JP2016515509A - トリペプチドエポキシケトンプロテアーゼ阻害剤 - Google Patents
トリペプチドエポキシケトンプロテアーゼ阻害剤 Download PDFInfo
- Publication number
- JP2016515509A JP2016515509A JP2016502301A JP2016502301A JP2016515509A JP 2016515509 A JP2016515509 A JP 2016515509A JP 2016502301 A JP2016502301 A JP 2016502301A JP 2016502301 A JP2016502301 A JP 2016502301A JP 2016515509 A JP2016515509 A JP 2016515509A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- compound according
- oxopropan
- group
- propanamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 title abstract description 6
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 3
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 292
- 150000001875 compounds Chemical class 0.000 claims abstract description 225
- 238000000034 method Methods 0.000 claims abstract description 97
- 150000003839 salts Chemical class 0.000 claims abstract description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 201000010099 disease Diseases 0.000 claims abstract description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 7
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 6
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 4
- -1 and R 3 Chemical group 0.000 claims description 171
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- 210000004027 cell Anatomy 0.000 claims description 45
- 125000000217 alkyl group Chemical group 0.000 claims description 44
- 108090000708 Proteasome Endopeptidase Complex Proteins 0.000 claims description 40
- 102000004245 Proteasome Endopeptidase Complex Human genes 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 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 17
- 239000007924 injection Substances 0.000 claims description 17
- 238000002347 injection Methods 0.000 claims description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 230000001404 mediated effect Effects 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 238000001727 in vivo Methods 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- 101001136986 Homo sapiens Proteasome subunit beta type-8 Proteins 0.000 claims description 6
- 102100035760 Proteasome subunit beta type-8 Human genes 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 208000011580 syndromic disease Diseases 0.000 claims description 6
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 5
- 210000003169 central nervous system Anatomy 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 238000000338 in vitro Methods 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 4
- 201000004624 Dermatitis Diseases 0.000 claims description 4
- 241000282414 Homo sapiens Species 0.000 claims description 4
- 101001136981 Homo sapiens Proteasome subunit beta type-9 Proteins 0.000 claims description 4
- 208000028622 Immune thrombocytopenia Diseases 0.000 claims description 4
- 102100035764 Proteasome subunit beta type-9 Human genes 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 4
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims description 4
- 210000000265 leukocyte Anatomy 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 201000009906 Meningitis Diseases 0.000 claims description 3
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 3
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 206010009887 colitis Diseases 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 claims description 3
- 206010014599 encephalitis Diseases 0.000 claims description 3
- 206010025135 lupus erythematosus Diseases 0.000 claims description 3
- 125000003566 oxetanyl group Chemical group 0.000 claims description 3
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 208000026872 Addison Disease Diseases 0.000 claims description 2
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 2
- 206010050245 Autoimmune thrombocytopenia Diseases 0.000 claims description 2
- 208000023328 Basedow disease Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 208000007465 Giant cell arteritis Diseases 0.000 claims description 2
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 2
- 208000015023 Graves' disease Diseases 0.000 claims description 2
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 2
- 206010028372 Muscular weakness Diseases 0.000 claims description 2
- 206010029240 Neuritis Diseases 0.000 claims description 2
- 206010034277 Pemphigoid Diseases 0.000 claims description 2
- 241000721454 Pemphigus Species 0.000 claims description 2
- 208000031845 Pernicious anaemia Diseases 0.000 claims description 2
- 206010036105 Polyneuropathy Diseases 0.000 claims description 2
- 208000003782 Raynaud disease Diseases 0.000 claims description 2
- 208000012322 Raynaud phenomenon Diseases 0.000 claims description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
- 206010072148 Stiff-Person syndrome Diseases 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 206010047115 Vasculitis Diseases 0.000 claims description 2
- 125000005275 alkylenearyl group Chemical group 0.000 claims description 2
- 125000005218 alkyleneheteroaryl group Chemical group 0.000 claims description 2
- 230000000172 allergic effect Effects 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 230000001363 autoimmune Effects 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 208000000594 bullous pemphigoid Diseases 0.000 claims description 2
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 206010012601 diabetes mellitus Diseases 0.000 claims description 2
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 2
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 2
- 208000030172 endocrine system disease Diseases 0.000 claims description 2
- 208000007475 hemolytic anemia Diseases 0.000 claims description 2
- 230000036473 myasthenia Effects 0.000 claims description 2
- 206010028417 myasthenia gravis Diseases 0.000 claims description 2
- 201000008383 nephritis Diseases 0.000 claims description 2
- 125000004193 piperazinyl group Chemical group 0.000 claims description 2
- 208000005987 polymyositis Diseases 0.000 claims description 2
- 230000007824 polyneuropathy Effects 0.000 claims description 2
- 201000000306 sarcoidosis Diseases 0.000 claims description 2
- 206010043207 temporal arteritis Diseases 0.000 claims description 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 4
- 150000002431 hydrogen Chemical class 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- 208000009137 Behcet syndrome Diseases 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 208000033464 Reiter syndrome Diseases 0.000 claims 1
- 208000034189 Sclerosis Diseases 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 208000037976 chronic inflammation Diseases 0.000 claims 1
- 230000006020 chronic inflammation Effects 0.000 claims 1
- 208000002574 reactive arthritis Diseases 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 12
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 291
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 202
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 162
- 238000005481 NMR spectroscopy Methods 0.000 description 159
- 238000004949 mass spectrometry Methods 0.000 description 150
- 235000019439 ethyl acetate Nutrition 0.000 description 144
- 239000000243 solution Substances 0.000 description 135
- 239000011541 reaction mixture Substances 0.000 description 102
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 100
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 99
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 94
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 93
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 91
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 90
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 88
- 238000003818 flash chromatography Methods 0.000 description 74
- 239000000741 silica gel Substances 0.000 description 74
- 229910002027 silica gel Inorganic materials 0.000 description 74
- 239000012267 brine Substances 0.000 description 63
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 63
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 54
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 52
- 235000002639 sodium chloride Nutrition 0.000 description 46
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 43
- 239000012074 organic phase Substances 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 40
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 39
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 38
- 239000003921 oil Substances 0.000 description 38
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 235000019198 oils Nutrition 0.000 description 37
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 37
- 239000007821 HATU Substances 0.000 description 34
- 239000003208 petroleum Substances 0.000 description 34
- 238000000746 purification Methods 0.000 description 34
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 33
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- 239000000706 filtrate Substances 0.000 description 32
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 30
- 239000007787 solid Substances 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 239000000284 extract Substances 0.000 description 27
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 27
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 26
- 239000000725 suspension Substances 0.000 description 26
- 239000008346 aqueous phase Substances 0.000 description 25
- 238000003756 stirring Methods 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 239000002253 acid Substances 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- 108090000623 proteins and genes Proteins 0.000 description 24
- 230000000694 effects Effects 0.000 description 22
- 102100023050 Nuclear factor NF-kappa-B p105 subunit Human genes 0.000 description 20
- 239000010410 layer Substances 0.000 description 19
- 230000002829 reductive effect Effects 0.000 description 19
- 239000012298 atmosphere Substances 0.000 description 18
- 230000005764 inhibitory process Effects 0.000 description 18
- 108010057466 NF-kappa B Proteins 0.000 description 17
- 102000004190 Enzymes Human genes 0.000 description 16
- 108090000790 Enzymes Proteins 0.000 description 16
- 229940088598 enzyme Drugs 0.000 description 16
- 235000018102 proteins Nutrition 0.000 description 16
- 102000004169 proteins and genes Human genes 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 15
- 230000000875 corresponding effect Effects 0.000 description 15
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000004480 active ingredient Substances 0.000 description 14
- 239000012230 colorless oil Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 13
- 239000000843 powder Substances 0.000 description 13
- 108050006400 Cyclin Proteins 0.000 description 12
- 102000016736 Cyclin Human genes 0.000 description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000003814 drug Substances 0.000 description 12
- 238000009472 formulation Methods 0.000 description 12
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 description 12
- 235000019260 propionic acid Nutrition 0.000 description 12
- 230000002797 proteolythic effect Effects 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 229940079156 Proteasome inhibitor Drugs 0.000 description 11
- 230000015556 catabolic process Effects 0.000 description 11
- 125000004122 cyclic group Chemical group 0.000 description 11
- 238000006731 degradation reaction Methods 0.000 description 11
- 108090000765 processed proteins & peptides Proteins 0.000 description 11
- 239000003207 proteasome inhibitor Substances 0.000 description 11
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 230000014509 gene expression Effects 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 230000008569 process Effects 0.000 description 10
- 230000017854 proteolysis Effects 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- BWRNWWSQZROEOA-UHFFFAOYSA-N 2-morpholin-4-ylacetamide Chemical compound NC(=O)CN1CCOCC1 BWRNWWSQZROEOA-UHFFFAOYSA-N 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 208000035475 disorder Diseases 0.000 description 9
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 9
- 229920001223 polyethylene glycol Polymers 0.000 description 9
- 238000012545 processing Methods 0.000 description 9
- 239000011701 zinc Substances 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 8
- 235000001014 amino acid Nutrition 0.000 description 8
- 150000003840 hydrochlorides Chemical class 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 239000000546 pharmaceutical excipient Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 125000006633 tert-butoxycarbonylamino group Chemical group 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 108090000695 Cytokines Proteins 0.000 description 7
- 108090000467 Interferon-beta Proteins 0.000 description 7
- VIWZVFVJPXTXPA-UHFFFAOYSA-N N-(2-Carboxymethyl)-morpholine Chemical compound OC(=O)CN1CCOCC1 VIWZVFVJPXTXPA-UHFFFAOYSA-N 0.000 description 7
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 7
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 150000001413 amino acids Chemical class 0.000 description 7
- 230000030741 antigen processing and presentation Effects 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 210000000988 bone and bone Anatomy 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 230000028993 immune response Effects 0.000 description 7
- 229910052738 indium Inorganic materials 0.000 description 7
- 239000002674 ointment Substances 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 102000004196 processed proteins & peptides Human genes 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 239000000829 suppository Substances 0.000 description 7
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
- 206010016654 Fibrosis Diseases 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 6
- 102100026720 Interferon beta Human genes 0.000 description 6
- 108010002350 Interleukin-2 Proteins 0.000 description 6
- 102000000588 Interleukin-2 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000002552 dosage form Substances 0.000 description 6
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000008273 gelatin Substances 0.000 description 6
- 229920000159 gelatin Polymers 0.000 description 6
- 229940014259 gelatin Drugs 0.000 description 6
