PT1091930E - Dipeptídeos oxamil de terminal c modificado como inibidores das proteases da cisteína da família eci/ced - 3 - Google Patents

Info

Publication number

PT1091930E

PT1091930E PT99932211T PT99932211T PT1091930E PT 1091930 E PT1091930 E PT 1091930E PT 99932211 T PT99932211 T PT 99932211T PT 99932211 T PT99932211 T PT 99932211T PT 1091930 E PT1091930 E PT 1091930E

Authority

PT

Portugal

Prior art keywords

naphthyl

compound

amino

phenyl

oxamyl

Prior art date

1998-07-02

Links

• Espacenet
• Global Dossier
• Discuss

• KZAUOCCYDRDERY-UHFFFAOYSA-N oxamyl Chemical group CNC(=O)ON=C(SC)C(=O)N(C)C KZAUOCCYDRDERY-UHFFFAOYSA-N 0.000 title claims description 181
• 239000003112 inhibitor Substances 0.000 title description 16
• 108010005843 Cysteine Proteases Proteins 0.000 title description 9
• 102000005927 Cysteine Proteases Human genes 0.000 title description 9
• 101150055276 ced-3 gene Proteins 0.000 title description 9
• 108010016626 Dipeptides Proteins 0.000 title description 2
• 210000004899 c-terminal region Anatomy 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 247
• 238000011282 treatment Methods 0.000 claims abstract description 18
• 210000000056 organ Anatomy 0.000 claims abstract description 15
• 230000035899 viability Effects 0.000 claims abstract description 7
• 238000002054 transplantation Methods 0.000 claims abstract description 3
• -1 2-benzoazolyl Chemical group 0.000 claims description 258
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 246
• 239000005950 Oxamyl Substances 0.000 claims description 179
• 125000000217 alkyl group Chemical group 0.000 claims description 117
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 111
• 239000000203 mixture Substances 0.000 claims description 110
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 88
• 125000001624 naphthyl group Chemical group 0.000 claims description 83
• 125000001072 heteroaryl group Chemical group 0.000 claims description 75
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 74
• 229910052739 hydrogen Inorganic materials 0.000 claims description 70
• 239000001257 hydrogen Substances 0.000 claims description 69
• JQDVYXJPZWVXRM-UHFFFAOYSA-N 2-amino-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound OC(=O)C(N)CC(=O)COC1=C(F)C(F)=CC(F)=C1F JQDVYXJPZWVXRM-UHFFFAOYSA-N 0.000 claims description 60
• 238000000034 method Methods 0.000 claims description 43
• 239000008194 pharmaceutical composition Substances 0.000 claims description 43
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 42
• 150000002431 hydrogen Chemical class 0.000 claims description 41
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 35
• HOSWPDPVFBCLSY-UHFFFAOYSA-N 2-azaniumyl-4-oxobutanoate Chemical compound OC(=O)C(N)CC=O HOSWPDPVFBCLSY-UHFFFAOYSA-N 0.000 claims description 27
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 20
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
• 210000004027 cell Anatomy 0.000 claims description 15
• 150000003839 salts Chemical class 0.000 claims description 14
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
• 125000003118 aryl group Chemical group 0.000 claims description 11
• 150000001413 amino acids Chemical class 0.000 claims description 10
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
• 201000010099 disease Diseases 0.000 claims description 9
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
• 230000004770 neurodegeneration Effects 0.000 claims description 8
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 8
• 125000004043 oxo group Chemical group O=* 0.000 claims description 8
• 208000023275 Autoimmune disease Diseases 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 229910052717 sulfur Inorganic materials 0.000 claims description 7
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
• 210000003958 hematopoietic stem cell Anatomy 0.000 claims description 6
• 239000001301 oxygen Substances 0.000 claims description 6
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 5
• 125000001153 fluoro group Chemical group F* 0.000 claims description 5
• 125000005843 halogen group Chemical group 0.000 claims description 5
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
• 125000004434 sulfur atom Chemical group 0.000 claims description 5
• ADDCQISNIHHAPN-UHFFFAOYSA-N 2-amino-5-fluoro-4-oxopentanoic acid Chemical compound OC(=O)C(N)CC(=O)CF ADDCQISNIHHAPN-UHFFFAOYSA-N 0.000 claims description 4
• 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 4
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 125000000623 heterocyclic group Chemical group 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
• 210000001616 monocyte Anatomy 0.000 claims description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• 125000004306 triazinyl group Chemical group 0.000 claims description 4
• 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 3
• 101100134929 Gallus gallus COR9 gene Proteins 0.000 claims description 3
• KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
• KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 125000002619 bicyclic group Chemical group 0.000 claims description 3
• 125000002837 carbocyclic group Chemical group 0.000 claims description 3
• ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 3
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 3
• 208000037906 ischaemic injury Diseases 0.000 claims description 3
• 230000007654 ischemic lesion Effects 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 239000004474 valine Substances 0.000 claims description 3
• RBSDOQWXALXACB-UHFFFAOYSA-N 2-amino-5-diphenylphosphoryloxy-4-oxopentanoic acid Chemical compound NC(CC(=O)COP(=O)(c1ccccc1)c1ccccc1)C(O)=O RBSDOQWXALXACB-UHFFFAOYSA-N 0.000 claims description 2
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
• 125000002078 anthracen-1-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C([*])=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 2
• 125000000748 anthracen-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C([H])=C([*])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 2
• 125000005605 benzo group Chemical group 0.000 claims description 2
• 239000004305 biphenyl Substances 0.000 claims description 2
• 235000010290 biphenyl Nutrition 0.000 claims description 2
• 210000001772 blood platelet Anatomy 0.000 claims description 2
• 210000005064 dopaminergic neuron Anatomy 0.000 claims description 2
• 230000002708 enhancing effect Effects 0.000 claims description 2
• 210000003743 erythrocyte Anatomy 0.000 claims description 2
• 210000003714 granulocyte Anatomy 0.000 claims description 2
• 210000003677 hemocyte Anatomy 0.000 claims description 2
• 210000004698 lymphocyte Anatomy 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
• 230000004083 survival effect Effects 0.000 claims description 2
• 125000004970 halomethyl group Chemical group 0.000 claims 4
• 125000004212 difluorophenyl group Chemical group 0.000 claims 3
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 2
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 2
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims 2
• 229910052805 deuterium Inorganic materials 0.000 claims 2
• MHERPFVRWOTBSF-UHFFFAOYSA-N methyl(phenyl)phosphane Chemical compound CPC1=CC=CC=C1 MHERPFVRWOTBSF-UHFFFAOYSA-N 0.000 claims 2
• FGMDZKPUCIHRBD-UHFFFAOYSA-N 2-amino-4-oxo-5-(2,4,6-trifluorophenoxy)pentanoic acid Chemical compound NC(C(=O)O)CC(COC1=C(C=C(C=C1F)F)F)=O FGMDZKPUCIHRBD-UHFFFAOYSA-N 0.000 claims 1
• 125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims 1
• 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 claims 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
• 125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 claims 1
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims 1
• 208000037979 autoimmune inflammatory disease Diseases 0.000 claims 1
• 230000001413 cellular effect Effects 0.000 claims 1
