ES2963508T3 - Derivados de 5-hidroxi-7-oxabiciclo[2.2.1]heptano-2-carboxamida para inducir condrogénesis para el tratamiento del daño articular - Google Patents

Info

Publication number

ES2963508T3

ES2963508T3 ES19821288T ES19821288T ES2963508T3 ES 2963508 T3 ES2963508 T3 ES 2963508T3 ES 19821288 T ES19821288 T ES 19821288T ES 19821288 T ES19821288 T ES 19821288T ES 2963508 T3 ES2963508 T3 ES 2963508T3

Authority

ES

Spain

Prior art keywords

trifluoromethyl

hydroxy

carboxamide

rac

pharmaceutically acceptable

Prior art date

2018-12-06

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Active

Links

• Espacenet
• Global Dossier
• Discuss

• 238000011282 treatment Methods 0.000 title claims description 21
• 230000006378 damage Effects 0.000 title abstract description 29
• 210000001503 joint Anatomy 0.000 title abstract description 25
• 230000022159 cartilage development Effects 0.000 title abstract description 4
• RSBJUAXUHBGHBC-UHFFFAOYSA-N 5-hydroxy-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical class OC1C2CC(C(C1)O2)C(=O)N RSBJUAXUHBGHBC-UHFFFAOYSA-N 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 195
• 206010003246 arthritis Diseases 0.000 claims abstract description 29
• 206010060820 Joint injury Diseases 0.000 claims abstract description 24
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 210000003035 hyaline cartilage Anatomy 0.000 claims abstract description 13
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 150000003839 salts Chemical class 0.000 claims description 69
• -1 chloro, methyl Chemical group 0.000 claims description 41
• 239000003814 drug Substances 0.000 claims description 23
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• 229940124597 therapeutic agent Drugs 0.000 claims description 19
• 210000000845 cartilage Anatomy 0.000 claims description 18
• 125000003545 alkoxy group Chemical group 0.000 claims description 17
• 201000008482 osteoarthritis Diseases 0.000 claims description 16
• 125000001188 haloalkyl group Chemical group 0.000 claims description 14
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 230000008439 repair process Effects 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 10
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
• 230000001939 inductive effect Effects 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 230000006872 improvement Effects 0.000 claims description 6
• 239000013543 active substance Substances 0.000 claims description 5
• 125000000623 heterocyclic group Chemical group 0.000 claims description 5
• 229910052760 oxygen Inorganic materials 0.000 claims description 5
• 230000002265 prevention Effects 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
• AIYDLTREJPNUNU-PNKHAZJDSA-N (1R,2R,3S,4R,5S)-5-hydroxy-3-(2-methylpyridin-4-yl)-N-[3-(trifluoromethyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound O[C@@H]1[C@H]2[C@@H]([C@H]([C@@H](C1)O2)C(=O)NC1=CC(=CC=C1)C(F)(F)F)C1=CC(=NC=C1)C AIYDLTREJPNUNU-PNKHAZJDSA-N 0.000 claims description 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
• 238000000034 method Methods 0.000 abstract description 147
• 238000002360 preparation method Methods 0.000 abstract description 5
• 230000000144 pharmacologic effect Effects 0.000 abstract 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 115
• 238000005160 1H NMR spectroscopy Methods 0.000 description 107
• YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 57
• DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 57
• 239000000203 mixture Substances 0.000 description 50
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 47
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 43
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
• 210000001612 chondrocyte Anatomy 0.000 description 32
• 238000004808 supercritical fluid chromatography Methods 0.000 description 29
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 26
• 239000000543 intermediate Substances 0.000 description 23
• 239000011541 reaction mixture Substances 0.000 description 22
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
• 210000004027 cell Anatomy 0.000 description 19
• 239000000243 solution Substances 0.000 description 19
• 230000014759 maintenance of location Effects 0.000 description 18
• 229910052805 deuterium Inorganic materials 0.000 description 17
• 230000004069 differentiation Effects 0.000 description 17
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 16
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
• 239000003795 chemical substances by application Substances 0.000 description 14
• 201000010099 disease Diseases 0.000 description 14
• 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 14
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
• 230000002648 chondrogenic effect Effects 0.000 description 12
• 208000035475 disorder Diseases 0.000 description 12
• 210000000130 stem cell Anatomy 0.000 description 12
• 238000010348 incorporation Methods 0.000 description 11
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 10
• 229910002091 carbon monoxide Inorganic materials 0.000 description 10
• 238000001514 detection method Methods 0.000 description 10
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
• 238000000926 separation method Methods 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 235000019439 ethyl acetate Nutrition 0.000 description 9
• 229910052757 nitrogen Inorganic materials 0.000 description 9
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
• 102000008186 Collagen Human genes 0.000 description 8
• 108010035532 Collagen Proteins 0.000 description 8
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 229920001436 collagen Polymers 0.000 description 8
• 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 8
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
• 239000000047 product Substances 0.000 description 8
• SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 8
• IAIRNHIXDCZUCV-UHFFFAOYSA-N 2-amino-4-(trifluoromethyl)benzonitrile Chemical compound NC1=CC(C(F)(F)F)=CC=C1C#N IAIRNHIXDCZUCV-UHFFFAOYSA-N 0.000 description 7
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• 239000003112 inhibitor Substances 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
• 241000124008 Mammalia Species 0.000 description 6
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
• 210000001188 articular cartilage Anatomy 0.000 description 6