- 235000019322 gelatine Nutrition 0.000 description 6
- 235000011852 gelatine desserts Nutrition 0.000 description 6
- 125000005842 heteroatom Chemical group 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- UGZBFCCHLUWCQI-LURJTMIESA-N methyl (2r)-3-iodo-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)[C@H](CI)NC(=O)OC(C)(C)C UGZBFCCHLUWCQI-LURJTMIESA-N 0.000 description 6
- 210000003205 muscle Anatomy 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- PJAZNVBLRNCMIO-JTQLQIEISA-N (2S)-3-(cyclopenten-1-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CC1=CCCC1)C(O)=O PJAZNVBLRNCMIO-JTQLQIEISA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 5
- 102000014303 Amyloid beta-Protein Precursor Human genes 0.000 description 5
- 108010079054 Amyloid beta-Protein Precursor Proteins 0.000 description 5
- 241000416162 Astragalus gummifer Species 0.000 description 5
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 5
- 102000004127 Cytokines Human genes 0.000 description 5
- 206010012289 Dementia Diseases 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 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 5
- 241000222722 Leishmania <genus> Species 0.000 description 5
- 108700018351 Major Histocompatibility Complex Proteins 0.000 description 5
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 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 5
- 229930006000 Sucrose Natural products 0.000 description 5
- 229920001615 Tragacanth Polymers 0.000 description 5
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 5
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 239000003963 antioxidant agent Substances 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- 230000021164 cell adhesion Effects 0.000 description 5
- 239000003995 emulsifying agent Substances 0.000 description 5
- 239000002158 endotoxin Substances 0.000 description 5
- 235000019441 ethanol Nutrition 0.000 description 5
- 230000004761 fibrosis Effects 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 208000014674 injury Diseases 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 229920006008 lipopolysaccharide Polymers 0.000 description 5
- 239000002502 liposome Substances 0.000 description 5
- UZNGRHDUJIVHQT-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].C[C-]=C UZNGRHDUJIVHQT-UHFFFAOYSA-M 0.000 description 5
- 230000003071 parasitic effect Effects 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 230000034190 positive regulation of NF-kappaB transcription factor activity Effects 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 5
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- QODDXXKYBMUIEE-ZETCQYMHSA-N (2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoic acid Chemical compound C[C@H](NC(=O)CN1CCOCC1)C(O)=O QODDXXKYBMUIEE-ZETCQYMHSA-N 0.000 description 4
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- 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 4
- ZIXLDMFVRPABBX-UHFFFAOYSA-N 2-methylcyclopentan-1-one Chemical compound CC1CCCC1=O ZIXLDMFVRPABBX-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 4
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- 102100038132 Endogenous retrovirus group K member 6 Pro protein Human genes 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 102000018745 NF-KappaB Inhibitor alpha Human genes 0.000 description 4
- 108010052419 NF-KappaB Inhibitor alpha Proteins 0.000 description 4
- 208000030852 Parasitic disease Diseases 0.000 description 4
- 108010073038 Penicillin Amidase Proteins 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 241000223960 Plasmodium falciparum Species 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- 201000003176 Severe Acute Respiratory Syndrome Diseases 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 210000001744 T-lymphocyte Anatomy 0.000 description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 4
- 230000009471 action Effects 0.000 description 4
- 150000001408 amides Chemical class 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 210000002449 bone cell Anatomy 0.000 description 4
- 229940112869 bone morphogenetic protein Drugs 0.000 description 4
- 230000022131 cell cycle Effects 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 4
- HAAOHBCJARVREN-UHFFFAOYSA-N cyclopenten-1-yl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC1=CCCC1 HAAOHBCJARVREN-UHFFFAOYSA-N 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000003701 inert diluent Substances 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- 235000010445 lecithin Nutrition 0.000 description 4
- 239000000787 lecithin Substances 0.000 description 4
- 229940067606 lecithin Drugs 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 208000011045 mucopolysaccharidosis type 3 Diseases 0.000 description 4
- HWWVAHCWJLGKLW-UHFFFAOYSA-N n,n-dimethylhydroxylamine;hydron;chloride Chemical compound Cl.CN(C)O HWWVAHCWJLGKLW-UHFFFAOYSA-N 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 230000000269 nucleophilic effect Effects 0.000 description 4
- 150000002894 organic compounds Chemical class 0.000 description 4
- DGOYLVBDCVINQZ-UHFFFAOYSA-N oxane-4-carboxamide Chemical compound NC(=O)C1CCOCC1 DGOYLVBDCVINQZ-UHFFFAOYSA-N 0.000 description 4
- 244000045947 parasite Species 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000003380 propellant Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 150000008163 sugars Chemical class 0.000 description 4
- 239000000454 talc Substances 0.000 description 4
- 229910052623 talc Inorganic materials 0.000 description 4
- 235000012222 talc Nutrition 0.000 description 4
- VCRLJOYXJMAZNY-OAQWYYJWSA-N tert-butyl N-[(2S)-3-(3-methylcyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound CC1CCC(C[C@H](NC(=O)OC(C)(C)C)C(=O)[C@@]2(C)CO2)=C1 VCRLJOYXJMAZNY-OAQWYYJWSA-N 0.000 description 4
- 235000010487 tragacanth Nutrition 0.000 description 4
- 239000000196 tragacanth Substances 0.000 description 4
- 229940116362 tragacanth Drugs 0.000 description 4
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- GBTWGGHVJJRREA-JTQLQIEISA-N (2s)-3-cyclopentyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1CCCC1 GBTWGGHVJJRREA-JTQLQIEISA-N 0.000 description 3
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 3
- MYYIMZRZXIQBGI-HVIRSNARSA-N 6alpha-Fluoroprednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 MYYIMZRZXIQBGI-HVIRSNARSA-N 0.000 description 3
- 108010022579 ATP dependent 26S protease Proteins 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- 108010024212 E-Selectin Proteins 0.000 description 3
- 102100023471 E-selectin Human genes 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 241000700721 Hepatitis B virus Species 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 3
- 240000007472 Leucaena leucocephala Species 0.000 description 3
- 208000015439 Lysosomal storage disease Diseases 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 241000711466 Murine hepatitis virus Species 0.000 description 3
- 206010028289 Muscle atrophy Diseases 0.000 description 3
- 229910019093 NaOCl Inorganic materials 0.000 description 3
- 108010035766 P-Selectin Proteins 0.000 description 3
- 102100023472 P-selectin Human genes 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 241000224016 Plasmodium Species 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 206010040070 Septic Shock Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- 241000223104 Trypanosoma Species 0.000 description 3
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 3
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 3
- 208000036142 Viral infection Diseases 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000003429 antifungal agent Substances 0.000 description 3
- 229940121375 antifungal agent Drugs 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 239000000440 bentonite Substances 0.000 description 3
- 229910000278 bentonite Inorganic materials 0.000 description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 239000007844 bleaching agent Substances 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 3
- 230000037012 chymotrypsin-like activity Effects 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 230000026374 cyclin catabolic process Effects 0.000 description 3
- CWTLVGQWYBAHTL-AXDSSHIGSA-N dimethyl (4S)-2-(2-aminoethyl)-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioate Chemical compound COC(=O)C(CCN)C[C@H](NC(=O)OC(C)(C)C)C(=O)OC CWTLVGQWYBAHTL-AXDSSHIGSA-N 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 3
- 239000000945 filler Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229960000618 fluprednisolone Drugs 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 238000010575 fractional recrystallization Methods 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 description 3
- USZLCYNVCCDPLQ-UHFFFAOYSA-N hydron;n-methoxymethanamine;chloride Chemical class Cl.CNOC USZLCYNVCCDPLQ-UHFFFAOYSA-N 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 230000003463 hyperproliferative effect Effects 0.000 description 3
- 210000000987 immune system Anatomy 0.000 description 3
- 239000002955 immunomodulating agent Substances 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 230000035800 maturation Effects 0.000 description 3
- WPUFSWHRJVPGBU-NSHDSACASA-N methyl (2s)-3-(cyclopenten-1-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CCCC1 WPUFSWHRJVPGBU-NSHDSACASA-N 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 201000000585 muscular atrophy Diseases 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 230000011164 ossification Effects 0.000 description 3
- PCPUMGYALMOCHF-UHFFFAOYSA-N oxolan-3-ylmethanol Chemical compound OCC1CCOC1 PCPUMGYALMOCHF-UHFFFAOYSA-N 0.000 description 3
- 239000006072 paste Substances 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 238000002953 preparative HPLC Methods 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 230000036303 septic shock Effects 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 230000020382 suppression by virus of host antigen processing and presentation of peptide antigen via MHC class I Effects 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 238000007910 systemic administration Methods 0.000 description 3
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
- 230000035897 transcription Effects 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- 230000009385 viral infection Effects 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- TXWJHEADRVGPQX-ZADZHZCXSA-N (2R)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]oxolane-2-carboxamide Chemical compound C1(CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H](CC1=CC=C(C=C1)OC)NC([C@@H](C)NC(=O)[C@@H]1OCCC1)=O)=O TXWJHEADRVGPQX-ZADZHZCXSA-N 0.000 description 2
- ZJMQURXHSNGKDX-GXSJLCMTSA-N (2S)-2-amino-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]propan-1-one Chemical compound C[C@@]1(CO1)C(=O)[C@@H](N)CC1=CCCC1 ZJMQURXHSNGKDX-GXSJLCMTSA-N 0.000 description 2
- ZBOZVXDMOZMHHC-KHQFGBGNSA-N (2S)-2-amino-3-[(1R)-3,3-difluorocyclopentyl]-1-[(2R)-2-methyloxiran-2-yl]propan-1-one Chemical compound C[C@@]1(CO1)C(=O)[C@@H](N)C[C@H]1CCC(F)(F)C1 ZBOZVXDMOZMHHC-KHQFGBGNSA-N 0.000 description 2
- ZBOZVXDMOZMHHC-OYNCUSHFSA-N (2S)-2-amino-3-[(1S)-3,3-difluorocyclopentyl]-1-[(2R)-2-methyloxiran-2-yl]propan-1-one Chemical compound C[C@@]1(CO1)C(=O)[C@@H](N)C[C@@H]1CCC(F)(F)C1 ZBOZVXDMOZMHHC-OYNCUSHFSA-N 0.000 description 2
- ADFOJOATDQVRNR-GXSJLCMTSA-N (2S)-2-amino-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]propan-1-one Chemical compound C[C@@]1(CO1)C(=O)[C@@H](N)CC1CCCC1 ADFOJOATDQVRNR-GXSJLCMTSA-N 0.000 description 2
- TXWJHEADRVGPQX-TWBQWIPNSA-N (2S)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]oxolane-2-carboxamide Chemical compound C1(CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H](CC1=CC=C(C=C1)OC)NC([C@@H](C)NC(=O)[C@H]1OCCC1)=O)=O TXWJHEADRVGPQX-TWBQWIPNSA-N 0.000 description 2
- GXSZHKBAXHJPPL-WCCKRBBISA-N (2s)-2-amino-3-hydroxy-2-methylpropanoic acid;hydrochloride Chemical compound Cl.OC[C@@](N)(C)C(O)=O GXSZHKBAXHJPPL-WCCKRBBISA-N 0.000 description 2
- JQQKPBWVLDZJFE-BBRMVZONSA-N (2s)-3-(4-methoxyphenyl)-2-[[(2s)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanoic acid Chemical compound C1=CC(OC)=CC=C1C[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)CN1CCOCC1 JQQKPBWVLDZJFE-BBRMVZONSA-N 0.000 description 2
- LAEUAIQGUIVNGY-UHFFFAOYSA-N (3-methylcyclopenten-1-yl)methanol Chemical compound CC1CCC(CO)=C1 LAEUAIQGUIVNGY-UHFFFAOYSA-N 0.000 description 2
- SYIPULVZSBBBDV-QWOQVESASA-N (3R)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]oxolane-3-carboxamide Chemical compound C1(CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H](CC1=CC=C(C=C1)OC)NC([C@@H](C)NC(=O)[C@H]1COCC1)=O)=O SYIPULVZSBBBDV-QWOQVESASA-N 0.000 description 2
- SYIPULVZSBBBDV-XHJSBQMMSA-N (3S)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]oxolane-3-carboxamide Chemical compound C1(CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H](CC1=CC=C(C=C1)OC)NC([C@@H](C)NC(=O)[C@@H]1COCC1)=O)=O SYIPULVZSBBBDV-XHJSBQMMSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- IROPXRINRLPOEM-UHFFFAOYSA-N 3-iodocyclopent-2-en-1-one Chemical compound IC1=CC(=O)CC1 IROPXRINRLPOEM-UHFFFAOYSA-N 0.000 description 2
- BMTZEAOGFDXDAD-UHFFFAOYSA-M 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholin-4-ium;chloride Chemical compound [Cl-].COC1=NC(OC)=NC([N+]2(C)CCOCC2)=N1 BMTZEAOGFDXDAD-UHFFFAOYSA-M 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- UCUHQXIAXJMZRI-UHFFFAOYSA-N 4-hydroxycyclohexane-1-carboxamide Chemical compound NC(=O)C1CCC(O)CC1 UCUHQXIAXJMZRI-UHFFFAOYSA-N 0.000 description 2
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- 208000010444 Acidosis Diseases 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 2
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 2
- 206010065687 Bone loss Diseases 0.000 description 2
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- JIZFEFKHYZSQJN-BLLLJJGKSA-N CC(C)(C)N([C@@H](CC1=CCCC1)C(=O)[C@@]1(C)CO1)C(O)=O Chemical class CC(C)(C)N([C@@H](CC1=CCCC1)C(=O)[C@@]1(C)CO1)C(O)=O JIZFEFKHYZSQJN-BLLLJJGKSA-N 0.000 description 2
- PRJCFBFSCJTTMI-ZIBATOQPSA-N C[C@@]1(CO1)C(=O)[C@H](C[C@@H]2CCOC2)N(C(=O)O)C(C)(C)C Chemical class C[C@@]1(CO1)C(=O)[C@H](C[C@@H]2CCOC2)N(C(=O)O)C(C)(C)C PRJCFBFSCJTTMI-ZIBATOQPSA-N 0.000 description 2