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
• 125000005059 halophenyl group Chemical group 0.000 claims 1
• 125000006303 iodophenyl group Chemical group 0.000 claims 1
• 210000004153 islets of langerhan Anatomy 0.000 claims 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 1
• 125000001909 leucine group Chemical group [H]N(*)C(C(*)=O)C([H])([H])C(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
• 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims 1
• JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims 1
• 239000003814 drug Substances 0.000 abstract description 5
• 208000035473 Communicable disease Diseases 0.000 abstract description 3
• 230000004968 inflammatory condition Effects 0.000 abstract description 2
• 238000004519 manufacturing process Methods 0.000 abstract description 2
• 208000015181 infectious disease Diseases 0.000 abstract 1
• 239000000243 solution Substances 0.000 description 216
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 128
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 126
• 239000011734 sodium Substances 0.000 description 103
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 95
• 238000003756 stirring Methods 0.000 description 79
• 239000000460 chlorine Substances 0.000 description 77
• 229910052757 nitrogen Inorganic materials 0.000 description 72
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 69
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 68
• 239000007787 solid Substances 0.000 description 64
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 63
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 61
• OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 59
• 235000019439 ethyl acetate Nutrition 0.000 description 56
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
• 239000000047 product Substances 0.000 description 44
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 41
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
• 239000012074 organic phase Substances 0.000 description 38
• 229920006395 saturated elastomer Polymers 0.000 description 38
• SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical class NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 32
• 150000001412 amines Chemical class 0.000 description 31
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 30
• 239000000741 silica gel Substances 0.000 description 29
• 229910002027 silica gel Inorganic materials 0.000 description 29
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
• 238000003818 flash chromatography Methods 0.000 description 27
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
• 125000006239 protecting group Chemical group 0.000 description 24
• CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 23
• 229960005261 aspartic acid Drugs 0.000 description 21
• 235000003704 aspartic acid Nutrition 0.000 description 20
• OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 20
• 239000003921 oil Substances 0.000 description 20
• 235000019198 oils Nutrition 0.000 description 20
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
• GSYSFVSGPABNNL-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-(phenylmethoxycarbonylamino)acetate Chemical group COC(=O)C(P(=O)(OC)OC)NC(=O)OCC1=CC=CC=C1 GSYSFVSGPABNNL-UHFFFAOYSA-N 0.000 description 18
• 229920005989 resin Polymers 0.000 description 18
• 239000011347 resin Substances 0.000 description 18
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 18
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 17
• 235000002639 sodium chloride Nutrition 0.000 description 17
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 16
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
• 239000006260 foam Substances 0.000 description 15
• NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 14
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 14
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 13
• 125000006242 amine protecting group Chemical group 0.000 description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 13
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 12
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
• 125000001424 substituent group Chemical group 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 11
• 239000012043 crude product Substances 0.000 description 11
• MWPIIMNHWGOFBL-UHFFFAOYSA-N dichloromethane;toluene Chemical compound ClCCl.CC1=CC=CC=C1 MWPIIMNHWGOFBL-UHFFFAOYSA-N 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• 102000004190 Enzymes Human genes 0.000 description 10
• 108090000790 Enzymes Proteins 0.000 description 10
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 239000002253 acid Substances 0.000 description 10
• 238000003556 assay Methods 0.000 description 10
• 229940088598 enzyme Drugs 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• 239000011521 glass Substances 0.000 description 10
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 10
• 238000001665 trituration Methods 0.000 description 10
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 9
• 229960003767 alanine Drugs 0.000 description 9
• 235000004279 alanine Nutrition 0.000 description 9
• 229940024606 amino acid Drugs 0.000 description 9
• 239000000284 extract Substances 0.000 description 9
• 238000002360 preparation method Methods 0.000 description 9
• 238000006467 substitution reaction Methods 0.000 description 9
• WVELHLIHMYYZAT-UHFFFAOYSA-N 2-(4-ethylphenoxy)acetic acid Chemical compound CCC1=CC=C(OCC(O)=O)C=C1 WVELHLIHMYYZAT-UHFFFAOYSA-N 0.000 description 8
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 8
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 8
• 235000001014 amino acid Nutrition 0.000 description 8
• 238000005859 coupling reaction Methods 0.000 description 8
• 239000006071 cream Substances 0.000 description 8
• CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 8
• 229910000343 potassium bisulfate Inorganic materials 0.000 description 8
• 229960004441 tyrosine Drugs 0.000 description 8
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 8
• XMAMNGJUQKAFSE-UHFFFAOYSA-N 2-amino-4-hydroxy-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound NC(C(=O)O)CC(COC1=C(C(=CC(=C1F)F)F)F)O XMAMNGJUQKAFSE-UHFFFAOYSA-N 0.000 description 7
• OSGZDPFBQZONOZ-UHFFFAOYSA-N [4-amino-5-[(2-methylpropan-2-yl)oxy]-2,5-dioxopentyl] 2,6-dichlorobenzoate Chemical compound CC(C)(C)OC(=O)C(N)CC(=O)COC(=O)C1=C(Cl)C=CC=C1Cl OSGZDPFBQZONOZ-UHFFFAOYSA-N 0.000 description 7
• ZCLSQRQRWNDNLV-UHFFFAOYSA-N acetic acid;dichloromethane;methanol Chemical compound OC.ClCCl.CC(O)=O ZCLSQRQRWNDNLV-UHFFFAOYSA-N 0.000 description 7
• 125000003277 amino group Chemical group 0.000 description 7
• 239000012298 atmosphere Substances 0.000 description 7
• 239000012299 nitrogen atmosphere Substances 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 238000005897 peptide coupling reaction Methods 0.000 description 7
• 238000010647 peptide synthesis reaction Methods 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 239000002904 solvent Substances 0.000 description 7
• 239000000758 substrate Substances 0.000 description 7
• TWYSODGJQICHJK-UHFFFAOYSA-N tert-butyl 2-amino-4-oxobutanoate Chemical compound CC(C)(C)OC(=O)C(N)CC=O TWYSODGJQICHJK-UHFFFAOYSA-N 0.000 description 7
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
• DSLBDPPHINVUID-REOHCLBHSA-N (2s)-2-aminobutanediamide Chemical compound NC(=O)[C@@H](N)CC(N)=O DSLBDPPHINVUID-REOHCLBHSA-N 0.000 description 6
• ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 6
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
• 239000004471 Glycine Substances 0.000 description 6
• 101000793880 Homo sapiens Caspase-3 Proteins 0.000 description 6
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
• 230000015572 biosynthetic process Effects 0.000 description 6
• 239000003795 chemical substances by application Substances 0.000 description 6
• 229960002449 glycine Drugs 0.000 description 6
