
• 229910052717 sulfur Inorganic materials 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000002278 tabletting lubricant Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• PAYQDIFQSGVMNY-OBGWFSINSA-N tert-butyl (2e)-2-(6-phenylmethoxy-1,2-dihydropyrrolo[1,2-a]indol-3-ylidene)acetate Chemical compound CC(C)(C)OC(=O)\C=C1/CCN(C2=CC=3)C1=CC2=CC=3OCC1=CC=CC=C1 PAYQDIFQSGVMNY-OBGWFSINSA-N 0.000 description 1
• NZCINCUYJNEEPZ-GOSISDBHSA-N tert-butyl 2-[(3r)-6-phenylmethoxy-2,3-dihydro-1h-pyrrolo[1,2-a]indol-3-yl]acetate Chemical compound C([C@@H]1CC(=O)OC(C)(C)C)CN(C2=CC=3)C1=CC2=CC=3OCC1=CC=CC=C1 NZCINCUYJNEEPZ-GOSISDBHSA-N 0.000 description 1
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 231100000027 toxicology Toxicity 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 230000032258 transport Effects 0.000 description 1
• 230000008733 trauma Effects 0.000 description 1
• 229940029284 trichlorofluoromethane Drugs 0.000 description 1
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
• YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 1
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 1
• FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
• 230000008728 vascular permeability Effects 0.000 description 1
• 210000005166 vasculature Anatomy 0.000 description 1
• 229940099259 vaseline Drugs 0.000 description 1
• 206010047470 viral myocarditis Diseases 0.000 description 1
• 239000011345 viscous material Substances 0.000 description 1
• 239000003039 volatile agent Substances 0.000 description 1
• 238000005303 weighing Methods 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• BEAZKUGSCHFXIQ-UHFFFAOYSA-L zinc;diacetate;dihydrate Chemical compound O.O.[Zn+2].CC([O-])=O.CC([O-])=O BEAZKUGSCHFXIQ-UHFFFAOYSA-L 0.000 description 1