- PRJCFBFSCJTTMI-JRPNMDOOSA-N C[C@@]1(CO1)C(=O)[C@H](C[C@H]2CCOC2)N(C(=O)O)C(C)(C)C Chemical class C[C@@]1(CO1)C(=O)[C@H](C[C@H]2CCOC2)N(C(=O)O)C(C)(C)C PRJCFBFSCJTTMI-JRPNMDOOSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 101710091045 Envelope protein Proteins 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 241000206602 Eukaryota Species 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 208000032007 Glycogen storage disease due to acid maltase deficiency Diseases 0.000 description 2
- 206010053185 Glycogen storage disease type II Diseases 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010021143 Hypoxia Diseases 0.000 description 2
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 2
- 206010021263 IgA nephropathy Diseases 0.000 description 2
- 102000013463 Immunoglobulin Light Chains Human genes 0.000 description 2
- 108010065825 Immunoglobulin Light Chains Proteins 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000010789 Interleukin-2 Receptors Human genes 0.000 description 2
- 108010038453 Interleukin-2 Receptors Proteins 0.000 description 2
- 150000008575 L-amino acids Chemical class 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- 102100033448 Lysosomal alpha-glucosidase Human genes 0.000 description 2
- 102000043129 MHC class I family Human genes 0.000 description 2
- 108091054437 MHC class I family Proteins 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- PFVDRKCXACZILF-NDJWTUBHSA-N N-[(2R)-1-[[(2S)-1-[[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]oxetane-3-carboxamide Chemical compound COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)C2COC2)C(=O)N[C@@H](CC2=CCCC2)C(=O)[C@@]2(C)CO2)cc1 PFVDRKCXACZILF-NDJWTUBHSA-N 0.000 description 2
- GDYKMAYHTRKLDG-RYGKCHDYSA-N N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-3-oxocyclobutane-1-carboxamide Chemical compound COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)C2CC(=O)C2)C(=O)N[C@@H](CC2CCCC2)C(=O)[C@@]2(C)CO2)cc1 GDYKMAYHTRKLDG-RYGKCHDYSA-N 0.000 description 2
- SCMIHBYCXDAYND-LTNBHBMDSA-N N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]cyclopentanecarboxamide Chemical compound COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)C2CCCC2)C(=O)N[C@@H](CC2CCCC2)C(=O)[C@@]2(C)CO2)cc1 SCMIHBYCXDAYND-LTNBHBMDSA-N 0.000 description 2
- JKVIBZGBRJNTFJ-LTNBHBMDSA-N N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]oxane-4-carboxamide Chemical compound COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)C2CCOCC2)C(=O)N[C@@H](CC2CCCC2)C(=O)[C@@]2(C)CO2)cc1 JKVIBZGBRJNTFJ-LTNBHBMDSA-N 0.000 description 2
- 108010020856 N-terminal nucleophile hydrolase Proteins 0.000 description 2
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 229920002732 Polyanhydride Polymers 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 229920001710 Polyorthoester Polymers 0.000 description 2
- ZTHYODDOHIVTJV-UHFFFAOYSA-N Propyl gallate Chemical compound CCCOC(=O)C1=CC(O)=C(O)C(O)=C1 ZTHYODDOHIVTJV-UHFFFAOYSA-N 0.000 description 2
- 239000004365 Protease Substances 0.000 description 2
- 102000001708 Protein Isoforms Human genes 0.000 description 2
- 108010029485 Protein Isoforms Proteins 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 101710188315 Protein X Proteins 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 206010063837 Reperfusion injury Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 206010052779 Transplant rejections Diseases 0.000 description 2
- 108700001567 Type I Schindler Disease Proteins 0.000 description 2
- 102000044159 Ubiquitin Human genes 0.000 description 2
- 108090000848 Ubiquitin Proteins 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000007950 acidosis Effects 0.000 description 2
- 208000026545 acidosis disease Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 2
- 235000010443 alginic acid Nutrition 0.000 description 2
- 229920000615 alginic acid Polymers 0.000 description 2
- 150000004781 alginic acids Chemical class 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 230000000890 antigenic effect Effects 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 2
- IMKALWCSZVTFSQ-RLFYNMQTSA-N benzyl N-[(2S)-3-[(1S)-3,3-difluorocyclopentyl]-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound C[C@@]1(CO1)C(=O)[C@H](C[C@@H]1CCC(F)(F)C1)NC(=O)OCc1ccccc1 IMKALWCSZVTFSQ-RLFYNMQTSA-N 0.000 description 2
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 210000000601 blood cell Anatomy 0.000 description 2
- 230000008468 bone growth Effects 0.000 description 2
- 210000001185 bone marrow Anatomy 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
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000010261 cell growth Effects 0.000 description 2
- 230000023715 cellular developmental process Effects 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 235000005687 corn oil Nutrition 0.000 description 2
- 239000002285 corn oil Substances 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 235000012343 cottonseed oil Nutrition 0.000 description 2
- 239000002385 cottonseed oil Substances 0.000 description 2
- 238000011262 co‐therapy Methods 0.000 description 2
- ADLKZHGHNJBOOC-UHFFFAOYSA-N cyclopent-3-en-1-ylmethanol Chemical compound OCC1CC=CC1 ADLKZHGHNJBOOC-UHFFFAOYSA-N 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-M ethanimidate Chemical compound CC([O-])=N DLFVBJFMPXGRIB-UHFFFAOYSA-M 0.000 description 2
- UIZCVGDHOSROCR-UHFFFAOYSA-N ethyl 1-methyl-2-oxocyclopentane-1-carboxylate Chemical compound CCOC(=O)C1(C)CCCC1=O UIZCVGDHOSROCR-UHFFFAOYSA-N 0.000 description 2
- MVEAAGBEUOMFRX-UHFFFAOYSA-N ethyl acetate;hydrochloride Chemical compound Cl.CCOC(C)=O MVEAAGBEUOMFRX-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 210000002950 fibroblast Anatomy 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 102000034356 gene-regulatory proteins Human genes 0.000 description 2
- 108091006104 gene-regulatory proteins Proteins 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 235000001727 glucose Nutrition 0.000 description 2
- 201000004502 glycogen storage disease II Diseases 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 210000003780 hair follicle Anatomy 0.000 description 2
- 201000010284 hepatitis E Diseases 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000007954 hypoxia Effects 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000007574 infarction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 229940102223 injectable solution Drugs 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 125000002346 iodo group Chemical group I* 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000011159 matrix material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- AAZUSOKPEIYCBI-NSHDSACASA-N methyl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(3-oxocyclopenten-1-yl)propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC(=O)CC1 AAZUSOKPEIYCBI-NSHDSACASA-N 0.000 description 2
- VFTUDAWTNMAEPN-NSHDSACASA-N methyl (2s)-3-(2-methoxypyridin-4-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=NC(OC)=C1 VFTUDAWTNMAEPN-NSHDSACASA-N 0.000 description 2
- SANNKFASHWONFD-LURJTMIESA-N methyl (2s)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound COC(=O)[C@H](CO)NC(=O)OC(C)(C)C SANNKFASHWONFD-LURJTMIESA-N 0.000 description 2
- TZHZMYGNHVTEFA-UHFFFAOYSA-N methyl 1-methyl-2-oxocyclopentane-1-carboxylate Chemical compound COC(=O)C1(C)CCCC1=O TZHZMYGNHVTEFA-UHFFFAOYSA-N 0.000 description 2
- CPWNUOJLLPXDNI-UHFFFAOYSA-N methyl 2-(oxetan-3-yl)-2-(phenylmethoxycarbonylamino)acetate Chemical compound C1OCC1C(C(=O)OC)NC(=O)OCC1=CC=CC=C1 CPWNUOJLLPXDNI-UHFFFAOYSA-N 0.000 description 2
- FMYPLDHLBRTIBX-UHFFFAOYSA-N methyl 2-hydroxy-3-methylcyclopentane-1-carboxylate Chemical compound COC(=O)C1CCC(C)C1O FMYPLDHLBRTIBX-UHFFFAOYSA-N 0.000 description 2
- XLXHNYUBTZYEQX-UHFFFAOYSA-N methyl 3-methyl-2-oxocyclopentane-1-carboxylate Chemical compound COC(=O)C1CCC(C)C1=O XLXHNYUBTZYEQX-UHFFFAOYSA-N 0.000 description 2
- MGQAYMJJBRADGQ-UHFFFAOYSA-N methyl 3-methylcyclopentene-1-carboxylate Chemical compound COC(=O)C1=CC(C)CC1 MGQAYMJJBRADGQ-UHFFFAOYSA-N 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 239000004530 micro-emulsion Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 230000011278 mitosis Effects 0.000 description 2
- 230000000394 mitotic effect Effects 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000006199 nebulizer Substances 0.000 description 2
- 210000000653 nervous system Anatomy 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 239000012038 nucleophile Substances 0.000 description 2
- OIPZNTLJVJGRCI-UHFFFAOYSA-M octadecanoyloxyaluminum;dihydrate Chemical compound O.O.CCCCCCCCCCCCCCCCCC(=O)O[Al] OIPZNTLJVJGRCI-UHFFFAOYSA-M 0.000 description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
- 230000006548 oncogenic transformation Effects 0.000 description 2
- KHDGSULFSVLOPM-UHFFFAOYSA-N oxane-3-carboxamide Chemical compound NC(=O)C1CCCOC1 KHDGSULFSVLOPM-UHFFFAOYSA-N 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 239000008389 polyethoxylated castor oil Substances 0.000 description 2
- 229920005862 polyol Polymers 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 229920000136 polysorbate 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
- 229920001592 potato starch Polymers 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 2
- 238000012746 preparative thin layer chromatography Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000001294 propane Substances 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 208000037803 restenosis Diseases 0.000 description 2
- 231100000241 scar Toxicity 0.000 description 2
- 239000008159 sesame oil Substances 0.000 description 2
- 235000011803 sesame oil Nutrition 0.000 description 2
- 230000011664 signaling Effects 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical compound COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 2
- 235000013599 spices Nutrition 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 229940032147 starch Drugs 0.000 description 2
- 239000008227 sterile water for injection Substances 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 150000005846 sugar alcohols Polymers 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- DBNPMCIDXJCZOJ-NSHDSACASA-N tert-butyl N-[(2S)-3-(furan-2-yl)-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@H](C(=O)N(C)OC)CC=1OC=CC=1)=O DBNPMCIDXJCZOJ-NSHDSACASA-N 0.000 description 2
- SCJHTSDYKFTJSN-ZDUSSCGKSA-N tert-butyl n-[(2s)-3-cyclohexyl-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)N(C)OC)CC1CCCCC1 SCJHTSDYKFTJSN-ZDUSSCGKSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 150000007970 thio esters Chemical class 0.000 description 2
- 150000003568 thioethers Chemical class 0.000 description 2
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 229960005294 triamcinolone Drugs 0.000 description 2
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 2
- 230000001810 trypsinlike Effects 0.000 description 2
- 108700026220 vif Genes Proteins 0.000 description 2
- 230000006648 viral gene expression Effects 0.000 description 2
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 1
- FMCGSUUBYTWNDP-ONGXEEELSA-N (1R,2S)-2-(dimethylamino)-1-phenyl-1-propanol Chemical compound CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 FMCGSUUBYTWNDP-ONGXEEELSA-N 0.000 description 1
- DVZTVIVLAFIUFZ-XVMARJQXSA-N (1s,5r,6r)-bicyclo[3.1.0]hex-2-ene-6-carbaldehyde Chemical compound C1C=C[C@@H]2[C@H](C=O)[C@@H]21 DVZTVIVLAFIUFZ-XVMARJQXSA-N 0.000 description 1
- XQFRIKPFJMPNQV-UHFFFAOYSA-N (2-methylcyclopenten-1-yl) trifluoromethanesulfonate Chemical compound CC1=C(OS(=O)(=O)C(F)(F)F)CCC1 XQFRIKPFJMPNQV-UHFFFAOYSA-N 0.000 description 1
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- CNPZXKIQKHKDHD-QMMMGPOBSA-N (2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(2-oxopyrrolidin-1-yl)propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CN1CCCC1=O)C(O)=O CNPZXKIQKHKDHD-QMMMGPOBSA-N 0.000 description 1
- SGEZHURZVQPFMU-ZFWWWQNUSA-N (2S)-3-(3-hydroxy-4-methylphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanoic acid Chemical compound C[C@H](NC(=O)CN1CCOCC1)C(=O)N[C@@H](Cc1ccc(C)c(O)c1)C(O)=O SGEZHURZVQPFMU-ZFWWWQNUSA-N 0.000 description 1
- UQYJHAGCDCPZLA-UMJHXOGRSA-N (2S)-3-(3-methylcyclopenten-1-yl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC1CCC(C[C@H](NC(=O)OC(C)(C)C)C(O)=O)=C1 UQYJHAGCDCPZLA-UMJHXOGRSA-N 0.000 description 1
- XKAIHYRHNXKGPY-QMMMGPOBSA-N (2S)-3-(4-chlorobutanoylamino)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CNC(=O)CCCCl)C(O)=O XKAIHYRHNXKGPY-QMMMGPOBSA-N 0.000 description 1
- ZHZBLVRAXXVBPV-UGKGYDQZSA-N (2S)-3-(4-methyl-3-phenylmethoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanoic acid Chemical compound C[C@H](NC(=O)CN1CCOCC1)C(=O)N[C@@H](Cc1ccc(C)c(OCc2ccccc2)c1)C(O)=O ZHZBLVRAXXVBPV-UGKGYDQZSA-N 0.000 description 1
- RXCGUZOPADOTOH-JTQLQIEISA-N (2S)-3-cyclopent-3-en-1-yl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CC1CC=CC1)C(O)=O RXCGUZOPADOTOH-JTQLQIEISA-N 0.000 description 1
- RCHATLGGLKJXKQ-ZETCQYMHSA-N (2S)-3-hydroxy-2-[(2-morpholin-4-ylacetyl)amino]propanoic acid Chemical compound OC[C@H](NC(=O)CN1CCOCC1)C(O)=O RCHATLGGLKJXKQ-ZETCQYMHSA-N 0.000 description 1
- ZCANDMMZIHRQCE-AFAVFJNCSA-N (2S,3R)-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanoic acid Chemical compound COc1ccc(cc1)[C@@H](O)[C@H](NC(=O)[C@H](C)NC(=O)CN1CCOCC1)C(O)=O ZCANDMMZIHRQCE-AFAVFJNCSA-N 0.000 description 1
- DNISEZBAYYIQFB-PHDIDXHHSA-N (2r,3r)-2,3-diacetyloxybutanedioic acid Chemical compound CC(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(C)=O DNISEZBAYYIQFB-PHDIDXHHSA-N 0.000 description 1
- AMKHAJIFPHJYMH-ZETCQYMHSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pent-4-ynoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC#C AMKHAJIFPHJYMH-ZETCQYMHSA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- KRJLRVZLNABMAT-YFKPBYRVSA-N (2s)-3-amino-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CN)C(O)=O KRJLRVZLNABMAT-YFKPBYRVSA-N 0.000 description 1
- MSZQAQJBXGTSHP-NSHDSACASA-N (2s)-3-cyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC1CCCCC1 MSZQAQJBXGTSHP-NSHDSACASA-N 0.000 description 1
- FHOAKXBXYSJBGX-YFKPBYRVSA-N (2s)-3-hydroxy-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](CO)C(O)=O FHOAKXBXYSJBGX-YFKPBYRVSA-N 0.000 description 1