• 229910052736 halogen Inorganic materials 0.000 description 6
• 150000002367 halogens Chemical class 0.000 description 6
• 208000027866 inflammatory disease Diseases 0.000 description 6
• 150000004702 methyl esters Chemical class 0.000 description 6
• KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
• 239000008188 pellet Substances 0.000 description 6
• 108090000765 processed proteins & peptides Proteins 0.000 description 6
• 150000007659 semicarbazones Chemical class 0.000 description 6
• 150000003462 sulfoxides Chemical class 0.000 description 6
• 239000006228 supernatant Substances 0.000 description 6
• 238000003786 synthesis reaction Methods 0.000 description 6
• KXOLECFIQWMQMG-UHFFFAOYSA-N tert-butyl 2-amino-5-bromo-4-oxopentanoate Chemical compound CC(C)(C)OC(=O)C(N)CC(=O)CBr KXOLECFIQWMQMG-UHFFFAOYSA-N 0.000 description 6
• 238000005406 washing Methods 0.000 description 6
• 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 5
• 102100029855 Caspase-3 Human genes 0.000 description 5
• 102000035195 Peptidases Human genes 0.000 description 5
• 108091005804 Peptidases Proteins 0.000 description 5
• 239000004365 Protease Substances 0.000 description 5
• 230000006907 apoptotic process Effects 0.000 description 5
• 150000001718 carbodiimides Chemical class 0.000 description 5
• 150000003857 carboxamides Chemical class 0.000 description 5
• 239000003153 chemical reaction reagent Substances 0.000 description 5
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 5
• 239000011698 potassium fluoride Substances 0.000 description 5
• 235000003270 potassium fluoride Nutrition 0.000 description 5
• 239000011780 sodium chloride Substances 0.000 description 5
• WQUVPVDYGDZFEQ-UHFFFAOYSA-N 1-(ethyliminomethylideneamino)-3-methylbutan-1-amine;hydrochloride Chemical compound Cl.CCN=C=NC(N)CC(C)C WQUVPVDYGDZFEQ-UHFFFAOYSA-N 0.000 description 4
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 4
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 4
• 102000000589 Interleukin-1 Human genes 0.000 description 4
• 108010002352 Interleukin-1 Proteins 0.000 description 4
• 239000012267 brine Substances 0.000 description 4
• 239000000872 buffer Substances 0.000 description 4
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 238000007429 general method Methods 0.000 description 4
• 238000010438 heat treatment Methods 0.000 description 4
• 230000002427 irreversible effect Effects 0.000 description 4
• 230000000302 ischemic effect Effects 0.000 description 4
• GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 4
• 238000002156 mixing Methods 0.000 description 4
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 4
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
• 239000000126 substance Substances 0.000 description 4
• LHJLQKGHMRXKBE-UHFFFAOYSA-N tert-butyl 2-amino-5-fluoro-4-hydroxypentanoate Chemical compound CC(C)(C)OC(=O)C(N)CC(O)CF LHJLQKGHMRXKBE-UHFFFAOYSA-N 0.000 description 4
• XYXYXSKSTZAEJW-VIFPVBQESA-N (2s)-2-(phenylmethoxycarbonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 XYXYXSKSTZAEJW-VIFPVBQESA-N 0.000 description 3
• 238000005160 1H NMR spectroscopy Methods 0.000 description 3
• KDKWAXNGHHRWIG-UHFFFAOYSA-N 2-amino-5-(2,6-dichlorobenzoyl)oxy-4-oxopentanoic acid Chemical compound OC(=O)C(N)CC(=O)COC(=O)C1=C(Cl)C=CC=C1Cl KDKWAXNGHHRWIG-UHFFFAOYSA-N 0.000 description 3
• APEZTBOLESJYDF-UHFFFAOYSA-N 2-amino-5-fluoro-4-hydroxypentanoic acid Chemical compound OC(=O)C(N)CC(O)CF APEZTBOLESJYDF-UHFFFAOYSA-N 0.000 description 3
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• 208000024827 Alzheimer disease Diseases 0.000 description 3
• PFEVXIQTUGRDJO-UHFFFAOYSA-N CC(C)(C)OC(=O)C(N)CC(=O)COC1=C(F)C(F)=CC(F)=C1F Chemical compound CC(C)(C)OC(=O)C(N)CC(=O)COC1=C(F)C(F)=CC(F)=C1F PFEVXIQTUGRDJO-UHFFFAOYSA-N 0.000 description 3
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 3
• FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 3
• ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 3
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
• 239000004472 Lysine Substances 0.000 description 3
• 208000018737 Parkinson disease Diseases 0.000 description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
• 239000007983 Tris buffer Substances 0.000 description 3
• 150000001241 acetals Chemical class 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 125000002252 acyl group Chemical group 0.000 description 3
• 150000001371 alpha-amino acids Chemical class 0.000 description 3
• 235000008206 alpha-amino acids Nutrition 0.000 description 3
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
• 150000001768 cations Chemical class 0.000 description 3
• 238000002512 chemotherapy Methods 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000012230 colorless oil Substances 0.000 description 3
• 230000008878 coupling Effects 0.000 description 3
• 239000007822 coupling agent Substances 0.000 description 3
• 238000010168 coupling process Methods 0.000 description 3
• 239000003085 diluting agent Substances 0.000 description 3
• 239000002270 dispersing agent Substances 0.000 description 3
• 238000010494 dissociation reaction Methods 0.000 description 3
• 230000005593 dissociations Effects 0.000 description 3
• 230000000694 effects Effects 0.000 description 3
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 238000007913 intrathecal administration Methods 0.000 description 3
• 208000017169 kidney disease Diseases 0.000 description 3
• 229960003136 leucine Drugs 0.000 description 3
• 229960003646 lysine Drugs 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 230000001404 mediated effect Effects 0.000 description 3
• 230000004060 metabolic process Effects 0.000 description 3
• 229930182817 methionine Natural products 0.000 description 3
• 229960004452 methionine Drugs 0.000 description 3
• 208000010125 myocardial infarction Diseases 0.000 description 3
• 229960003104 ornithine Drugs 0.000 description 3
• 238000007254 oxidation reaction Methods 0.000 description 3
• 229920001223 polyethylene glycol Polymers 0.000 description 3
• 238000000746 purification Methods 0.000 description 3
• 238000001953 recrystallisation Methods 0.000 description 3
• 239000007790 solid phase Substances 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 230000000699 topical effect Effects 0.000 description 3
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
• 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
• LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 2
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
• PBYIIRLNRCVTMQ-UHFFFAOYSA-N 2,3,5,6-tetrafluorophenol Chemical compound OC1=C(F)C(F)=CC(F)=C1F PBYIIRLNRCVTMQ-UHFFFAOYSA-N 0.000 description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
• 125000002103 4,4'-dimethoxytriphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)(C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H])C1=C([H])C([H])=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
• RQJDUEKERVZLLU-UHFFFAOYSA-N 4-Hydroxybenzylamine Chemical compound NCC1=CC=C(O)C=C1 RQJDUEKERVZLLU-UHFFFAOYSA-N 0.000 description 2
• 239000004475 Arginine Substances 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
• 101150047706 CASP6 gene Proteins 0.000 description 2
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
• 229920002261 Corn starch Polymers 0.000 description 2
• 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
• 206010061218 Inflammation Diseases 0.000 description 2
• 108010063738 Interleukins Proteins 0.000 description 2
• 102000015696 Interleukins Human genes 0.000 description 2
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 2
• ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 2
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 2
• HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 2
• ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 2
• LRQKBLKVPFOOQJ-YFKPBYRVSA-N L-norleucine Chemical compound CCCC[C@H]([NH3+])C([O-])=O LRQKBLKVPFOOQJ-YFKPBYRVSA-N 0.000 description 2