• 210000002950 fibroblast Anatomy 0.000 description 6
• 238000000338 in vitro Methods 0.000 description 6
• 230000008569 process Effects 0.000 description 6
• 125000006239 protecting group Chemical group 0.000 description 6
• 206010039073 rheumatoid arthritis Diseases 0.000 description 6
• 239000000741 silica gel Substances 0.000 description 6
• 229910002027 silica gel Inorganic materials 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• 238000001356 surgical procedure Methods 0.000 description 6
• 239000003643 water by type Substances 0.000 description 6
• 206010007710 Cartilage injury Diseases 0.000 description 5
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
• 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 5
• 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• 239000004698 Polyethylene Substances 0.000 description 5
• CSCPPACGZOOCGX-WFGJKAKNSA-N acetone d6 Chemical compound [2H]C([2H])([2H])C(=O)C([2H])([2H])[2H] CSCPPACGZOOCGX-WFGJKAKNSA-N 0.000 description 5
• 229910052799 carbon Inorganic materials 0.000 description 5
• 238000006243 chemical reaction Methods 0.000 description 5
• 239000000306 component Substances 0.000 description 5
• 239000006184 cosolvent Substances 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 210000002744 extracellular matrix Anatomy 0.000 description 5
• 238000001727 in vivo Methods 0.000 description 5
• 230000001965 increasing effect Effects 0.000 description 5
• 230000000155 isotopic effect Effects 0.000 description 5
• 239000011159 matrix material Substances 0.000 description 5
• 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 5
• 102000002260 Alkaline Phosphatase Human genes 0.000 description 4
• 108020004774 Alkaline Phosphatase Proteins 0.000 description 4
• 102000008131 Bone Morphogenetic Protein 7 Human genes 0.000 description 4
• 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 description 4
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
• 238000005481 NMR spectroscopy Methods 0.000 description 4
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
• 206010048873 Traumatic arthritis Diseases 0.000 description 4
• 239000002253 acid Substances 0.000 description 4
• 239000004480 active ingredient Substances 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 125000001309 chloro group Chemical group Cl* 0.000 description 4
• HOXDXGRSZJEEKN-UHFFFAOYSA-N cycloocta-1,5-diene;rhodium Chemical class [Rh].C1CC=CCCC=C1 HOXDXGRSZJEEKN-UHFFFAOYSA-N 0.000 description 4
• 239000012847 fine chemical Substances 0.000 description 4
• 239000003102 growth factor Substances 0.000 description 4
• 238000002347 injection Methods 0.000 description 4
• 239000007924 injection Substances 0.000 description 4
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
• 230000000670 limiting effect Effects 0.000 description 4
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
• 238000000746 purification Methods 0.000 description 4
• 239000000523 sample Substances 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• 208000024891 symptom Diseases 0.000 description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
• 102100025668 Angiopoietin-related protein 3 Human genes 0.000 description 3
• 101710085848 Angiopoietin-related protein 3 Proteins 0.000 description 3
• NXLJYICPRAMRQY-UHFFFAOYSA-N CN1N=C(C(F)(F)F)C(C2C(C(C3)O)OC3C2C(NC(C=C2C(F)(F)F)=NC=C2Cl)=O)=C1 Chemical compound CN1N=C(C(F)(F)F)C(C2C(C(C3)O)OC3C2C(NC(C=C2C(F)(F)F)=NC=C2Cl)=O)=C1 NXLJYICPRAMRQY-UHFFFAOYSA-N 0.000 description 3
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• VTHHCPMWBUGLPI-UHFFFAOYSA-N N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-(2-methoxypyridin-4-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound COC1=NC=CC(=C1)C2C(C3CC(C2O3)O)C(=O)NC4=C(C=CC(=C4)C(F)(F)F)C#N VTHHCPMWBUGLPI-UHFFFAOYSA-N 0.000 description 3
• GKKMWYPPJBZBTH-UHFFFAOYSA-N N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C(#N)C1=C(C=C(C=C1)C(F)(F)F)NC(=O)C1C2CC(C(C1C=1C(=NN(C=1)C)C(F)(F)F)O2)O GKKMWYPPJBZBTH-UHFFFAOYSA-N 0.000 description 3
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
• CVTMJOHFLLGAIA-UHFFFAOYSA-N [1-methyl-3-(trifluoromethyl)pyrazol-4-yl]boronic acid Chemical compound CN1C=C(B(O)O)C(C(F)(F)F)=N1 CVTMJOHFLLGAIA-UHFFFAOYSA-N 0.000 description 3
• 150000001412 amines Chemical class 0.000 description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 229910002092 carbon dioxide Inorganic materials 0.000 description 3
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
• 238000000105 evaporative light scattering detection Methods 0.000 description 3
• 239000012091 fetal bovine serum Substances 0.000 description 3
• 238000003818 flash chromatography Methods 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 238000004128 high performance liquid chromatography Methods 0.000 description 3
• 229920002674 hyaluronan Polymers 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 239000001301 oxygen Substances 0.000 description 3
• 239000002953 phosphate buffered saline Substances 0.000 description 3
• 230000002285 radioactive effect Effects 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• 239000002904 solvent Substances 0.000 description 3
• 238000010186 staining Methods 0.000 description 3
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 3
• 238000002560 therapeutic procedure Methods 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• 239000011701 zinc Substances 0.000 description 3
• PDJQCHVMABBNQW-MIXQCLKLSA-L (1z,5z)-cycloocta-1,5-diene;rhodium;dichloride Chemical compound [Cl-].[Cl-].[Rh].[Rh].C\1C\C=C/CC\C=C/1.C\1C\C=C/CC\C=C/1 PDJQCHVMABBNQW-MIXQCLKLSA-L 0.000 description 2
• KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 2
• YNTJKQDWYXUTLZ-UHFFFAOYSA-N 2-(3-chlorophenoxy)propanoic acid Chemical compound OC(=O)C(C)OC1=CC=CC(Cl)=C1 YNTJKQDWYXUTLZ-UHFFFAOYSA-N 0.000 description 2
• SLUINPGXGFUMLL-UHFFFAOYSA-N 2-[(4-phenylphenyl)carbamoyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)NC1=CC=C(C=2C=CC=CC=2)C=C1 SLUINPGXGFUMLL-UHFFFAOYSA-N 0.000 description 2
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 2
• 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 2
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
• ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 description 2
• ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 206010071155 Autoimmune arthritis Diseases 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