- WEOUCKRTUSZUMJ-GIEZAXBTSA-N (3R)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-5-oxopyrrolidine-3-carboxamide Chemical compound C1(CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H](CC1=CC=C(C=C1)OC)NC([C@@H](C)NC(=O)[C@H]1CNC(C1)=O)=O)=O WEOUCKRTUSZUMJ-GIEZAXBTSA-N 0.000 description 1
- RKPFVMJLWKSSON-GUSQGKPTSA-N (3R)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-6-oxopiperidine-3-carboxamide Chemical compound COc1ccc(C[C@H](NC(=O)[C@@H](C)NC(=O)[C@@H]2CCC(=O)NC2)C(=O)N[C@@H](CC2CCCC2)C(=O)[C@@]2(C)CO2)cc1 RKPFVMJLWKSSON-GUSQGKPTSA-N 0.000 description 1
- WEOUCKRTUSZUMJ-FUCCIRSBSA-N (3S)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-5-oxopyrrolidine-3-carboxamide Chemical compound O=C1C[C@@H](CN1)C(=O)N[C@@H](C(=O)N[C@H](C(=O)N[C@H](C(=O)[C@@]1(OC1)C)CC1CCCC1)CC1=CC=C(C=C1)OC)C WEOUCKRTUSZUMJ-FUCCIRSBSA-N 0.000 description 1
- RKPFVMJLWKSSON-XUNDOJSBSA-N (3S)-N-[(2R)-1-[[(2S)-1-[[(2S)-3-cyclopentyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]amino]-3-(4-methoxyphenyl)-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]-6-oxopiperidine-3-carboxamide Chemical compound C1(CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H](CC1=CC=C(C=C1)OC)NC([C@@H](C)NC(=O)[C@@H]1CNC(CC1)=O)=O)=O RKPFVMJLWKSSON-XUNDOJSBSA-N 0.000 description 1
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 1
- ZJTDCIZEZMJDEN-UHFFFAOYSA-N (4-methoxyphenyl) propanoate Chemical compound CCC(=O)OC1=CC=C(OC)C=C1 ZJTDCIZEZMJDEN-UHFFFAOYSA-N 0.000 description 1
- TYHGKLBJBHACOI-UHFFFAOYSA-N (4-methoxyphenyl)methyl 2,2,2-trichloroethanimidate Chemical compound COC1=CC=C(COC(=N)C(Cl)(Cl)Cl)C=C1 TYHGKLBJBHACOI-UHFFFAOYSA-N 0.000 description 1
- FOYHOBVZPWIGJM-KCHLEUMXSA-N (4s)-4-[[(2s)-4-methyl-2-[[(2s)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]-5-[(4-methyl-2-oxochromen-7-yl)amino]-5-oxopentanoic acid Chemical compound N([C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NC=1C=C2OC(=O)C=C(C)C2=CC=1)C(=O)OCC1=CC=CC=C1 FOYHOBVZPWIGJM-KCHLEUMXSA-N 0.000 description 1
- 125000006718 (C3-C7) heterocycloalkenyl 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
- GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- KNTZCGBYFGEMFR-UHFFFAOYSA-N (propan-2-ylazaniumyl)formate Chemical compound CC(C)NC(O)=O KNTZCGBYFGEMFR-UHFFFAOYSA-N 0.000 description 1
- DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 1
- LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
- QIKXBZHVPPOVID-UHFFFAOYSA-N 1-oxopropan-2-ylcarbamic acid Chemical compound O=CC(C)NC(O)=O QIKXBZHVPPOVID-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 1
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- OMWHXJYPAIQNIX-UHFFFAOYSA-N 2-(4-hydroxypiperidin-1-ium-1-yl)acetate Chemical compound OC1CCN(CC(O)=O)CC1 OMWHXJYPAIQNIX-UHFFFAOYSA-N 0.000 description 1
- UZYQSNQJLWTICD-UHFFFAOYSA-N 2-(n-benzoylanilino)-2,2-dinitroacetic acid Chemical compound C=1C=CC=CC=1N(C(C(=O)O)([N+]([O-])=O)[N+]([O-])=O)C(=O)C1=CC=CC=C1 UZYQSNQJLWTICD-UHFFFAOYSA-N 0.000 description 1
- QUIQKYAAGXIAFF-UHFFFAOYSA-N 2-(phosphonoamino)acetic acid Chemical compound OC(=O)CNP(O)(O)=O QUIQKYAAGXIAFF-UHFFFAOYSA-N 0.000 description 1
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 1
- ZNOVTXRBGFNYRX-UHFFFAOYSA-N 2-[[4-[(2-amino-5-methyl-4-oxo-1,6,7,8-tetrahydropteridin-6-yl)methylamino]benzoyl]amino]pentanedioic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-UHFFFAOYSA-N 0.000 description 1
- IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical compound OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 description 1
- JTTHKOPSMAVJFE-UHFFFAOYSA-N 2-azaniumyl-4-phenylbutanoate Chemical compound OC(=O)C(N)CCC1=CC=CC=C1 JTTHKOPSMAVJFE-UHFFFAOYSA-N 0.000 description 1
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
- REXUYBKPWIPONM-UHFFFAOYSA-N 2-bromoacetonitrile Chemical compound BrCC#N REXUYBKPWIPONM-UHFFFAOYSA-N 0.000 description 1
- PHMRPWPDDRGGGF-UHFFFAOYSA-N 2-bromoprop-1-ene Chemical compound CC(Br)=C PHMRPWPDDRGGGF-UHFFFAOYSA-N 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- JNODDICFTDYODH-UHFFFAOYSA-N 2-hydroxytetrahydrofuran Chemical compound OC1CCCO1 JNODDICFTDYODH-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
- FIUFLISGGHNPSM-UHFFFAOYSA-M 3-(4-methoxyphenyl)propanoate Chemical compound COC1=CC=C(CCC([O-])=O)C=C1 FIUFLISGGHNPSM-UHFFFAOYSA-M 0.000 description 1
- UJXHPFDJZCXTQR-UHFFFAOYSA-N 3-(iodomethyl)oxolane Chemical compound ICC1CCOC1 UJXHPFDJZCXTQR-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 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
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 1
- IENOFRJPUPTEMI-UHFFFAOYSA-N 3-oxocyclobutane-1-carboxylic acid Chemical compound OC(=O)C1CC(=O)C1 IENOFRJPUPTEMI-UHFFFAOYSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 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
- YTXSYWAKVMZICI-PVCZSOGJSA-N 4-(carboxymethyl)-2-[(1r)-1-[[2-[(2,5-dichlorobenzoyl)amino]acetyl]amino]-3-methylbutyl]-6-oxo-1,3,2-dioxaborinane-4-carboxylic acid Chemical compound N([C@@H](CC(C)C)B1OC(CC(O)=O)(CC(=O)O1)C(O)=O)C(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl YTXSYWAKVMZICI-PVCZSOGJSA-N 0.000 description 1
- JBUPUPVSIWQTFU-UHFFFAOYSA-N 4-(iodomethyl)cyclopentene Chemical compound ICC1CC=CC1 JBUPUPVSIWQTFU-UHFFFAOYSA-N 0.000 description 1
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 1
- YFTGMMXMLPTTAY-UHFFFAOYSA-N 4-bromo-2-methoxypyridine Chemical compound COC1=CC(Br)=CC=N1 YFTGMMXMLPTTAY-UHFFFAOYSA-N 0.000 description 1
- CDIIZULDSLKBKV-UHFFFAOYSA-N 4-chlorobutanoyl chloride Chemical compound ClCCCC(Cl)=O CDIIZULDSLKBKV-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
- NRJADRDKYOBCKH-UHFFFAOYSA-N 4-hydroxy-1-methylcyclohexane-1-carboxylic acid Chemical compound OC(=O)C1(C)CCC(O)CC1 NRJADRDKYOBCKH-UHFFFAOYSA-N 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
- HCJMNOSIAGSZBM-UHFFFAOYSA-N 6-methylsalicylic acid Chemical compound CC1=CC=CC(O)=C1C(O)=O HCJMNOSIAGSZBM-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [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
- 208000021959 Abnormal metabolism Diseases 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- 208000000230 African Trypanosomiasis Diseases 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010001935 American trypanosomiasis Diseases 0.000 description 1
- 241000224489 Amoeba Species 0.000 description 1
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000203069 Archaea Species 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- IVKMLPKBZQTAMQ-LURJTMIESA-N Boc-beta-cyano-L-alanine Chemical compound CC(C)(C)OC(=O)N[C@H](C(O)=O)CC#N IVKMLPKBZQTAMQ-LURJTMIESA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- DGGZCXUXASNDAC-QQNGCVSVSA-N C-1027 chromophore Chemical compound COc1cc2OC(=C)C(=O)Nc2c(c1)C(=O)O[C@H]3COC(=O)C[C@H](N)c4cc(O)c(O[C@@H]5C#C\C=C\3/C#CC6=CC=C[C@]56O[C@@H]7OC(C)(C)[C@H]([C@@H](O)[C@H]7O)N(C)C)c(Cl)c4 DGGZCXUXASNDAC-QQNGCVSVSA-N 0.000 description 1
- QPZVNRKVVUZQGZ-UHFFFAOYSA-N C1(CC=CC1)CC1=CC=C(C=C1)C Chemical compound C1(CC=CC1)CC1=CC=C(C=C1)C QPZVNRKVVUZQGZ-UHFFFAOYSA-N 0.000 description 1
- UQESUPWADJOPIW-ZDUSSCGKSA-N CC(=C)C(=O)[C@H](CC1=CCCC1)NC(=O)OC(C)(C)C Chemical compound CC(=C)C(=O)[C@H](CC1=CCCC1)NC(=O)OC(C)(C)C UQESUPWADJOPIW-ZDUSSCGKSA-N 0.000 description 1
- AUTHLWGFRLVCPN-AXDSSHIGSA-N CC(C)(C)N([C@@H](CC1CCNC1=O)C(=O)N(C)OC)C(=O)O Chemical compound CC(C)(C)N([C@@H](CC1CCNC1=O)C(=O)N(C)OC)C(=O)O AUTHLWGFRLVCPN-AXDSSHIGSA-N 0.000 description 1
- VIAOEUVBVGIRHR-HNNXBMFYSA-N CC1=C(CCC1)C[C@@](C)(C(=O)O)NC(=O)OC(C)(C)C Chemical class CC1=C(CCC1)C[C@@](C)(C(=O)O)NC(=O)OC(C)(C)C VIAOEUVBVGIRHR-HNNXBMFYSA-N 0.000 description 1
- 102000009728 CDC2 Protein Kinase Human genes 0.000 description 1
- 108010034798 CDC2 Protein Kinase Proteins 0.000 description 1
- SJKWHQGEBMBOCM-LBPRGKRZSA-N CON(C)C(=O)[C@H](CC1=CCCC1)NC(=O)OC(C)(C)C Chemical compound CON(C)C(=O)[C@H](CC1=CCCC1)NC(=O)OC(C)(C)C SJKWHQGEBMBOCM-LBPRGKRZSA-N 0.000 description 1
- WIECZWMSJPADFU-DTIOYNMSSA-N C[C@@H](C(C)(C)C(C)CC#N)NC(=O)OC(C)(C)C Chemical compound C[C@@H](C(C)(C)C(C)CC#N)NC(=O)OC(C)(C)C WIECZWMSJPADFU-DTIOYNMSSA-N 0.000 description 1
- ZJMQURXHSNGKDX-HCCKASOXSA-N C[C@@]1(CO1)C(=O)C(N)CC1=CCCC1 Chemical compound C[C@@]1(CO1)C(=O)C(N)CC1=CCCC1 ZJMQURXHSNGKDX-HCCKASOXSA-N 0.000 description 1
- BBQKSHOOXPWUMP-PHTLISSDSA-N C[C@@]1(CO1)C(=O)[C@H](CC2CCNC2=O)N(C(=O)O)C(C)(C)C Chemical compound C[C@@]1(CO1)C(=O)[C@H](CC2CCNC2=O)N(C(=O)O)C(C)(C)C BBQKSHOOXPWUMP-PHTLISSDSA-N 0.000 description 1
- PXXYUWFGHVNWEC-JRPNMDOOSA-N C[C@@]1(CO1)C(=O)[C@H](C[C@H]2CCCO2)N(C(=O)O)C(C)(C)C Chemical class C[C@@]1(CO1)C(=O)[C@H](C[C@H]2CCCO2)N(C(=O)O)C(C)(C)C PXXYUWFGHVNWEC-JRPNMDOOSA-N 0.000 description 1
- FRVCTZTYNPZMRU-WDEREUQCSA-N C[C@]1(CO1)C[C@H](CC2=CCCC2)N Chemical compound C[C@]1(CO1)C[C@H](CC2=CCCC2)N FRVCTZTYNPZMRU-WDEREUQCSA-N 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- 241001640117 Callaeum Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 208000024699 Chagas disease Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 208000032544 Cicatrix Diseases 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000029147 Collagen-vascular disease Diseases 0.000 description 1
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 1
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 206010010317 Congenital absence of bile ducts Diseases 0.000 description 1
- 206010056370 Congestive cardiomyopathy Diseases 0.000 description 1
- 241000711573 Coronaviridae Species 0.000 description 1
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 241000709675 Coxsackievirus B3 Species 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 0.000 description 1
- 241000223935 Cryptosporidium Species 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 208000006313 Delayed Hypersensitivity Diseases 0.000 description 1
- 208000034423 Delivery Diseases 0.000 description 1
- 206010012438 Dermatitis atopic Diseases 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 238000009007 Diagnostic Kit Methods 0.000 description 1
- 206010012713 Diaphragmatic hernia Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 201000010046 Dilated cardiomyopathy Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 208000024720 Fabry Disease Diseases 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 201000008892 GM1 Gangliosidosis Diseases 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Polymers OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 108700025685 HIV Enhancer Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 241000700739 Hepadnaviridae Species 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 102000008949 Histocompatibility Antigens Class I Human genes 0.000 description 1
- 108010088652 Histocompatibility Antigens Class I Proteins 0.000 description 1
- 102000018713 Histocompatibility Antigens Class II Human genes 0.000 description 1
- 108010027412 Histocompatibility Antigens Class II Proteins 0.000 description 1
- 101001124792 Homo sapiens Proteasome subunit beta type-10 Proteins 0.000 description 1
- 102000031927 Host cell factor Human genes 0.000 description 1
- 108091010040 Host cell factor Proteins 0.000 description 1
- 102100030355 Host cell factor 1 Human genes 0.000 description 1
- 108091010871 Host cell factor 1 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 102000004157 Hydrolases Human genes 0.000 description 1
- 108090000604 Hydrolases Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 102100023915 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 102000001702 Intracellular Signaling Peptides and Proteins Human genes 0.000 description 1
- 108010068964 Intracellular Signaling Peptides and Proteins Proteins 0.000 description 1
- 208000028226 Krabbe disease Diseases 0.000 description 1
- QAQJMLQRFWZOBN-LAUBAEHRSA-N L-ascorbyl-6-palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](O)[C@H]1OC(=O)C(O)=C1O QAQJMLQRFWZOBN-LAUBAEHRSA-N 0.000 description 1
- 239000011786 L-ascorbyl-6-palmitate Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 206010024229 Leprosy Diseases 0.000 description 1
- 201000001779 Leukocyte adhesion deficiency Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 102000052508 Lipopolysaccharide-binding protein Human genes 0.000 description 1
- 108010053632 Lipopolysaccharide-binding protein Proteins 0.000 description 1
- 208000004852 Lung Injury Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 206010027236 Meningitis fungal Diseases 0.000 description 1
- 206010027260 Meningitis viral Diseases 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- 208000008955 Mucolipidoses Diseases 0.000 description 1
- 206010072927 Mucolipidosis type I Diseases 0.000 description 1
- 206010028095 Mucopolysaccharidosis IV Diseases 0.000 description 1
- 206010056893 Mucopolysaccharidosis VII Diseases 0.000 description 1
- 208000025797 Mucopolysaccharidosis type 4A Diseases 0.000 description 1
- 208000025923 Mucopolysaccharidosis type 4B Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- FMCGSUUBYTWNDP-UHFFFAOYSA-N N-Methylephedrine Natural products CN(C)C(C)C(O)C1=CC=CC=C1 FMCGSUUBYTWNDP-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- 125000000729 N-terminal amino-acid group Chemical group 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 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
- 208000001132 Osteoporosis Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 101800000628 PDH precursor-related peptide Proteins 0.000 description 1
- 101100272976 Panax ginseng CYP716A53v2 gene Proteins 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 208000030831 Peripheral arterial occlusive disease Diseases 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 241000233870 Pneumocystis Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 102100029081 Proteasome subunit beta type-10 Human genes 0.000 description 1
- 108010001859 Proto-Oncogene Proteins c-rel Proteins 0.000 description 1
- 102000000850 Proto-Oncogene Proteins c-rel Human genes 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 239000007868 Raney catalyst Substances 0.000 description 1
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000019485 Safflower oil Nutrition 0.000 description 1