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
• AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 2
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
• 229910010082 LiAlH Inorganic materials 0.000 description 2
• VZUNGTLZRAYYDE-UHFFFAOYSA-N N-methyl-N'-nitro-N-nitrosoguanidine Chemical compound O=NN(C)C(=N)N[N+]([O-])=O VZUNGTLZRAYYDE-UHFFFAOYSA-N 0.000 description 2
• FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 2
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 2
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
• 239000002202 Polyethylene glycol Substances 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 2
• 239000004473 Threonine Substances 0.000 description 2
• 238000010521 absorption reaction Methods 0.000 description 2
• 230000009471 action Effects 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 150000001299 aldehydes Chemical class 0.000 description 2
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
• 125000003342 alkenyl group Chemical group 0.000 description 2
• 125000002877 alkyl aryl group Chemical group 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 125000000304 alkynyl group Chemical group 0.000 description 2
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 2
• MMCPOSDMTGQNKG-UHFFFAOYSA-N anilinium chloride Chemical compound Cl.NC1=CC=CC=C1 MMCPOSDMTGQNKG-UHFFFAOYSA-N 0.000 description 2
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 2
• 229960003121 arginine Drugs 0.000 description 2
• 235000009697 arginine Nutrition 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 230000008901 benefit Effects 0.000 description 2
• 235000019445 benzyl alcohol Nutrition 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
• 239000002775 capsule Substances 0.000 description 2
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
• 239000000969 carrier Substances 0.000 description 2
• 150000001767 cationic compounds Chemical class 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 230000001684 chronic effect Effects 0.000 description 2
• 239000008120 corn starch Substances 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 230000008025 crystallization Effects 0.000 description 2
• 125000004093 cyano group Chemical group *C#N 0.000 description 2
• 125000004122 cyclic group Chemical group 0.000 description 2
• 229960002433 cysteine Drugs 0.000 description 2
• 235000018417 cysteine Nutrition 0.000 description 2
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 230000018109 developmental process Effects 0.000 description 2
• 235000014113 dietary fatty acids Nutrition 0.000 description 2
• 229940079593 drug Drugs 0.000 description 2
• 238000010828 elution Methods 0.000 description 2
• 239000000194 fatty acid Substances 0.000 description 2
• 229930195729 fatty acid Natural products 0.000 description 2
• 150000004665 fatty acids Chemical class 0.000 description 2
• 239000011737 fluorine Substances 0.000 description 2
• 229910052731 fluorine Inorganic materials 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 125000005456 glyceride group Chemical group 0.000 description 2
• OTTZHAVKAVGASB-UHFFFAOYSA-N hept-2-ene Chemical compound CCCCC=CC OTTZHAVKAVGASB-UHFFFAOYSA-N 0.000 description 2
• 229960002885 histidine Drugs 0.000 description 2
• HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 2
• 235000014304 histidine Nutrition 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• DCPMPXBYPZGNDC-UHFFFAOYSA-N hydron;methanediimine;chloride Chemical compound Cl.N=C=N DCPMPXBYPZGNDC-UHFFFAOYSA-N 0.000 description 2
• USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical compound Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 2
• 230000004957 immunoregulator effect Effects 0.000 description 2
• 239000012442 inert solvent Substances 0.000 description 2
• 230000004054 inflammatory process Effects 0.000 description 2
• 229910001411 inorganic cation Inorganic materials 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 150000002576 ketones Chemical class 0.000 description 2
• 239000008101 lactose Substances 0.000 description 2
• 239000010410 layer Substances 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 2
• ZXUQEPZWVQIOJE-UHFFFAOYSA-N methyl 2-chloro-2-oxoacetate Chemical compound COC(=O)C(Cl)=O ZXUQEPZWVQIOJE-UHFFFAOYSA-N 0.000 description 2
• BZCKRPHEZOHHBK-UHFFFAOYSA-N methyl 2-phenoxyacetate Chemical compound COC(=O)COC1=CC=CC=C1 BZCKRPHEZOHHBK-UHFFFAOYSA-N 0.000 description 2
• QYYVGUHQHRXRNA-UHFFFAOYSA-N methyl 6-(4-hydroxyanilino)-6-oxohexanoate Chemical compound COC(=O)CCCCC(=O)NC1=CC=C(O)C=C1 QYYVGUHQHRXRNA-UHFFFAOYSA-N 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 235000010446 mineral oil Nutrition 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• 201000006417 multiple sclerosis Diseases 0.000 description 2
• VVVJBDNHHIBWTD-UHFFFAOYSA-N n,n-dimethylformamide;pyrrolidine Chemical compound CN(C)C=O.C1CCNC1 VVVJBDNHHIBWTD-UHFFFAOYSA-N 0.000 description 2
• WSZXJUNYWNMAOE-UHFFFAOYSA-N n-phenyl-2-(2h-tetrazol-5-yl)acetamide Chemical compound C=1C=CC=CC=1NC(=O)CC1=NN=NN1 WSZXJUNYWNMAOE-UHFFFAOYSA-N 0.000 description 2
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 239000000346 nonvolatile oil Substances 0.000 description 2
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
• 230000003287 optical effect Effects 0.000 description 2
• 230000003647 oxidation Effects 0.000 description 2
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
• 230000001575 pathological effect Effects 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 2
• 229960005190 phenylalanine Drugs 0.000 description 2
• 235000021317 phosphate Nutrition 0.000 description 2
• 229920005990 polystyrene resin Polymers 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• KAQHZJVQFBJKCK-UHFFFAOYSA-L potassium pyrosulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OS([O-])(=O)=O KAQHZJVQFBJKCK-UHFFFAOYSA-L 0.000 description 2
• 102000004196 processed proteins & peptides Human genes 0.000 description 2
• 239000000651 prodrug Substances 0.000 description 2
• 229940002612 prodrug Drugs 0.000 description 2
• 230000000770 proinflammatory effect Effects 0.000 description 2
• 150000003180 prostaglandins Chemical class 0.000 description 2
• 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
• 125000002098 pyridazinyl group Chemical group 0.000 description 2
• 239000011541 reaction mixture Substances 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000025915 regulation of apoptotic process Effects 0.000 description 2
• 230000002441 reversible effect Effects 0.000 description 2
• 230000036303 septic shock Effects 0.000 description 2
• QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
• 239000001632 sodium acetate Substances 0.000 description 2
• 235000017281 sodium acetate Nutrition 0.000 description 2
• 239000012279 sodium borohydride Substances 0.000 description 2
• 229910000033 sodium borohydride Inorganic materials 0.000 description 2
• 229910052938 sodium sulfate Inorganic materials 0.000 description 2
• 235000011152 sodium sulphate Nutrition 0.000 description 2
• 239000012453 solvate Substances 0.000 description 2
• 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
• 239000011593 sulfur Substances 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
• HHEDTMQFVNVGQF-RGURZIINSA-N tert-butyl (3s)-3-amino-4-hydroxy-5-(2,3,5,6-tetrafluorophenoxy)pentanoate Chemical compound CC(C)(C)OC(=O)C[C@H](N)C(O)COC1=C(F)C(F)=CC(F)=C1F HHEDTMQFVNVGQF-RGURZIINSA-N 0.000 description 2
• 229960002898 threonine Drugs 0.000 description 2
• 238000011200 topical administration Methods 0.000 description 2
• 125000004953 trihalomethyl group Chemical group 0.000 description 2
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
• 229960004295 valine Drugs 0.000 description 2
• MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
