JP2002504091A - コルチコステロイドに対する応答性を調整するための方法及び組成物 - Google Patents
コルチコステロイドに対する応答性を調整するための方法及び組成物Info
- Publication number
- JP2002504091A JP2002504091A JP54063398A JP54063398A JP2002504091A JP 2002504091 A JP2002504091 A JP 2002504091A JP 54063398 A JP54063398 A JP 54063398A JP 54063398 A JP54063398 A JP 54063398A JP 2002504091 A JP2002504091 A JP 2002504091A
- Authority
- JP
- Japan
- Prior art keywords
- patient
- corticosteroids
- patients
- acid
- administered
- 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.)
- Pending
Links
- 239000003246 corticosteroid Substances 0.000 title claims abstract description 180
- 238000000034 method Methods 0.000 title claims abstract description 171
- 229960001334 corticosteroids Drugs 0.000 title claims abstract description 117
- 230000004043 responsiveness Effects 0.000 title claims abstract description 41
- 239000000203 mixture Substances 0.000 title abstract description 44
- 102000013462 Interleukin-12 Human genes 0.000 claims abstract description 80
- 108010065805 Interleukin-12 Proteins 0.000 claims abstract description 80
- 229940117681 interleukin-12 Drugs 0.000 claims abstract description 79
- 239000005557 antagonist Substances 0.000 claims abstract description 78
- 239000003112 inhibitor Substances 0.000 claims abstract description 61
- 108010074328 Interferon-gamma Proteins 0.000 claims abstract description 58
- 238000004519 manufacturing process Methods 0.000 claims abstract description 58
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 56
- 102100037850 Interferon gamma Human genes 0.000 claims abstract description 51
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 43
- 210000000822 natural killer cell Anatomy 0.000 claims abstract description 35
- 102000011727 Caspases Human genes 0.000 claims abstract description 27
- 108010076667 Caspases Proteins 0.000 claims abstract description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 108091005804 Peptidases Proteins 0.000 claims abstract description 22
- 239000004365 Protease Substances 0.000 claims abstract description 22
- 208000035475 disorder Diseases 0.000 claims abstract description 22
- 101000828805 Cowpox virus (strain Brighton Red) Serine proteinase inhibitor 2 Proteins 0.000 claims abstract description 19
- 229940124748 beta 2 agonist Drugs 0.000 claims abstract description 17
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 17
- 239000003937 drug carrier Substances 0.000 claims abstract description 15
- 229960003130 interferon gamma Drugs 0.000 claims abstract description 11
- 150000004713 phosphodiesters Chemical class 0.000 claims abstract description 4
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract 3
- -1 bird Amsinolone Chemical compound 0.000 claims description 186
- 239000003814 drug Substances 0.000 claims description 79
- 229940079593 drug Drugs 0.000 claims description 72
- 238000011282 treatment Methods 0.000 claims description 64
- 230000000694 effects Effects 0.000 claims description 63
- 150000003431 steroids Chemical class 0.000 claims description 61
- 238000006243 chemical reaction Methods 0.000 claims description 46
- 210000004027 cell Anatomy 0.000 claims description 39
- 206010040070 Septic Shock Diseases 0.000 claims description 31
- 230000036303 septic shock Effects 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 21
- 230000004044 response Effects 0.000 claims description 20
- 102000035195 Peptidases Human genes 0.000 claims description 19
- 229960003957 dexamethasone Drugs 0.000 claims description 18
- 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 claims description 18
- 208000011580 syndromic disease Diseases 0.000 claims description 18
- 201000004624 Dermatitis Diseases 0.000 claims description 16
- 108091008324 binding proteins Proteins 0.000 claims description 16
- 208000023275 Autoimmune disease Diseases 0.000 claims description 15
- 208000006673 asthma Diseases 0.000 claims description 15
- 102000008394 Immunoglobulin Fragments Human genes 0.000 claims description 14
- 108010021625 Immunoglobulin Fragments Proteins 0.000 claims description 14
- 230000035945 sensitivity Effects 0.000 claims description 14
- 230000001739 rebound effect Effects 0.000 claims description 13
- 102000004560 Interleukin-12 Receptors Human genes 0.000 claims description 12
- 108010017515 Interleukin-12 Receptors Proteins 0.000 claims description 12
- 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 claims description 12
- 230000001154 acute effect Effects 0.000 claims description 11
- 206010025135 lupus erythematosus Diseases 0.000 claims description 11
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 claims description 10
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 claims description 10
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 claims description 10
- 229950005741 rolipram Drugs 0.000 claims description 10
- 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 claims description 9
- 206010061218 Inflammation Diseases 0.000 claims description 9
- 206010052779 Transplant rejections Diseases 0.000 claims description 9
- 230000004054 inflammatory process Effects 0.000 claims description 9
- 206010023332 keratitis Diseases 0.000 claims description 9
- 201000010666 keratoconjunctivitis Diseases 0.000 claims description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 9
- 102000004557 Interleukin-18 Receptors Human genes 0.000 claims description 8
- 108010017537 Interleukin-18 Receptors Proteins 0.000 claims description 8
- 102000005886 STAT4 Transcription Factor Human genes 0.000 claims description 8
- 108010019992 STAT4 Transcription Factor Proteins 0.000 claims description 8
- 208000037976 chronic inflammation Diseases 0.000 claims description 8
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 8
- 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 claims description 8
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 7
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 201000004681 Psoriasis Diseases 0.000 claims description 7
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 7
- 208000026935 allergic disease Diseases 0.000 claims description 7
- 208000024908 graft versus host disease Diseases 0.000 claims description 7
- 230000000495 immunoinflammatory effect Effects 0.000 claims description 7
- 229960004618 prednisone Drugs 0.000 claims description 7
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone 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]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 7
- 208000032116 Autoimmune Experimental Encephalomyelitis Diseases 0.000 claims description 6
- 208000003456 Juvenile Arthritis Diseases 0.000 claims description 6
- 206010059176 Juvenile idiopathic arthritis Diseases 0.000 claims description 6
- 201000009906 Meningitis Diseases 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 6
- 208000019069 chronic childhood arthritis Diseases 0.000 claims description 6
- 201000002215 juvenile rheumatoid arthritis Diseases 0.000 claims description 6
- 229960004584 methylprednisolone Drugs 0.000 claims description 6
- 201000006417 multiple sclerosis Diseases 0.000 claims description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 5
- 241000238421 Arthropoda Species 0.000 claims description 5
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 claims description 5
- 208000033222 Biliary cirrhosis primary Diseases 0.000 claims description 5
- 206010008909 Chronic Hepatitis Diseases 0.000 claims description 5
- 206010010741 Conjunctivitis Diseases 0.000 claims description 5
- 208000019872 Drug Eruptions Diseases 0.000 claims description 5
- 206010015150 Erythema Diseases 0.000 claims description 5
- 206010016717 Fistula Diseases 0.000 claims description 5
- 208000030836 Hashimoto thyroiditis Diseases 0.000 claims description 5
- 206010020112 Hirsutism Diseases 0.000 claims description 5
- 206010024229 Leprosy Diseases 0.000 claims description 5
- 201000011152 Pemphigus Diseases 0.000 claims description 5
- 206010065159 Polychondritis Diseases 0.000 claims description 5
- 208000012654 Primary biliary cholangitis Diseases 0.000 claims description 5
- 206010036774 Proctitis Diseases 0.000 claims description 5
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 5
- 206010039710 Scleroderma Diseases 0.000 claims description 5
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 claims description 5
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 claims description 5
- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 claims description 5
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
- 206010046851 Uveitis Diseases 0.000 claims description 5
- 206010046914 Vaginal infection Diseases 0.000 claims description 5
- 201000008100 Vaginitis Diseases 0.000 claims description 5
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 5
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 5
- 208000007502 anemia Diseases 0.000 claims description 5
- 208000002399 aphthous stomatitis Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 208000020670 canker sore Diseases 0.000 claims description 5
- 229960001145 deflazacort Drugs 0.000 claims description 5
- FBHSPRKOSMHSIF-GRMWVWQJSA-N deflazacort Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)=N[C@@]3(C(=O)COC(=O)C)[C@@]1(C)C[C@@H]2O FBHSPRKOSMHSIF-GRMWVWQJSA-N 0.000 claims description 5
- 238000001647 drug administration Methods 0.000 claims description 5
- 230000003890 fistula Effects 0.000 claims description 5
- 229960000676 flunisolide Drugs 0.000 claims description 5