- 208000021811 Sandhoff disease Diseases 0.000 description 1
- 241000146987 Sarcocystis neurona Species 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- 206010040799 Skin atrophy Diseases 0.000 description 1
- 102000009822 Sterol Regulatory Element Binding Proteins Human genes 0.000 description 1
- 108010020396 Sterol Regulatory Element Binding Proteins Proteins 0.000 description 1
- 101710172711 Structural protein Proteins 0.000 description 1
- 208000002847 Surgical Wound Diseases 0.000 description 1
- LGGHDPFKSSRQNS-UHFFFAOYSA-N Tariquidar Chemical compound C1=CC=CC2=CC(C(=O)NC3=CC(OC)=C(OC)C=C3C(=O)NC3=CC=C(C=C3)CCN3CCC=4C=C(C(=CC=4C3)OC)OC)=CN=C21 LGGHDPFKSSRQNS-UHFFFAOYSA-N 0.000 description 1
- 235000009470 Theobroma cacao Nutrition 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- 102000006289 Transcription Factor TFIIA Human genes 0.000 description 1
- 108010083262 Transcription Factor TFIIA Proteins 0.000 description 1
- 101710195626 Transcriptional activator protein Proteins 0.000 description 1
- 102000004357 Transferases Human genes 0.000 description 1
- 108090000992 Transferases Proteins 0.000 description 1
- 206010069363 Traumatic lung injury Diseases 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 241000223109 Trypanosoma cruzi Species 0.000 description 1
- 102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
- 108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
- 108010005705 Ubiquitinated Proteins Proteins 0.000 description 1
- 201000004810 Vascular dementia Diseases 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- 241000251539 Vertebrata <Metazoa> Species 0.000 description 1
- CYMBAKFTWRNHPS-APRQOCPKSA-N [2-[(6s,8s,9s,10r,11s,13s,14s,17r)-6-fluoro-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@@](C(=O)COC(=O)C)(O)[C@@]2(C)C[C@@H]1O CYMBAKFTWRNHPS-APRQOCPKSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003655 absorption accelerator Substances 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229940022663 acetate 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
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 208000038016 acute inflammation Diseases 0.000 description 1
- 230000006022 acute inflammation Effects 0.000 description 1
- 125000002015 acyclic group Chemical group 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229960001900 algestone Drugs 0.000 description 1
- LSWBQIAZNGURQV-WTBIUSKOSA-N algestone acetonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)C)[C@@]1(C)CC2 LSWBQIAZNGURQV-WTBIUSKOSA-N 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 201000008333 alpha-mannosidosis Diseases 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 210000001691 amnion Anatomy 0.000 description 1
- 230000019552 anatomical structure morphogenesis Effects 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- MDJRZSNPHZEMJH-MTMZYOSNSA-N artisone acetate Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 MDJRZSNPHZEMJH-MTMZYOSNSA-N 0.000 description 1
- 235000010385 ascorbyl palmitate Nutrition 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- 201000008937 atopic dermatitis Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- XTKDAFGWCDAMPY-UHFFFAOYSA-N azaperone Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCN(C=2N=CC=CC=2)CC1 XTKDAFGWCDAMPY-UHFFFAOYSA-N 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 125000004532 benzofuran-3-yl group Chemical group O1C=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- YGYLYUIRSJSFJS-MRVPVSSYSA-N benzyl (2r)-2-aminopropanoate Chemical compound C[C@@H](N)C(=O)OCC1=CC=CC=C1 YGYLYUIRSJSFJS-MRVPVSSYSA-N 0.000 description 1
- IMKALWCSZVTFSQ-RVKKMQEKSA-N benzyl N-[(2S)-3-[(1R)-3,3-difluorocyclopentyl]-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound C[C@@]1(CO1)C(=O)[C@H](C[C@H]1CCC(F)(F)C1)NC(=O)OCc1ccccc1 IMKALWCSZVTFSQ-RVKKMQEKSA-N 0.000 description 1
- 229960002903 benzyl benzoate Drugs 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 201000006486 beta-mannosidosis Diseases 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 201000005271 biliary atresia Diseases 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- CGVWPQOFHSAKRR-NDEPHWFRSA-N biricodar Chemical compound COC1=C(OC)C(OC)=CC(C(=O)C(=O)N2[C@@H](CCCC2)C(=O)OC(CCCC=2C=NC=CC=2)CCCC=2C=NC=CC=2)=C1 CGVWPQOFHSAKRR-NDEPHWFRSA-N 0.000 description 1
- 229950005124 biricodar Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960001467 bortezomib Drugs 0.000 description 1
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 150000005693 branched-chain amino acids Chemical class 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- FATUQANACHZLRT-KMRXSBRUSA-L calcium glucoheptonate Chemical compound [Ca+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)C([O-])=O FATUQANACHZLRT-KMRXSBRUSA-L 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- CVXBEEMKQHEXEN-UHFFFAOYSA-N carbaryl Chemical compound C1=CC=C2C(OC(=O)NC)=CC=CC2=C1 CVXBEEMKQHEXEN-UHFFFAOYSA-N 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- BLMPQMFVWMYDKT-NZTKNTHTSA-N carfilzomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)[C@]1(C)OC1)NC(=O)CN1CCOCC1)CC1=CC=CC=C1 BLMPQMFVWMYDKT-NZTKNTHTSA-N 0.000 description 1
- 229960002438 carfilzomib Drugs 0.000 description 1
- 108010021331 carfilzomib Proteins 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 230000006652 catabolic pathway Effects 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000009134 cell regulation Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000002113 chemopreventative effect Effects 0.000 description 1
- 150000005827 chlorofluoro hydrocarbons Chemical class 0.000 description 1
- 229950006229 chloroprednisone Drugs 0.000 description 1
- NPSLCOWKFFNQKK-ZPSUVKRCSA-N chloroprednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](Cl)C2=C1 NPSLCOWKFFNQKK-ZPSUVKRCSA-N 0.000 description 1
- CRQQGFGUEAVUIL-UHFFFAOYSA-N chlorothalonil Chemical compound ClC1=C(Cl)C(C#N)=C(Cl)C(C#N)=C1Cl CRQQGFGUEAVUIL-UHFFFAOYSA-N 0.000 description 1
- 201000009950 chronic meningitis Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229960002842 clobetasol Drugs 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- 238000011278 co-treatment Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 201000005890 congenital diaphragmatic hernia Diseases 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 description 1
- PNZXMIKHJXIPEK-UHFFFAOYSA-N cyclohexanecarboxamide Chemical compound NC(=O)C1CCCCC1 PNZXMIKHJXIPEK-UHFFFAOYSA-N 0.000 description 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 description 1
- ZKZNEHVKHYJJCK-UHFFFAOYSA-N cyclopent-3-en-1-ylmethyl 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OCC1CC=CC1 ZKZNEHVKHYJJCK-UHFFFAOYSA-N 0.000 description 1
- XVSYDLITVYBCBD-UHFFFAOYSA-N cyclopent-3-ene-1-carboxylic acid Chemical compound OC(=O)C1CC=CC1 XVSYDLITVYBCBD-UHFFFAOYSA-N 0.000 description 1
- LOGSONSNCYTHPS-UHFFFAOYSA-N cyclopentane-1,3-dione Chemical compound O=C1CCC(=O)C1 LOGSONSNCYTHPS-UHFFFAOYSA-N 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229960001305 cysteine hydrochloride Drugs 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000000593 degrading effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 206010061811 demyelinating polyneuropathy Diseases 0.000 description 1
- 230000002638 denervation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003662 desonide Drugs 0.000 description 1
- WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 description 1
- 229960002593 desoximetasone Drugs 0.000 description 1
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- QNSPKWUAZQIIGZ-QMMMGPOBSA-N dimethyl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioate Chemical compound COC(=O)CC[C@@H](C(=O)OC)NC(=O)OC(C)(C)C QNSPKWUAZQIIGZ-QMMMGPOBSA-N 0.000 description 1
- QVTOOWHELURIDU-AXDSSHIGSA-N dimethyl (4S)-2-(cyanomethyl)-4-[(2-methylpropan-2-yl)oxycarbonylamino]pentanedioate Chemical compound COC(=O)C(CC#N)C[C@H](NC(=O)OC(C)(C)C)C(=O)OC QVTOOWHELURIDU-AXDSSHIGSA-N 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical class CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 239000012156 elution solvent Substances 0.000 description 1
- 210000001163 endosome Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960003720 enoxolone Drugs 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 229950009760 epratuzumab Drugs 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- JHZPNBKZPAWCJD-UHFFFAOYSA-N ethyl 2-oxocyclopentane-1-carboxylate Chemical compound CCOC(=O)C1CCCC1=O JHZPNBKZPAWCJD-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000003176 fibrotic effect Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960003469 flumetasone Drugs 0.000 description 1
- WXURHACBFYSXBI-GQKYHHCASA-N flumethasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O WXURHACBFYSXBI-GQKYHHCASA-N 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229960001347 fluocinolone acetonide Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 229960001048 fluorometholone Drugs 0.000 description 1
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- 230000004907 flux Effects 0.000 description 1
- 239000006260 foam 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
- 239000012458 free base Substances 0.000 description 1
- 201000008049 fucosidosis Diseases 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 201000010056 fungal meningitis Diseases 0.000 description 1
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical class O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 1
- 230000008571 general function Effects 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-L glutarate(2-) Chemical compound [O-]C(=O)CCCC([O-])=O JFCQEDHGNNZCLN-UHFFFAOYSA-L 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 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
- 229940096919 glycogen Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 201000008977 glycoproteinosis Diseases 0.000 description 1
- 150000002339 glycosphingolipids Chemical class 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 229960002475 halometasone Drugs 0.000 description 1
- GGXMRPUKBWXVHE-MIHLVHIWSA-N halometasone Chemical compound C1([C@@H](F)C2)=CC(=O)C(Cl)=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O GGXMRPUKBWXVHE-MIHLVHIWSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- UDOAKURRCZMWOJ-UHFFFAOYSA-N hept-5-enal Chemical compound CC=CCCCC=O UDOAKURRCZMWOJ-UHFFFAOYSA-N 0.000 description 1
- 239000000833 heterodimer Substances 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 208000029080 human African trypanosomiasis Diseases 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 235000003642 hunger Nutrition 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 208000003532 hypothyroidism Diseases 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 230000000266 injurious effect Effects 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000035992 intercellular communication Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 239000007925 intracardiac injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 238000000752 ionisation method Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000000644 isotonic solution Substances 0.000 description 1
- 229960003648 ixazomib Drugs 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 201000006370 kidney failure Diseases 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- TULGGJGJQXESOO-UHFFFAOYSA-N laniquidar Chemical compound C12=CC=CC=C2CCN2C(C(=O)OC)=CN=C2C1=C1CCN(CCC=2C=CC(OCC=3N=C4C=CC=CC4=CC=3)=CC=2)CC1 TULGGJGJQXESOO-UHFFFAOYSA-N 0.000 description 1
- 229950010652 laniquidar Drugs 0.000 description 1
- 150000002605 large molecules Chemical class 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 229960001798 loteprednol Drugs 0.000 description 1
- YPZVAYHNBBHPTO-MXRBDKCISA-N loteprednol Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)OCCl)[C@@H]4[C@@H]3CCC2=C1 YPZVAYHNBBHPTO-MXRBDKCISA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 231100000515 lung injury Toxicity 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- RMGJCSHZTFKPNO-UHFFFAOYSA-M magnesium;ethene;bromide Chemical compound [Mg+2].[Br-].[CH-]=C RMGJCSHZTFKPNO-UHFFFAOYSA-M 0.000 description 1
- DQEUYIQDSMINEY-UHFFFAOYSA-M magnesium;prop-1-ene;bromide Chemical compound [Mg+2].[Br-].[CH2-]C=C DQEUYIQDSMINEY-UHFFFAOYSA-M 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 229950002736 marizomib Drugs 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 229960001810 meprednisone Drugs 0.000 description 1
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000006371 metabolic abnormality Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000003458 metachromatic effect Effects 0.000 description 1
- AWIJRPNMLHPLNC-UHFFFAOYSA-N methanethioic s-acid Chemical compound SC=O AWIJRPNMLHPLNC-UHFFFAOYSA-N 0.000 description 1
- WROUJJYWYLILBR-QMMMGPOBSA-N methyl (2S)-2-amino-3-(2-methoxypyridin-4-yl)propanoate Chemical compound COC(=O)[C@@H](N)Cc1ccnc(OC)c1 WROUJJYWYLILBR-QMMMGPOBSA-N 0.000 description 1
- SYJQHBPNVZEBBK-HNNXBMFYSA-N methyl (2S)-2-amino-3-(4-methoxy-3-phenylmethoxyphenyl)propanoate Chemical compound COC(=O)[C@@H](N)Cc1ccc(OC)c(OCc2ccccc2)c1 SYJQHBPNVZEBBK-HNNXBMFYSA-N 0.000 description 1
- KUDUQFFZRMHOPN-INIZCTEOSA-N methyl (2S)-2-amino-3-(4-methyl-3-phenylmethoxyphenyl)propanoate Chemical compound COC(=O)[C@@H](N)Cc1ccc(C)c(OCc2ccccc2)c1 KUDUQFFZRMHOPN-INIZCTEOSA-N 0.000 description 1
- PGZOBBJGVPITLV-SCZZXKLOSA-N methyl (2S,3R)-3-hydroxy-2-[(2-morpholin-4-ylacetyl)amino]butanoate Chemical compound COC(=O)[C@@H](NC(=O)CN1CCOCC1)[C@@H](C)O PGZOBBJGVPITLV-SCZZXKLOSA-N 0.000 description 1
- HTQMBOWAEPNWLI-GKAPJAKFSA-N methyl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(2-oxopyrrolidin-3-yl)propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1CCNC1=O HTQMBOWAEPNWLI-GKAPJAKFSA-N 0.000 description 1
- CDCIQNBPLQWUQS-PPHPATTJSA-N methyl (2s)-2-amino-3-(4-methoxyphenyl)propanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CC1=CC=C(OC)C=C1 CDCIQNBPLQWUQS-PPHPATTJSA-N 0.000 description 1
- NQIFXJSLCUJHBB-LBPRGKRZSA-N methyl (2s)-3-(4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1=CC=C(O)C=C1 NQIFXJSLCUJHBB-LBPRGKRZSA-N 0.000 description 1
- FALUXMVPGFKLAM-LBPRGKRZSA-N methyl (2s)-3-cyclohexyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OC)CC1CCCCC1 FALUXMVPGFKLAM-LBPRGKRZSA-N 0.000 description 1