• PAORVUMOXXAMPL-VIFPVBQESA-N (2r)-3,3,3-trifluoro-2-methoxy-2-phenylpropanoyl chloride Chemical compound CO[C@@](C(Cl)=O)(C(F)(F)F)C1=CC=CC=C1 PAORVUMOXXAMPL-VIFPVBQESA-N 0.000 description 1
• LDDMACCNBZAMSG-BDVNFPICSA-N (2r,3r,4s,5r)-3,4,5,6-tetrahydroxy-2-(methylamino)hexanal Chemical compound CN[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO LDDMACCNBZAMSG-BDVNFPICSA-N 0.000 description 1
• BVAUMRCGVHUWOZ-ZETCQYMHSA-N (2s)-2-(cyclohexylazaniumyl)propanoate Chemical compound OC(=O)[C@H](C)NC1CCCCC1 BVAUMRCGVHUWOZ-ZETCQYMHSA-N 0.000 description 1
• MSJVZYZBQGBEQX-BYPYZUCNSA-N (2s)-2-(ethenylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC=C MSJVZYZBQGBEQX-BYPYZUCNSA-N 0.000 description 1
• WTKYBFQVZPCGAO-LURJTMIESA-N (2s)-2-(pyridin-3-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=CN=C1 WTKYBFQVZPCGAO-LURJTMIESA-N 0.000 description 1
• SAAQPSNNIOGFSQ-LURJTMIESA-N (2s)-2-(pyridin-4-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC1=CC=NC=C1 SAAQPSNNIOGFSQ-LURJTMIESA-N 0.000 description 1
• WRQSUCJAKAMYMQ-YFKPBYRVSA-N (2s)-2-(thiophen-3-ylamino)propanoic acid Chemical compound OC(=O)[C@H](C)NC=1C=CSC=1 WRQSUCJAKAMYMQ-YFKPBYRVSA-N 0.000 description 1
• JOWKLGMNVUYQGV-INIZCTEOSA-N (2s)-2-[cyclohexyl(9h-fluoren-9-ylmethoxycarbonyl)amino]propanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1COC(=O)N([C@@H](C)C(O)=O)C1CCCCC1 JOWKLGMNVUYQGV-INIZCTEOSA-N 0.000 description 1
• VZXOCAKIHSMHOS-ZDUSSCGKSA-N (2s)-2-[cyclohexyl(phenylmethoxycarbonyl)amino]propanoic acid Chemical compound C=1C=CC=CC=1COC(=O)N([C@@H](C)C(O)=O)C1CCCCC1 VZXOCAKIHSMHOS-ZDUSSCGKSA-N 0.000 description 1
• FVNKWWBXNSNIAR-BYPYZUCNSA-N (2s)-2-amino-3-(2-sulfanylidene-1,3-dihydroimidazol-4-yl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CNC(=S)N1 FVNKWWBXNSNIAR-BYPYZUCNSA-N 0.000 description 1
• RXZQHZDTHUUJQJ-LURJTMIESA-N (2s)-2-amino-3-(furan-2-yl)propanoic acid Chemical compound OC(=O)[C@@H](N)CC1=CC=CO1 RXZQHZDTHUUJQJ-LURJTMIESA-N 0.000 description 1
• VWTFNYVAFGYEKI-QMMMGPOBSA-N (2s)-2-azaniumyl-3-(3,4-dimethoxyphenyl)propanoate Chemical compound COC1=CC=C(C[C@H](N)C(O)=O)C=C1OC VWTFNYVAFGYEKI-QMMMGPOBSA-N 0.000 description 1
• LOVUSASSMLUWRR-REOHCLBHSA-N (2s)-2-hydrazinylpropanoic acid Chemical compound NN[C@@H](C)C(O)=O LOVUSASSMLUWRR-REOHCLBHSA-N 0.000 description 1
• JMWZQAPWKOIMCR-QSWZWQGQSA-N (3S,5S)-2,5-diamino-3-[1-hydroxy-2-(2,3,5,6-tetrafluorophenoxy)ethyl]-4-oxohexanoic acid Chemical compound N[C@@H](C)C(=O)[C@@H](C(C(=O)O)N)C(COC1=C(C(=CC(=C1F)F)F)F)O JMWZQAPWKOIMCR-QSWZWQGQSA-N 0.000 description 1
• UZHDUADBTIFEKW-PKPIPKONSA-N (3s)-3-amino-4-hydroxy-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound OC(=O)C[C@H](N)C(O)COC1=C(F)C(F)=CC(F)=C1F UZHDUADBTIFEKW-PKPIPKONSA-N 0.000 description 1
• VQMHMZQOKXCVJZ-JUGFDQIVSA-N (5S)-2,5-diamino-3-(2-fluoro-1-hydroxyethyl)-7-methyl-4-oxooctanoic acid Chemical compound N[C@@H](CC(C)C)C(=O)C(C(C(=O)O)N)C(CF)O VQMHMZQOKXCVJZ-JUGFDQIVSA-N 0.000 description 1
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 1
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
• NYPYHUZRZVSYKL-UHFFFAOYSA-N -3,5-Diiodotyrosine Natural products OC(=O)C(N)CC1=CC(I)=C(O)C(I)=C1 NYPYHUZRZVSYKL-UHFFFAOYSA-N 0.000 description 1
• BWKMGYQJPOAASG-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid Chemical compound C1=CC=C2CNC(C(=O)O)CC2=C1 BWKMGYQJPOAASG-UHFFFAOYSA-N 0.000 description 1
• OSJVTYVKQNOXPP-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)CCC2=C1 OSJVTYVKQNOXPP-UHFFFAOYSA-N 0.000 description 1
• QZHGMNYYHDNFPX-UHFFFAOYSA-N 1,3-bis(2,3,4,5-tetrafluorophenoxy)propan-2-one Chemical compound FC1=C(F)C(F)=CC(OCC(=O)COC=2C(=C(F)C(F)=C(F)C=2)F)=C1F QZHGMNYYHDNFPX-UHFFFAOYSA-N 0.000 description 1
• DVVGIUUJYPYENY-UHFFFAOYSA-N 1-methylpyridin-2-one Chemical compound CN1C=CC=CC1=O DVVGIUUJYPYENY-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
• 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
• RZYHXKLKJRGJGP-UHFFFAOYSA-N 2,2,2-trifluoro-n,n-bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)N([Si](C)(C)C)C(=O)C(F)(F)F RZYHXKLKJRGJGP-UHFFFAOYSA-N 0.000 description 1
• ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical compound OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 description 1
• MRUDNSFOFOQZDA-UHFFFAOYSA-N 2,6-dichlorobenzoic acid Chemical compound OC(=O)C1=C(Cl)C=CC=C1Cl MRUDNSFOFOQZDA-UHFFFAOYSA-N 0.000 description 1
• KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 description 1
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
• JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
• YWQDZLIVCPYGGO-UHFFFAOYSA-N 2-amino-5-bromo-4-oxopentanoic acid Chemical compound OC(=O)C(N)CC(=O)CBr YWQDZLIVCPYGGO-UHFFFAOYSA-N 0.000 description 1
• FMHPSVZSLZOGKT-UHFFFAOYSA-N 2-amino-5-diazo-4-oxopentanoic acid Chemical compound NC(C(=O)O)CC(C=[N+]=[N-])=O FMHPSVZSLZOGKT-UHFFFAOYSA-N 0.000 description 1
• IRZQDMYEJPNDEN-UHFFFAOYSA-N 2-azaniumyl-3-phenylbutanoate Chemical compound OC(=O)C(N)C(C)C1=CC=CC=C1 IRZQDMYEJPNDEN-UHFFFAOYSA-N 0.000 description 1
• DMSDCBKFWUBTKX-UHFFFAOYSA-N 2-methyl-1-nitrosoguanidine Chemical compound CN=C(N)NN=O DMSDCBKFWUBTKX-UHFFFAOYSA-N 0.000 description 1
• LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
• NMFFUUFPJJOWHK-UHFFFAOYSA-N 2-phenoxyaniline Chemical compound NC1=CC=CC=C1OC1=CC=CC=C1 NMFFUUFPJJOWHK-UHFFFAOYSA-N 0.000 description 1
• UYWWLYCGNNCLKE-UHFFFAOYSA-N 2-pyridin-4-yl-1h-benzimidazole Chemical compound N=1C2=CC=CC=C2NC=1C1=CC=NC=C1 UYWWLYCGNNCLKE-UHFFFAOYSA-N 0.000 description 1
• AEIOZWYBDBVCGW-UHFFFAOYSA-N 2-tert-butylaniline Chemical compound CC(C)(C)C1=CC=CC=C1N AEIOZWYBDBVCGW-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
• JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 1
• 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• NYPYHUZRZVSYKL-ZETCQYMHSA-N 3,5-diiodo-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC(I)=C(O)C(I)=C1 NYPYHUZRZVSYKL-ZETCQYMHSA-N 0.000 description 1
• WZTKTNRVJAMKAS-UHFFFAOYSA-N 3-(2-aminoethyl)-1h-indol-6-ol Chemical compound OC1=CC=C2C(CCN)=CNC2=C1 WZTKTNRVJAMKAS-UHFFFAOYSA-N 0.000 description 1
• PFDUUKDQEHURQC-UHFFFAOYSA-N 3-Methoxytyrosine Chemical compound COC1=CC(CC(N)C(O)=O)=CC=C1O PFDUUKDQEHURQC-UHFFFAOYSA-N 0.000 description 1
• UMCMPZBLKLEWAF-BCTGSCMUSA-N 3-[(3-cholamidopropyl)dimethylammonio]propane-1-sulfonate Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCC[N+](C)(C)CCCS([O-])(=O)=O)C)[C@@]2(C)[C@@H](O)C1 UMCMPZBLKLEWAF-BCTGSCMUSA-N 0.000 description 1
• RMPQWJZTCGUTRY-UHFFFAOYSA-N 3-amino-5-fluoro-4-hydroxypentanoic acid Chemical compound OC(=O)CC(N)C(O)CF RMPQWJZTCGUTRY-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
• 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 1
• FBTSQILOGYXGMD-LURJTMIESA-N 3-nitro-L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C([N+]([O-])=O)=C1 FBTSQILOGYXGMD-LURJTMIESA-N 0.000 description 1
• 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 1
• 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 1
• 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
• UJTTUOLQLCQZEA-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl n-(4-hydroxybutyl)carbamate Chemical compound C1=CC=C2C(COC(=O)NCCCCO)C3=CC=CC=C3C2=C1 UJTTUOLQLCQZEA-UHFFFAOYSA-N 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 241000024188 Andala Species 0.000 description 1
• DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
• 241000408939 Atalopedes campestris Species 0.000 description 1
• 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
• 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
• 206010050245 Autoimmune thrombocytopenia Diseases 0.000 description 1
• 208000023328 Basedow disease Diseases 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 208000020084 Bone disease Diseases 0.000 description 1
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• NLMPOGYLKNUIFH-JKIOLJMWSA-N CC(C)C[C@@H](C(=O)[C@H](C=O)C(C(=O)OC(C)(C)C)N)N Chemical compound CC(C)C[C@@H](C(=O)[C@H](C=O)C(C(=O)OC(C)(C)C)N)N NLMPOGYLKNUIFH-JKIOLJMWSA-N 0.000 description 1