• 241000282472 Canis lupus familiaris Species 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 102000010907 Cyclooxygenase 2 Human genes 0.000 description 2
• 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
• 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 2
• 241000282412 Homo Species 0.000 description 2
• 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 2
• 102000004877 Insulin Human genes 0.000 description 2
• 108090001061 Insulin Proteins 0.000 description 2
• 206010061246 Intervertebral disc degeneration Diseases 0.000 description 2
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
• 229940122245 Janus kinase inhibitor Drugs 0.000 description 2
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
• BWAWGZUMTXRMNA-UHFFFAOYSA-N N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound CN1C(=CC(=N1)C(F)(F)F)C2C(C3CC(C2O3)O)C(=O)NC4=C(C=CC(=C4)C(F)(F)F)C#N BWAWGZUMTXRMNA-UHFFFAOYSA-N 0.000 description 2
• BFFTYRILEHLYDO-UHFFFAOYSA-N N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-[3-(trifluoromethyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1C(C2C(C(C1O2)C(=O)NC3=C(C=CC(=C3)C(F)(F)F)C#N)C4=CC(=CC=C4)C(F)(F)F)O BFFTYRILEHLYDO-UHFFFAOYSA-N 0.000 description 2
• OURSPUYWWBBMMC-UHFFFAOYSA-N N-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-5-hydroxy-3-[3-(trifluoromethyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1C(C2C(C(C1O2)C(=O)NC3=NC(=C(C=C3)C(F)(F)F)Cl)C4=CC(=CC=C4)C(F)(F)F)O OURSPUYWWBBMMC-UHFFFAOYSA-N 0.000 description 2
• 244000025272 Persea americana Species 0.000 description 2
• 235000008673 Persea americana Nutrition 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
• 241000288906 Primates Species 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 2
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 230000032683 aging Effects 0.000 description 2
• 150000001298 alcohols Chemical class 0.000 description 2
• 230000004075 alteration Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 125000003118 aryl group Chemical group 0.000 description 2
• 238000003556 assay Methods 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 2
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• 239000011230 binding agent Substances 0.000 description 2
• 239000012267 brine Substances 0.000 description 2
• BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 2
• 239000011575 calcium Substances 0.000 description 2
• 229910052791 calcium Inorganic materials 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 208000015100 cartilage disease Diseases 0.000 description 2
• 230000003848 cartilage regeneration Effects 0.000 description 2
• 239000003054 catalyst Substances 0.000 description 2
• 238000012512 characterization method Methods 0.000 description 2
• PBAYDYUZOSNJGU-UHFFFAOYSA-N chelidonic acid Natural products OC(=O)C1=CC(=O)C=C(C(O)=O)O1 PBAYDYUZOSNJGU-UHFFFAOYSA-N 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 230000011227 chondrocyte hypertrophy Effects 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 230000037319 collagen production Effects 0.000 description 2
• 238000004440 column chromatography Methods 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 230000007547 defect Effects 0.000 description 2
• 206010012601 diabetes mellitus Diseases 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 239000003085 diluting agent Substances 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 239000000975 dye Substances 0.000 description 2
• 230000002500 effect on skin Effects 0.000 description 2
• 150000002081 enamines Chemical class 0.000 description 2
• 150000002148 esters Chemical class 0.000 description 2
• 239000000706 filtrate Substances 0.000 description 2
• 235000003599 food sweetener Nutrition 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 230000014509 gene expression Effects 0.000 description 2
• 239000001963 growth medium Substances 0.000 description 2
• 208000005252 hepatitis A Diseases 0.000 description 2
• 125000001072 heteroaryl group Chemical group 0.000 description 2
• 229960003160 hyaluronic acid Drugs 0.000 description 2
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
• 230000002401 inhibitory effect Effects 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• 229940125396 insulin Drugs 0.000 description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• 239000011777 magnesium Substances 0.000 description 2
• 229910052749 magnesium Inorganic materials 0.000 description 2
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
• 235000019341 magnesium sulphate Nutrition 0.000 description 2
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000002609 medium Substances 0.000 description 2
• 210000002901 mesenchymal stem cell Anatomy 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 230000002503 metabolic effect Effects 0.000 description 2
• PITMUHRRCBFULF-UHFFFAOYSA-N methyl 3-bromoprop-2-ynoate Chemical compound COC(=O)C#CBr PITMUHRRCBFULF-UHFFFAOYSA-N 0.000 description 2
• IMAKHNTVDGLIRY-UHFFFAOYSA-N methyl prop-2-ynoate Chemical compound COC(=O)C#C IMAKHNTVDGLIRY-UHFFFAOYSA-N 0.000 description 2
• 150000007522 mineralic acids Chemical class 0.000 description 2
• 125000002950 monocyclic group Chemical group 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 150000007524 organic acids Chemical class 0.000 description 2
• 235000005985 organic acids Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000011591 potassium Substances 0.000 description 2
• 229910052700 potassium Inorganic materials 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000004007 reversed phase HPLC Methods 0.000 description 2
• 238000012216 screening Methods 0.000 description 2
• 239000000377 silicon dioxide Substances 0.000 description 2
• 238000002603 single-photon emission computed tomography Methods 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 150000003431 steroids Chemical class 0.000 description 2
• 210000005065 subchondral bone plate Anatomy 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 239000003765 sweetening agent Substances 0.000 description 2
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 230000001225 therapeutic effect Effects 0.000 description 2
• 238000004809 thin layer chromatography Methods 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 230000000472 traumatic effect Effects 0.000 description 2
• JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 2
• QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 2
• 229910052725 zinc Inorganic materials 0.000 description 2
• VTHHCPMWBUGLPI-XJWCYLOLSA-N (1R,2R,3S,4R,5S)-N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-(2-methoxypyridin-4-yl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound COC1=NC=CC(=C1)[C@@H]2[C@H]([C@H]3C[C@@H]([C@@H]2O3)O)C(=O)NC4=C(C=CC(=C4)C(F)(F)F)C#N VTHHCPMWBUGLPI-XJWCYLOLSA-N 0.000 description 1
• BFFTYRILEHLYDO-JKEDJMADSA-N (1R,2R,3S,4R,5S)-N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-[3-(trifluoromethyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1[C@@H]([C@H]2[C@@H]([C@H]([C@@H]1O2)C(=O)NC3=C(C=CC(=C3)C(F)(F)F)C#N)C4=CC(=CC=C4)C(F)(F)F)O BFFTYRILEHLYDO-JKEDJMADSA-N 0.000 description 1
• OURSPUYWWBBMMC-RIMJYPKNSA-N (1R,2R,3S,4R,5S)-N-[6-chloro-5-(trifluoromethyl)pyridin-2-yl]-5-hydroxy-3-[3-(trifluoromethyl)phenyl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound C1[C@@H]([C@H]2[C@@H]([C@H]([C@@H]1O2)C(=O)NC3=NC(=C(C=C3)C(F)(F)F)Cl)C4=CC(=CC=C4)C(F)(F)F)O OURSPUYWWBBMMC-RIMJYPKNSA-N 0.000 description 1
• JBBWIOOUTUWSMJ-FSDCSDTHSA-N (1R,2R,3S,4S)-3-(2-aminopyridin-4-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound NC1=NC=CC(=C1)[C@@H]1[C@H]([C@H]2CC[C@@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl JBBWIOOUTUWSMJ-FSDCSDTHSA-N 0.000 description 1
• HNLJEOAFXYIQQM-YVSFHVDLSA-N (1R,2R,3S,4S)-N-(3,4-dichlorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC=NC=C1)O2 HNLJEOAFXYIQQM-YVSFHVDLSA-N 0.000 description 1
• PAIQAKBTYYBSKX-SJXGUFTOSA-N (1R,2S,3R,4S)-N-(3,4-dichlorophenyl)-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@H]1C1=CC(=NN1C)C(F)(F)F)O2 PAIQAKBTYYBSKX-SJXGUFTOSA-N 0.000 description 1
• HNLJEOAFXYIQQM-VVLHAWIVSA-N (1R,2S,3S,4S)-N-(3,4-dichlorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@@H]1[C@H]2CC[C@@H]([C@@H]1C1=CC=NC=C1)O2 HNLJEOAFXYIQQM-VVLHAWIVSA-N 0.000 description 1
• HNLJEOAFXYIQQM-TWMKSMIVSA-N (1S,2R,3R,4R)-N-(3,4-dichlorophenyl)-3-pyridin-4-yl-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound ClC=1C=C(C=CC1Cl)NC(=O)[C@H]1[C@@H]2CC[C@H]([C@H]1C1=CC=NC=C1)O2 HNLJEOAFXYIQQM-TWMKSMIVSA-N 0.000 description 1
• JBBWIOOUTUWSMJ-YALNPMBYSA-N (1S,2S,3R,4R)-3-(2-aminopyridin-4-yl)-N-(3,4-dichlorophenyl)-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound NC1=NC=CC(=C1)[C@H]1[C@@H]([C@@H]2CC[C@H]1O2)C(=O)NC2=CC(=C(C=C2)Cl)Cl JBBWIOOUTUWSMJ-YALNPMBYSA-N 0.000 description 1
• BWAWGZUMTXRMNA-PNDGYWDASA-N (1S,2S,3R,4S,5R)-N-[2-cyano-5-(trifluoromethyl)phenyl]-5-hydroxy-3-[2-methyl-5-(trifluoromethyl)pyrazol-3-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound CN1C(=CC(=N1)C(F)(F)F)[C@H]2[C@@H]([C@@H]3C[C@H]([C@H]2O3)O)C(=O)NC4=C(C=CC(=C4)C(F)(F)F)C#N BWAWGZUMTXRMNA-PNDGYWDASA-N 0.000 description 1
• DHQMUJSACXTPEA-UHFFFAOYSA-N (2-methoxypyridin-4-yl)boronic acid Chemical compound COC1=CC(B(O)O)=CC=N1 DHQMUJSACXTPEA-UHFFFAOYSA-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
• QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-N 0.000 description 1
• LNETULKMXZVUST-UHFFFAOYSA-N 1-naphthoic acid Chemical compound C1=CC=C2C(C(=O)O)=CC=CC2=C1 LNETULKMXZVUST-UHFFFAOYSA-N 0.000 description 1
• PRDFBSVERLRRMY-UHFFFAOYSA-N 2'-(4-ethoxyphenyl)-5-(4-methylpiperazin-1-yl)-2,5'-bibenzimidazole Chemical compound C1=CC(OCC)=CC=C1C1=NC2=CC=C(C=3NC4=CC(=CC=C4N=3)N3CCN(C)CC3)C=C2N1 PRDFBSVERLRRMY-UHFFFAOYSA-N 0.000 description 1
• 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
• YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
• CPUXOJVJEJZOSP-UHFFFAOYSA-N 2,4-difluoro-N-[2-methoxy-5-[4-methyl-8-[(3-methyloxetan-3-yl)methoxy]quinazolin-6-yl]pyridin-3-yl]benzenesulfonamide Chemical compound COc1ncc(cc1NS(=O)(=O)c1ccc(F)cc1F)-c1cc(OCC2(C)COC2)c2ncnc(C)c2c1 CPUXOJVJEJZOSP-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
• AKSVALRPYDVQBS-CABCVRRESA-N 2-[(3R)-3-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-(trifluoromethyl)pyrazolo[3,4-b]pyrazin-6-yl]azetidin-3-yl]piperidin-1-yl]ethanol Chemical compound ClC1=C(C=CC(=C1)Cl)[C@@H](C)N1N=C(C=2C1=NC(=CN=2)N1CC(C1)[C@@H]1CN(CCC1)CCO)C(F)(F)F AKSVALRPYDVQBS-CABCVRRESA-N 0.000 description 1
• BWSQKOKULIALEW-UHFFFAOYSA-N 2-[2-[4-fluoro-3-(trifluoromethyl)phenyl]-3-[2-(piperidin-3-ylamino)pyrimidin-4-yl]imidazol-4-yl]acetonitrile Chemical compound FC1=C(C=C(C=C1)C=1N(C(=CN=1)CC#N)C1=NC(=NC=C1)NC1CNCCC1)C(F)(F)F BWSQKOKULIALEW-UHFFFAOYSA-N 0.000 description 1
• WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
• OVKXDANNQWXYKF-UHFFFAOYSA-N 2-methyloctanamide Chemical compound CCCCCCC(C)C(N)=O OVKXDANNQWXYKF-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
• RWGBXAQMUBGGKQ-UHFFFAOYSA-N 4-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC(C(F)(F)F)=CC=N1 RWGBXAQMUBGGKQ-UHFFFAOYSA-N 0.000 description 1
• LLARVKAOQLUCQI-UHFFFAOYSA-L 4-benzamido-2,5-dimethoxybenzenediazonium;tetrachlorozinc(2-) Chemical compound [Cl-].[Cl-].Cl[Zn]Cl.COC1=CC([N+]#N)=C(OC)C=C1NC(=O)C1=CC=CC=C1.COC1=CC([N+]#N)=C(OC)C=C1NC(=O)C1=CC=CC=C1 LLARVKAOQLUCQI-UHFFFAOYSA-L 0.000 description 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
• RVHOCQUEFYITIV-UHFFFAOYSA-N 5-chloro-4-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=CC(C(F)(F)F)=C(Cl)C=N1 RVHOCQUEFYITIV-UHFFFAOYSA-N 0.000 description 1
• KITGEMDAROEPQW-UHFFFAOYSA-N 5-hydroxy-3-[1-methyl-3-(trifluoromethyl)pyrazol-4-yl]-N-[4-(trifluoromethyl)pyridin-2-yl]-7-oxabicyclo[2.2.1]heptane-2-carboxamide Chemical compound OC1C2C(C(C(C1)O2)C(=O)NC1=NC=CC(=C1)C(F)(F)F)C=1C(=NN(C=1)C)C(F)(F)F KITGEMDAROEPQW-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• XTJZKALDRPVFSN-HNNXBMFYSA-N 8-n-[(2s)-3,3-dimethylbutan-2-yl]-2-n-[2-methoxy-4-(1-methylpyrazol-4-yl)phenyl]pyrido[3,4-d]pyrimidine-2,8-diamine Chemical compound C=1C=C(NC=2N=C3C(N[C@@H](C)C(C)(C)C)=NC=CC3=CN=2)C(OC)=CC=1C=1C=NN(C)C=1 XTJZKALDRPVFSN-HNNXBMFYSA-N 0.000 description 1
• 229920001817 Agar Polymers 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
• 102000009840 Angiopoietins Human genes 0.000 description 1
• 108010009906 Angiopoietins Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 241000972773 Aulopiformes Species 0.000 description 1
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