- OZSJLLVVZFTDEY-HJXLNUONSA-N methyl (2s,3r)-2-amino-3-hydroxybutanoate;hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)[C@@H](C)O OZSJLLVVZFTDEY-HJXLNUONSA-N 0.000 description 1
- PZBBESSUKAHBHD-UHFFFAOYSA-N methyl 2-oxocyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1=O PZBBESSUKAHBHD-UHFFFAOYSA-N 0.000 description 1
- STZCRXQWRGQSJD-GEEYTBSJSA-M methyl orange Chemical compound [Na+].C1=CC(N(C)C)=CC=C1\N=N\C1=CC=C(S([O-])(=O)=O)C=C1 STZCRXQWRGQSJD-GEEYTBSJSA-M 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 238000010208 microarray analysis Methods 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 229960001664 mometasone Drugs 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 208000025919 mucopolysaccharidosis type 7 Diseases 0.000 description 1
- 208000012091 mucopolysaccharidosis type IVB Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- VMESOKCXSYNAKD-UHFFFAOYSA-N n,n-dimethylhydroxylamine Chemical compound CN(C)O VMESOKCXSYNAKD-UHFFFAOYSA-N 0.000 description 1
- KRKPYFLIYNGWTE-UHFFFAOYSA-N n,o-dimethylhydroxylamine Chemical compound CNOC KRKPYFLIYNGWTE-UHFFFAOYSA-N 0.000 description 1
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 description 1
- AGVKXDPPPSLISR-UHFFFAOYSA-N n-ethylcyclohexanamine Chemical compound CCNC1CCCCC1 AGVKXDPPPSLISR-UHFFFAOYSA-N 0.000 description 1
- RIWRFSMVIUAEBX-UHFFFAOYSA-N n-methyl-1-phenylmethanamine Chemical compound CNCC1=CC=CC=C1 RIWRFSMVIUAEBX-UHFFFAOYSA-N 0.000 description 1
- 229940073569 n-methylephedrine Drugs 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 239000007908 nanoemulsion Substances 0.000 description 1
- 125000005487 naphthalate group Chemical group 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 239000006218 nasal suppository Substances 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002829 nitrogen Chemical group 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000006959 non-competitive inhibition Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000004072 osteoblast differentiation Effects 0.000 description 1
- 238000012261 overproduction Methods 0.000 description 1
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 1
- GSUBXIVOZXWGKF-UHFFFAOYSA-N oxolane-3-carbaldehyde Chemical compound O=CC1CCOC1 GSUBXIVOZXWGKF-UHFFFAOYSA-N 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- KNEPBZMJMJUNQX-UHFFFAOYSA-N pent-4-ynamide Chemical compound NC(=O)CCC#C KNEPBZMJMJUNQX-UHFFFAOYSA-N 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 229940021222 peritoneal dialysis isotonic solution Drugs 0.000 description 1
- 230000036377 pgph activity Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 1
- 229960000395 phenylpropanolamine Drugs 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- ACVYVLVWPXVTIT-UHFFFAOYSA-M phosphinate Chemical compound [O-][PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-M 0.000 description 1
- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 201000000317 pneumocystosis Diseases 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 230000001323 posttranslational effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- VJZLQIPZNBPASX-OJJGEMKLSA-L prednisolone sodium phosphate Chemical compound [Na+].[Na+].O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP([O-])([O-])=O)[C@@H]4[C@@H]3CCC2=C1 VJZLQIPZNBPASX-OJJGEMKLSA-L 0.000 description 1
- BOFKYYWJAOZDPB-FZNHGJLXSA-N prednival Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O BOFKYYWJAOZDPB-FZNHGJLXSA-N 0.000 description 1
- 229950000696 prednival Drugs 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 230000007319 proteasomal degradation pathway Effects 0.000 description 1
- 230000020978 protein processing Effects 0.000 description 1
- 230000004844 protein turnover Effects 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 230000001698 pyrogenic effect Effects 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 description 1
- NGWSFRIPKNWYAO-UHFFFAOYSA-N salinosporamide A Natural products N1C(=O)C(CCCl)C2(C)OC(=O)C21C(O)C1CCCC=C1 NGWSFRIPKNWYAO-UHFFFAOYSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 230000037387 scars Effects 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229960001153 serine Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 208000011985 sialidosis Diseases 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 201000002612 sleeping sickness Diseases 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 208000020431 spinal cord injury Diseases 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- WNIFXKPDILJURQ-UHFFFAOYSA-N stearyl glycyrrhizinate Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=O)OCCCCCCCCCCCCCCCCCC)(C)CC5C4=CC(=O)C3C21C WNIFXKPDILJURQ-UHFFFAOYSA-N 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000003206 sterilizing agent Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000008054 sulfonate salts Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229950005890 tariquidar Drugs 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- DXSSLKYJRVANSE-PIJUOVFKSA-N tert-butyl N-[(2R)-1-(3,3-difluorocyclopentyl)-4-methyl-3-oxopent-4-en-2-yl]carbamate Chemical compound C(C)(C)(C)OC(N[C@H](CC1CC(CC1)(F)F)C(C(=C)C)=O)=O DXSSLKYJRVANSE-PIJUOVFKSA-N 0.000 description 1
- GYLHTDJGCXZLNH-AWEZNQCLSA-N tert-butyl N-[(2S)-1-cyclohexyl-4-methyl-3-oxopent-4-en-2-yl]carbamate Chemical compound CC(=C)C(=O)[C@H](CC1CCCCC1)NC(=O)OC(C)(C)C GYLHTDJGCXZLNH-AWEZNQCLSA-N 0.000 description 1
- OTMQMNQEDGHAGN-LBPRGKRZSA-N tert-butyl N-[(2S)-1-cyclopentyl-3-oxopent-4-en-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC1CCCC1)C(=O)C=C OTMQMNQEDGHAGN-LBPRGKRZSA-N 0.000 description 1
- TZSYOOXYLHDVKZ-IINYFYTJSA-N tert-butyl N-[(2S)-3-(3,3-difluorocyclobutyl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC1CC(F)(F)C1)C(=O)[C@@]1(C)CO1 TZSYOOXYLHDVKZ-IINYFYTJSA-N 0.000 description 1
- PZVDHXNLPMCHKS-SUMWQHHRSA-N tert-butyl N-[(2S)-3-cyclohexyl-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC1CCCCC1)C(=O)[C@@]1(C)CO1 PZVDHXNLPMCHKS-SUMWQHHRSA-N 0.000 description 1
- CHFPLRQOSZGQGQ-NWDGAFQWSA-N tert-butyl N-[(2S)-3-cyclopentyl-1-[(2R)-oxiran-2-yl]-1-oxopropan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H](CC1CCCC1)C(=O)[C@H]1CO1 CHFPLRQOSZGQGQ-NWDGAFQWSA-N 0.000 description 1
- JAGHSXMAJLEHBC-LBPRGKRZSA-N tert-butyl N-[(2S)-3-cyclopentyl-1-[methoxy(methyl)amino]-1-oxopropan-2-yl]carbamate Chemical compound CON(C)C(=O)[C@H](CC1CCCC1)NC(=O)OC(C)(C)C JAGHSXMAJLEHBC-LBPRGKRZSA-N 0.000 description 1
- XTLWGMKPJXXKER-DTIOYNMSSA-N tert-butyl N-[(2S)-4-methyl-3-oxo-1-(2-oxopyrrolidin-3-yl)pent-4-en-2-yl]carbamate Chemical compound CC(=C)C(=O)[C@H](CC1CCNC1=O)NC(=O)OC(C)(C)C XTLWGMKPJXXKER-DTIOYNMSSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000001685 thyroid gland Anatomy 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 239000008181 tonicity modifier Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 108091006106 transcriptional activators Proteins 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229960000575 trastuzumab Drugs 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 230000008736 traumatic injury Effects 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229950006782 triamcinolone benetonide Drugs 0.000 description 1
- GUYPYYARYIIWJZ-CYEPYHPTSA-N triamcinolone benetonide Chemical compound O=C([C@]12[C@H](OC(C)(C)O1)C[C@@H]1[C@@]2(C[C@H](O)[C@]2(F)[C@@]3(C)C=CC(=O)C=C3CC[C@H]21)C)COC(=O)C(C)CNC(=O)C1=CC=CC=C1 GUYPYYARYIIWJZ-CYEPYHPTSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 230000006663 ubiquitin-proteasome pathway Effects 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
- 230000006967 uncompetitive inhibition Effects 0.000 description 1
- 230000009677 vaginal delivery Effects 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 201000010044 viral meningitis Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D303/00—Compounds containing three-membered rings having one oxygen atom as the only ring hetero atom
- C07D303/02—Compounds containing oxirane rings
- C07D303/12—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms
- C07D303/32—Compounds containing oxirane rings with hydrocarbon radicals, substituted by singly or doubly bound oxygen atoms by aldehydo- or ketonic radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0205—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-(X)3-C(=0)-, e.g. statine or derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/0606—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing heteroatoms not provided for by C07K5/06086 - C07K5/06139, e.g. Ser, Met, Cys, Thr
- C07K5/06069—Ser-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06104—Dipeptides with the first amino acid being acidic
- C07K5/06113—Asp- or Asn-amino acid
- C07K5/06121—Asp- or Asn-amino acid the second amino acid being aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06147—Dipeptides with the first amino acid being heterocyclic and His-amino acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06173—Dipeptides with the first amino acid being heterocyclic and Glp-amino acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/081—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing O or S as heteroatoms, e.g. Cys, Ser
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0812—Tripeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0821—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp
- C07K5/0823—Tripeptides with the first amino acid being heterocyclic, e.g. His, Pro, Trp and Pro-amino acid; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0827—Tripeptides containing heteroatoms different from O, S, or N
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Crystallography & Structural Chemistry (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Neurology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Neurosurgery (AREA)
- Emergency Medicine (AREA)
Abstract
Description
本出願は、米国仮特許出願第61/941,798号(2014年2月19日に出願)、同第61/883,798号(2013年9月27日に出願)、同第61/856,847号(2013年7月22日に出願)、同第61/847,780号(2013年7月18日に出願)、同第61/786,086号(2013年3月14日に出願)、同第61/883,843号(2013年9月27日に出願)、及び同第61/785,608号(2013年3月14日に出願)の利益を主張するものであり、当該出願の各々は、参照によりその全体が本明細書に組み込まれる。
真核生物において、タンパク質分解は、破壊の標的となるタンパク質が76アミノ酸のポリペプチドユビキチンに結合するユビキチン経路によって主に媒介される。標的とされると、ユビキチン化タンパク質は、次いで、3つの主要なタンパク質分解活性の作用によりタンパク質を短鎖ペプチドに切断する多触媒性プロテアーゼである26Sプロテアソームの基質として機能する。細胞内タンパク質代謝回転における一般的機能を有する一方で、プロテアソーム媒介分解はまた、主要組織適合性複合体(MHC)クラスI抗原の提示、アポトーシス、細胞増殖調節、NF−κB活性化、抗原処理、及び炎症性シグナルの変換等の多くのプロセスにおいて重要な役割を果たす。
の化合物が本明細書に提供され、このうち置換基は、以下に詳細に論じられるように定義される。
「例えば」及び「等」という用語及びその文法的等価物に関しては、特に明記されない限り、「これらに限定されない」という語句が後に続くように理解される。本明細書で使用される場合、「約」という用語は、実験誤差による変動を説明することを意図している。本明細書に報告されるすべての測定値は、特に明示的に規定されない限り、用語が明示的に用いられるか否かにかかわらず、「約」という用語によって修飾されると理解される。本明細書で使用される場合、単数形「1つの(a)」、「1つの(an)」、及び「その(the)」は、文脈により特に明確に示されない限り、複数形の指示対象を含む。
)で示された1つ以上の立体中心を含む化学構造は、化学構造中に存在する立体中心(複数を含む)の絶対立体化学を示すことを意図している。本明細書で使用される場合、単純な線で表される結合は、立体選択性を示さない。特に反対の記載がない限り、絶対または相対立体化学を示すことなく本明細書に例示される1つ以上の立体中心を含む化学構造は、化合物(例えば、ジアステレオ異性体、鏡像異性体)のすべての可能な立体異性形態及びその混合物を包含する。単太字または破線、及び少なくとも1つのさらなる単純な線を含む構造は、すべての可能なジアステレオ異性体の一連の単一鏡像異性体を包含する。
によって表すことができる部分を指し、式中、各R基は、独立して、水素、アルキル、アルケニル、−;(CH2)b−;T、またはR基のうちの2つを表し、それらが結合するN原子と一緒になって環構造中に4〜8個の原子を有するヘテロシクリルを形成し、Tは、アリール、シクロアルキル、シクロアルケニル、ヘテロシクリル、またはポリシクリルを表し、bはゼロであるか、または1〜8の整数である。ある特定の実施形態において、アミノ基は塩基性であり、そのプロトン化形態は7.00を超えるpKaを有することを意味する。いくつかの実施形態において、「アミン」及び「アミノ」という用語は、非置換または置換の窒素原子と共有結合する部分を指す。
で表され得る部分を含む。いくつかの実施形態において、アミドは、不安定であり得るイミドは含まない。
によって表されるもの等のC=O基を含有する部分を含み、式中、Xは結合であるか、または酸素もしくは硫黄を表し、Rは、水素、アルキル、アルケニル、−(CH2)b−T、または薬学的に許容される塩を表し、R’は、水素、アルキル、アルケニル、または−(CH2)b−Tを表し、m及びTは、上で定義された通りである。Xが酸素であり、RまたはR’が水素でない場合、式は、「エステル」を表す。Xが酸素であり、Rが水素である場合、式は、「カルボン酸」を表す。
一態様において、本開示は、式(X)の構造を有する化合物であって、
式中、
m及びnが、それぞれ独立して、0、1、または2であり、m+n=2、3、または4であり、
pが、0または1であり、
qが、0、1、または2であり、
Kが、CR5R6、NR7、N(C=O)OR7、−NH−(C=O)−、O、S、SO、及びSO2からなる群から選択され、
Eが、NまたはCR7であり、
R1が、H、C1−6アルキル、C2−6アルケニル、C2−6アルキニル、C3−6シクロアルキル、及び3〜6員ヘテロシクロアルキルからなる群から選択され、R1が、任意に、ハロ、OR7、SR7、N(R7)2、CN、及び(C=O)N(R7)2からなる群から選択される1つ以上の置換基で置換され、
R2が、C1−2アルキレン−Gまたは(C=O)−Gであり、式中、Gが、アリール、ヘテロアリール、及びピリジノンからなる群から選択されるが、但し、R2がCH2フェニルであるとき、フェニルが、OR7、ハロ、C1−3アルキル、OCF3、SO2R7、(C=O)N(R7)2、CN、及びSO2N(R7)2からなる群から選択される1つ以上の置換基で置換されるものとし、
R3が、C3−7シクロアルキル、C3−7シクロアルケニル、3〜7員ヘテロシクロアルキル、及び3〜7員ヘテロシクロアルケニルからなる群から選択され、R3が、ハロ、=O、OR7、SR7、N(R7)2、O(C=O)N(R7)2、及びC1−6アルキルからなる群から選択される1つ以上の置換基で任意に置換され、
R4が、HまたはC1−3アルキルであり、
R5及びR6が、それぞれ独立して、H、OH、ハロ、C1−3アルキル、及びCF3からなる群から選択されるか、またはR5及びR6が、それらが結合している炭素と一緒に、C=Oまたは
を形成し、式中、Wが、OまたはNR7であり、rが、1、2、または3であり、
各R7が独立して、HまたはC1−6アルキルである、化合物、またはその薬学的に許容される塩を提供する。
を形成し、式中、rは1である。例えば、Kは、CH(OH)、C(CH3)(OH)、C=O、CH2、CF2、CH(Cl)、CH(CF3)、
、及びCOH(CH3)から選択される。場合によっては、KはCH(OH)である。様々な実施形態において、KはNR7であり、R7は、H、CH2CH3、またはCH3である。例えば、Kは、NCH3またはNCH2CH3を含むことができる。いくつかの実施形態において、Kは、N(C=O)OR7(例えば、N(C=O)OHまたはN(C=O)OCH3)、−NH−(C=O)−、S、SO、またはSO2である。様々な実施形態において、KはOである。
からなる群から選択される。様々な場合において、
から選択される。
からなる群から選択される。様々な実施形態において、R2は、
からなる群から選択される。場合によっては、R2は、
である。様々な実施形態において、R2は、
からなる群から選択される。いくつかの実施形態において、R2は、
からなる群から選択される。場合によっては、R2は、
からなる群から選択される。
からなる群から選択され得る。場合によっては、R3は、
である。場合によっては、R3は、
または
であり、qは、0または1であるか、あるいはqは1である。
、段落[0054]に記載されるR1、段落[0055]に記載されるR2、段落[0056]に記載されるR3、及び段落[0057]に記載されるR4を含む、式Xの化合物が企図される。
であり、R4はメチルであり、R5はHであり、R6はOHであり、R7はHである。
から選択されるか、またはその薬学的に許容される塩である。
からなる群から選択されるか、またはその薬学的に許容される塩である。
からなる群から選択され得るか、またはその薬学的に許容される塩であり得る。
を有する。
から選択されるか、またはその薬学的に許容される塩である。
から選択される構造を有するトリペプチドエポキシケトン化合物、またはその薬学的に許容される塩を提供する。
からなる群から選択されるトリペプチドエポキシケトン化合物、またはその薬学的に許容される塩を提供する。
から選択されるトリペプチドエポキシケトン化合物、またはその薬学的に許容される塩を提供する。
から選択されるトリペプチドエポキシケトン化合物、またはその薬学的に許容される塩を提供する。
式中、
Bが不在であり、
LがC=Oであり、
各Mが独立して、不在であるか、またはC1−12アルキルであり、
Qが不在であり、
XがOであり、
R1が、水素、−C1−6アルキル−B、C1−6ヒドロキシアルキル、及びC1−6アルコキシアルキ(alkoxyalky)から選択され、
R2が、
から選択され、
式中、Dが、水素、メトキシ、t−ブトキシ、ヒドロキシ、ハロゲン、シアノ、トリフルオロメチル、及びC1−4アルキルから選択されるが、但し、R2がベンジルであるとき、Dが水素以外であるものとし、
R3が、カルボシクリルM−及びカルボシクリルから選択され、
R4がN(R5)L−Q−R6であり、
R5が水素であり、
R6が、ヘテロシクリルM−及びカルボシクリルM−から選択され、
R7及びR8が、水素であり、
R15が、水素、C1−6アルキル、及びC1−6ヒドロキシアルキルから選択される、化合物、またはその薬学的に許容される塩が、本明細書に提供される。
として表され得る。
であり、Dは、メトキシ、ヒドロキシ、トリフルオロメチル、及びC1−4アルキルから選択される。
は、
からなる群から選択される。
からなる群から選択される。
からなる群から選択される。いくつかの実施形態において、R3はカルボシクリルCH2−であり、該カルボシクリルは、
である。