• CETDAVAZWZKUJV-ZDGBYWQASA-N CC(C)[C@@H](C(=O)[C@H](C=O)C(C(=O)OC(C)(C)C)N)N Chemical compound CC(C)[C@@H](C(=O)[C@H](C=O)C(C(=O)OC(C)(C)C)N)N CETDAVAZWZKUJV-ZDGBYWQASA-N 0.000 description 1
• BMJHTUVYFBHIOI-UNZODLGPSA-N C[C@@H](C(=O)[C@H](C(COC1=C(C(=CC(=C1F)F)F)F)O)C(C(=O)O)N)NC2CCCCC2 Chemical compound C[C@@H](C(=O)[C@H](C(COC1=C(C(=CC(=C1F)F)F)F)O)C(C(=O)O)N)NC2CCCCC2 BMJHTUVYFBHIOI-UNZODLGPSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 241000819038 Chichester Species 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• 235000001258 Cinchona calisaya Nutrition 0.000 description 1
• 102000029816 Collagenase Human genes 0.000 description 1
• 108060005980 Collagenase Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 0.000 description 1
• LJCWONGJFPCTTL-SSDOTTSWSA-N D-4-hydroxyphenylglycine Chemical compound [O-]C(=O)[C@H]([NH3+])C1=CC=C(O)C=C1 LJCWONGJFPCTTL-SSDOTTSWSA-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
• BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
• GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 1
• 241000792859 Enema Species 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
• 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 241000282412 Homo Species 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• 102000006992 Interferon-alpha Human genes 0.000 description 1
• 108010047761 Interferon-alpha Proteins 0.000 description 1
• 102000003777 Interleukin-1 beta Human genes 0.000 description 1
• 108090000193 Interleukin-1 beta Proteins 0.000 description 1
• 108010002350 Interleukin-2 Proteins 0.000 description 1
• SNDPXSYFESPGGJ-BYPYZUCNSA-N L-2-aminopentanoic acid Chemical compound CCC[C@H](N)C(O)=O SNDPXSYFESPGGJ-BYPYZUCNSA-N 0.000 description 1
• QUOGESRFPZDMMT-UHFFFAOYSA-N L-Homoarginine Natural products OC(=O)C(N)CCCCNC(N)=N QUOGESRFPZDMMT-UHFFFAOYSA-N 0.000 description 1
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
• DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
• RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-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
• ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
• QUOGESRFPZDMMT-YFKPBYRVSA-N L-homoarginine Chemical compound OC(=O)[C@@H](N)CCCCNC(N)=N QUOGESRFPZDMMT-YFKPBYRVSA-N 0.000 description 1
• FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical class OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
• AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
• SNDPXSYFESPGGJ-UHFFFAOYSA-N L-norVal-OH Natural products CCCC(N)C(O)=O SNDPXSYFESPGGJ-UHFFFAOYSA-N 0.000 description 1
• DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical compound OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 description 1
• KKCIOUWDFWQUBT-AWEZNQCLSA-N L-thyronine Chemical compound C1=CC(C[C@H](N)C(O)=O)=CC=C1OC1=CC=C(O)C=C1 KKCIOUWDFWQUBT-AWEZNQCLSA-N 0.000 description 1
• QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
• URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
• 239000000867 Lipoxygenase Inhibitor Substances 0.000 description 1
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• 201000009906 Meningitis Diseases 0.000 description 1
• RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 description 1
• 206010028980 Neoplasm Diseases 0.000 description 1
• 239000005642 Oleic acid Substances 0.000 description 1
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 102000015439 Phospholipases Human genes 0.000 description 1
• 108010064785 Phospholipases Proteins 0.000 description 1
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
• 239000004698 Polyethylene Substances 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 239000004793 Polystyrene Substances 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 206010063837 Reperfusion injury Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 101100386054 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CYS3 gene Proteins 0.000 description 1
• 208000007893 Salpingitis Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 206010040047 Sepsis Diseases 0.000 description 1
• MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
• FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
• HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
• 229930006000 Sucrose Natural products 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
• 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
• 206010043781 Thyroiditis chronic Diseases 0.000 description 1
• QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
• 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
• 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 1
• JFBZPFYRPYOZCQ-UHFFFAOYSA-N [Li].[Al] Chemical compound [Li].[Al] JFBZPFYRPYOZCQ-UHFFFAOYSA-N 0.000 description 1
• ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 description 1
• LMHSIBRZJLSPFZ-UHFFFAOYSA-N [diazo(trimethylsilyl)methyl]-trimethylsilane Chemical compound C[Si](C)(C)C(=[N+]=[N-])[Si](C)(C)C LMHSIBRZJLSPFZ-UHFFFAOYSA-N 0.000 description 1
• 229940124532 absorption promoter Drugs 0.000 description 1
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
• 229960001413 acetanilide Drugs 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
• MLPSGIDDQNVPBO-UHFFFAOYSA-N acetic acid;formaldehyde;oxolane;2,2,2-trifluoroacetic acid Chemical compound O=C.CC(O)=O.C1CCOC1.OC(=O)C(F)(F)F MLPSGIDDQNVPBO-UHFFFAOYSA-N 0.000 description 1
• ZCHPKWUIAASXPV-UHFFFAOYSA-N acetic acid;methanol Chemical compound OC.CC(O)=O ZCHPKWUIAASXPV-UHFFFAOYSA-N 0.000 description 1
• 238000010669 acid-base reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 125000004423 acyloxy group Chemical group 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 238000001042 affinity chromatography Methods 0.000 description 1
• 239000003570 air Substances 0.000 description 1
• 125000003172 aldehyde group Chemical group 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 208000026935 allergic disease Diseases 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940024548 aluminum oxide Drugs 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 150000001408 amides Chemical class 0.000 description 1
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 1
• 238000004873 anchoring Methods 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 229940031955 anhydrous lanolin Drugs 0.000 description 1
• 239000005557 antagonist Substances 0.000 description 1
• 239000002260 anti-inflammatory agent Substances 0.000 description 1
• 229940121363 anti-inflammatory agent Drugs 0.000 description 1
• 230000001064 anti-interferon Effects 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• 125000006615 aromatic heterocyclic group Chemical group 0.000 description 1
• 206010003246 arthritis Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 229960001230 asparagine Drugs 0.000 description 1
• 235000009582 asparagine Nutrition 0.000 description 1
• 150000001510 aspartic acids Chemical class 0.000 description 1
• 125000004429 atom Chemical group 0.000 description 1
• 201000005000 autoimmune gastritis Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• 229910052788 barium Inorganic materials 0.000 description 1
• DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
• 210000003651 basophil Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• WGQKYBSKWIADBV-UHFFFAOYSA-O benzylaminium Chemical compound [NH3+]CC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-O 0.000 description 1
• WTOFYLAWDLQMBZ-LURJTMIESA-N beta(2-thienyl)alanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CS1 WTOFYLAWDLQMBZ-LURJTMIESA-N 0.000 description 1
• 230000003851 biochemical process Effects 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 125000006267 biphenyl group Chemical group 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-O bis(2-hydroxyethyl)azanium Chemical compound OCC[NH2+]CCO ZBCBWPMODOFKDW-UHFFFAOYSA-O 0.000 description 1