• 239000005711 Benzoic acid Substances 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• GKKMWYPPJBZBTH-LYYZXLFJSA-N CN1N=C(C(F)(F)F)C([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC(C=C(C(F)(F)F)C=C2)=C2C#N)=O)=C1 Chemical compound CN1N=C(C(F)(F)F)C([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC(C=C(C(F)(F)F)C=C2)=C2C#N)=O)=C1 GKKMWYPPJBZBTH-LYYZXLFJSA-N 0.000 description 1
• NXLJYICPRAMRQY-JPKGWIMLSA-N CN1N=C(C(F)(F)F)C([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC(C=C2C(F)(F)F)=NC=C2Cl)=O)=C1 Chemical compound CN1N=C(C(F)(F)F)C([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC(C=C2C(F)(F)F)=NC=C2Cl)=O)=C1 NXLJYICPRAMRQY-JPKGWIMLSA-N 0.000 description 1
• KITGEMDAROEPQW-JPKGWIMLSA-N CN1N=C(C(F)(F)F)C([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC2=NC=CC(C(F)(F)F)=C2)=O)=C1 Chemical compound CN1N=C(C(F)(F)F)C([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC2=NC=CC(C(F)(F)F)=C2)=O)=C1 KITGEMDAROEPQW-JPKGWIMLSA-N 0.000 description 1
• NXLJYICPRAMRQY-MYALOSSISA-N CN1N=C(C(F)(F)F)C([C@H]2[C@H]([C@H](C3)O)O[C@H]3[C@@H]2C(NC(C=C2C(F)(F)F)=NC=C2Cl)=O)=C1 Chemical compound CN1N=C(C(F)(F)F)C([C@H]2[C@H]([C@H](C3)O)O[C@H]3[C@@H]2C(NC(C=C2C(F)(F)F)=NC=C2Cl)=O)=C1 NXLJYICPRAMRQY-MYALOSSISA-N 0.000 description 1
• VTHHCPMWBUGLPI-UWAKZDDMSA-N COC1=NC=CC([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC(C=C(C(F)(F)F)C=C2)=C2C#N)=O)=C1 Chemical compound COC1=NC=CC([C@@H]2[C@@H]([C@@H](C3)O)O[C@@H]3[C@H]2C(NC(C=C(C(F)(F)F)C=C2)=C2C#N)=O)=C1 VTHHCPMWBUGLPI-UWAKZDDMSA-N 0.000 description 1
• 102000055006 Calcitonin Human genes 0.000 description 1
• 108060001064 Calcitonin Proteins 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
• 241000700198 Cavia Species 0.000 description 1
• 241000282693 Cercopithecidae Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
• 206010061762 Chondropathy Diseases 0.000 description 1
• 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 208000015943 Coeliac disease Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
• FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
• FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
• 208000016192 Demyelinating disease Diseases 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• 206010012442 Dermatitis contact Diseases 0.000 description 1
• 238000005698 Diels-Alder reaction Methods 0.000 description 1
• 206010061818 Disease progression Diseases 0.000 description 1
• 206010013883 Dwarfism Diseases 0.000 description 1
• 208000002197 Ehlers-Danlos syndrome Diseases 0.000 description 1
• 102000004190 Enzymes Human genes 0.000 description 1
• 108090000790 Enzymes Proteins 0.000 description 1
• 206010015218 Erythema multiforme Diseases 0.000 description 1
• OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
• 208000004332 Evans syndrome Diseases 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 208000004262 Food Hypersensitivity Diseases 0.000 description 1
• 206010016946 Food allergy Diseases 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 208000009329 Graft vs Host Disease Diseases 0.000 description 1
• 208000003807 Graves Disease Diseases 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 208000005331 Hepatitis D Diseases 0.000 description 1
• 208000037319 Hepatitis infectious Diseases 0.000 description 1
• 101001033249 Homo sapiens Interleukin-1 beta Proteins 0.000 description 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
• 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
• 208000028622 Immune thrombocytopenia Diseases 0.000 description 1
• 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
• 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
• 208000026350 Inborn Genetic disease Diseases 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• 208000002658 Intra-Articular Fractures Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• 239000002144 L01XE18 - Ruxolitinib Substances 0.000 description 1
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
• 206010065433 Ligament rupture Diseases 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 102000055008 Matrilin Proteins Human genes 0.000 description 1
• 108010072582 Matrilin Proteins Proteins 0.000 description 1
• 206010072970 Meniscus injury Diseases 0.000 description 1
• 208000023178 Musculoskeletal disease Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• BFFTYRILEHLYDO-ICBNADEASA-N N#CC(C=CC(C(F)(F)F)=C1)=C1NC([C@H]([C@H](C1)O[C@@H]2[C@@H]1O)[C@@H]2C1=CC(C(F)(F)F)=CC=C1)=O Chemical compound N#CC(C=CC(C(F)(F)F)=C1)=C1NC([C@H]([C@H](C1)O[C@@H]2[C@@H]1O)[C@@H]2C1=CC(C(F)(F)F)=CC=C1)=O BFFTYRILEHLYDO-ICBNADEASA-N 0.000 description 1
• QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-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
• 229910002651 NO3 Inorganic materials 0.000 description 1
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 1
• 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 1
• GZMYLSJUNSCMTD-MOPGFXCFSA-N OC[C@@H](C)NC1=NC(=CC(=C1)C=1C=C(C=CC=1C)NC(=O)N1C[C@@H](CC1)CC(F)(F)F)N1CCOCC1 Chemical compound OC[C@@H](C)NC1=NC(=CC(=C1)C=1C=C(C=CC=1C)NC(=O)N1C[C@@H](CC1)CC(F)(F)F)N1CCOCC1 GZMYLSJUNSCMTD-MOPGFXCFSA-N 0.000 description 1
• OURSPUYWWBBMMC-XVLPMQGWSA-N O[C@H](C1)[C@H]([C@H]2C3=CC(C(F)(F)F)=CC=C3)O[C@@H]1[C@H]2C(NC1=NC(Cl)=C(C(F)(F)F)C=C1)=O Chemical compound O[C@H](C1)[C@H]([C@H]2C3=CC(C(F)(F)F)=CC=C3)O[C@@H]1[C@H]2C(NC1=NC(Cl)=C(C(F)(F)F)C=C1)=O OURSPUYWWBBMMC-XVLPMQGWSA-N 0.000 description 1
• 241000283973 Oryctolagus cuniculus Species 0.000 description 1
• 201000009859 Osteochondrosis Diseases 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229930040373 Paraformaldehyde Natural products 0.000 description 1
• 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
• 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 102000016611 Proteoglycans Human genes 0.000 description 1
• 108010067787 Proteoglycans Proteins 0.000 description 1
• 201000004681 Psoriasis Diseases 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
• 206010039085 Rhinitis allergic Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
• 208000021386 Sjogren Syndrome Diseases 0.000 description 1
• 206010040954 Skin wrinkling Diseases 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
• 208000006045 Spondylarthropathies Diseases 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• 208000013201 Stress fracture Diseases 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 229930006000 Sucrose Natural products 0.000 description 1
• 241000282887 Suidae Species 0.000 description 1
• 201000009594 Systemic Scleroderma Diseases 0.000 description 1
• 208000004732 Systemic Vasculitis Diseases 0.000 description 1
• 206010042953 Systemic sclerosis 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
• 208000000491 Tendinopathy Diseases 0.000 description 1
• 208000023835 Tendon disease Diseases 0.000 description 1
• DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
• 239000004012 Tofacitinib Substances 0.000 description 1
• 229920001615 Tragacanth Polymers 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 206010048302 Tubulointerstitial nephritis Diseases 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000024780 Urticaria Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• 241000700605 Viruses Species 0.000 description 1
• QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
• 208000027207 Whipple disease Diseases 0.000 description 1
• 102000013814 Wnt Human genes 0.000 description 1
• 108050003627 Wnt Proteins 0.000 description 1
• 208000027418 Wounds and injury Diseases 0.000 description 1
• XPUNXPPXMANQGF-UHFFFAOYSA-N [2-methyl-5-(trifluoromethyl)pyrazol-3-yl]boronic acid Chemical compound CN1N=C(C(F)(F)F)C=C1B(O)O XPUNXPPXMANQGF-UHFFFAOYSA-N 0.000 description 1
• WOAORAPRPVIATR-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1 WOAORAPRPVIATR-UHFFFAOYSA-N 0.000 description 1
• IOMLBTHPCVDRHM-UHFFFAOYSA-N [3-[(2,4-dimethylphenyl)carbamoyl]naphthalen-2-yl] dihydrogen phosphate Chemical compound CC1=CC(C)=CC=C1NC(=O)C1=CC2=CC=CC=C2C=C1OP(O)(O)=O IOMLBTHPCVDRHM-UHFFFAOYSA-N 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 238000005299 abrasion Methods 0.000 description 1
• 239000002250 absorbent Substances 0.000 description 1
• 230000002745 absorbent Effects 0.000 description 1
• 239000003070 absorption delaying agent Substances 0.000 description 1
• 150000001241 acetals Chemical class 0.000 description 1
• 159000000021 acetate salts Chemical class 0.000 description 1
• 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 1
• 150000007513 acids Chemical class 0.000 description 1
• 208000033017 acquired idiopathic inflammatory myopathy Diseases 0.000 description 1
• 125000002252 acyl group Chemical group 0.000 description 1
• 229960001456 adenosine triphosphate Drugs 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 239000003463 adsorbent Substances 0.000 description 1
• 239000008272 agar Substances 0.000 description 1
• 235000010419 agar Nutrition 0.000 description 1
• 239000000783 alginic acid Substances 0.000 description 1
• 235000010443 alginic acid Nutrition 0.000 description 1
• 229920000615 alginic acid Polymers 0.000 description 1
• 229960001126 alginic acid Drugs 0.000 description 1
• 150000004781 alginic acids Chemical class 0.000 description 1
• 239000012670 alkaline solution Substances 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• 201000010105 allergic rhinitis Diseases 0.000 description 1
• 230000000735 allogeneic effect Effects 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• SNAAJJQQZSMGQD-UHFFFAOYSA-N aluminum magnesium Chemical compound [Mg].[Al] SNAAJJQQZSMGQD-UHFFFAOYSA-N 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 238000004458 analytical method Methods 0.000 description 1
• 150000001448 anilines Chemical class 0.000 description 1
• 239000003242 anti bacterial agent Substances 0.000 description 1
• 229940088710 antibiotic agent Drugs 0.000 description 1
• 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 238000011882 arthroplasty Methods 0.000 description 1
• 210000000544 articulatio talocruralis Anatomy 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229940009098 aspartate Drugs 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 208000010927 atrophic thyroiditis Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 229950000971 baricitinib Drugs 0.000 description 1
• XUZMWHLSFXCVMG-UHFFFAOYSA-N baricitinib Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2C=3C=CNC=3N=CN=2)=C1 XUZMWHLSFXCVMG-UHFFFAOYSA-N 0.000 description 1
• 230000009286 beneficial effect Effects 0.000 description 1
• JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 235000010233 benzoic acid Nutrition 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 210000003445 biliary tract Anatomy 0.000 description 1
• 238000004166 bioassay Methods 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 239000012620 biological material Substances 0.000 description 1
• 230000031018 biological processes and functions Effects 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000000988 bone and bone Anatomy 0.000 description 1
• 210000001185 bone marrow Anatomy 0.000 description 1
• 125000005620 boronic acid group Chemical class 0.000 description 1
• 229940098773 bovine serum albumin Drugs 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000006172 buffering agent Substances 0.000 description 1
• 208000019748 bullous skin disease Diseases 0.000 description 1
• KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
• 229960004015 calcitonin Drugs 0.000 description 1
• 229960003773 calcitonin (salmon synthetic) Drugs 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound 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
• 239000001569 carbon dioxide Substances 0.000 description 1
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 210000003321 cartilage cell Anatomy 0.000 description 1
• 230000015556 catabolic process Effects 0.000 description 1
• 238000004113 cell culture Methods 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 1
• 230000007882 cirrhosis Effects 0.000 description 1
• 208000019425 cirrhosis of liver Diseases 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 208000010247 contact dermatitis Diseases 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000011461 current therapy Methods 0.000 description 1
• 238000007256 debromination reaction Methods 0.000 description 1
• GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 208000018180 degenerative disc disease Diseases 0.000 description 1
• 230000003412 degenerative effect Effects 0.000 description 1
• 238000006731 degradation reaction Methods 0.000 description 1
• 206010061811 demyelinating polyneuropathy Diseases 0.000 description 1
• 201000001981 dermatomyositis Diseases 0.000 description 1
• 210000004207 dermis Anatomy 0.000 description 1
• 239000011903 deuterated solvents‎ Substances 0.000 description 1
• 150000001975 deuterium Chemical group 0.000 description 1
• 125000004431 deuterium atom Chemical group 0.000 description 1
• 238000011161 development Methods 0.000 description 1
• 230000018109 developmental process Effects 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
• 208000010643 digestive system disease Diseases 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 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
• 230000005750 disease progression Effects 0.000 description 1
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 239000002612 dispersion medium Substances 0.000 description 1
• MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
• 229940043264 dodecyl sulfate Drugs 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000005553 drilling Methods 0.000 description 1
• XUZICJHIIJCKQQ-ZDUSSCGKSA-N eclitasertib Chemical compound C(C1=CC=CC=C1)C=1NC(=NN=1)C(=O)N[C@@H]1C(N(C2=C(OC1)C=CC=N2)C)=O XUZICJHIIJCKQQ-ZDUSSCGKSA-N 0.000 description 1
• 210000001513 elbow Anatomy 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000003821 enantio-separation Methods 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 238000011067 equilibration Methods 0.000 description 1
• AFAXGSQYZLGZPG-UHFFFAOYSA-L ethane-1,2-disulfonate Chemical compound [O-]S(=O)(=O)CCS([O-])(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-L 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 201000001155 extrinsic allergic alveolitis Diseases 0.000 description 1
• 210000001145 finger joint Anatomy 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Chemical group 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 210000003108 foot joint Anatomy 0.000 description 1
• 229940050411 fumarate Drugs 0.000 description 1
• 239000001530 fumaric acid Substances 0.000 description 1
• 235000011087 fumaric acid Nutrition 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
• 208000016361 genetic disease Diseases 0.000 description 1
• 229960001731 gluceptate Drugs 0.000 description 1
• KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• JFCQEDHGNNZCLN-UHFFFAOYSA-N glutaric acid Chemical compound OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
• 208000024908 graft versus host disease Diseases 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 201000007192 granulomatous hepatitis Diseases 0.000 description 1
• 230000012010 growth Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000035876 healing Effects 0.000 description 1
• 230000036074 healthy skin Effects 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 201000010284 hepatitis E Diseases 0.000 description 1
• 230000001553 hepatotropic effect Effects 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
• 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
• 238000004896 high resolution mass spectrometry Methods 0.000 description 1
• 210000004394 hip joint Anatomy 0.000 description 1
• 210000004276 hyalin Anatomy 0.000 description 1
• KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 1
• 229940099552 hyaluronan Drugs 0.000 description 1
• 238000006197 hydroboration reaction Methods 0.000 description 1
• 150000002431 hydrogen Chemical group 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 208000022098 hypersensitivity pneumonitis Diseases 0.000 description 1
• 210000003559 hypertrophic chondrocyte Anatomy 0.000 description 1
• 230000001969 hypertrophic effect Effects 0.000 description 1
• 238000003384 imaging method Methods 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 208000026278 immune system disease Diseases 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 230000001976 improved effect Effects 0.000 description 1
• 238000000099 in vitro assay Methods 0.000 description 1
• 238000005462 in vivo assay Methods 0.000 description 1
• 238000011065 in-situ storage Methods 0.000 description 1
• 230000006698 induction Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 239000013067 intermediate product Substances 0.000 description 1
• 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
• 201000006334 interstitial nephritis Diseases 0.000 description 1
• 208000021600 intervertebral disc degenerative disease Diseases 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 239000007951 isotonicity adjuster Substances 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 238000010983 kinetics study Methods 0.000 description 1
• 210000000629 knee joint Anatomy 0.000 description 1
• 229940001447 lactate Drugs 0.000 description 1
• 229940099584 lactobionate Drugs 0.000 description 1
• JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 210000003041 ligament Anatomy 0.000 description 1
• 239000007788 liquid Substances 0.000 description 1
• 238000011068 loading method Methods 0.000 description 1
• 238000005461 lubrication Methods 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 229960003646 lysine Drugs 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• 230000036244 malformation Effects 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
• 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
• 239000000463 material Substances 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 239000012528 membrane Substances 0.000 description 1
• 230000005499 meniscus Effects 0.000 description 1
• 229910052751 metal Inorganic materials 0.000 description 1
• 239000002184 metal Substances 0.000 description 1
• 150000002739 metals Chemical class 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 1
• NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 1
• CQDVLGWMGVDHFS-XIVJJUGBSA-N methyl (1R,4S,5S)-3-bromo-5-hydroxy-7-oxabicyclo[2.2.1]hept-2-ene-2-carboxylate Chemical compound [C@H]1(O)C[C@@H]2C(=C(Br)[C@H]1O2)C(=O)OC CQDVLGWMGVDHFS-XIVJJUGBSA-N 0.000 description 1
• FIYSWKITUMBNQB-UHFFFAOYSA-N methyl 3-bromo-7-oxabicyclo[2.2.1]hepta-2,5-diene-2-carboxylate Chemical compound BrC1=C(C2C=CC1O2)C(=O)OC FIYSWKITUMBNQB-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 150000004702 methyl esters Chemical class 0.000 description 1
• JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• CPZBTYRIGVOOMI-UHFFFAOYSA-N methylsulfanyl(methylsulfanylmethoxy)methane Chemical compound CSCOCSC CPZBTYRIGVOOMI-UHFFFAOYSA-N 0.000 description 1
• 238000004452 microanalysis Methods 0.000 description 1
• 238000000386 microscopy Methods 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• GUOONOJYWQOJJP-DCMFLLSESA-N n-[(2s,3r)-3-hydroxy-1-phenyl-4-[[3-(trifluoromethoxy)phenyl]methylamino]butan-2-yl]-3-[methyl(methylsulfonyl)amino]-5-[(2r)-2-(4-methyl-1,3-thiazol-2-yl)pyrrolidine-1-carbonyl]benzamide Chemical compound C1([C@H]2CCCN2C(=O)C=2C=C(C=C(C=2)N(C)S(C)(=O)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)[C@H](O)CNCC=2C=C(OC(F)(F)F)C=CC=2)=NC(C)=CS1 GUOONOJYWQOJJP-DCMFLLSESA-N 0.000 description 1
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 235000001968 nicotinic acid Nutrition 0.000 description 1
• 239000011664 nicotinic acid Substances 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• 238000005016 nuclear Overhauser enhanced spectroscopy Methods 0.000 description 1
• 150000007523 nucleic acids Chemical class 0.000 description 1
• 108020004707 nucleic acids Proteins 0.000 description 1
• 102000039446 nucleic acids Human genes 0.000 description 1
• QIQXTHQIDYTFRH-UHFFFAOYSA-M octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC([O-])=O QIQXTHQIDYTFRH-UHFFFAOYSA-M 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 229940049964 oleate Drugs 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 210000000963 osteoblast Anatomy 0.000 description 1
• 208000007656 osteochondritis dissecans Diseases 0.000 description 1
• 235000006408 oxalic acid Nutrition 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 238000004806 packaging method and process Methods 0.000 description 1
• 229920002866 paraformaldehyde Polymers 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000006072 paste Substances 0.000 description 1
• 235000019371 penicillin G benzathine Nutrition 0.000 description 1
• 230000000737 periodic effect Effects 0.000 description 1
• 210000001428 peripheral nervous system Anatomy 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 239000000546 pharmaceutical excipient Substances 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• 239000008055 phosphate buffer solution Substances 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Chemical group 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229960005141 piperazine Drugs 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000005936 piperidyl group Chemical group 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 208000005987 polymyositis Diseases 0.000 description 1
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
• 238000002600 positron emission tomography Methods 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000000843 powder Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 238000011321 prophylaxis Methods 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 230000004952 protein activity Effects 0.000 description 1
• 235000018102 proteins Nutrition 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 201000009732 pulmonary eosinophilia Diseases 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 238000011002 quantification 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
• 238000002278 reconstructive surgery Methods 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 230000001172 regenerating effect Effects 0.000 description 1
• 230000008929 regeneration Effects 0.000 description 1
• 238000011069 regeneration method Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 229910052703 rhodium Inorganic materials 0.000 description 1
• 239000010948 rhodium Substances 0.000 description 1
• MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
• 229960000215 ruxolitinib Drugs 0.000 description 1
• HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 description 1
• MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
• 235000019515 salmon Nutrition 0.000 description 1
• 108010068072 salmon calcitonin Proteins 0.000 description 1
• 201000000306 sarcoidosis Diseases 0.000 description 1
• 229920006395 saturated elastomer Polymers 0.000 description 1
• 208000010157 sclerosing cholangitis Diseases 0.000 description 1
• 229940116351 sebacate Drugs 0.000 description 1
• CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 210000002832 shoulder Anatomy 0.000 description 1
• 229910052709 silver Inorganic materials 0.000 description 1
• 239000004332 silver Substances 0.000 description 1
• 229910001961 silver nitrate Inorganic materials 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 208000017520 skin disease Diseases 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 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
• 239000000600 sorbitol Substances 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
• 201000005671 spondyloarthropathy Diseases 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 229940114926 stearate Drugs 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 230000004936 stimulating effect Effects 0.000 description 1
• 230000000638 stimulation Effects 0.000 description 1
• 230000035882 stress Effects 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 229940086735 succinate Drugs 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229940071103 sulfosalicylate Drugs 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 230000001629 suppression Effects 0.000 description 1
• 239000004094 surface-active agent Substances 0.000 description 1
• 208000011580 syndromic disease Diseases 0.000 description 1
• 210000001179 synovial fluid Anatomy 0.000 description 1
• 238000007910 systemic administration Methods 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 210000002435 tendon Anatomy 0.000 description 1
• 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 125000001544 thienyl group Chemical group 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• 201000003067 thrombocytopenia due to platelet alloimmunization Diseases 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• 229960001350 tofacitinib Drugs 0.000 description 1
• UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 238000003325 tomography Methods 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• 230000008736 traumatic injury Effects 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• 229960000281 trometamol Drugs 0.000 description 1
• 229910052721 tungsten Inorganic materials 0.000 description 1
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
• 235000005282 vitamin D3 Nutrition 0.000 description 1
• 239000011647 vitamin D3 Substances 0.000 description 1
• 229940021056 vitamin d3 Drugs 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 230000037303 wrinkles Effects 0.000 description 1
• 210000000707 wrist Anatomy 0.000 description 1
• 229950000339 xinafoate Drugs 0.000 description 1