本明細書に開示される化合物は、免疫プロテアソーム(iP)の阻害剤であり得る。場合によっては、本明細書に開示される化合物は、iPサブユニットLMP7を阻害する。LMP7活性は、以下の実施例に記載されるプロテアソームサブユニットアッセイにおいて測定されるように、少なくとも10%、少なくとも20%、少なくとも30%、少なくとも40%、少なくとも50%、少なくとも60%、少なくとも70%、または少なくとも80%阻害され得る。1つ以上のさらなるiPサブユニットは、本明細書に開示される化合物、例えば、LMP2、MECL−1、β1、β2、及びβ5によって阻害され得る。様々な実施形態において、本明細書に開示される化合物は、LMP7ならびにLMP2及びMECL−1のうちの1つまたはその両方を阻害する。本明細書に開示される化合物は、例えば、IL−2、MHC−I、IL−6、TNFα、及びIFN−βのうちの1つ以上のサイトカイン活性または発現を減少させ得る。したがって、本明細書に開示される化合物は、以下の実施例に記載されるアッセイにおいて測定されるように、IL−2、MHC−I、IL−6、TNFα、及びIFN−βのうちの1つ以上の発現または活性を、少なくとも10%、少なくとも20%、少なくとも30%、少なくとも40%、少なくとも50%、少なくとも60%、少なくとも70%、または少なくとも80%阻害する、方法が提供される。
本明細書に提供される方法には、本明細書に提供される化合物のうちの1つ以上を含む、薬学的組成物の製造及びその使用が含まれる。また、薬学的組成物自体も含まれる。いくつかの実施形態において、本明細書に提供される化合物は、米国特許第7,737,112号及び米国特許出願第13/614,829号(これらの各々は、参照によりそれらの全体が本明細書に組み込まれる)に記載されるように製剤化され得る。薬学的組成物は、典型的に、薬学的に許容される担体を含む。
本開示はその詳細な説明と併せて理解されるが、前述の説明は、例示することを意図しており、添付の特許請求の範囲によって定義される本開示の範囲を制限しないことが理解される。他の態様、利点、及び修正は、以下の特許請求の範囲内である。
1Hの核磁気共鳴(NMR)スペクトルを、400MHzで記録した。化学シフト(δ)は、内部標準テトラメチルシランからの低磁場側にppmで表し、結合定数(J値)をヘルツ(Hz)で表した。質量分析(MS)は、荷電分子または分子断片を作製するために化合物をイオン化し、それらの質量対電荷比(m/z)を測定することによって、化合物の質量を確認するために使用された。イオン化法として、EI(電子衝撃)イオン化を使用した。
実施例1
(1r,4R)−N−((R)−1−(((S)−1−(((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)アミノ)−3−(4−メトキシフェニル)−1−オキソプロパン−2−イル)アミノ)−1−オキソプロパン−2−イル)−4−ヒドロキシ−4−メチルシクロヘキサンカルボキサミド(C−1087):
(S)−N−((S)−3−(シクロヘキサ−1−エン−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−2−((S)−3−ヒドロキシ−2−(2−モルホリノアセトアミド)プロパンアミド)−3−(3−ヒドロキシ−4−メトキシフェニル)プロパンアミド(C−1109):
(S)−N−((S)−3−(シクロヘキサ−1−エン−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−2−((S)−3−ヒドロキシ−2−(2−モルホリノアセトアミド)プロパンアミド)−3−(4−(メチルスルホニル)フェニル)プロパンアミド(C−1110):
(1r,4R)−N−((R)−1−(((S)−1−(((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)アミノ)−3−(4−メトキシフェニル)−1−オキソプロパン−2−イル)アミノ)−1−オキソプロパン−2−イル)−4−ヒドロキシ−1−メチルシクロヘキサンカルボキサミド(C−1111):
(S)−N−((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)−4−フェニルブタンアミド(C−1128):
(S)−N−((S)−3−(シクロヘキサ−1−エン−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(4−メトキシフェニル)−2−((S)−2−(2−モルホリノアセトアミド)−2−(オキセタン−3−イル)アセトアミド)プロパンアミド(C−1138):
(S)−N−((S)−1−(((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)アミノ)−3−(4−メトキシフェニル)−1−オキソプロパン−2−イル)−2−(2−モルホリノアセトアミド)ペンタ−4−インアミド(C−1139):
(S)−N−((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(2−メトキシピリジン−4−イル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1141):
(S)−N−((S)−3−((1R,3r,5S)−ビシクロ[3.1.0]ヘキサン−3−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(4−メトキシフェニル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1095):
(S)−3−シアノ−N−((S)−1−(((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)アミノ)−3−(4−メトキシフェニル)−1−オキソプロパン−2−イル)−2−(2−モルホリノアセトアミド)プロパンアミド(C−1135):
(S)−N−((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(4−メトキシフェニル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1009):
(2S,3R)−N−((S)−3−シクロペンチル−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−ヒドロキシ−3−(4−メトキシフェニル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1022):
(2S,3R)−N−((S)−3−(シクロヘキサ−1−エン−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−ヒドロキシ−2−((S)−3−ヒドロキシ−2−(2−モルホリノアセトアミド)プロパンアミド)−3−(4−メトキシフェニル)プロパンアミド(C−1116):
HATU(645mg、1.70mmol)及びDIEA(0.99mL、5.7mmol)を、DMF(8mL)中の(2S,3R)−ベンジル2−アミノ−3−ヒドロキシ−3−(4−メトキシフェニル)プロパン酸塩(HCl塩、477mg、1.41mmol)及びBoc−Ser−OH(290mg、1.41mmol)の0℃の溶液に順次添加した。反応混合物を周囲温度まで加温し、30分間撹拌した。混合物を濃縮し、残渣をシリカゲル上のフラッシュカラムクロマトグラフィー(石油エーテル/EtOAc=2:1)によって2回精製して、無色固体として(2S,3R)−ベンジル2−((S)−2−((tert−ブトキシカルボニル)アミノ)−3−ヒドロキシプロパンアミド)−3−ヒドロキシ−3−(4−メトキシフェニル)プロパン酸塩(646mg、収率93%)を得た。
(S)−N−((S)−3−シクロペンチル−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(3−ヒドロキシ−4−メチルフェニル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1117):
(S)−N−((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−2−((S)−2−(2−(4−ヒドロキシピペリジン−1−イル)アセトアミド)プロパンアミド)−3−(4−メトキシフェニル)プロパンアミド(C−1118):
(2S,3R)−N−((S)−1−(((S)−3−(シクロヘキサ−1−エン−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)アミノ)−3−(4−メトキシフェニル)−1−オキソプロパン−2−イル)−3−ヒドロキシ−2−(2−モルホリノアセトアミド)ブタンアミド(C−1148):
合成手順−断片
実施例17
tert−ブチル((2S)−3−(3−メチルシクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−((R)−テトラヒドロフラン−3−イル)プロパン−2−イル)カルバミン酸塩及びtert−ブチル(S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−((S)−テトラヒドロフラン−3−イル)プロパン−2−イルカルバミン酸塩:
tert−ブチル((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−((R)−テトラヒドロフラン−2−イル)プロパン−2−イル)カルバミン酸塩及びtert−ブチル((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−((S)−テトラヒドロフラン−2−イル)プロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−((R)−テトラヒドロフラン−3−イル)プロパン−2−イル)カルバミン酸塩及びtert−ブチル(S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−((S)−テトラヒドロフラン−3−イル)プロパン−2−イルカルバミン酸塩と同様の様式で合成を行い、(S)−tert−ブチル3−(フラン−2−イル)−1−(メトキシ(メチル)アミノ)−1−オキソプロパン−2−イルカルバミン酸塩の還元を以下の通りに行った。
tert−ブチル((S)−3−((1R,5S,6r)−ビシクロ[3.1.0]ヘキサン−6−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−3−((1R,3r,5S)−ビシクロ[3.1.0]ヘキサン−3−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
(S)−3−((1R,3r,5S)−ビシクロ[3.1.0]ヘキサン−3−イル)−2−((tert−ブトキシカルボニル)アミノ)プロパン酸を、(2S)−2−(tert−ブトキシカルボニルアミノ)−3−(テトラヒドロフラン−3−イル)プロパン酸の合成と同様の様式で(1R,3r,5S)−3−(ヨードメチル)ビシクロ[3.1.0]ヘキサンから合成した。
tert−ブチル((S)−3−(2−メチルシクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−(2−オキソピロリジン−1−イル)プロパン−2−イル)カルバミン酸塩:
tert−ブチル((2S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−(2−オキソピロリジン−3−イル)プロパン−2−イル)カルバミン酸塩:
tert−ブチル((2S)−3−(1−メチル−2−オキソピロリジン−3−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
(S)−2−アミノ−3−((S)−3,3−ジフルオロシクロペンチル)−1−((R)−2−メチルオキシラン−2−イル)プロパン−1−オン及び(S)−2−アミノ−3−((R)−3,3−ジフルオロシクロペンチル)−1−((R)−2−メチルオキシラン−2−イル)プロパン−1−オン:
tert−ブチル((S)−3−((1r,4S)−4−((4−メトキシベンジル)オキシ)シクロヘキシル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−3−シクロヘキシル−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−3−シクロペンチル−1−((R)−オキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
tert−ブチル((S)−3−シクロペンチル−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
メタノール(500mL)中の(S)−2−(tert−ブトキシカルボニルアミノ)−3−シクロペンテニルプロパン酸(56g、0.22mol)の溶液に、Pd/C(23g、0.022mol、10%)を添加した。混合物を、水素雰囲気下(1atm)、周囲温度で一晩撹拌し、次いで、セライトパッドを通して濾過した。濾液を減圧下で濃縮して、粘性油として(S)−2−(tert−ブトキシカルボニルアミノ)−3−シクロペンチルプロパン酸(55g、収率97%)を得、これをさらに精製することなく次の工程で使用した。
tert−ブチル((S)−3−(3,3−ジフルオロシクロブチル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
DMF(200mL)中の3−オキソシクロブタンカルボン酸(25g、0.22mol)、臭化ベンジル(45.14g、0.26mol)、及び炭酸カリウム(60.7g、0.44mol)の混合物を周囲温度で一晩撹拌した。混合物を濾過して除き、濾液を水(200mL)中に注ぎ入れた。得られた混合物をEtOAc(200mL×3)で抽出した。有機抽出物を合わせて、無水硫酸ナトリウム上で乾燥させ、濃縮した。残渣をシリカゲル上のフラッシュカラムクロマトグラフィー(石油エーテル/EtOAc=100:1〜20:1)によって精製して、ベンジルエステル(38g、収率84%)を得た。
tert−ブチル((S)−3−((1R,5S,6s)−ビシクロ[3.1.0]ヘキサン−6−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)カルバミン酸塩:
(S)−メチル2−アミノ−3−(1H−インドール−5−イル)プロパン酸塩:
(S)−メチル2−アミノ−3−(3−(ベンジルオキシ)−4−メチルフェニル)プロパン酸塩:
Boc−L−4−メチルスルホニルフェニルアランリンメチルエステル及びBoc−L−3−メチルスルホニルフェニルアランリンメチルエステル:
6−ブロモ−3,4−ジヒドロ−1H−ベンゾ[c][1,2]チアジン2,2−二酸化物:
(R)−メチル2−((tert−ブトキシカルボニル)アミノ)−3−(2−(2,4−ジメトキシベンジル)−1,1−ジオキシド−3,4−ジヒドロ−2H−ベンゾ[e][1,2]チアジン−6−イル)プロパン酸塩:
(S)−4−(3−(ベンジルオキシ)−2−((tert−ブトキシカルボニル)アミノ)−3−オキソプロピル)ピリジン1−酸化物:
(2S,3R)−ベンジル2−アミノ−3−ヒドロキシ−3−(4−メトキシフェニル)プロパン酸塩:
(2S,3S)−2−((tert−ブトキシカルボニル)アミノ)−3−ヒドロキシ−3−(4−メトキシフェニル)プロパン酸:
5−ブロモ−1−メチルピリジン−2(1H)−オン:
(R)−2−((1R,3S)−3−ヒドロキシシクロペンタンカルボキサミド)プロパン酸及び(R)−2−((1S,3R)−3−ヒドロキシシクロペンタンカルボキサミド)プロパン酸:
(R)−2−((1R,3R)−3−ヒドロキシシクロペンタンカルボキサミド)プロパン酸:
(S)−6−オキソピペリジン−3−カルボン酸:
(S)−テトラヒドロ−2H−ピラン−3−カルボン酸及び(R)−テトラヒドロ−2H−ピラン−3−カルボン酸:
(S)−テトラヒドロフラン−3−カルボン酸:
2−(3−オキソピペラジン−1−イル)酢酸:
2−(4−ヒドロキシ−4−メチルピペリジン−1−イル)酢酸:
(S)−4,5,6,7−テトラヒドロ−1H−インダゾール−5−カルボン酸及び(R)−4,5,6,7−テトラヒドロ−1H−インダゾール−5−カルボン酸:
(S)−2−(2−モルホリノアセトアミド)プロパン酸:
(R)−1−(2,4−ジメトキシベンジル)−5−オキソピロリジン−3−カルボン酸及び(S)−1−(2,4−ジメトキシベンジル)−5−オキソピロリジン−3−カルボン酸:
(1r,4r)−4−ヒドロキシ−1−メチルシクロヘキサンカルボン酸:
(1r,4r)−4−ヒドロキシ−4−メチルシクロヘキサンカルボン酸:
(1s,4s)−4−ヒドロキシ−1−メチルシクロヘキサンカルボン酸:
2−(4−ヒドロキシピペリジン−1−イル)酢酸:
2−(3,3−ジフルオロピペリジン−1−イル)酢酸、2−(4,4−ジフルオロピペリジン−1−イル)酢酸、2−(3,3−ジフルオロピロリジン−1−イル)酢酸、2−(4−(トリフルオロメチル)ピペリジン−1−イル)酢酸、及び2−(4−クロロピペリジン−1−イル)酢酸:
(S)−2−((R)−2−((1r,3R)−3−ヒドロキシシクロブタンカルボキサミド)プロパンアミド)−3−(4−メトキシフェニル)プロパン酸:
DCM(10mL)中の(S)−ベンジル2−((R)−2−((tert−ブトキシカルボニル)アミノ)プロパンアミド)−3−(4−メトキシフェニル)プロパン酸塩(1.2g、2.6mmol)の溶液に、TFA(3mL)を添加した。混合物を周囲温度で0.5時間撹拌し、次いで、乾燥するまで濃縮して粗アミン(TFA塩)にした。
(S)−2−((tert−ブトキシカルボニル)アミノ)−3−シアノプロパン酸:
2−((tert−ブトキシカルボニル)アミノ)−3,3,3−トリフルオロプロパン酸:
(S)−3−(3,4−ビス(ベンジルオキシ)フェニル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパン酸:
(S)−2−アミノ−N−((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(4−メトキシフェニル)プロパンアミドTFA塩:
(S)−2−((S)−2−アミノプロパンアミド)−N−((S)−3−(シクロペンタ−1−エン−1−イル)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソプロパン−2−イル)−3−(4−メトキシフェニル)プロパンアミド(TFA塩):
(S)−3−ヒドロキシ−2−(2−モルホリノアセトアミド)プロパン酸:
(S)−2−アミノ−1−((R)−2−メチルオキシラン−2−イル)−3−フェニルプロパン−1−オンTFA塩を、参照文献:国際公開第WO2007/149512A2号(参照することによりその全体が本明細書に組み込まれる)に記載される方法を用いて調製した。
実施例67
(S)−3−シクロプロピル−N−((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−フェニルプロパン−2−イル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1224):
(S)−N−((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−フェニルプロパン−2−イル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)−3−(ピリジン−2−イル)プロパンアミド(C−1505):
(S)−3−(3,4−ジメトキシフェニル)−N−((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−フェニルプロパン−2−イル)−2−((S)−2−(2−モルホリノアセトアミド)プロパンアミド)プロパンアミド(C−1160):
(S)−3−ヒドロキシ−N−((S)−3−(4−メトキシフェニル)−1−(((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−フェニルプロパン−2−イル)アミノ)−1−オキソプロパン−2−イル)−2−(2−モルホリノアセトアミド)プロパンアミド(C−1159):
(2S,3S)−3−ヒドロキシ−N−((S)−3−(4−メトキシフェニル)−1−(((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−フェニルプロパン−2−イル)アミノ)−1−オキソプロパン−2−イル)−2−((3−モルホリノプロパ−1−エン−2−イル)アミノ)ブタンアミド(C−1174):
(R)−N−((S)−1−(((S)−3−(4−メトキシフェニル)−1−(((S)−1−((R)−2−メチルオキシラン−2−イル)−1−オキソ−3−フェニルプロパン−2−イル)アミノ)−1−オキソプロパン−2−イル)アミノ)−1−オキソプロパン−2−イル)テトラヒドロフラン−2−カルボキサミド(C−1166)の合成
実施例73−プロテアソーム活性部位ELISA
Parlati F,Lee SJ,Aujay M,et al.Blood(2009)114:3439−3447において前述される、ELISAに基づく技術であるプロテアソーム構成型/免疫プロテアソームサブユニット酵素結合免疫吸着(ProCISE)アッセイが、サブユニットに特異的な活性の定量的評価のために使用された。試験化合物は、DMSO中で100倍の濃度で、次いで、水性低張溶解緩衝液中で10倍まで段階的に希釈された。ヒト急性リンパ性白血病細胞株MOLT−4からの溶解物は、化合物の最終濃度が1倍となるように25℃で1時間処理した。次いで、処理した細胞溶解物を、ビオチン化したプロテアソーム活性部位結合プローブで、25℃で2時間インキュベートした。その後、溶解物を塩酸グアニジン中で変性させ、プローブに結合したサブユニットをストレプトアビジン複合型セファロースビーズで単離した。個々のサブユニット(例えば、β5、LMP7、LMP2、MECL−1)を、サブユニットに特異的な一次抗体でプローブし、続いて、HRP複合型二次抗体でプローブした。化学発光基質を使用して、HRPの結合に伴うシグナルを生成し、これをプレートリーダー上で検出した。発光シグナルをタンパク質含有量に正規化し、次いで、DMSOで処理された対照と比較してパーセント活性を計算し、IC50曲線を作成した。
NT−試験せず
本明細書に提供される様々な化合物に対するプロテアソームキモトリプシン様活性、カスパーゼ様活性、及びトリプシン様活性は、それぞれ、スクシニル−Leu−Leu−Val−Tyr−AMC(10Amol/L)、Z−Leu−Leu−Glu−AMC(10Amol/L)、及びBoc−Leu−Arg−Arg−AMC(50Amol/L)を用いて、精製したヒト20Sプロテアソーム(それぞれ、2、4、及び8.0nmol/L)またはHT−29細胞溶解物(それぞれ、0.125、0.25、及び0.25Agタンパク質/mL)で決定された。アッセイ緩衝液は、0.03% SDSを含む(20S)または0.03% SDSを含まない(細胞溶解物)、TE緩衝液[20mmol/L Tris(pH8.0)、0.5mmol/L EDTA]から構成された。酵素または溶解物の付加により反応を開始し、プレートベースの分光蛍光光度計(spectofluorometer)(Tecan)を用いて、27jCでAMC生成物形成についてモニタリングした。60〜75分の間に測定された反応速度に基づいて、IC50値を決定した。Demo,S.D.et al.,Cancer Res.2007,67,6383−6391も参照のこと。
Claims (97)
- 式(X)の化合物であって、
式中、
m及びnが、それぞれ独立して、0、1、または2であり、m+n=2、3、または4であり、
pが、0または1であり、
qが、0、1、または2であり、
Kが、CR5R6、NR7、N(C=O)OR7、−NH−(C=O)−、O、S、SO、及びSO2からなる群から選択され、
Eが、NまたはCR7であり、
R1が、H、C1−6アルキル、C2−6アルケニル、C2−6アルキニル、C3−6シクロアルキル、及び3〜6員ヘテロシクロアルキルからなる群から選択され、R1が、ハロ、OR7、SR7、N(R7)2、CN、及び(C=O)N(R7)2からなる群から選択される1つ以上の置換基で任意に置換され、
R2が、C1−2アルキレン−Gまたは(C=O)−Gであり、式中、Gが、アリール、ヘテロアリール、及びピリジノンからなる群から選択されるが、但し、R2がCH2フェニルであるとき、前記フェニルが、OR7、ハロ、C1−3アルキル、OCF3、SO2R7、(C=O)N(R7)2、CN、及びSO2N(R7)2からなる群から選択される1つ以上の置換基で置換されるものとし、
R3が、C3−7シクロアルキル、C3−7シクロアルケニル、3〜7員ヘテロシクロアルキル、及び3〜7員ヘテロシクロアルケニルからなる群から選択され、R3が、ハロ、=O、OR7、SR7、N(R7)2、O(C=O)N(R7)2、及びC1−6アルキルからなる群から選択される1つ以上の置換基で任意に置換され、
R4が、HまたはC1−3アルキルであり、
R5及びR6が、それぞれ独立して、H、OH、ハロ、C1−3アルキル、及びCF3からなる群から選択されるか、またはR5及びR6が、それらが結合している炭素と一緒に、C=Oまたは
を形成し、式中、Wが、OまたはNR7であり、rが、1、2、または3であり、
各R7が独立して、HまたはC1−6アルキルである、前記化合物、
またはその薬学的に許容される塩。 - mが0である、請求項1に記載の前記化合物。
- mが1である、請求項1に記載の前記化合物。
- mが2である、請求項1に記載の前記化合物。
- nが2である、請求項1〜4のいずれか一項に記載の前記化合物。
- nが1である、請求項1、3、または4に記載の前記化合物。
- nが0である、請求項1または4に記載の前記化合物。
- pが0である、請求項1〜7のいずれか一項に記載の前記化合物。
- pが1である、請求項1〜7のいずれか一項に記載の前記化合物。
- qが0である、請求項1〜9のいずれか一項に記載の前記化合物。
- qが1である、請求項1〜9のいずれか一項に記載の前記化合物。
- qが2である、請求項1〜9のいずれか一項に記載の前記化合物。
- KがCR5R6である、請求項1〜12のいずれか一項に記載の前記化合物。
- Kが、CH(OH)、C(CH3)(OH)、C=O、CH2、CF2、CH(Cl)、CH(CF3)、
及びCOH(CH3)からなる群から選択される、請求項13に記載の前記化合物。 - KがNR7である、請求項1〜12のいずれか一項に記載の前記化合物。
- Kが、NCH3またはNCH2CH3である、請求項15に記載の前記化合物。
- Kが、N(C=O)OR7 、−NH−(C=O)−、S、SO、またはSO2である、請求項1〜12のいずれか一項に記載の前記化合物。
- KがOである、請求項1〜12のいずれか一項に記載の前記化合物。
- EがNである、請求項1〜18のいずれか一項に記載の前記化合物。
- EがCR7である、請求項1〜18のいずれか一項に記載の前記化合物。
- Eが、CHまたはC(CH3)である、請求項20に記載の前記化合物。
- からなる群から選択される、請求項1〜21のいずれか一項に記載の前記化合物。
- からなる群から選択される、請求項1〜22のいずれか一項に記載の前記化合物。
- R1がC1−6アルキルである、請求項1〜23のいずれか一項に記載の前記化合物。
- R1がC1−3アルキルである、請求項24に記載の前記化合物。
- R1が、CH3、CH2OH、CF3、CH(OH)CH3、CH2CN、またはCH2CH3である、請求項1〜23のいずれか一項に記載の前記化合物。
- R1が、CH3、CH2OH、CH(OH)CH3、CH2CNである、請求項26に記載の前記化合物。
- R1が、C2−6アルケニルまたはC2−6アルキニルである、請求項1〜23のいずれか一項に記載の前記化合物。
- R1がCH2CCHである、請求項28に記載の前記化合物。
- R1がC3−6シクロアルキルである、請求項1〜23のいずれか一項に記載の前記化合物。
- R1が、シクロプロピル、シクロブチル、シクロペンチル、またはシクロヘキシルである、請求項30に記載の前記化合物。
- R1が3〜6員ヘテロシクロアルキルである、請求項1〜23のいずれか一項に記載の前記化合物。
- R1が、オキセタニル、テトラヒドロフラニル、またはピペラジニルである、請求項32に記載の前記化合物。
- R2がC1−2アルキレン−ヘテロアリールである、請求項1〜33のいずれか一項に記載の前記化合物。
- R2がCH2−ヘテロアリールである、請求項34に記載の前記化合物。
- R2がC1−2アルキレン−ピリジノンである、請求項1〜33のいずれか一項に記載の前記化合物。
- R2がC1−2アルキレン−アリールである、請求項1〜33のいずれか一項に記載の前記化合物。
- R2がCH2−アリールである、請求項37に記載の前記化合物。
- R2が、
からなる群から選択される、請求項1〜37のいずれか一項に記載の前記化合物。 - R2が、
からなる群から選択される、請求項1〜33のいずれか一項に記載の前記化合物。 - R2が、
からなる群から選択される、請求項40に記載の前記化合物。 - R2が、
からなる群から選択される、請求項1〜33のいずれか一項に記載の前記化合物。 - R2が、
からなる群から選択される、請求項1〜33のいずれか一項に記載の前記化合物。 - R2が、
からなる群から選択される、請求項1〜33のいずれか一項に記載の前記化合物。 - R3がC3−7シクロアルキルである、請求項1〜44のいずれか一項に記載の前記化合物。
- 前記C3−7シクロアルキルが、OH、F、Me、NH2、及びO(CO)NH2からなる群から選択される少なくとも1つの置換基で置換される、請求項45に記載の前記化合物。
- R3が、シクロプロピル、シクロブチル、シクロペンチル、またはシクロヘキシルである、請求項45に記載の前記化合物。
- R3が、シクロペンチルまたはシクロヘキシルである、請求項47に記載の前記化合物。
- R3がC3−7シクロアルケニルである、請求項1〜44のいずれか一項に記載の前記化合物。
- 前記C3−7シクロアルケニルが、OH及びMeからなる群から選択される少なくとも1つの置換基で置換される、請求項49に記載の前記化合物。
- R3が、シクロペンテニルまたはシクロヘキセニルである、請求項49に記載の前記化合物。
- R3が、3〜7員ヘテロシクロアルキルである、請求項1〜44のいずれか一項に記載の前記化合物。
- R3が、テトロヒドロフラニル、テトラヒドロピラニル、ピロリンジニル、またはピロリジノニルである、請求項52に記載の前記化合物。
- R3が3〜7員ヘテロシクロアルケニルである、請求項1〜44のいずれか一項に記載の前記化合物。
- R3が、ジヒドロピラニルまたはジヒドロフラニルである、請求項54に記載の前記化合物。
- R3が、
からなる群から選択される、請求項1〜44のいずれか一項に記載の前記化合物。 - R3が、
からなる群から選択される、請求項1〜44のいずれか一項に記載の前記化合物。 - R4がC1−3アルキルである、請求項1〜57のいずれか一項に記載の前記化合物。
- R4がメチルである、請求項58に記載の前記化合物。
- R4がHである、請求項1〜57のいずれか一項に記載の前記化合物。
- m及びnが、それぞれ独立して、2であり、
pが1であり、
qが1であり、
Kが、CR5R6またはOであり、
Eが、NまたはCR7であり、
R1が、CH3、CH2OH、CH(OH)CH3、またはCH2CNであり、
R2が、
であり、
R3が、
であり、
R4がメチルであり、
R5がHであり、
R6がOHであり、
R7がHである、
請求項1に記載の前記化合物。 -
からなる群から選択される構造を有する、請求項1に記載の前記化合物、
またはその薬学的に許容される塩。 -
からなる群から選択される構造を有する、請求項62に記載の前記化合物、
またはその薬学的に許容される塩。 - からなる群から選択される構造を有する、請求項62に記載の前記化合物、
またはその薬学的に許容される塩。 - 前記化合物が、立体化学的構造、
を有する、請求項1〜64のいずれか一項に記載の前記化合物。 - からなる群から選択される構造を有する、請求項1に記載の前記化合物、またはその薬学的に許容される塩。