• SIOVKLKJSOKLIF-UHFFFAOYSA-N bis(trimethylsilyl)acetamide Chemical compound C[Si](C)(C)OC(C)=N[Si](C)(C)C SIOVKLKJSOKLIF-UHFFFAOYSA-N 0.000 description 1
• 210000004369 blood Anatomy 0.000 description 1
• 239000008280 blood Substances 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
• 210000004900 c-terminal fragment Anatomy 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 201000011510 cancer Diseases 0.000 description 1
• MOIPGXQKZSZOQX-UHFFFAOYSA-N carbonyl bromide Chemical compound BrC(Br)=O MOIPGXQKZSZOQX-UHFFFAOYSA-N 0.000 description 1
• 150000001728 carbonyl compounds Chemical class 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 125000006244 carboxylic acid protecting group Chemical group 0.000 description 1
• 231100001012 cardiac lesion Toxicity 0.000 description 1
• 239000004359 castor oil Substances 0.000 description 1
• 235000019438 castor oil Nutrition 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical group S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 description 1
• 239000001913 cellulose Substances 0.000 description 1
• 229920002678 cellulose Polymers 0.000 description 1
• 235000010980 cellulose Nutrition 0.000 description 1
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000002490 cerebral effect Effects 0.000 description 1
• 229940081733 cetearyl alcohol Drugs 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 1
• 208000003167 cholangitis Diseases 0.000 description 1
• 210000001612 chondrocyte Anatomy 0.000 description 1
• LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 1
• 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
• NNBZCPXTIHJBJL-AOOOYVTPSA-N cis-decalin Chemical compound C1CCC[C@H]2CCCC[C@H]21 NNBZCPXTIHJBJL-AOOOYVTPSA-N 0.000 description 1
• 235000013477 citrulline Nutrition 0.000 description 1
• 229960002173 citrulline Drugs 0.000 description 1
• 229940110456 cocoa butter Drugs 0.000 description 1
• 235000019868 cocoa butter Nutrition 0.000 description 1
• 206010009887 colitis Diseases 0.000 description 1
• 229960002424 collagenase Drugs 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000002860 competitive effect Effects 0.000 description 1
• 239000002299 complementary DNA Substances 0.000 description 1
• 238000007796 conventional method Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 125000004802 cyanophenyl group Chemical group 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
• 239000002852 cysteine proteinase inhibitor Substances 0.000 description 1
• 150000001945 cysteines Chemical class 0.000 description 1
• KJOZJSGOIJQCGA-UHFFFAOYSA-N dichloromethane;2,2,2-trifluoroacetic acid Chemical compound ClCCl.OC(=O)C(F)(F)F KJOZJSGOIJQCGA-UHFFFAOYSA-N 0.000 description 1
• SQKZZFWTOOPCDQ-UHFFFAOYSA-N dichloromethane;ethyl acetate;hexane Chemical compound ClCCl.CCCCCC.CCOC(C)=O SQKZZFWTOOPCDQ-UHFFFAOYSA-N 0.000 description 1
• PXSFGMATQMURKO-UHFFFAOYSA-N dichloromethane;methanol;propan-2-one Chemical compound OC.ClCCl.CC(C)=O PXSFGMATQMURKO-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• 229940116901 diethyldithiocarbamate Drugs 0.000 description 1
• LMBWSYZSUOEYSN-UHFFFAOYSA-N diethyldithiocarbamic acid Chemical compound CCN(CC)C(S)=S LMBWSYZSUOEYSN-UHFFFAOYSA-N 0.000 description 1
• 230000004069 differentiation Effects 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• BEQVQKJCLJBTKZ-UHFFFAOYSA-N diphenylphosphinic acid Chemical compound C=1C=CC=CC=1P(=O)(O)C1=CC=CC=C1 BEQVQKJCLJBTKZ-UHFFFAOYSA-N 0.000 description 1
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 1
• 239000002552 dosage form Substances 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000003995 emulsifying agent Substances 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 206010014599 encephalitis Diseases 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940095399 enema Drugs 0.000 description 1
• 238000005516 engineering process Methods 0.000 description 1
• 238000006911 enzymatic reaction Methods 0.000 description 1
• 238000001952 enzyme assay Methods 0.000 description 1
• 239000002532 enzyme inhibitor Substances 0.000 description 1
• 229940125532 enzyme inhibitor Drugs 0.000 description 1
• 210000003979 eosinophil Anatomy 0.000 description 1
• 230000032050 esterification Effects 0.000 description 1
• 238000005886 esterification reaction Methods 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
• VTNFLVJEOPKVIC-PPHPATTJSA-N ethyl (2s)-2,3-dihydro-1h-indole-2-carboxylate;hydrochloride Chemical compound Cl.C1=CC=C2N[C@H](C(=O)OCC)CC2=C1 VTNFLVJEOPKVIC-PPHPATTJSA-N 0.000 description 1
• KISPUTPAKVZNBI-UHFFFAOYSA-N ethyl 2,3-dihydro-1h-indole-2-carboxylate Chemical compound C1=CC=C2NC(C(=O)OCC)CC2=C1 KISPUTPAKVZNBI-UHFFFAOYSA-N 0.000 description 1
• 239000002024 ethyl acetate extract Substances 0.000 description 1
• MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
• WHQLQYRFIHPMNA-UHFFFAOYSA-N ethyl acetate;oxolane Chemical compound C1CCOC1.CCOC(C)=O WHQLQYRFIHPMNA-UHFFFAOYSA-N 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000029142 excretion Effects 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 238000013213 extrapolation Methods 0.000 description 1
• 210000002950 fibroblast Anatomy 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
• 239000012634 fragment Substances 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 229960002989 glutamic acid Drugs 0.000 description 1
• 235000013922 glutamic acid Nutrition 0.000 description 1
• 239000004220 glutamic acid Substances 0.000 description 1
• ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
• 229960002743 glutamine Drugs 0.000 description 1
• 235000004554 glutamine Nutrition 0.000 description 1
• ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
• 230000003394 haemopoietic effect Effects 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• RBBOWEDMXHTEPA-UHFFFAOYSA-N hexane;toluene Chemical compound CCCCCC.CC1=CC=CC=C1 RBBOWEDMXHTEPA-UHFFFAOYSA-N 0.000 description 1
• 230000036571 hydration Effects 0.000 description 1
• 238000006703 hydration reaction Methods 0.000 description 1
• 125000005597 hydrazone group Chemical group 0.000 description 1
• 229960002591 hydroxyproline Drugs 0.000 description 1
• 230000009610 hypersensitivity Effects 0.000 description 1
• 239000002955 immunomodulating agent Substances 0.000 description 1
• 229940121354 immunomodulator Drugs 0.000 description 1
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
• 230000002757 inflammatory effect Effects 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 238000007917 intracranial administration Methods 0.000 description 1
• 238000007919 intrasynovial administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 238000005342 ion exchange Methods 0.000 description 1
• 239000013038 irreversible inhibitor Substances 0.000 description 1
• 208000023589 ischemic disease Diseases 0.000 description 1
• 229960000310 isoleucine Drugs 0.000 description 1
• AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
• 201000010901 lateral sclerosis Diseases 0.000 description 1
• 235000010445 lecithin Nutrition 0.000 description 1
• 239000000787 lecithin Substances 0.000 description 1
• 229940067606 lecithin Drugs 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000004324 lymphatic system Anatomy 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 239000003771 matrix metalloproteinase inhibitor Substances 0.000 description 1
• 229940121386 matrix metalloproteinase inhibitor Drugs 0.000 description 1
• 230000002503 metabolic effect Effects 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• 229940098779 methanesulfonic acid Drugs 0.000 description 1
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
• CXQTTWVBUDFUNO-LURJTMIESA-N methyl (2s)-piperidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCCN1 CXQTTWVBUDFUNO-LURJTMIESA-N 0.000 description 1
• RYNVPGCCNZBBCS-UHFFFAOYSA-N methyl 2-[4-(2-aminoethyl)phenoxy]acetate Chemical compound COC(=O)COC1=CC=C(CCN)C=C1 RYNVPGCCNZBBCS-UHFFFAOYSA-N 0.000 description 1
• AEVHVVDLIHWAGR-UHFFFAOYSA-N methyl 2-amino-2-oxoacetate Chemical compound COC(=O)C(N)=O AEVHVVDLIHWAGR-UHFFFAOYSA-N 0.000 description 1
• GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 description 1
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
• BDGDWWGTAFXEEW-UHFFFAOYSA-N methylsulfinylmethane;oxalyl dichloride Chemical compound CS(C)=O.ClC(=O)C(Cl)=O BDGDWWGTAFXEEW-UHFFFAOYSA-N 0.000 description 1
• 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
• 229940042472 mineral oil Drugs 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 208000005264 motor neuron disease Diseases 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
• CMWYAOXYQATXSI-UHFFFAOYSA-N n,n-dimethylformamide;piperidine Chemical compound CN(C)C=O.C1CCNCC1 CMWYAOXYQATXSI-UHFFFAOYSA-N 0.000 description 1
• DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 description 1
• 229960003086 naltrexone Drugs 0.000 description 1
• NVSYANRBXPURRQ-UHFFFAOYSA-N naphthalen-1-ylmethanamine Chemical compound C1=CC=C2C(CN)=CC=CC2=C1 NVSYANRBXPURRQ-UHFFFAOYSA-N 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 125000006501 nitrophenyl group Chemical group 0.000 description 1
• 231100000344 non-irritating Toxicity 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• 230000001473 noxious effect Effects 0.000 description 1
• GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
• 239000004006 olive oil Substances 0.000 description 1
• 235000008390 olive oil Nutrition 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 150000002892 organic cations Chemical class 0.000 description 1
• 239000012044 organic layer Substances 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 150000002923 oximes Chemical class 0.000 description 1
• TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
• 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
• 229910052763 palladium Inorganic materials 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 210000000496 pancreas Anatomy 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 230000008506 pathogenesis Effects 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 125000001151 peptidyl group Chemical group 0.000 description 1
• 210000005259 peripheral blood Anatomy 0.000 description 1
• 239000011886 peripheral blood Substances 0.000 description 1
• 239000012071 phase Substances 0.000 description 1
• ASUOLLHGALPRFK-UHFFFAOYSA-N phenylphosphonoylbenzene Chemical group C=1C=CC=CC=1P(=O)C1=CC=CC=C1 ASUOLLHGALPRFK-UHFFFAOYSA-N 0.000 description 1
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 125000005544 phthalimido group Chemical group 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 229920001230 polyarylate Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
• 235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
• 229920001451 polypropylene glycol Polymers 0.000 description 1
• 229940113124 polysorbate 60 Drugs 0.000 description 1
• 229920000053 polysorbate 80 Polymers 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
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• 230000001376 precipitating effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 239000003755 preservative agent Substances 0.000 description 1
• 150000003141 primary amines Chemical class 0.000 description 1
• MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
• 229960004919 procaine Drugs 0.000 description 1
• 230000035755 proliferation Effects 0.000 description 1
• 229960002429 proline Drugs 0.000 description 1
• 235000013930 proline Nutrition 0.000 description 1
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 229950008679 protamine sulfate Drugs 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
• 230000017854 proteolysis Effects 0.000 description 1
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 229960000948 quinine Drugs 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 229940100618 rectal suppository Drugs 0.000 description 1
• 239000006215 rectal suppository Substances 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000020129 regulation of cell death Effects 0.000 description 1
• 230000002629 repopulating effect Effects 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 230000000630 rising effect Effects 0.000 description 1
• 208000013223 septicemia Diseases 0.000 description 1
• 229960001153 serine Drugs 0.000 description 1
• 150000003355 serines Chemical class 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• WSWCOQWTEOXDQX-MQQKCMAXSA-N sorbic acid group Chemical group C(\C=C\C=C\C)(=O)O WSWCOQWTEOXDQX-MQQKCMAXSA-N 0.000 description 1
• 239000001587 sorbitan monostearate Substances 0.000 description 1
• 235000011076 sorbitan monostearate Nutrition 0.000 description 1
• 229940035048 sorbitan monostearate Drugs 0.000 description 1
• 241000894007 species Species 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 101150035983 str1 gene Proteins 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005017 substituted alkenyl group Chemical group 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 210000001179 synovial fluid Anatomy 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 239000003826 tablet Substances 0.000 description 1
• FXHXDVSVXUUFFK-MJVOBMLWSA-N tert-butyl (3S,5S)-2,5-diamino-3-[1-hydroxy-2-(2,3,5,6-tetrafluorophenoxy)ethyl]-6-methyl-4-oxoheptanoate Chemical compound C(C)(C)(C)OC(C([C@@H](C(COC1=C(C(=CC(=C1F)F)F)F)O)C([C@@H](N)C(C)C)=O)N)=O FXHXDVSVXUUFFK-MJVOBMLWSA-N 0.000 description 1
• RTBHEJSAOKPNHQ-ZHEBCZLYSA-N tert-butyl (3S,5S)-2-amino-5-(cyclohexylamino)-3-[1-hydroxy-2-(2,3,5,6-tetrafluorophenoxy)ethyl]-4-oxohexanoate Chemical compound C(C)(C)(C)OC(C([C@@H](C(COC1=C(C(=CC(=C1F)F)F)F)O)C([C@@H](NC1CCCCC1)C)=O)N)=O RTBHEJSAOKPNHQ-ZHEBCZLYSA-N 0.000 description 1
• QVTSLNADKNHWRK-ZLMIFYAYSA-N tert-butyl (5S)-2,5-diamino-3-(2-fluoro-1-hydroxyethyl)-7-methyl-4-oxooctanoate Chemical compound C(C)(C)(C)OC(C(C(C(CF)O)C([C@@H](N)CC(C)C)=O)N)=O QVTSLNADKNHWRK-ZLMIFYAYSA-N 0.000 description 1
• COXUQTRSJXNTSH-UHFFFAOYSA-N tert-butyl 2-amino-5-diphenylphosphoryloxy-4-oxopentanoate Chemical compound C(C)(C)(C)OC(C(CC(COP(=O)(C1=CC=CC=C1)C1=CC=CC=C1)=O)N)=O COXUQTRSJXNTSH-UHFFFAOYSA-N 0.000 description 1
• AECNGSKDJGEXJS-UHFFFAOYSA-N tert-butyl 2-amino-5-fluoro-4-oxopentanoate Chemical compound C(C)(C)(C)OC(C(CC(CF)=O)N)=O AECNGSKDJGEXJS-UHFFFAOYSA-N 0.000 description 1
• GAOCYGMWQJTKPG-UHFFFAOYSA-N tert-butyl 3-amino-5-fluoro-4-hydroxypentanoate Chemical compound CC(C)(C)OC(=O)CC(N)C(O)CF GAOCYGMWQJTKPG-UHFFFAOYSA-N 0.000 description 1
• FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
• DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
• ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 1
• 238000012360 testing method Methods 0.000 description 1
• MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
• 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
• FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 1
• NNBZCPXTIHJBJL-UHFFFAOYSA-N trans-decahydronaphthalene Natural products C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
• NNBZCPXTIHJBJL-MGCOHNPYSA-N trans-decalin Chemical compound C1CCC[C@@H]2CCCC[C@H]21 NNBZCPXTIHJBJL-MGCOHNPYSA-N 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• CAPORZWUTKSILW-UHFFFAOYSA-N triazolealanine Chemical compound OC(=O)C(N)CC1=NC=NN1 CAPORZWUTKSILW-UHFFFAOYSA-N 0.000 description 1
• 150000003852 triazoles Chemical class 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
• 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
• 229960004799 tryptophan Drugs 0.000 description 1
• 229940099259 vaseline Drugs 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 239000001993 wax Substances 0.000 description 1
• 239000000080 wetting agent Substances 0.000 description 1
• 239000003871 white petrolatum Substances 0.000 description 1
• 230000029663 wound healing Effects 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1