- 208000006454 hepatitis Diseases 0.000 claims description 5
- 229960000890 hydrocortisone Drugs 0.000 claims description 5
- 201000004614 iritis Diseases 0.000 claims description 5
- 206010028417 myasthenia gravis Diseases 0.000 claims description 5
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 5
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 5
- 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 claims description 5
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 229940092705 beclomethasone Drugs 0.000 claims description 4
- 229960004544 cortisone Drugs 0.000 claims description 4
- 229960005205 prednisolone Drugs 0.000 claims description 4
- 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 claims description 4
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 3
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 claims description 3
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims description 3
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 claims description 3
- 229940095074 cyclic amp Drugs 0.000 claims description 3
- 229960001022 fenoterol Drugs 0.000 claims description 3
- 229960004017 salmeterol Drugs 0.000 claims description 3
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 2
- 229940039009 isoproterenol Drugs 0.000 claims description 2
- 208000002691 Choroiditis Diseases 0.000 claims 4
- 206010012438 Dermatitis atopic Diseases 0.000 claims 4
- 208000022873 Ocular disease Diseases 0.000 claims 4
- 208000003971 Posterior uveitis Diseases 0.000 claims 4
- 208000012287 Prolapse Diseases 0.000 claims 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims 4
- 201000008937 atopic dermatitis Diseases 0.000 claims 4
- 230000005784 autoimmunity Effects 0.000 claims 4
- 102000023732 binding proteins Human genes 0.000 claims 4
- 231100000321 erythema Toxicity 0.000 claims 4
- 210000003924 normoblast Anatomy 0.000 claims 4
- 230000002685 pulmonary effect Effects 0.000 claims 4
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound 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)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 claims 3
- 208000001715 Osteoblastoma Diseases 0.000 claims 3
- 239000003550 marker Substances 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 abstract description 9
- 208000026278 immune system disease Diseases 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 description 98
- 108090000426 Caspase-1 Proteins 0.000 description 70
- 102100035904 Caspase-1 Human genes 0.000 description 69
- 239000002253 acid Substances 0.000 description 66
- 239000001257 hydrogen Substances 0.000 description 60
- 229910052739 hydrogen Inorganic materials 0.000 description 60
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 58
- 241000699670 Mus sp. Species 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- 239000002158 endotoxin Substances 0.000 description 36
- 229920006008 lipopolysaccharide Polymers 0.000 description 36
- 239000000047 product Substances 0.000 description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 29
- 125000003118 aryl group Chemical group 0.000 description 29
- 150000002148 esters Chemical class 0.000 description 26
- 150000002431 hydrogen Chemical class 0.000 description 26
- 150000001408 amides Chemical class 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 22
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 22
- 125000001072 heteroaryl group Chemical group 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 210000002966 serum Anatomy 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 19
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 17
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 17
- 239000012634 fragment Substances 0.000 description 17
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
- 238000002560 therapeutic procedure Methods 0.000 description 17
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 16
- 238000000921 elemental analysis Methods 0.000 description 16
- 230000005764 inhibitory process Effects 0.000 description 16
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 241000699666 Mus <mouse, genus> Species 0.000 description 15
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 15
- 238000001819 mass spectrum Methods 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 14
- 150000003839 salts Chemical class 0.000 description 14
- 230000002950 deficient Effects 0.000 description 13
- 230000002401 inhibitory effect Effects 0.000 description 13
- 102000014914 Carrier Proteins Human genes 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 230000002378 acidificating effect Effects 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 125000000623 heterocyclic group Chemical group 0.000 description 11
- 239000002609 medium Substances 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 10
- 150000002576 ketones Chemical class 0.000 description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 9
- 241001024304 Mino Species 0.000 description 9
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 9
- 150000001413 amino acids Chemical group 0.000 description 9
- 239000007822 coupling agent Chemical class 0.000 description 9
- 125000000753 cycloalkyl group Chemical group 0.000 description 9
- 238000001990 intravenous administration Methods 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 102000005962 receptors Human genes 0.000 description 9
- 108020003175 receptors Proteins 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 239000012467 final product Substances 0.000 description 8
- 229940002612 prodrug Drugs 0.000 description 8
- 239000000651 prodrug Substances 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 229910001868 water Inorganic materials 0.000 description 8
- 102000008070 Interferon-gamma Human genes 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 239000000427 antigen Substances 0.000 description 7
- 102000036639 antigens Human genes 0.000 description 7
- 108091007433 antigens Proteins 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- 125000001151 peptidyl group Chemical class 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 125000003107 substituted aryl group Chemical group 0.000 description 7
- 229910052717 sulfur Inorganic materials 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 239000010409 thin film Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 102100029855 Caspase-3 Human genes 0.000 description 6
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- 102000004889 Interleukin-6 Human genes 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
- 239000002131 composite material Substances 0.000 description 6
- 230000003993 interaction Effects 0.000 description 6
- 125000001624 naphthyl group Chemical group 0.000 description 6
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 6
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 5
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 5
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 5
- 208000011231 Crohn disease Diseases 0.000 description 5
- 241000186427 Cutibacterium acnes Species 0.000 description 5
- 239000001263 FEMA 3042 Substances 0.000 description 5
- 101000793880 Homo sapiens Caspase-3 Proteins 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 102000000589 Interleukin-1 Human genes 0.000 description 5
- 108010002352 Interleukin-1 Proteins 0.000 description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 5
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 description 5
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 5
- FXXACINHVKSMDR-UHFFFAOYSA-N acetyl bromide Chemical compound CC(Br)=O FXXACINHVKSMDR-UHFFFAOYSA-N 0.000 description 5
- 235000003704 aspartic acid Nutrition 0.000 description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 5
- 235000004554 glutamine Nutrition 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 5
- 229940090044 injection Drugs 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 230000019734 interleukin-12 production Effects 0.000 description 5
- 230000000670 limiting effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 150000004702 methyl esters Chemical class 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 108090000765 processed proteins & peptides Proteins 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229940124530 sulfonamide Drugs 0.000 description 5
- 150000003456 sulfonamides Chemical class 0.000 description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 5
- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 5
- 229920002258 tannic acid Polymers 0.000 description 5
- 229940033123 tannic acid Drugs 0.000 description 5
- 235000015523 tannic acid Nutrition 0.000 description 5
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- QEWYKACRFQMRMB-UHFFFAOYSA-N fluoroacetic acid Chemical compound OC(=O)CF QEWYKACRFQMRMB-UHFFFAOYSA-N 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000007726 management method Methods 0.000 description 4
- 239000011698 potassium fluoride Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 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
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 3
- VKIHFBOXDHZUTR-UHFFFAOYSA-N 2-(propanoylamino)pentanoic acid Chemical compound CCCC(C(O)=O)NC(=O)CC VKIHFBOXDHZUTR-UHFFFAOYSA-N 0.000 description 3
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 3
- CWARULQNYJKOMP-LURJTMIESA-N 4-o-tert-butyl 1-o-methyl (2s)-2-aminobutanedioate Chemical compound COC(=O)[C@@H](N)CC(=O)OC(C)(C)C CWARULQNYJKOMP-LURJTMIESA-N 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 108090000567 Caspase 7 Proteins 0.000 description 3
- 102100025597 Caspase-4 Human genes 0.000 description 3
- 102100038902 Caspase-7 Human genes 0.000 description 3
- 102000004091 Caspase-8 Human genes 0.000 description 3
- 108090000538 Caspase-8 Proteins 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- 241000588724 Escherichia coli Species 0.000 description 3
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 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 3
- 108010010677 Phosphodiesterase I Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 description 3
- 239000004473 Threonine Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 125000005042 acyloxymethyl group Chemical group 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 230000003042 antagnostic effect Effects 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
- 229940009098 aspartate Drugs 0.000 description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 125000004663 dialkyl amino group Chemical group 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000002612 dispersion medium Substances 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- 235000013922 glutamic acid Nutrition 0.000 description 3
- 239000004220 glutamic acid Substances 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000002650 immunosuppressive therapy Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 210000003734 kidney Anatomy 0.000 description 3
- 235000018977 lysine Nutrition 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 3
- 235000003270 potassium fluoride Nutrition 0.000 description 3
- 239000002516 radical scavenger Substances 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 235000004400 serine Nutrition 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 235000008521 threonine Nutrition 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 235000014393 valine Nutrition 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- 210000004885 white matter Anatomy 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical class CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- QWCKQJZIFLGMSD-UHFFFAOYSA-N 2-Aminobutanoic acid Natural products CCC(N)C(O)=O QWCKQJZIFLGMSD-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical class CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- ZBDOVKKGNBQTDB-UHFFFAOYSA-N 3-[(2-carbamoylcyclopentanecarbonyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound NC(=O)C1CCCC1C(=O)NC(CC(O)=O)C(=O)COC(=O)CC1=CC=CC2=CC=CC=C12 ZBDOVKKGNBQTDB-UHFFFAOYSA-N 0.000 description 2
- ZAKQYEVTJLBATK-UHFFFAOYSA-N 3-[[3-(benzenesulfonyl)-2-methylpropanoyl]amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CS(=O)(=O)C1=CC=CC=C1 ZAKQYEVTJLBATK-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
- BSGKMZVMFKUQAD-UHFFFAOYSA-N 4-oxo-5-[(2-oxo-3h-indol-1-yl)oxy]-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound O=C1CC2=CC=CC=C2N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 BSGKMZVMFKUQAD-UHFFFAOYSA-N 0.000 description 2
- 208000020154 Acnes Diseases 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 101150047706 CASP6 gene Proteins 0.000 description 2
- 101710090338 Caspase-4 Proteins 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 2
- QWCKQJZIFLGMSD-GSVOUGTGSA-N D-alpha-aminobutyric acid Chemical compound CC[C@@H](N)C(O)=O QWCKQJZIFLGMSD-GSVOUGTGSA-N 0.000 description 2
- 101100382568 Danio rerio caspa gene Proteins 0.000 description 2
- YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 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
- 239000004471 Glycine Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 2
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 2
- 208000016604 Lyme disease Diseases 0.000 description 2
- 244000246386 Mentha pulegium Species 0.000 description 2
- 235000016257 Mentha pulegium Nutrition 0.000 description 2
- 235000004357 Mentha x piperita Nutrition 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 241000208474 Protea Species 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 108020004511 Recombinant DNA Proteins 0.000 description 2
- 206010040047 Sepsis Diseases 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 108091023040 Transcription factor Proteins 0.000 description 2
- 102000040945 Transcription factor Human genes 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000004423 acyloxy group Chemical group 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 150000001510 aspartic acids Chemical class 0.000 description 2
- 229940098032 beconase Drugs 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 2
- PUJDIJCNWFYVJX-UHFFFAOYSA-N benzyl carbamate Chemical group NC(=O)OCC1=CC=CC=C1 PUJDIJCNWFYVJX-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
- 229960002537 betamethasone Drugs 0.000 description 2
- 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 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000000988 bone and bone Anatomy 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- 239000013043 chemical agent Substances 0.000 description 2
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 2
- 125000004965 chloroalkyl group Chemical group 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 2
- 235000018417 cysteine Nutrition 0.000 description 2
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 239000000539 dimer Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- VKKHNYLKBHUDEG-UHFFFAOYSA-N ethyl 2-(2-phenylmethoxyiminocyclohexyl)acetate Chemical compound CCOC(=O)CC1CCCCC1=NOCC1=CC=CC=C1 VKKHNYLKBHUDEG-UHFFFAOYSA-N 0.000 description 2
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 2
- 125000004494 ethyl ester group Chemical group 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- OIYFAQRHWMVENL-UHFFFAOYSA-N gamma-Pyrone-3-acetic acid Natural products OC(=O)CC1=COC=CC1=O OIYFAQRHWMVENL-UHFFFAOYSA-N 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 235000001050 hortel pimenta Nutrition 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 239000007943 implant Substances 0.000 description 2
- 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 239000012948 isocyanate Substances 0.000 description 2
- 238000006317 isomerization reaction Methods 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 244000005700 microbiome Species 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
- 238000012544 monitoring process Methods 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- PARWUHTVGZSQPD-UHFFFAOYSA-N phenylsilane Chemical group [SiH3]C1=CC=CC=C1 PARWUHTVGZSQPD-UHFFFAOYSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 239000006187 pill Chemical group 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 230000002797 proteolythic effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 125000003226 pyrazolyl group Chemical class 0.000 description 2
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 102220240796 rs553605556 Human genes 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000001629 suppression Effects 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- 239000000052 vinegar Substances 0.000 description 2
- 235000021419 vinegar Nutrition 0.000 description 2
- QSAWQNUELGIYBC-PHDIDXHHSA-N (1r,2r)-cyclohexane-1,2-dicarboxylic acid Chemical compound OC(=O)[C@@H]1CCCC[C@H]1C(O)=O QSAWQNUELGIYBC-PHDIDXHHSA-N 0.000 description 1
- OILXMJHPFNGGTO-UHFFFAOYSA-N (22E)-(24xi)-24-methylcholesta-5,22-dien-3beta-ol Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)C=CC(C)C(C)C)C1(C)CC2 OILXMJHPFNGGTO-UHFFFAOYSA-N 0.000 description 1
- XYXYXSKSTZAEJW-VIFPVBQESA-N (2s)-2-(phenylmethoxycarbonylamino)butanedioic acid Chemical compound OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 XYXYXSKSTZAEJW-VIFPVBQESA-N 0.000 description 1
- RPAJSBKBKSSMLJ-DFWYDOINSA-N (2s)-2-aminopentanedioic acid;hydrochloride Chemical class Cl.OC(=O)[C@@H](N)CCC(O)=O RPAJSBKBKSSMLJ-DFWYDOINSA-N 0.000 description 1
- HLSLRFBLVZUVIE-LBPRGKRZSA-N (2s)-4-[(2-methylpropan-2-yl)oxy]-4-oxo-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound CC(C)(C)OC(=O)C[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 HLSLRFBLVZUVIE-LBPRGKRZSA-N 0.000 description 1
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- LPIARALSGDVZEP-SJVNDZIOSA-N (3s)-3-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylbutanoyl]amino]propanoyl]amino]-4-oxobutanoic acid Chemical compound OC(=O)C[C@@H](C=O)NC(=O)[C@H](C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(C)=O)CC1=CC=C(O)C=C1 LPIARALSGDVZEP-SJVNDZIOSA-N 0.000 description 1
- PFYUGICSQBZWOO-IBGZPJMESA-N (3s)-5-(2-naphthalen-1-ylacetyl)oxy-4-oxo-3-[(2-thiophen-2-ylacetyl)amino]pentanoic acid Chemical compound N([C@@H](CC(=O)O)C(=O)COC(=O)CC=1C2=CC=CC=C2C=CC=1)C(=O)CC1=CC=CS1 PFYUGICSQBZWOO-IBGZPJMESA-N 0.000 description 1
- DSSYKIVIOFKYAU-OMNKOJBGSA-N (4s)-4,7,7-trimethylbicyclo[2.2.1]heptan-3-one Chemical class C1C[C@]2(C)C(=O)CC1C2(C)C DSSYKIVIOFKYAU-OMNKOJBGSA-N 0.000 description 1
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N 1,1'-Carbonyldiimidazole Substances C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- AIQSXWLOKKCHFH-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonyl-5-oxopyrrolidine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C(=O)CCC1C(O)=O AIQSXWLOKKCHFH-UHFFFAOYSA-N 0.000 description 1
- PYTNPSPLGMPZKM-UHFFFAOYSA-N 1-hydroxy-3h-indol-2-one Chemical compound C1=CC=C2N(O)C(=O)CC2=C1 PYTNPSPLGMPZKM-UHFFFAOYSA-N 0.000 description 1
- JQBCKRZQAMELAD-UHFFFAOYSA-N 1-hydroxypyrrolidin-2-one Chemical compound ON1CCCC1=O JQBCKRZQAMELAD-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- IDDATTQMCPGIMG-UHFFFAOYSA-N 1h-triazol-1-ium;hydroxide Chemical compound O.C1=CNN=N1 IDDATTQMCPGIMG-UHFFFAOYSA-N 0.000 description 1
- CLLAGJLNTASDCF-UHFFFAOYSA-N 2-acetamido-5-(benzenesulfonamido)-4-hydroxy-3-(1-oxo-3,4-dihydroisoquinolin-2-yl)pentanoic acid Chemical compound C1CC2=CC=CC=C2C(=O)N1C(C(NC(=O)C)C(O)=O)C(O)CNS(=O)(=O)C1=CC=CC=C1 CLLAGJLNTASDCF-UHFFFAOYSA-N 0.000 description 1
- PPVGNPSAUJFBJY-UHFFFAOYSA-N 2-hydroxy-3a,4,7,7a-tetrahydro-octahydro-1h-4,7-epoxyisoindole-1,3-dione Chemical compound C1=CC2OC1C1C2C(=O)N(O)C1=O PPVGNPSAUJFBJY-UHFFFAOYSA-N 0.000 description 1
- 125000006304 2-iodophenyl group Chemical group [H]C1=C([H])C(I)=C(*)C([H])=C1[H] 0.000 description 1
- HJBXKPCOWFEFOI-UHFFFAOYSA-N 2-phenyl-n-phenylmethoxyacetamide Chemical compound C=1C=CC=CC=1CONC(=O)CC1=CC=CC=C1 HJBXKPCOWFEFOI-UHFFFAOYSA-N 0.000 description 1
- BHJLKXUSXXENEO-UHFFFAOYSA-N 3-(1-methylsulfonylpropan-2-ylsulfanylamino)-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NSC(CS(C)(=O)=O)C)=CC=CC2=C1 BHJLKXUSXXENEO-UHFFFAOYSA-N 0.000 description 1
- GOLORTLGFDVFDW-UHFFFAOYSA-N 3-(1h-benzimidazol-2-yl)-7-(diethylamino)chromen-2-one Chemical compound C1=CC=C2NC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 GOLORTLGFDVFDW-UHFFFAOYSA-N 0.000 description 1
- IICMJXDXRZGNCA-UHFFFAOYSA-N 3-(2-benzylsulfonylpropanoylamino)-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)S(=O)(=O)CC1=CC=CC=C1 IICMJXDXRZGNCA-UHFFFAOYSA-N 0.000 description 1
- HPSYQEDMOHOQLX-UHFFFAOYSA-N 3-(benzenesulfonamido)-4-oxo-5-(2-phenylethylsulfonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1CCS(=O)(=O)NCC(=O)C(CC(=O)O)NS(=O)(=O)C1=CC=CC=C1 HPSYQEDMOHOQLX-UHFFFAOYSA-N 0.000 description 1
- ARJSZYACXWGGSD-UHFFFAOYSA-N 3-(benzenesulfonamido)-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NS(=O)(=O)C1=CC=CC=C1 ARJSZYACXWGGSD-UHFFFAOYSA-N 0.000 description 1
- ZFXQQBFTFVQULM-UHFFFAOYSA-N 3-(butanoylamino)-5-(2-naphthalen-2-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=CC2=CC(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)CCC)=CC=C21 ZFXQQBFTFVQULM-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- HKMZZFUORAUAEQ-UHFFFAOYSA-N 3-(methoxycarbonylamino)-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OC)=CC=CC2=C1 HKMZZFUORAUAEQ-UHFFFAOYSA-N 0.000 description 1
- SOPTVKGASLUFRH-UHFFFAOYSA-N 3-[(1-acetyl-4-phenylmethoxypyrrolidine-2-carbonyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1C(C(=O)NC(CC(O)=O)C(=O)COC(=O)CC=2C3=CC=CC=C3C=CC=2)N(C(=O)C)CC1OCC1=CC=CC=C1 SOPTVKGASLUFRH-UHFFFAOYSA-N 0.000 description 1
- VOVBOUGKEDQPRA-UHFFFAOYSA-N 3-[(2-acetamido-3-methylbutanoyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(NC(C)=O)C(C)C)=CC=CC2=C1 VOVBOUGKEDQPRA-UHFFFAOYSA-N 0.000 description 1
- HRWXEMCPXIJGAR-UHFFFAOYSA-N 3-[(2-acetamidoacetyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)CNC(=O)C)=CC=CC2=C1 HRWXEMCPXIJGAR-UHFFFAOYSA-N 0.000 description 1
- NBYIWLYSUCDGON-UHFFFAOYSA-N 3-[(2-benzylphenyl)sulfonylamino]-4-oxobutanoic acid Chemical compound OC(=O)CC(C=O)NS(=O)(=O)C1=CC=CC=C1CC1=CC=CC=C1 NBYIWLYSUCDGON-UHFFFAOYSA-N 0.000 description 1
- MJTTVZRUGHPIPQ-UHFFFAOYSA-N 3-[(2-carbamoylbicyclo[2.2.1]heptane-3-carbonyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C3C4CCC(C4)C3C(=O)N)=CC=CC2=C1 MJTTVZRUGHPIPQ-UHFFFAOYSA-N 0.000 description 1
- PLTYCTXGLSVQRZ-UHFFFAOYSA-N 3-[(2-methoxycarbonylcyclohexanecarbonyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound COC(=O)C1CCCCC1C(=O)NC(CC(O)=O)C(=O)COC(=O)CC1=CC=CC2=CC=CC=C12 PLTYCTXGLSVQRZ-UHFFFAOYSA-N 0.000 description 1
- NWKQEJSOXMWBSO-UHFFFAOYSA-N 3-[(2-methyl-3-phenylsulfanylpropanoyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CSC1=CC=CC=C1 NWKQEJSOXMWBSO-UHFFFAOYSA-N 0.000 description 1
- YZNGEUVYJCYOPG-UHFFFAOYSA-N 3-[(3-benzylsulfanyl-2-methylpropanoyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CSCC1=CC=CC=C1 YZNGEUVYJCYOPG-UHFFFAOYSA-N 0.000 description 1
- DDOQCEWVASKNCF-UHFFFAOYSA-N 3-[(3-benzylsulfonyl-2-methylpropanoyl)amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CS(=O)(=O)CC1=CC=CC=C1 DDOQCEWVASKNCF-UHFFFAOYSA-N 0.000 description 1
- IQYLXIMWJABGGQ-UHFFFAOYSA-N 3-[2-(3-methylbutanoylamino)propanoylamino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)NC(=O)CC(C)C)=CC=CC2=C1 IQYLXIMWJABGGQ-UHFFFAOYSA-N 0.000 description 1
- UUAHUFPOMILLEC-UHFFFAOYSA-N 3-[2-(carbamoylamino)propanoylamino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(NC(N)=O)C)=CC=CC2=C1 UUAHUFPOMILLEC-UHFFFAOYSA-N 0.000 description 1
- WXLQHGCLOBBTFV-UHFFFAOYSA-N 3-[2-[(5-amino-5-oxopentanoyl)amino]propanoylamino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(NC(=O)CCCC(N)=O)C)=CC=CC2=C1 WXLQHGCLOBBTFV-UHFFFAOYSA-N 0.000 description 1
- MOWCXCJKNZUOFC-UHFFFAOYSA-N 3-[[2-(1-methylimidazol-4-yl)acetyl]amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound CN1C=NC(CC(=O)NC(CC(O)=O)C(=O)COC(=O)CC=2C3=CC=CC=C3C=CC=2)=C1 MOWCXCJKNZUOFC-UHFFFAOYSA-N 0.000 description 1
- WNTOASSRVASZRP-UHFFFAOYSA-N 3-[[2-(3-acetamido-2-oxopyridin-1-yl)acetyl]amino]-5-(2-benzyl-3-phenylpropanoyl)oxy-4-oxopentanoic acid Chemical compound O=C1C(NC(=O)C)=CC=CN1CC(=O)NC(CC(O)=O)C(=O)COC(=O)C(CC=1C=CC=CC=1)CC1=CC=CC=C1 WNTOASSRVASZRP-UHFFFAOYSA-N 0.000 description 1
- PXPLKNHZRKMIFR-UHFFFAOYSA-N 3-[[2-(3-methylphenoxy)phenyl]sulfonylamino]-4-oxobutanoic acid Chemical compound CC1=CC=CC(OC=2C(=CC=CC=2)S(=O)(=O)NC(CC(O)=O)C=O)=C1 PXPLKNHZRKMIFR-UHFFFAOYSA-N 0.000 description 1
- QNTJBVIFZUJKAX-UHFFFAOYSA-N 3-[[2-(4-methylphenoxy)phenyl]sulfonylamino]-4-oxobutanoic acid Chemical compound C1=CC(C)=CC=C1OC1=CC=CC=C1S(=O)(=O)NC(CC(O)=O)C=O QNTJBVIFZUJKAX-UHFFFAOYSA-N 0.000 description 1
- ZYIBFJCDPOZVQM-UHFFFAOYSA-N 3-[[2-(4-methylphenyl)phenyl]sulfonylamino]-4-oxobutanoic acid Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1S(=O)(=O)NC(CC(O)=O)C=O ZYIBFJCDPOZVQM-UHFFFAOYSA-N 0.000 description 1
- QFHPSKJHQFTSGX-UHFFFAOYSA-N 3-[[2-methyl-3-(2-phenylethylsulfanyl)propanoyl]amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CSCCC1=CC=CC=C1 QFHPSKJHQFTSGX-UHFFFAOYSA-N 0.000 description 1
- VDCKRFBQNXDWIF-UHFFFAOYSA-N 3-[[2-methyl-4-oxo-4-(2-phenylethylamino)butanoyl]amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CC(=O)NCCC1=CC=CC=C1 VDCKRFBQNXDWIF-UHFFFAOYSA-N 0.000 description 1
- LHADZMBKUVYEET-UHFFFAOYSA-N 3-[[3-(benzenesulfonyl)-2-methylpropanoyl]amino]-5-(2-benzyl-3-phenylpropanoyl)oxy-4-oxopentanoic acid Chemical compound C=1C=CC=CC=1CC(CC=1C=CC=CC=1)C(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)CS(=O)(=O)C1=CC=CC=C1 LHADZMBKUVYEET-UHFFFAOYSA-N 0.000 description 1
- RDDHSLIJBMZGSS-UHFFFAOYSA-N 3-[[3-(carboxymethylsulfonyl)-2-methylpropanoyl]amino]-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(CS(=O)(=O)CC(O)=O)C)=CC=CC2=C1 RDDHSLIJBMZGSS-UHFFFAOYSA-N 0.000 description 1
- SOPYVOBOVZGWOI-UHFFFAOYSA-N 3-acetamido-5-(2-naphthalen-1-ylacetyl)oxy-4-oxopentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C)=CC=CC2=C1 SOPYVOBOVZGWOI-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
- MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 1
- VZILXHLDXQPZIC-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-(2,2,3-trimethyl-5-oxopyrrolidin-1-yl)oxypentanoic acid Chemical compound CC1(C)C(C)CC(=O)N1OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 VZILXHLDXQPZIC-UHFFFAOYSA-N 0.000 description 1
- YUOLUWHYLSRICO-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-(3-phenyl-3-pyridin-3-ylpropanoyl)oxypentanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=NC=CC=1)CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 YUOLUWHYLSRICO-UHFFFAOYSA-N 0.000 description 1
- ZJVMUXGJUHXFOJ-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-(3-phenyl-3-pyridin-4-ylpropanoyl)oxypentanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CN=CC=1)CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 ZJVMUXGJUHXFOJ-UHFFFAOYSA-N 0.000 description 1
- KUAMWKZHUPCZEW-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-(3-pyridin-3-ylpropanoyloxy)pentanoic acid Chemical compound C=1C=CN=CC=1CCC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 KUAMWKZHUPCZEW-UHFFFAOYSA-N 0.000 description 1
- KFQRUMBVOVKPHZ-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-[2-(1,2,3,4-tetrahydronaphthalen-2-yl)acetyl]oxypentanoic acid Chemical compound C1CC2=CC=CC=C2CC1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 KFQRUMBVOVKPHZ-UHFFFAOYSA-N 0.000 description 1
- RBHRZGJIMRJOSH-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-[2-(2,3,5,6-tetramethylphenyl)acetyl]oxypentanoic acid Chemical compound CC1=CC(C)=C(C)C(CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC=2C=CC=CC=2)=C1C RBHRZGJIMRJOSH-UHFFFAOYSA-N 0.000 description 1
- ZOEULOMXXMGMBB-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-[2-(4-phenylnaphthalen-1-yl)acetyl]oxypentanoic acid Chemical compound C=1C=C(C=2C=CC=CC=2)C2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 ZOEULOMXXMGMBB-UHFFFAOYSA-N 0.000 description 1
- WWUMMWNOABCWRH-UHFFFAOYSA-N 4-oxo-3-(phenylmethoxycarbonylamino)-5-[2-(4-thiophen-2-ylnaphthalen-1-yl)acetyl]oxypentanoic acid Chemical compound C=1C=C(C=2SC=CC=2)C2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 WWUMMWNOABCWRH-UHFFFAOYSA-N 0.000 description 1
- ADQPILLGDRMIMS-UHFFFAOYSA-N 4-oxo-3-[(2-phenoxyphenyl)sulfonylamino]butanoic acid Chemical compound OC(=O)CC(C=O)NS(=O)(=O)C1=CC=CC=C1OC1=CC=CC=C1 ADQPILLGDRMIMS-UHFFFAOYSA-N 0.000 description 1
- BNTOPIQKUZXNNH-UHFFFAOYSA-N 4-oxo-3-[(2-phenylphenyl)sulfonylamino]butanoic acid Chemical compound OC(=O)CC(C=O)NS(=O)(=O)C1=CC=CC=C1C1=CC=CC=C1 BNTOPIQKUZXNNH-UHFFFAOYSA-N 0.000 description 1
- MVEIBLBGUNBZMN-UHFFFAOYSA-N 4-oxo-3-[[2-(1-oxo-3,4-dihydro-2h-naphthalen-2-yl)acetyl]amino]-5-[2-(1-oxo-3,4-dihydro-2h-naphthalen-2-yl)acetyl]oxypentanoic acid Chemical compound C1CC2=CC=CC=C2C(=O)C1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)CC1C(=O)C2=CC=CC=C2CC1 MVEIBLBGUNBZMN-UHFFFAOYSA-N 0.000 description 1
- PWCLQQGIHYPUBH-UHFFFAOYSA-N 4-oxo-3-[[2-(3-propan-2-ylphenoxy)phenyl]sulfonylamino]butanoic acid Chemical compound CC(C)C1=CC=CC(OC=2C(=CC=CC=2)S(=O)(=O)NC(CC(O)=O)C=O)=C1 PWCLQQGIHYPUBH-UHFFFAOYSA-N 0.000 description 1
- AEPYMMPLKGNMAN-UHFFFAOYSA-N 4-oxo-3-[[2-(4-propan-2-ylphenoxy)phenyl]sulfonylamino]butanoic acid Chemical compound C1=CC(C(C)C)=CC=C1OC1=CC=CC=C1S(=O)(=O)NC(CC(O)=O)C=O AEPYMMPLKGNMAN-UHFFFAOYSA-N 0.000 description 1
- XEGCIXXHXOFOMO-UHFFFAOYSA-N 4-oxo-5-[(2-oxo-3a,4,5,6,7,7a-hexahydro-3h-indol-1-yl)oxy]-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C12CCCCC2CC(=O)N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 XEGCIXXHXOFOMO-UHFFFAOYSA-N 0.000 description 1
- UKAWMWVLXHAART-UHFFFAOYSA-N 4-oxo-5-[(2-phenylacetyl)amino]oxy-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1CC(=O)NOCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 UKAWMWVLXHAART-UHFFFAOYSA-N 0.000 description 1
- BZGPFOISNISPDA-UHFFFAOYSA-N 4-oxo-5-[(3-oxo-1h-isoindol-2-yl)oxy]-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C1C2=CC=CC=C2C(=O)N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 BZGPFOISNISPDA-UHFFFAOYSA-N 0.000 description 1
- IGIPQPUYZJTZBT-UHFFFAOYSA-N 4-oxo-5-[2-(1-oxo-3,4-dihydroisoquinolin-2-yl)acetyl]oxy-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C1CC2=CC=CC=C2C(=O)N1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 IGIPQPUYZJTZBT-UHFFFAOYSA-N 0.000 description 1
- PDUXMHXBBXXJFQ-UHFFFAOYSA-N 5,6-diethoxy-1-benzothiophene-2-carboxylic acid Chemical compound C1=C(OCC)C(OCC)=CC2=C1SC(C(O)=O)=C2 PDUXMHXBBXXJFQ-UHFFFAOYSA-N 0.000 description 1
- LGOVWSCGCWLWDE-UHFFFAOYSA-N 5-(1,3-dioxoisoindol-2-yl)oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound O=C1C2=CC=CC=C2C(=O)N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 LGOVWSCGCWLWDE-UHFFFAOYSA-N 0.000 description 1
- MYKXTJZABHEHER-UHFFFAOYSA-N 5-(2,5-dioxopyrrolidin-1-yl)oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound O=C1CCC(=O)N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 MYKXTJZABHEHER-UHFFFAOYSA-N 0.000 description 1
- FGPKCCISHKPXGF-UHFFFAOYSA-N 5-(2-benzyl-3-phenylpropanoyl)oxy-3-(2-benzylsulfonylpropanoylamino)-4-oxopentanoic acid Chemical compound C=1C=CC=CC=1CS(=O)(=O)C(C)C(=O)NC(CC(O)=O)C(=O)COC(=O)C(CC=1C=CC=CC=1)CC1=CC=CC=C1 FGPKCCISHKPXGF-UHFFFAOYSA-N 0.000 description 1
- QNNDRWJBBSOHBB-UHFFFAOYSA-N 5-(2-benzyl-3-phenylpropanoyl)oxy-3-[[3-(3-carboxypropylsulfanyl)-2-methylpropanoyl]amino]-4-oxopentanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)OCC(=O)C(CC(O)=O)NC(=O)C(CSCCCC(O)=O)C)CC1=CC=CC=C1 QNNDRWJBBSOHBB-UHFFFAOYSA-N 0.000 description 1
- RKRGMBOTTYMKAH-UHFFFAOYSA-N 5-(2-benzyl-3-phenylpropanoyl)oxy-3-[[3-(3-carboxypropylsulfonyl)-2-methylpropanoyl]amino]-4-oxopentanoic acid Chemical compound C=1C=CC=CC=1CC(C(=O)OCC(=O)C(CC(O)=O)NC(=O)C(CS(=O)(=O)CCCC(O)=O)C)CC1=CC=CC=C1 RKRGMBOTTYMKAH-UHFFFAOYSA-N 0.000 description 1
- SIOSWRNHUJAUKM-UHFFFAOYSA-N 5-(2-benzyl-3-phenylpropanoyl)oxy-4-oxo-3-[[2-(1-oxo-3,4-dihydro-2h-naphthalen-2-yl)acetyl]amino]pentanoic acid Chemical compound C1CC2=CC=CC=C2C(=O)C1CC(=O)NC(CC(=O)O)C(=O)COC(=O)C(CC=1C=CC=CC=1)CC1=CC=CC=C1 SIOSWRNHUJAUKM-UHFFFAOYSA-N 0.000 description 1
- HGAUHJYHPRSZGO-UHFFFAOYSA-N 5-(2-cyclohexylethylsulfonylamino)-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C1CCCCC1CCS(=O)(=O)NCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 HGAUHJYHPRSZGO-UHFFFAOYSA-N 0.000 description 1
- MYFOEFSUBUCRRN-UHFFFAOYSA-N 5-(2-naphthalen-1-ylacetyl)oxy-4-oxo-3-(3-phenylpropanoylamino)pentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)CCC1=CC=CC=C1 MYFOEFSUBUCRRN-UHFFFAOYSA-N 0.000 description 1
- FSLLWNQLDUVEBP-UHFFFAOYSA-N 5-(2-naphthalen-1-ylacetyl)oxy-4-oxo-3-(thiophene-3-carbonylamino)pentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)C=1C=CSC=1 FSLLWNQLDUVEBP-UHFFFAOYSA-N 0.000 description 1
- BFFNMWAFANPDJB-UHFFFAOYSA-N 5-(2-naphthalen-1-ylacetyl)oxy-4-oxo-3-[2-(phenylmethoxycarbonylamino)propanoylamino]pentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)NC(=O)OCC1=CC=CC=C1 BFFNMWAFANPDJB-UHFFFAOYSA-N 0.000 description 1
- KKOVJRCPQULLSZ-UHFFFAOYSA-N 5-(2-naphthalen-1-ylacetyl)oxy-4-oxo-3-[[2-(1-oxo-3,4-dihydro-2h-naphthalen-2-yl)acetyl]amino]pentanoic acid Chemical compound C1=CC=C2C(CC(=O)OCC(=O)C(NC(=O)CC3C(C4=CC=CC=C4CC3)=O)CC(=O)O)=CC=CC2=C1 KKOVJRCPQULLSZ-UHFFFAOYSA-N 0.000 description 1
- IUPLKIGJGSNGBY-UHFFFAOYSA-N 5-(2-naphthalen-1-yloxyacetyl)oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC2=CC=CC=C2C=1OCC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 IUPLKIGJGSNGBY-UHFFFAOYSA-N 0.000 description 1
- QIQGWTHLLPEOOC-UHFFFAOYSA-N 5-(3,3-diphenylpropanoyloxy)-3-[[3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]-4-oxopentanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)NC(=O)OCC1=CC=CC=C1 QIQGWTHLLPEOOC-UHFFFAOYSA-N 0.000 description 1
- KXCXBOIGYGEZTG-UHFFFAOYSA-N 5-(3,3-diphenylpropanoyloxy)-4-oxo-3-[2-(4-phenylbutanoylamino)propanoylamino]pentanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)CC(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C)NC(=O)CCCC1=CC=CC=C1 KXCXBOIGYGEZTG-UHFFFAOYSA-N 0.000 description 1
- UZWYPHMZTHYELM-UHFFFAOYSA-N 5-(3-anilino-3-phenylpropanoyl)oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1NC(C=1C=CC=CC=1)CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 UZWYPHMZTHYELM-UHFFFAOYSA-N 0.000 description 1
- SYDHINXUYZXVBF-UHFFFAOYSA-N 5-(benzenesulfonamido)-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1S(=O)(=O)NCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 SYDHINXUYZXVBF-UHFFFAOYSA-N 0.000 description 1
- GXVYYCIDJIOQIZ-UHFFFAOYSA-N 5-[(1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl)oxy]-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound O=C1C2CCCCC2C(=O)N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 GXVYYCIDJIOQIZ-UHFFFAOYSA-N 0.000 description 1
- QFSJGQAIQKSIJN-UHFFFAOYSA-N 5-[(9-fluorofluoren-9-yl)methylsulfonylamino]-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1(F)CS(=O)(=O)NCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 QFSJGQAIQKSIJN-UHFFFAOYSA-N 0.000 description 1
- RHYZGRPALHUONC-UHFFFAOYSA-N 5-[2-(1-benzothiophen-4-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC=2SC=CC=2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 RHYZGRPALHUONC-UHFFFAOYSA-N 0.000 description 1
- YIYJYNBMIJOWJH-UHFFFAOYSA-N 5-[2-(1-benzothiophen-7-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC=2C=CSC=2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 YIYJYNBMIJOWJH-UHFFFAOYSA-N 0.000 description 1
- WSDQSIQOSIODCX-UHFFFAOYSA-N 5-[2-(1h-indol-3-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1NC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 WSDQSIQOSIODCX-UHFFFAOYSA-N 0.000 description 1
- RFWBDEXTEKQDTA-UHFFFAOYSA-N 5-[2-(2,3-dichlorophenyl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC(Cl)=C(Cl)C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 RFWBDEXTEKQDTA-UHFFFAOYSA-N 0.000 description 1
- LFPHIZMEXVUEIF-UHFFFAOYSA-N 5-[2-(2-fluoronaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound FC=1C=CC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 LFPHIZMEXVUEIF-UHFFFAOYSA-N 0.000 description 1
- NQJWHWKBHRZOIX-UHFFFAOYSA-N 5-[2-(2-methylnaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound CC1=CC=C2C=CC=CC2=C1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 NQJWHWKBHRZOIX-UHFFFAOYSA-N 0.000 description 1
- TULDPHYVPOFMBT-UHFFFAOYSA-N 5-[2-(3,4-dihydronaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1CCC2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 TULDPHYVPOFMBT-UHFFFAOYSA-N 0.000 description 1
- RVCHDWVCDODQHX-UHFFFAOYSA-N 5-[2-(4-fluoronaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=C(F)C2=CC=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 RVCHDWVCDODQHX-UHFFFAOYSA-N 0.000 description 1
- GVISUYOCGPGXGU-UHFFFAOYSA-N 5-[2-(4-methylnaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C(C)=CC=C1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 GVISUYOCGPGXGU-UHFFFAOYSA-N 0.000 description 1
- QAIOTQBSUOZICX-UHFFFAOYSA-N 5-[2-(5-cyanonaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC2=C(C#N)C=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 QAIOTQBSUOZICX-UHFFFAOYSA-N 0.000 description 1
- NQGOLYARLVCANZ-UHFFFAOYSA-N 5-[2-(5-methoxynaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C1=CC=C2C(OC)=CC=CC2=C1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 NQGOLYARLVCANZ-UHFFFAOYSA-N 0.000 description 1
- DPBKOHUVTXHPEC-UHFFFAOYSA-N 5-[2-(5-methylnaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C1=CC=C2C(C)=CC=CC2=C1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 DPBKOHUVTXHPEC-UHFFFAOYSA-N 0.000 description 1
- JGBYVHLSTRLYQE-UHFFFAOYSA-N 5-[2-(6-hydroxynaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC2=CC(O)=CC=C2C=1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 JGBYVHLSTRLYQE-UHFFFAOYSA-N 0.000 description 1
- ZLYXGQNTKUKFSM-UHFFFAOYSA-N 5-[2-(6-methoxynaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC2=CC(OC)=CC=C2C=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 ZLYXGQNTKUKFSM-UHFFFAOYSA-N 0.000 description 1
- KAFNXHZVLAJBMX-UHFFFAOYSA-N 5-[2-(8-methylnaphthalen-1-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=12C(C)=CC=CC2=CC=CC=1CC(=O)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 KAFNXHZVLAJBMX-UHFFFAOYSA-N 0.000 description 1
- IBVJJWKHTNSYMW-UHFFFAOYSA-N 5-[2-(9h-fluoren-9-yl)acetyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C12=CC=CC=C2C2=CC=CC=C2C1CC(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 IBVJJWKHTNSYMW-UHFFFAOYSA-N 0.000 description 1
- VNFDCHFUEPTDEC-UHFFFAOYSA-N 5-[3-(4-bromophenyl)-2,5-dioxopyrrol-1-yl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound O=C1C=C(C=2C=CC(Br)=CC=2)C(=O)N1OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 VNFDCHFUEPTDEC-UHFFFAOYSA-N 0.000 description 1
- UXYQCCMPJGMFFL-UHFFFAOYSA-N 5-[3-(4-hydroxyphenyl)-2-naphthalen-1-ylpropanoyl]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=C(O)C=CC=1CC(C=1C2=CC=CC=C2C=CC=1)C(=O)OCC(=O)C(CC(=O)O)NC(=O)OCC1=CC=CC=C1 UXYQCCMPJGMFFL-UHFFFAOYSA-N 0.000 description 1
- STRQHQJEMXGFEM-OCJFHSIUSA-N 5-[[(4r)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methylsulfonylamino]-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C([C@]12CCC(CC2=O)C1(C)C)S(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 STRQHQJEMXGFEM-OCJFHSIUSA-N 0.000 description 1
- STRQHQJEMXGFEM-PVWAMWICSA-N 5-[[(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methylsulfonylamino]-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C([C@@]12CCC(CC2=O)C1(C)C)S(=O)(=O)NCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 STRQHQJEMXGFEM-PVWAMWICSA-N 0.000 description 1
- CBZQPMYFABXICX-UHFFFAOYSA-N 5-[[1-[[4-(2-benzyl-3-phenylpropanoyl)oxy-1-carboxy-3-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxo-4-(3-phenylpropanoylamino)pentanoic acid Chemical compound C=1C=CC=CC=1CC(CC=1C=CC=CC=1)C(=O)OCC(=O)C(CC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CCC(O)=O)NC(=O)CCC1=CC=CC=C1 CBZQPMYFABXICX-UHFFFAOYSA-N 0.000 description 1
- ZSYCMOKJFLTTCF-UHFFFAOYSA-N 5-[[7-(2-methoxy-2-oxoethyl)-2-oxo-3a,4,5,6,7,7a-hexahydro-3h-indol-1-yl]oxy]-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C12C(CC(=O)OC)CCCC2CC(=O)N1OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 ZSYCMOKJFLTTCF-UHFFFAOYSA-N 0.000 description 1
- KTINDHDTYTVTNG-UHFFFAOYSA-N 5-[methyl-(2-phenylacetyl)amino]oxy-4-oxo-3-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C=1C=CC=CC=1CC(=O)N(C)OCC(=O)C(CC(O)=O)NC(=O)OCC1=CC=CC=C1 KTINDHDTYTVTNG-UHFFFAOYSA-N 0.000 description 1
- VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical compound BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 1
- BJLLOMORJCWXON-UHFFFAOYSA-N 5-oxopyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCC(=O)N1C(O)=O BJLLOMORJCWXON-UHFFFAOYSA-N 0.000 description 1
- OQMZNAMGEHIHNN-UHFFFAOYSA-N 7-Dehydrostigmasterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)C=CC(CC)C(C)C)CCC33)C)C3=CC=C21 OQMZNAMGEHIHNN-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PWJFNRJRHXWEPT-UHFFFAOYSA-N ADP ribose Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OCC(O)C(O)C(O)C=O)C(O)C1O PWJFNRJRHXWEPT-UHFFFAOYSA-N 0.000 description 1
- SRNWOUGRCWSEMX-KEOHHSTQSA-N ADP-beta-D-ribose Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H]1O)O)N1C=2N=CN=C(C=2N=C1)N)OP(O)(=O)OP(O)(=O)OC[C@H]1O[C@@H](O)[C@H](O)[C@@H]1O SRNWOUGRCWSEMX-KEOHHSTQSA-N 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- 208000002874 Acne Vulgaris Diseases 0.000 description 1
- 240000001606 Adenanthera pavonina Species 0.000 description 1
- 235000011470 Adenanthera pavonina Nutrition 0.000 description 1
- 206010027654 Allergic conditions Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 206010071155 Autoimmune arthritis Diseases 0.000 description 1
- 208000031729 Bacteremia Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010006811 Bursitis Diseases 0.000 description 1
- GSBUSVWXPHNTPE-YGYNJSFOSA-N C(N)(=O)[C@@H]1C[C@H](CC1)C(=O)NC(CC(=O)O)C(COC(CC1=CC=CC2=CC=CC=C12)=O)=O Chemical compound C(N)(=O)[C@@H]1C[C@H](CC1)C(=O)NC(CC(=O)O)C(COC(CC1=CC=CC2=CC=CC=C12)=O)=O GSBUSVWXPHNTPE-YGYNJSFOSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000004018 Caspase 6 Human genes 0.000 description 1
- 108090000425 Caspase 6 Proteins 0.000 description 1
- 102000004041 Caspase 7 Human genes 0.000 description 1
- 102000004068 Caspase-10 Human genes 0.000 description 1
- 108090000572 Caspase-10 Proteins 0.000 description 1
- 102000004046 Caspase-2 Human genes 0.000 description 1
- 108090000552 Caspase-2 Proteins 0.000 description 1
- 102100038916 Caspase-5 Human genes 0.000 description 1
- 101710090333 Caspase-5 Proteins 0.000 description 1
- 102100026550 Caspase-9 Human genes 0.000 description 1
- 108090000566 Caspase-9 Proteins 0.000 description 1
- 206010007764 Cataract subcapsular Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 208000027932 Collagen disease Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010012442 Dermatitis contact Diseases 0.000 description 1
- USURYVONRGTVIF-AMQKJUDNSA-N Dihydroxycholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C(O)O)[C@@]1(C)CC2 USURYVONRGTVIF-AMQKJUDNSA-N 0.000 description 1
- 241000255925 Diptera Species 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000037487 Endotoxemia Diseases 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 101000933112 Homo sapiens Caspase-4 Proteins 0.000 description 1
- 101000741014 Homo sapiens Caspase-7 Proteins 0.000 description 1
- 101000945351 Homo sapiens Killer cell immunoglobulin-like receptor 3DL1 Proteins 0.000 description 1
- 101000917858 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-A Proteins 0.000 description 1
- 101000917839 Homo sapiens Low affinity immunoglobulin gamma Fc region receptor III-B Proteins 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 241000018427 Iphisa elegans Species 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 1
- 102100033627 Killer cell immunoglobulin-like receptor 3DL1 Human genes 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102100029185 Low affinity immunoglobulin gamma Fc region receptor III-B Human genes 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010026865 Mass Diseases 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 101100059157 Mus musculus Casp2 gene Proteins 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
- ARALXKBRKMNUHN-UHFFFAOYSA-N NC(C(C(COC(CC1=COC2=C1C=CC=C2)=O)=O)C(OCC1=CC=CC=C1)=O)C(O)=O Chemical compound NC(C(C(COC(CC1=COC2=C1C=CC=C2)=O)=O)C(OCC1=CC=CC=C1)=O)C(O)=O ARALXKBRKMNUHN-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 206010031264 Osteonecrosis Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033645 Pancreatitis 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
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010039085 Rhinitis allergic Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical compound O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 description 1
- 241000906446 Theraps Species 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 206010070517 Type 2 lepra reaction Diseases 0.000 description 1
- HZYXFRGVBOPPNZ-UHFFFAOYSA-N UNPD88870 Natural products C1C=C2CC(O)CCC2(C)C2C1C1CCC(C(C)=CCC(CC)C(C)C)C1(C)CC2 HZYXFRGVBOPPNZ-UHFFFAOYSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- FPVRUILUEYSIMD-RPRRAYFGSA-N [(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11-hydroxy-17-(2-hydroxyacetyl)-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] acetate 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)(OC(C)=O)[C@@]1(C)C[C@@H]2O FPVRUILUEYSIMD-RPRRAYFGSA-N 0.000 description 1
- 238000005299 abrasion Methods 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 201000010105 allergic rhinitis Diseases 0.000 description 1
- 208000004631 alopecia areata Diseases 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 235000009582 asparagine Nutrition 0.000 description 1
- 229960001230 asparagine Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000000305 astragalus gummifer gum Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 201000004982 autoimmune uveitis Diseases 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-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
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 1
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 1
- LGJMUZUPVCAVPU-UHFFFAOYSA-N beta-Sitostanol Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(C)CCC(CC)C(C)C)C1(C)CC2 LGJMUZUPVCAVPU-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- BWBZTXSPTHTBBM-UHFFFAOYSA-L bis(3-methylimidazol-3-ium-1-yl)methanone;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.CN1C=C[N+](C(=O)[N+]2=CN(C)C=C2)=C1 BWBZTXSPTHTBBM-UHFFFAOYSA-L 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000003491 cAMP production Effects 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- JHRWWRDRBPCWTF-OLQVQODUSA-N captafol Chemical compound C1C=CC[C@H]2C(=O)N(SC(Cl)(Cl)C(Cl)Cl)C(=O)[C@H]21 JHRWWRDRBPCWTF-OLQVQODUSA-N 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 101150055276 ced-3 gene Proteins 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 208000010247 contact dermatitis Diseases 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- FZCHYNWYXKICIO-FZNHGJLXSA-N cortisol 17-valerate Chemical compound C1CC2=CC(=O)CC[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 FZCHYNWYXKICIO-FZNHGJLXSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003657 dexamethasone acetate Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- FDSGHYHRLSWSLQ-UHFFFAOYSA-N dichloromethane;propan-2-one Chemical compound ClCCl.CC(C)=O FDSGHYHRLSWSLQ-UHFFFAOYSA-N 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- JZBWUTVDIDNCMW-UHFFFAOYSA-L dipotassium;oxido sulfate Chemical compound [K+].[K+].[O-]OS([O-])(=O)=O JZBWUTVDIDNCMW-UHFFFAOYSA-L 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 229940124645 emergency medicine Drugs 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 230000002449 erythroblastic effect Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- ZZWSNYNCRUZSPR-UHFFFAOYSA-N ethyl 2-(2-oxocyclohexyl)acetate Chemical compound CCOC(=O)CC1CCCCC1=O ZZWSNYNCRUZSPR-UHFFFAOYSA-N 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- DJPWEXJHYGPFIU-UHFFFAOYSA-N hexadecyl carbamate Chemical compound CCCCCCCCCCCCCCCCOC(N)=O DJPWEXJHYGPFIU-UHFFFAOYSA-N 0.000 description 1
- 229920001519 homopolymer Polymers 0.000 description 1
- 102000057041 human TNF Human genes 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 229940010073 hydrocortisone injection Drugs 0.000 description 1
- 229960000631 hydrocortisone valerate Drugs 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000001165 hydrophobic group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000013256 infectious meningitis Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229940125369 inhaled corticosteroids Drugs 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- ZFSLODLOARCGLH-UHFFFAOYSA-N isocyanuric acid Chemical compound OC1=NC(O)=NC(O)=N1 ZFSLODLOARCGLH-UHFFFAOYSA-N 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- QWTDNUCVQCZILF-UHFFFAOYSA-N isopentane Chemical compound CCC(C)C QWTDNUCVQCZILF-UHFFFAOYSA-N 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- CAHGCLMLTWQZNJ-RGEKOYMOSA-N lanosterol Chemical group C([C@]12C)C[C@@H](O)C(C)(C)[C@H]1CCC1=C2CC[C@]2(C)[C@H]([C@H](CCC=C(C)C)C)CC[C@@]21C CAHGCLMLTWQZNJ-RGEKOYMOSA-N 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 108091005601 modified peptides Proteins 0.000 description 1
- 229940125645 monoclonal antibody drug Drugs 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 229940100661 nasal inhalant Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- HYDZPXNVHXJHBG-UHFFFAOYSA-N o-benzylhydroxylamine;hydron;chloride Chemical compound Cl.NOCC1=CC=CC=C1 HYDZPXNVHXJHBG-UHFFFAOYSA-N 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 210000003695 paranasal sinus Anatomy 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 238000002823 phage display Methods 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- RJKFOVLPORLFTN-UHFFFAOYSA-N progesterone acetate Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C(=O)C)C1(C)CC2 RJKFOVLPORLFTN-UHFFFAOYSA-N 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 description 1
- OAWXZFGKDDFTGS-UHFFFAOYSA-N pyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCN1C(O)=O OAWXZFGKDDFTGS-UHFFFAOYSA-N 0.000 description 1
- 150000008515 quinazolinediones Chemical class 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012552 review Methods 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
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- SRRKNRDXURUMPP-UHFFFAOYSA-N sodium disulfide Chemical compound [Na+].[Na+].[S-][S-] SRRKNRDXURUMPP-UHFFFAOYSA-N 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 229960001922 sodium perborate Drugs 0.000 description 1
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- HCXVJBMSMIARIN-PHZDYDNGSA-N stigmasterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)/C=C/[C@@H](CC)C(C)C)[C@@]1(C)CC2 HCXVJBMSMIARIN-PHZDYDNGSA-N 0.000 description 1
- 229940032091 stigmasterol Drugs 0.000 description 1
- 235000016831 stigmasterol Nutrition 0.000 description 1
- BFDNMXAIBMJLBB-UHFFFAOYSA-N stigmasterol Natural products CCC(C=CC(C)C1CCCC2C3CC=C4CC(O)CCC4(C)C3CCC12C)C(C)C BFDNMXAIBMJLBB-UHFFFAOYSA-N 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- PBVFTOAYKLEQQO-ZDUSSCGKSA-N tert-butyl (3s)-5-bromo-4-oxo-3-(phenylmethoxycarbonylamino)pentanoate Chemical compound CC(C)(C)OC(=O)C[C@@H](C(=O)CBr)NC(=O)OCC1=CC=CC=C1 PBVFTOAYKLEQQO-ZDUSSCGKSA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- SCSLUABEVMLYEA-UHFFFAOYSA-N tert-butyl pentanoate Chemical compound CCCCC(=O)OC(C)(C)C SCSLUABEVMLYEA-UHFFFAOYSA-N 0.000 description 1
- WHMMUPNCJVWVEF-UHFFFAOYSA-N tert-butyl sulfamoylformate Chemical compound CC(C)(C)OC(=O)S(N)(=O)=O WHMMUPNCJVWVEF-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000004797 therapeutic response Effects 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
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical compound BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229950009528 tibenelast Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- 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 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000009966 trimming Methods 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 150000004799 α-ketoamides Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
- C07K16/244—Interleukins [IL]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Emergency Medicine (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Cell Biology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Obesity (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/820,692 US6054487A (en) | 1997-03-18 | 1997-03-18 | Methods and compositions for modulating responsiveness to corticosteroids |
| US08/820,692 | 1997-03-18 | ||
| US1634698A | 1998-01-30 | 1998-01-30 | |
| PCT/US1998/004916 WO1998041232A2 (en) | 1997-03-18 | 1998-03-12 | Compositions for modulating responsiveness to corticosteroids |
| US09/016,346 | 1998-10-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002504091A true JP2002504091A (ja) | 2002-02-05 |
Family
ID=26688484
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP54063398A Pending JP2002504091A (ja) | 1997-03-18 | 1998-03-12 | コルチコステロイドに対する応答性を調整するための方法及び組成物 |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0998300A1 (bg) |
| JP (1) | JP2002504091A (bg) |
| KR (1) | KR20000076420A (bg) |
| CN (1) | CN1269722A (bg) |
| AU (1) | AU734756B2 (bg) |
| BG (1) | BG103808A (bg) |
| BR (1) | BR9810409A (bg) |
| CA (1) | CA2282845A1 (bg) |
| DE (1) | DE998300T1 (bg) |
| ES (1) | ES2146192T1 (bg) |
| HU (1) | HUP0104439A3 (bg) |
| ID (1) | ID22975A (bg) |
| IL (1) | IL131815A0 (bg) |
| NO (1) | NO994506L (bg) |
| NZ (1) | NZ337769A (bg) |
| PL (1) | PL336464A1 (bg) |
| SI (1) | SI20110A (bg) |
| SK (1) | SK122199A3 (bg) |
| TR (1) | TR199902615T2 (bg) |
| WO (1) | WO1998041232A2 (bg) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2005110450A1 (ja) * | 2004-05-17 | 2005-11-24 | Keio University | 医薬組成物及び治療方法 |
| WO2006009114A1 (ja) * | 2004-07-16 | 2006-01-26 | Atsuo Sekiyama | Ｉｌ－１８レセプターアンタゴニスト、および当該アンタゴニストを含む薬学的組成物 |
| JP2006503905A (ja) * | 2002-09-24 | 2006-02-02 | コンビナトアールエックス インコーポレーティッド | 炎症性サイトカインのレベルの増大と関連する病気および障害の治療のための方法および試薬 |
| WO2006041121A1 (ja) * | 2004-10-13 | 2006-04-20 | Kyowa Hakko Kogyo Co., Ltd. | 慢性皮膚疾患の治療および／または予防剤 |
| JP2015155423A (ja) * | 2006-10-17 | 2015-08-27 | ネオセティクス，インク． | 甲状腺眼症の治療のための方法、組成物及び製剤 |
Families Citing this family (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US6706264B1 (en) | 1994-03-14 | 2004-03-16 | Genetics Institute, Llc | Use of IL-12 antagonists in the treatment of conditions promoted by an increase in levels of IFN-y |
| ZA95960B (en) * | 1994-03-14 | 1995-10-10 | Genetics Inst | Use of interleukin-12 antagonists in the treatment of autoimmune diseases |
| US7220717B2 (en) | 1997-08-14 | 2007-05-22 | Yeda Research And Development Company Ltd. | Interleukin-18 binding proteins, their preparation and use |
| IL121860A0 (en) | 1997-08-14 | 1998-02-22 | Yeda Res & Dev | Interleukin-18 binding proteins their preparation and use |
| US7704944B2 (en) | 1997-08-14 | 2010-04-27 | Yeda Research And Development Company Ltd. | Interleukin-18 binding proteins, their preparation and use for the treatment of sepsis |
| US6184210B1 (en) | 1997-10-10 | 2001-02-06 | Cytovia, Inc. | Dipeptide apoptosis inhibitors and the use thereof |
| AR015966A1 (es) * | 1997-10-17 | 2001-05-30 | Smithkline Beecham Corp | Uso de un compuesto inhibidor de pde4 para la preparacion de un medicamento util para el tratamiento de prurito |
| EP1516630A3 (en) * | 1997-10-31 | 2006-05-03 | Wyeth | Use of anti-il-12 antibodies in transplantation rejection |
| EP0969867B1 (en) * | 1997-10-31 | 2004-09-01 | Wyeth | Use of anti-il-12 antibodies in transplantation rejection |
| WO1999025737A1 (en) * | 1997-11-19 | 1999-05-27 | Tanox Pharma B.V. | Compositions and methods for treatment of autoimmune diseases, using a monoclonal antibody to the interleukin-12 beta2-chain |
| CN1297354A (zh) * | 1998-03-16 | 2001-05-30 | 西托维亚公司 | 二肽卡斯帕酶抑制剂及其用途 |
| EP1140206A4 (en) * | 1998-11-27 | 2002-04-10 | Technion Res & Dev Foundation | VACCINE BASED ON INTERFERON GAMMA INDUCTION FACTOR AND USE THEREOF FOR PROVIDING PROTECTION IMMUNITY AGAINST MULTIPLE SCLEROSIS |
| JP3579355B2 (ja) * | 1998-12-09 | 2004-10-20 | プロテイン デザイン ラブス インコーポレイティド | ヒトの乾癬を予防及び治療するための乾癬モデル動物 |
| ATE336480T1 (de) | 1999-03-16 | 2006-09-15 | Cytovia Inc | Substituierte 2-aminobenzamin caspase inhibitoren und ihre verwendung |
| US7883704B2 (en) | 1999-03-25 | 2011-02-08 | Abbott Gmbh & Co. Kg | Methods for inhibiting the activity of the P40 subunit of human IL-12 |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| DE19915465A1 (de) * | 1999-04-06 | 2000-10-19 | Apotech Res & Dev Ltd | Verwendung eines Caspase-Inhibitors zur Proliferationshemmung von Zellen und Verwendung eines oder mehrerer Caspase-Inhibitors/en zur Behandlung von Erkrankungen beruhend auf Lymphozyten-Hyperproliferation oder zur Suppression einer Immunantwort durch Lymphozyten |
| BR0009610A (pt) | 1999-04-09 | 2002-02-13 | Cytovia Inc | Inibidores de caspase e uso dos mesmos |
| IL131047A0 (en) * | 1999-07-22 | 2001-01-28 | Yeda Res & Dev | Use of il-18 inhibitors |
| CA2383002A1 (en) | 1999-08-27 | 2001-03-08 | Cytovia, Inc. | Substituted .alpha.-hydroxy acid caspase inhibitors and the use thereof |
| WO2001019373A2 (en) * | 1999-09-17 | 2001-03-22 | Basf Aktiengesellschaft | Methods and compositions for modulating responsiveness to corticosteroids |
| US6566338B1 (en) | 1999-10-12 | 2003-05-20 | Cytovia, Inc. | Caspase inhibitors for the treatment and prevention of chemotherapy and radiation therapy induced cell death |
| EP1257585A2 (en) | 2000-02-10 | 2002-11-20 | Basf Aktiengesellschaft | Antibodies that bind human interleukin-18 and methods of making and using |
| ES2267778T3 (es) * | 2000-06-06 | 2007-03-16 | Glaxo Group Limited | Composicion para el tratamiento del cancer, que contiene un agente anti-neoplastico y un inhibidor de pde4. |
| AU7250301A (en) * | 2000-06-22 | 2002-01-02 | Willy Ben Moussa Ben Mohammed | Use of glucocorticosteroids for producing a medicament to treat oligotrichia |
| US20020025317A1 (en) * | 2000-07-20 | 2002-02-28 | Schering Ag | Bispecific monoclonal antibodies to IL-12 and IL-18 |
| AU2000270300A1 (en) * | 2000-09-13 | 2002-03-26 | Isis Innovation Limited | Use of phosphodiesterase inhibitors for the treatment of anorectal disorders |
| EP1188438A1 (en) * | 2000-09-15 | 2002-03-20 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of Il-12 production |
| EP1199074A1 (en) * | 2000-09-15 | 2002-04-24 | Warner-Lambert Company | Pharmaceutical composition for preventing or treating a disease associated with an excess of il-12 production |
| EA010180B1 (ru) * | 2001-01-29 | 2008-06-30 | Лаборатуар Сероно Са | Применение ингибитора il-18 для приготовления лекарственного средства для лечения и/или профилактики кардиомиопатии |
| ES2334773T3 (es) * | 2001-05-16 | 2010-03-16 | Yeda Research And Development Co. Ltd. | Uso de inhibidores de il-18 para el tratamiento o prevencion de la sepsis. |
| TR201809008T4 (tr) | 2001-06-26 | 2018-07-23 | Amgen Fremont Inc | Opgl ye karşi antikorlar. |
| US7253155B2 (en) * | 2001-10-05 | 2007-08-07 | Combinatorx, Inc. | Combinations for the treatment of immunoinflammatory disorders |
| JP2003342196A (ja) * | 2002-05-31 | 2003-12-03 | Mukku:Kk | 静脈注射用組成物、その製造法およびその製剤 |
| AU2003263717A1 (en) * | 2002-09-25 | 2004-04-19 | Astrazeneca Ab | A COMBINATION OF A LONG-ACTING Beta2-AGONIST AND A GLUCOCORTICOSTEROID IN THE TREATMENT OF FIBROTIC DISEASES |
| US20060083714A1 (en) * | 2003-01-27 | 2006-04-20 | Warner James M | Combination of a pde iv inhibitor and a tnf-alpha antagonist |
| US20050100965A1 (en) | 2003-11-12 | 2005-05-12 | Tariq Ghayur | IL-18 binding proteins |
| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
| WO2007011743A2 (en) | 2005-07-14 | 2007-01-25 | Lipothera, Inc. | Sustained release enhanced lipolytic formulation for regional adipose tissue treatment |
| CN104524567A (zh) | 2007-01-16 | 2015-04-22 | 阿布维公司 | 用于治疗银屑病的方法 |
| KR20100014674A (ko) | 2007-03-29 | 2010-02-10 | 아보트 러보러터리즈 | 결정성 항-사람 ｉｌ-12 항체 |
| RU2497545C2 (ru) | 2008-03-18 | 2013-11-10 | Эбботт Лэборетриз | Способ лечения псориаза (варианты) |
| US9132084B2 (en) | 2009-05-27 | 2015-09-15 | Neothetics, Inc. | Methods for administration and formulations for the treatment of regional adipose tissue |
| CN103269693A (zh) | 2010-11-24 | 2013-08-28 | 利赛拉公司 | 选择性、亲脂性及长效型β激动剂单一治疗调配物和用于肥胖及外形凸起的美容治疗的方法 |
| WO2015063669A1 (en) | 2013-10-30 | 2015-05-07 | Wockhardt Limited | Pharmaceutical compositions comprising combination of roflumilast and acebrophylline or pharmaceutically acceptable salts thereof |
| EP4291162A1 (en) | 2021-02-10 | 2023-12-20 | Iolyx Therapeutics, Inc. | Methods for ophthalmic delivery of roflumilast |
| CA3231766A1 (en) * | 2021-09-22 | 2023-03-30 | Elizabeth W. JEFFORDS | Methods of treating ocular inflammatory diseases |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3320125A (en) * | 1964-04-28 | 1967-05-16 | Merck & Co Inc | Inhalation aerosol composition |
| CA2024872C (en) * | 1989-09-08 | 2002-07-09 | James Barry Douglas Palmer | Medicaments |
| IL104068A (en) * | 1991-12-12 | 1998-10-30 | Glaxo Group Ltd | Pharmaceutical preparations in a spray without surfactant containing 1, 1, 1, 2 tetrafluoroethane or 1,1,2,3,3 petafluor N propane as propellant |
| GB9202519D0 (en) * | 1992-02-06 | 1992-03-25 | Glaxo Group Ltd | Medicaments |
| MX9304585A (es) * | 1992-07-31 | 1994-03-31 | Glaxo Group Ltd | Formulacion farmaceutica en aerosol, lata adecuada para liberar la formulacion e inhalador de dosis dosificada que comprende la lata. |
| GB9426252D0 (en) * | 1994-12-24 | 1995-02-22 | Glaxo Group Ltd | Pharmaceutical composition |
| KR19980703850A (ko) * | 1995-04-14 | 1998-12-05 | 그레이엄브레레톤 | 베클로메타손 디프로피오네이트용 계량 흡입기 |
-
1998
- 1998-03-12 ES ES98912929T patent/ES2146192T1/es active Pending
- 1998-03-12 ID IDW991185A patent/ID22975A/id unknown
- 1998-03-12 CA CA002282845A patent/CA2282845A1/en not_active Abandoned
- 1998-03-12 EP EP98912929A patent/EP0998300A1/en not_active Withdrawn
- 1998-03-12 PL PL98336464A patent/PL336464A1/xx unknown
- 1998-03-12 CN CN98805124A patent/CN1269722A/zh active Pending
- 1998-03-12 SK SK1221-99A patent/SK122199A3/sk unknown
- 1998-03-12 DE DE0998300T patent/DE998300T1/de active Pending
- 1998-03-12 KR KR1019997008524A patent/KR20000076420A/ko not_active Application Discontinuation
- 1998-03-12 WO PCT/US1998/004916 patent/WO1998041232A2/en not_active Application Discontinuation
- 1998-03-12 HU HU0104439A patent/HUP0104439A3/hu unknown
- 1998-03-12 SI SI9820032A patent/SI20110A/sl unknown
- 1998-03-12 IL IL13181598A patent/IL131815A0/xx unknown
- 1998-03-12 NZ NZ337769A patent/NZ337769A/xx unknown
- 1998-03-12 JP JP54063398A patent/JP2002504091A/ja active Pending
- 1998-03-12 BR BR9810409-8A patent/BR9810409A/pt not_active IP Right Cessation
- 1998-03-12 AU AU67604/98A patent/AU734756B2/en not_active Ceased
- 1998-03-12 TR TR1999/02615T patent/TR199902615T2/xx unknown
-
1999
- 1999-09-17 NO NO994506A patent/NO994506L/no unknown
- 1999-10-13 BG BG103808A patent/BG103808A/bg unknown
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006503905A (ja) * | 2002-09-24 | 2006-02-02 | コンビナトアールエックス インコーポレーティッド | 炎症性サイトカインのレベルの増大と関連する病気および障害の治療のための方法および試薬 |
| WO2005110450A1 (ja) * | 2004-05-17 | 2005-11-24 | Keio University | 医薬組成物及び治療方法 |
| WO2006009114A1 (ja) * | 2004-07-16 | 2006-01-26 | Atsuo Sekiyama | Ｉｌ－１８レセプターアンタゴニスト、および当該アンタゴニストを含む薬学的組成物 |
| US7887802B2 (en) | 2004-07-16 | 2011-02-15 | Atsuo Sekiyama | IL-18 receptor antagonist and pharmaceutical composition containing the antagonist |
| WO2006041121A1 (ja) * | 2004-10-13 | 2006-04-20 | Kyowa Hakko Kogyo Co., Ltd. | 慢性皮膚疾患の治療および／または予防剤 |
| JP2015155423A (ja) * | 2006-10-17 | 2015-08-27 | ネオセティクス，インク． | 甲状腺眼症の治療のための方法、組成物及び製剤 |
| JP2015163612A (ja) * | 2006-10-17 | 2015-09-10 | ネオセティクス，インク． | 甲状腺眼症の治療のための方法、組成物及び製剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1269722A (zh) | 2000-10-11 |
| DE998300T1 (de) | 2001-03-01 |
| CA2282845A1 (en) | 1998-09-24 |
| AU6760498A (en) | 1998-10-12 |
| HUP0104439A3 (en) | 2002-08-28 |
| NO994506L (no) | 1999-11-17 |
| ID22975A (id) | 1999-12-23 |
| NO994506D0 (no) | 1999-09-17 |
| HUP0104439A2 (hu) | 2002-04-29 |
| WO1998041232A3 (en) | 2000-10-05 |
| BG103808A (bg) | 2000-07-31 |
| SK122199A3 (en) | 2000-12-11 |
| ES2146192T1 (es) | 2000-08-01 |
| KR20000076420A (ko) | 2000-12-26 |
| TR199902615T2 (xx) | 2000-03-21 |
| WO1998041232A2 (en) | 1998-09-24 |
| BR9810409A (pt) | 2000-08-22 |
| EP0998300A1 (en) | 2000-05-10 |
| SI20110A (sl) | 2000-06-30 |
| IL131815A0 (en) | 2001-03-19 |
| AU734756B2 (en) | 2001-06-21 |
| PL336464A1 (en) | 2000-06-19 |
| NZ337769A (en) | 2002-09-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2002504091A (ja) | コルチコステロイドに対する応答性を調整するための方法及び組成物 | |
| US6054487A (en) | Methods and compositions for modulating responsiveness to corticosteroids | |
| JP4504570B2 (ja) | 炭素環式カリウムチャンネル阻害薬 | |
| JP4676676B2 (ja) | カスパーゼ阻害剤としての複素環ジカルバミド | |
| JPH10501244A (ja) | インターロイキン−１β変換酵素の二環式ラクタム阻害剤 | |
| JPH09511249A (ja) | インターロイキン阻害剤としてのピリミジニル誘導体 | |
| WO2001019373A2 (en) | Methods and compositions for modulating responsiveness to corticosteroids | |
| JPH10511935A (ja) | タチキニンアンタゴニスト | |
| JP2001517246A (ja) | α▲下４▼β▲下１▼媒介細胞接着の阻止剤 | |
| JP2002502873A (ja) | 化合物 | |
| KR20000064454A (ko) | 인터류킨-1베타전환효소의억제제 | |
| JPH02209854A (ja) | Ａｉｄｓの治療に有用なｈｉｖプロテアーゼ阻害剤 | |
| JP2003531199A (ja) | アルキルおよびアリールアラニンｐ２部分を含むｃ型肝炎ウイルスに対する大員環ｎｓ３−セリンプロテアーゼ阻害剤 | |
| TW201802110A (zh) | 新穎環孢素衍生物及其用途 | |
| JP2001518922A (ja) | アリール−またはヘテロアリール−スルホンアミドで置換されたヒドロキサム酸誘導体、その製法およびその医薬としての使用 | |
| JP2002509153A (ja) | インターロイキン−１β変換酵素（ＩＣＥ）のインビボ阻害剤としてのＮ−［２−（５−ベンジルオキシカルボニル−アミノ−６−オキソ−２−（４−フルオロフェニル）−１，６−ジヒドロ−１−ピリミジニル）アセトキシル］−Ｌ−アスパラギン酸アルデヒド | |
| JP2000508666A (ja) | 成長ホルモン放出特性を有する化合物 | |
| JPH11511481A (ja) | 免疫抑制活性を有するトリテルペン誘導体 | |
| JP2003532727A (ja) | Ｃｄ２３の阻害剤としてのｎ−スルホニルヒドロキサム酸誘導体 | |
| JP3922431B2 (ja) | 可溶性ヒトｃｄ２３形成阻害剤としてのヒドロキサム酸誘導体 | |
| JP4181220B2 (ja) | Ｉｌ―４およびｇ―ｃｓｆに影響するナフチリジン類 | |
| JP2021523138A (ja) | Ｉｌ−２３抗体を使用してうつを治療する方法 | |
| JPH08511783A (ja) | Ｎ−置換アザ複素環式カルボン酸類とそのエステル類 | |
| JPH06271533A (ja) | 免疫抑制剤としての新規なアミノメチレン誘導体 | |
| CZ312799A3 (cs) | Přípravky pro modulaci reakce na kortikosteroidy |