- からなる群から選択される構造を有する、請求項66に記載の前記化合物、またはその薬学的に許容される塩。
- からなる群から選択される構造を有する化合物、またはその薬学的に許容される塩。
- からなる群から選択される構造を有する化合物、またはその薬学的に許容される塩。
- からなる群から選択される構造を有する化合物、またはその薬学的に許容される塩。
- からなる群から選択される構造を有する化合物、またはその薬学的に許容される塩。
- からなる群から選択される構造を有する化合物、またはその薬学的に許容される塩。
- 式(I)の構造を有する化合物であって、
式中、
Bが不在であり、
LがC=Oであり、
各Mが独立して、不在であるか、またはC1−12アルキルであり、
Qが不在であり、
XがOであり、
R1が、水素、−C1−6アルキル−B、C1−6ヒドロキシアルキル、及びC1−6アルコキシアルキ(alkoxyalky)から選択され、
R2が、
から選択され、
式中、Dが、水素、メトキシ、t−ブトキシ、ヒドロキシ、ハロゲン、シアノ、トリフルオロメチル、及びC1−4アルキルから選択されるが、但し、R2がベンジルであるとき、Dが水素以外であり、かつRが水素であるものとし、
R3が、カルボシクリルM−及びカルボシクリルから選択され、
R4がN(R5)L−Q−R6であり、
R5が水素であり、
R6が、ヘテロシクリルM−及びカルボシクリルMから選択され、
R7及びR8が、水素であり、
R15が、水素、C1−6アルキル、及びC1−6ヒドロキシアルキルから選択される、前記化合物、
またはその薬学的に許容される塩。 - R6がヘテロシクリルM−である、請求項73に記載の前記化合物。
- R6がカルボシクリルM−である、請求項73に記載の前記化合物。
- R2が、
であり、Dが、メトキシ、ヒドロキシ、トリフルオロメチル、及びC1−4アルキルから選択される、請求項73〜75のいずれか一項に記載の前記化合物。 - R3がカルボシクリルM−である、請求項73〜76のいずれか一項に記載の前記化合物。
- Mが不在である、請求項73〜77のいずれか一項に記載の前記化合物。
- MがC1−12アルキルである、請求項73〜77のいずれか一項に記載の前記化合物。
- 請求項1〜79のいずれか一項に記載の前記化合物、またはその薬学的に許容される塩、及び薬学的に許容される担体または希釈剤を含む、薬学的組成物。
- 細胞の免疫プロテアソームを阻害する方法であって、前記細胞を、前記細胞中の前記免疫プロテアソームを阻害するのに有効に、請求項1〜79のいずれか一項に記載の化合物、または請求項81に記載の前記組成物と接触させることを含む、前記方法。
- 前記化合物が、β5i(LMP7)を阻害する、請求項81に記載の前記方法。
- 前記化合物が、LMP2及びMECL−1のうちの一方または両方をさらに阻害する、請求項82に記載の前記方法。
- 前記接触がインビトロでの接触である、請求項81〜83のいずれか一項に記載の前記方法。
- 前記接触がインビボでの接触である、請求項84に記載の前記方法。
- 前記接触が、前記化合物または前記組成物を対象に投与することを含む、請求項81〜83及び85のいずれか一項に記載の前記方法。
- 前記投与が、経口、非経口、注射を介する、吸入を介する、経皮、または経粘膜投与である、請求項86に記載の前記方法。
- 前記対象が哺乳動物である、請求項86または87に記載の前記方法。
- 前記対象がヒトである、請求項88に記載の前記方法。
- 前記対象が、自己免疫疾患を患っている、請求項86〜89のいずれか一項に記載の前記方法。
- 前記自己免疫疾患が、乾癬、皮膚炎、全身性硬皮症、硬化症、クローン病、潰瘍性大腸炎;呼吸窮迫症候群、髄膜炎;脳炎;ブドウ膜炎;大腸炎;糸球体腎炎;湿疹、喘息、慢性炎症;アテローム性動脈硬化症;白血球接着不全症;リウマチ性関節炎;全身性エリテマトーデス(SLE);真性糖尿病;多発性硬化症;レイノー症候群;自己免疫性甲状腺炎;アレルギー性脳脊髄炎;シェーグレン症候群;若年型糖尿病;結核、サルコイドーシス、多発性筋炎、肉芽腫症、及び血管炎;悪性貧血(アジソン病);白血球漏出を伴う疾患;中枢神経系(CNS)炎症性障害;多臓器損傷症候群;溶血性貧血;重症筋無力症;抗原−抗体複合体媒介性疾患;抗糸球体基底膜疾患;抗リン脂質抗体症候群;アレルギー性神経炎;グレーブス病;ランバート−イートン筋無力症症候群;水疱性類天疱瘡;天疱瘡;自己免疫多発性内分泌症;ライター病;スティッフマン症候群;ベーチェット病;巨細胞動脈炎;免疫複合体性腎炎;IgA腎症;IgM多発性神経障害;免疫性血小板減少性紫斑病(ITP)または自己免疫性血小板減少症である、請求項90に記載の前記方法。
- 免疫関連疾患の治療のための方法であって、治療有効量の請求項1〜79のいずれか一項に記載の前記化合物または請求項80に記載の前記組成物を、それを必要とする対象に投与することを含む、前記方法。
- 前記免疫関連疾患が、リウマチ性関節炎、狼瘡、炎症性腸疾患、多発性硬化症、またはクローン病である、請求項92に記載の前記方法。
- 炎症の治療のための方法であって、治療有効量の請求項1〜79のいずれか一項に記載の前記化合物または請求項80に記載の前記組成物を、それを必要とする対象に投与することを含む、前記方法。
- 感染症を治療するための方法であって、治療有効量の請求項1〜79のいずれか一項に記載の前記化合物の化合物または請求項80に記載の前記組成物を、それを必要とする対象に投与することを含む、前記方法。
- 神経変性疾患を治療するための方法であって、治療有効量の請求項1〜79のいずれか一項に記載の前記化合物または請求項80に記載の前記組成物を、それを必要とする対象に投与することを含む、前記方法。
- 前記神経変性疾患が、多発性硬化症である、請求項96に記載の前記方法。
Applications Claiming Priority (17)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361786086P | 2013-03-14 | 2013-03-14 | |
US201361785608P | 2013-03-14 | 2013-03-14 | |
US61/786,086 | 2013-03-14 | ||
US61/785,608 | 2013-03-14 | ||
US201361847780P | 2013-07-18 | 2013-07-18 | |
US61/847,780 | 2013-07-18 | ||
US201361856847P | 2013-07-22 | 2013-07-22 | |
US61/856,847 | 2013-07-22 | ||
US201361883843P | 2013-09-27 | 2013-09-27 | |
US201361883798P | 2013-09-27 | 2013-09-27 | |
US61/883,843 | 2013-09-27 | ||
US61/883,798 | 2013-09-27 | ||
US201461941798P | 2014-02-19 | 2014-02-19 | |
US61/941,798 | 2014-02-19 | ||
ARP20140100970 | 2014-03-13 | ||
ARP140100970A AR095426A1 (es) | 2013-03-14 | 2014-03-13 | Inhibidores tripeptídicos de la epoxicetona proteasa |
PCT/US2014/026987 WO2014152134A1 (en) | 2013-03-14 | 2014-03-14 | Tripeptide epoxy ketone protease inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2016515509A true JP2016515509A (ja) | 2016-05-30 |
JP6483657B2 JP6483657B2 (ja) | 2019-03-13 |
Family
ID=51581125
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016502301A Active JP6483657B2 (ja) | 2013-03-14 | 2014-03-14 | トリペプチドエポキシケトンプロテアーゼ阻害剤 |
Country Status (29)
Country | Link |
---|---|
US (4) | US9434761B2 (ja) |
EP (1) | EP2970224B1 (ja) |
JP (1) | JP6483657B2 (ja) |
CN (1) | CN105143212B (ja) |
AR (1) | AR095426A1 (ja) |
AU (1) | AU2014240129B2 (ja) |
BR (1) | BR112015023298B1 (ja) |
CA (1) | CA2903720C (ja) |
CL (1) | CL2015002706A1 (ja) |
CY (1) | CY1119645T1 (ja) |
DK (1) | DK2970224T3 (ja) |
EA (1) | EA029548B1 (ja) |
ES (1) | ES2642765T3 (ja) |
HK (1) | HK1213249A1 (ja) |
HR (1) | HRP20171572T1 (ja) |
HU (1) | HUE034769T2 (ja) |
IL (1) | IL241170B (ja) |
LT (1) | LT2970224T (ja) |
ME (1) | ME02912B (ja) |
MX (2) | MX366200B (ja) |
PE (1) | PE20151558A1 (ja) |
PH (1) | PH12015502002B1 (ja) |
PL (1) | PL2970224T3 (ja) |
PT (1) | PT2970224T (ja) |
RS (1) | RS56500B1 (ja) |
SG (1) | SG11201507033RA (ja) |
SI (1) | SI2970224T1 (ja) |
WO (1) | WO2014152134A1 (ja) |
ZA (1) | ZA201506572B (ja) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019527205A (ja) * | 2016-06-29 | 2019-09-26 | ケザール ライフ サイエンシズKezar Life Sciences | ペプチドエポキシケトン免疫プロテアソーム阻害剤の結晶塩 |
JP2019527677A (ja) * | 2016-06-29 | 2019-10-03 | ケザール ライフ サイエンシズKezar Life Sciences | ペプチドエポキシケトン免疫プロテアソーム阻害剤、およびその前駆体の調製プロセス |
JP2020531494A (ja) * | 2017-08-23 | 2020-11-05 | ケザール ライフ サイエンシズKezar Life Sciences | 自己免疫疾患の治療における免疫プロテアソーム阻害剤および免疫抑制剤 |
Families Citing this family (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108707140B (zh) | 2013-03-14 | 2022-07-22 | 勃林格殷格翰国际有限公司 | 蛋白酶c抑制剂 |
AR095426A1 (es) | 2013-03-14 | 2015-10-14 | Onyx Therapeutics Inc | Inhibidores tripeptídicos de la epoxicetona proteasa |
MX363600B (es) | 2014-03-13 | 2019-03-28 | Univ Indiana Res & Tech Corp | Moduladores alostericos de proteina nucleo de hepatitis b. |
EA031376B1 (ru) | 2014-09-12 | 2018-12-28 | Бёрингер Ингельхайм Интернациональ Гмбх | Спироциклические ингибиторы катепсина с |
TWI721016B (zh) | 2015-09-15 | 2021-03-11 | 美商艾森伯利生物科學公司 | B型肝炎核心蛋白質調節劑 |
CN107417767B (zh) * | 2016-08-18 | 2021-09-03 | 杭州市西溪医院 | 哌啶或哌嗪构建的二肽化合物、其制备方法和应用 |
AU2017326356A1 (en) | 2016-09-15 | 2019-04-11 | Assembly Biosciences, Inc. | Hepatitis B core protein modulators |
ES2898217T3 (es) | 2017-03-02 | 2022-03-04 | Assembly Biosciences Inc | Compuestos de sulfamida cíclica y métodos de uso de los mismos |
CN110612300B (zh) | 2017-03-13 | 2023-10-20 | 组装生物科学股份有限公司 | 制备乙型肝炎核心蛋白调节剂的方法 |
US11357817B2 (en) * | 2017-05-15 | 2022-06-14 | The Regents Of The University Of California | Immunoproteasome inhibitor |
WO2019060651A1 (en) | 2017-09-21 | 2019-03-28 | Kezar Life Sciences | POLY THERAPY FOR IMMUNOLOGICAL DISEASES |
EP3833374A4 (en) * | 2018-08-06 | 2022-04-27 | University Of Kentucky Research Foundation | PROTEASOME INHIBITORS |
TWI827694B (zh) | 2018-10-04 | 2024-01-01 | 美商凱薩爾生活科學公司 | 免疫蛋白酶體抑制劑調配物 |
CN110078643A (zh) * | 2019-05-27 | 2019-08-02 | 吉尔生化(上海)有限公司 | 一种Nα-叔丁氧羰基-DL-间羟基酪氨酸的合成方法 |
CN110204500A (zh) * | 2019-07-17 | 2019-09-06 | 九江德思光电材料有限公司 | 一种叶菌唑的制备方法 |
JP2023522691A (ja) * | 2020-04-21 | 2023-05-31 | ユニバーシティ オブ ロチェスター | ヒト精巣上体タンパク質4の阻害剤 |
CN111440079B (zh) * | 2020-04-29 | 2024-03-08 | 山东普洛汉兴医药有限公司 | 一种dl-苏式-对氯苯丝氨酸的合成方法 |
CN115322130B (zh) * | 2022-08-02 | 2024-05-14 | 南京正济医药研究有限公司 | 制备(s)-2-(boc-氨基)-3-[(s)-2-氧代-3-吡咯烷基]丙酸甲酯 |
CN115124634B (zh) * | 2022-08-10 | 2023-10-20 | 杭州小菱科技有限公司 | 一种茂金属主催化剂及其制备方法 |
CN115650881A (zh) * | 2022-09-06 | 2023-01-31 | 浙江医药股份有限公司新昌制药厂 | 一种利用微反应器合成喹诺酮类化合物中间体的工艺方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007537265A (ja) * | 2004-05-10 | 2007-12-20 | プロテオリックス, インコーポレイテッド | 酵素阻害のための化合物 |
JP2009514971A (ja) * | 2005-11-09 | 2009-04-09 | プロテオリックス, インコーポレイテッド | 酵素阻害のための化合物 |
JP2009541327A (ja) * | 2006-06-19 | 2009-11-26 | プロテオリックス, インコーポレイテッド | 酵素阻害のための化合物 |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4522811A (en) | 1982-07-08 | 1985-06-11 | Syntex (U.S.A.) Inc. | Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides |
US5340736A (en) | 1991-05-13 | 1994-08-23 | The President & Fellows Of Harvard College | ATP-dependent protease and use of inhibitors for same in the treatment of cachexia and muscle wasting |
US5858784A (en) | 1991-12-17 | 1999-01-12 | The Regents Of The University Of California | Expression of cloned genes in the lung by aerosol- and liposome-based delivery |
WO1998010779A1 (en) | 1996-09-13 | 1998-03-19 | New York University | Method for treating parasitic diseases with proteasome inhibitors |
US6042820A (en) | 1996-12-20 | 2000-03-28 | Connaught Laboratories Limited | Biodegradable copolymer containing α-hydroxy acid and α-amino acid units |
US6472375B1 (en) | 1998-04-16 | 2002-10-29 | John Wayne Cancer Institute | DNA vaccine and methods for its use |
PL206255B1 (pl) * | 2000-07-21 | 2010-07-30 | Dendreon Corporationdendreon Corporation | Inhibitor proteazy wirusa zapalenia wątroby C, zawierająca go kompozycja farmaceutyczna i zastosowanie inhibitora do wytwarzania leku do leczenia chorób związanych z HCV oraz zastosowanie do wytwarzania kompozycji do stosowania w kombinowanej terapii |
US7232818B2 (en) | 2004-04-15 | 2007-06-19 | Proteolix, Inc. | Compounds for enzyme inhibition |
ATE499109T1 (de) | 2004-12-07 | 2011-03-15 | Proteolix Inc | Zusammensetzung zur proteasomhemmung |
EP1863513A2 (en) | 2005-03-11 | 2007-12-12 | The University of North Carolina at Chapel Hill | Potent and specific immunoproteasome inhibitors |
MX2011004225A (es) | 2008-10-21 | 2011-06-21 | Onyx Therapeutics Inc | Terapia de combinacion con epoxicetonas peptidicas. |
US20130303482A1 (en) | 2012-05-08 | 2013-11-14 | Onyx Therapeutics, Inc. | Cylodextrin Complexation Methods for Formulating Peptide Proteasome Inhibitors |
AR095426A1 (es) | 2013-03-14 | 2015-10-14 | Onyx Therapeutics Inc | Inhibidores tripeptídicos de la epoxicetona proteasa |
-
2014
- 2014-03-13 AR ARP140100970A patent/AR095426A1/es unknown
- 2014-03-14 EA EA201591751A patent/EA029548B1/ru not_active IP Right Cessation
- 2014-03-14 EP EP14722443.0A patent/EP2970224B1/en active Active
- 2014-03-14 WO PCT/US2014/026987 patent/WO2014152134A1/en active Application Filing
- 2014-03-14 BR BR112015023298-1A patent/BR112015023298B1/pt active IP Right Grant
- 2014-03-14 ES ES14722443.0T patent/ES2642765T3/es active Active
- 2014-03-14 RS RS20171125A patent/RS56500B1/sr unknown
- 2014-03-14 MX MX2015011766A patent/MX366200B/es active IP Right Grant
- 2014-03-14 PT PT147224430T patent/PT2970224T/pt unknown
- 2014-03-14 CA CA2903720A patent/CA2903720C/en active Active
- 2014-03-14 ME MEP-2017-255A patent/ME02912B/me unknown
- 2014-03-14 CN CN201480022700.9A patent/CN105143212B/zh active Active
- 2014-03-14 JP JP2016502301A patent/JP6483657B2/ja active Active
- 2014-03-14 LT LTEP14722443.0T patent/LT2970224T/lt unknown
- 2014-03-14 US US14/210,806 patent/US9434761B2/en not_active Ceased
- 2014-03-14 PE PE2015001916A patent/PE20151558A1/es active IP Right Grant
- 2014-03-14 AU AU2014240129A patent/AU2014240129B2/en active Active
- 2014-03-14 HU HUE14722443A patent/HUE034769T2/en unknown
- 2014-03-14 DK DK14722443.0T patent/DK2970224T3/en active
- 2014-03-14 SG SG11201507033RA patent/SG11201507033RA/en unknown
- 2014-03-14 SI SI201430467T patent/SI2970224T1/sl unknown
- 2014-03-14 PL PL14722443T patent/PL2970224T3/pl unknown
-
2015
- 2015-09-03 IL IL24117015A patent/IL241170B/en active IP Right Grant
- 2015-09-07 ZA ZA2015/06572A patent/ZA201506572B/en unknown
- 2015-09-07 MX MX2019007950A patent/MX2019007950A/es unknown
- 2015-09-08 PH PH12015502002A patent/PH12015502002B1/en unknown
- 2015-09-14 CL CL2015002706A patent/CL2015002706A1/es unknown
-
2016
- 2016-02-01 HK HK16101100.7A patent/HK1213249A1/zh unknown
- 2016-08-30 US US15/251,688 patent/US10647744B2/en active Active
-
2017
- 2017-06-23 US US15/631,276 patent/USRE47302E1/en active Active
- 2017-10-16 HR HRP20171572TT patent/HRP20171572T1/hr unknown
- 2017-12-01 CY CY20171101263T patent/CY1119645T1/el unknown
-
2020
- 2020-03-13 US US16/818,731 patent/US11078233B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007537265A (ja) * | 2004-05-10 | 2007-12-20 | プロテオリックス, インコーポレイテッド | 酵素阻害のための化合物 |
JP2009514971A (ja) * | 2005-11-09 | 2009-04-09 | プロテオリックス, インコーポレイテッド | 酵素阻害のための化合物 |
JP2009541327A (ja) * | 2006-06-19 | 2009-11-26 | プロテオリックス, インコーポレイテッド | 酵素阻害のための化合物 |
Non-Patent Citations (2)
Title |
---|
J. PPHARMACOL. EXP. THER. (2012) VOL.341, NO.1, P.174-182, JPN6018013280, ISSN: 0003779735 * |
WOOIN LEE, CURRENT TOPICS IN MEDICINAL CHEMISTRY, vol. V11 N23, JPN5016003945, 1 December 2011 (2011-12-01), pages 2923 - 2930, ISSN: 0003779736 * |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2019527205A (ja) * | 2016-06-29 | 2019-09-26 | ケザール ライフ サイエンシズKezar Life Sciences | ペプチドエポキシケトン免疫プロテアソーム阻害剤の結晶塩 |
JP2019527677A (ja) * | 2016-06-29 | 2019-10-03 | ケザール ライフ サイエンシズKezar Life Sciences | ペプチドエポキシケトン免疫プロテアソーム阻害剤、およびその前駆体の調製プロセス |
JP7065044B2 (ja) | 2016-06-29 | 2022-05-11 | ケザール ライフ サイエンシズ | ペプチドエポキシケトン免疫プロテアソーム阻害剤、およびその前駆体の調製プロセス |
JP7132855B2 (ja) | 2016-06-29 | 2022-09-07 | ケザール ライフ サイエンシズ | ペプチドエポキシケトン免疫プロテアソーム阻害剤の結晶塩 |
JP7392031B2 (ja) | 2016-06-29 | 2023-12-05 | ケザール ライフ サイエンシズ | ペプチドエポキシケトン免疫プロテアソーム阻害剤、およびその前駆体の調製プロセス |
US11891383B2 (en) | 2016-06-29 | 2024-02-06 | Kezar Life Sciences | Crystalline salts of peptide epoxyketone immunoproteasome inhibitor |
US11976053B2 (en) | 2016-06-29 | 2024-05-07 | Kezar Life Sciences, Inc. | Process of preparing a peptide epoxyketone immunoproteasome inhibitor, and precursors thereof |
JP2020531494A (ja) * | 2017-08-23 | 2020-11-05 | ケザール ライフ サイエンシズKezar Life Sciences | 自己免疫疾患の治療における免疫プロテアソーム阻害剤および免疫抑制剤 |
JP7289828B2 (ja) | 2017-08-23 | 2023-06-12 | ケザール ライフ サイエンシズ | 自己免疫疾患の治療における免疫プロテアソーム阻害剤および免疫抑制剤 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11078233B2 (en) | Tripeptide epoxy ketone protease inhibitors | |
TWI662047B (zh) | 三肽環氧酮蛋白酶體抑制劑 | |
KR20130094185A (ko) | 결정성 펩티드 에폭시케톤 면역프로테아좀 저해제 | |
JP2016501831A (ja) | ケトアミド免疫プロテアソーム阻害剤 | |
KR102365509B1 (ko) | 트리펩타이드 에폭시 케톤 프로테이스 억제제 | |
NZ711715B2 (en) | Tripeptide epoxy ketone protease inhibitors | |
SA515361045B1 (ar) | مثبطات إيبوكسي كيتون بروتياز ثلاثي الببتيد | |
NZ711794B2 (en) | Dipeptide and tripeptide epoxy ketone protease inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20170309 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20180424 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20180720 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180925 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180925 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20190122 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20190214 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6483657 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |