CA2436770A1 - Methods of treating inflammatory and immune diseases using inhibitors of ikb kinase (ikk) - Google Patents

Methods of treating inflammatory and immune diseases using inhibitors of ikb kinase (ikk) Download PDF

Info

Publication number: CA2436770A1
Authority: CA; Canada
Prior art keywords: ikk; inhibitor; activity; disease; inflammatory
Prior art date: 2001-02-01
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.): Abandoned

Application number

CA002436770A

Other languages

English (en)

French (fr)

Inventor

James R. Burke

Steven Nadler

Yuping Qiu

Robert M. Townsend

Fred Christopher Zusi

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

2001-02-01

Filing date

2002-02-01

Publication date

2002-08-08

2001-09-27 Priority claimed from US09/965,977 external-priority patent/US6960585B2/en

2002-02-01 Application filed by Individual filed Critical Individual

2002-08-08 Publication of CA2436770A1 publication Critical patent/CA2436770A1/en

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 113
230000002757 inflammatory effect Effects 0.000 title claims abstract description 51
108091000080 Phosphotransferase Proteins 0.000 title claims abstract description 20
102000020233 phosphotransferase Human genes 0.000 title claims abstract description 20
208000027866 inflammatory disease Diseases 0.000 title claims description 21
239000003112 inhibitor Substances 0.000 title abstract description 29
208000026278 immune system disease Diseases 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims abstract description 245
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 136
239000003458 I kappa b kinase inhibitor Substances 0.000 claims abstract description 118
201000010099 disease Diseases 0.000 claims abstract description 92
PSPFQEBFYXJZEV-UHFFFAOYSA-N N'-(1,8-dimethyl-4-imidazo[1,2-a]quinoxalinyl)ethane-1,2-diamine Chemical compound C1=C(C)C=C2N3C(C)=CN=C3C(NCCN)=NC2=C1 PSPFQEBFYXJZEV-UHFFFAOYSA-N 0.000 claims abstract description 45
208000035475 disorder Diseases 0.000 claims abstract description 44
150000003839 salts Chemical class 0.000 claims abstract description 42
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
230000000694 effects Effects 0.000 claims description 82
-1 4(2'-aminoethyl)amino-1,8-dimethylimidazo(1,2-a) quinoxaline compound Chemical class 0.000 claims description 69
230000005764 inhibitory process Effects 0.000 claims description 47
230000002401 inhibitory effect Effects 0.000 claims description 38
230000026731 phosphorylation Effects 0.000 claims description 33
238000006366 phosphorylation reaction Methods 0.000 claims description 33
230000004913 activation Effects 0.000 claims description 25
239000003814 drug Substances 0.000 claims description 25
230000003197 catalytic effect Effects 0.000 claims description 24
230000001419 dependent effect Effects 0.000 claims description 18
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 16
230000014509 gene expression Effects 0.000 claims description 15
241000124008 Mammalia Species 0.000 claims description 14
239000013543 active substance Substances 0.000 claims description 14
229940079593 drug Drugs 0.000 claims description 14
206010052779 Transplant rejections Diseases 0.000 claims description 13
206010003246 arthritis Diseases 0.000 claims description 11
239000003085 diluting agent Substances 0.000 claims description 11
239000000546 pharmaceutical excipient Substances 0.000 claims description 11
208000019693 Lung disease Diseases 0.000 claims description 10
208000006673 asthma Diseases 0.000 claims description 9
210000000056 organ Anatomy 0.000 claims description 8
208000024827 Alzheimer disease Diseases 0.000 claims description 7
201000001320 Atherosclerosis Diseases 0.000 claims description 7
208000018737 Parkinson disease Diseases 0.000 claims description 6
229940088597 hormone Drugs 0.000 claims description 6
239000005556 hormone Substances 0.000 claims description 6
201000006417 multiple sclerosis Diseases 0.000 claims description 6
201000006474 Brain Ischemia Diseases 0.000 claims description 5
201000004681 Psoriasis Diseases 0.000 claims description 5
208000032851 Subarachnoid Hemorrhage Diseases 0.000 claims description 5
208000030886 Traumatic Brain injury Diseases 0.000 claims description 5
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
230000009529 traumatic brain injury Effects 0.000 claims description 5
230000001684 chronic effect Effects 0.000 claims description 4
230000000414 obstructive effect Effects 0.000 claims description 4
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 3
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 3
230000027405 negative regulation of phosphorylation Effects 0.000 claims description 2
206010039083 rhinitis Diseases 0.000 claims 3
206010038687 Respiratory distress Diseases 0.000 claims 1
230000001154 acute effect Effects 0.000 claims 1
208000011580 syndromic disease Diseases 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 54
238000001727 in vivo Methods 0.000 abstract description 17
230000002265 prevention Effects 0.000 abstract description 9
239000000203 mixture Substances 0.000 description 65
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
238000002360 preparation method Methods 0.000 description 58
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 56
125000000217 alkyl group Chemical group 0.000 description 56
108090000623 proteins and genes Proteins 0.000 description 42
239000007787 solid Substances 0.000 description 39
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
238000012360 testing method Methods 0.000 description 35
210000004027 cell Anatomy 0.000 description 34
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 32
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
238000005481 NMR spectroscopy Methods 0.000 description 32
239000000243 solution Substances 0.000 description 32
235000019439 ethyl acetate Nutrition 0.000 description 30
108060008682 Tumor Necrosis Factor Proteins 0.000 description 28
102000004169 proteins and genes Human genes 0.000 description 28
102000003390 tumor necrosis factor Human genes 0.000 description 28
235000018102 proteins Nutrition 0.000 description 27
125000001072 heteroaryl group Chemical group 0.000 description 26
241000699670 Mus sp. Species 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 25
206010061218 Inflammation Diseases 0.000 description 24
230000004054 inflammatory process Effects 0.000 description 24
238000003818 flash chromatography Methods 0.000 description 19
229910052757 nitrogen Inorganic materials 0.000 description 19
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 19
239000002904 solvent Substances 0.000 description 19
239000000725 suspension Substances 0.000 description 19
239000003981 vehicle Substances 0.000 description 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
125000003118 aryl group Chemical group 0.000 description 18
239000003795 chemical substances by application Substances 0.000 description 18
238000010172 mouse model Methods 0.000 description 18
125000000547 substituted alkyl group Chemical group 0.000 description 18
239000012267 brine Substances 0.000 description 17
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
238000003556 assay Methods 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
241001465754 Metazoa Species 0.000 description 15
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
239000002253 acid Substances 0.000 description 15
239000013058 crude material Substances 0.000 description 15
125000000753 cycloalkyl group Chemical group 0.000 description 15
230000001225 therapeutic effect Effects 0.000 description 15
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 14
108700012920 TNF Proteins 0.000 description 14
208000027418 Wounds and injury Diseases 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 14
230000006378 damage Effects 0.000 description 14
208000014674 injury Diseases 0.000 description 14
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 13
239000012044 organic layer Substances 0.000 description 13
239000011541 reaction mixture Substances 0.000 description 13
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 12
229910052739 hydrogen Inorganic materials 0.000 description 12
125000004435 hydrogen atom Chemical class [H]* 0.000 description 12
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 11
229930105110 Cyclosporin A Natural products 0.000 description 11
108010036949 Cyclosporine Proteins 0.000 description 11
102000004190 Enzymes Human genes 0.000 description 11
108090000790 Enzymes Proteins 0.000 description 11
208000009386 Experimental Arthritis Diseases 0.000 description 11
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
150000001412 amines Chemical class 0.000 description 11
239000003153 chemical reaction reagent Substances 0.000 description 11
239000002158 endotoxin Substances 0.000 description 11
210000002216 heart Anatomy 0.000 description 11
239000001257 hydrogen Substances 0.000 description 11
229920006008 lipopolysaccharide Polymers 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
241000282412 Homo Species 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
238000010171 animal model Methods 0.000 description 10
230000028993 immune response Effects 0.000 description 10
230000007246 mechanism Effects 0.000 description 10
125000001424 substituent group Chemical group 0.000 description 10
210000001519 tissue Anatomy 0.000 description 10
XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical class OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
125000003545 alkoxy group Chemical group 0.000 description 9
230000015556 catabolic process Effects 0.000 description 9
210000001072 colon Anatomy 0.000 description 9
238000006731 degradation reaction Methods 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
125000005842 heteroatom Chemical group 0.000 description 9
125000000623 heterocyclic group Chemical group 0.000 description 9
239000000047 product Substances 0.000 description 9
239000000523 sample Substances 0.000 description 9
229920006395 saturated elastomer Polymers 0.000 description 9
125000004414 alkyl thio group Chemical group 0.000 description 8
125000002619 bicyclic group Chemical group 0.000 description 8
230000015572 biosynthetic process Effects 0.000 description 8
230000001186 cumulative effect Effects 0.000 description 8
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 8
229910052736 halogen Inorganic materials 0.000 description 8
150000002367 halogens Chemical class 0.000 description 8
210000004969 inflammatory cell Anatomy 0.000 description 8
238000004519 manufacturing process Methods 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
150000003141 primary amines Chemical class 0.000 description 8
239000007858 starting material Substances 0.000 description 8
239000000126 substance Substances 0.000 description 8
229940124597 therapeutic agent Drugs 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
206010035664 Pneumonia Diseases 0.000 description 7
230000008595 infiltration Effects 0.000 description 7
238000001764 infiltration Methods 0.000 description 7
210000004072 lung Anatomy 0.000 description 7
125000004433 nitrogen atom Chemical group N* 0.000 description 7
239000003960 organic solvent Substances 0.000 description 7
239000000651 prodrug Substances 0.000 description 7
229940002612 prodrug Drugs 0.000 description 7
238000010992 reflux Methods 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
125000005346 substituted cycloalkyl group Chemical group 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
102000004127 Cytokines Human genes 0.000 description 6
108090000695 Cytokines Proteins 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000004480 active ingredient Substances 0.000 description 6
230000003110 anti-inflammatory effect Effects 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
125000004093 cyano group Chemical group *C#N 0.000 description 6
208000037765 diseases and disorders Diseases 0.000 description 6
125000005843 halogen group Chemical group 0.000 description 6
238000004128 high performance liquid chromatography Methods 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
230000004048 modification Effects 0.000 description 6
238000012986 modification Methods 0.000 description 6
125000002950 monocyclic group Chemical group 0.000 description 6
230000037361 pathway Effects 0.000 description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
239000000758 substrate Substances 0.000 description 6
230000004083 survival effect Effects 0.000 description 6
239000003826 tablet Substances 0.000 description 6
238000002560 therapeutic procedure Methods 0.000 description 6
IIRWITSTDWORDS-UHFFFAOYSA-N 1,8-dimethyl-5h-imidazo[1,2-a]quinoxalin-4-one Chemical compound CC1=CC=C2NC(=O)C3=NC=C(C)N3C2=C1 IIRWITSTDWORDS-UHFFFAOYSA-N 0.000 description 5
108010058846 Ovalbumin Proteins 0.000 description 5
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 5
230000002378 acidificating effect Effects 0.000 description 5
125000003342 alkenyl group Chemical group 0.000 description 5
125000000304 alkynyl group Chemical group 0.000 description 5
BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
230000027455 binding Effects 0.000 description 5
239000002775 capsule Substances 0.000 description 5
239000012320 chlorinating reagent Substances 0.000 description 5
229940126214 compound 3 Drugs 0.000 description 5
229940125898 compound 5 Drugs 0.000 description 5
210000000805 cytoplasm Anatomy 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000009472 formulation Methods 0.000 description 5
125000002883 imidazolyl group Chemical group 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
229940092253 ovalbumin Drugs 0.000 description 5
230000002018 overexpression Effects 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
229920001223 polyethylene glycol Polymers 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
206010039073 rheumatoid arthritis Diseases 0.000 description 5
239000011734 sodium Substances 0.000 description 5
125000004434 sulfur atom Chemical group 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
238000002054 transplantation Methods 0.000 description 5
230000034512 ubiquitination Effects 0.000 description 5
238000010798 ubiquitination Methods 0.000 description 5
DZBGUIUMPUTEMS-UHFFFAOYSA-N 3-iodonaphthalene-2-carboxylic acid Chemical class C1=CC=C2C=C(I)C(C(=O)O)=CC2=C1 DZBGUIUMPUTEMS-UHFFFAOYSA-N 0.000 description 4
JJFAGUZOWDICTQ-UHFFFAOYSA-N 4-chloro-1-methylbenzo[g]imidazo[1,2-a]quinoxaline Chemical compound C1=CC=C2C=C(N3C(C)=CN=C3C(Cl)=N3)C3=CC2=C1 JJFAGUZOWDICTQ-UHFFFAOYSA-N 0.000 description 4
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 4
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
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 4
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
241000725303 Human immunodeficiency virus Species 0.000 description 4
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 4
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 4
229930195725 Mannitol Natural products 0.000 description 4
101150091206 Nfkbia gene Proteins 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
229940124639 Selective inhibitor Drugs 0.000 description 4
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 4
230000009471 action Effects 0.000 description 4
208000028004 allergic respiratory disease Diseases 0.000 description 4
229940121363 anti-inflammatory agent Drugs 0.000 description 4
239000002260 anti-inflammatory agent Substances 0.000 description 4
239000002585 base Substances 0.000 description 4
230000008901 benefit Effects 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
239000001768 carboxy methyl cellulose Substances 0.000 description 4
230000000536 complexating effect Effects 0.000 description 4
229940125904 compound 1 Drugs 0.000 description 4
229940125782 compound 2 Drugs 0.000 description 4
125000004122 cyclic group Chemical group 0.000 description 4
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 4
239000008298 dragée Substances 0.000 description 4
238000011156 evaluation Methods 0.000 description 4
150000002430 hydrocarbons Chemical group 0.000 description 4
125000004356 hydroxy functional group Chemical group O* 0.000 description 4
210000000987 immune system Anatomy 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
239000008101 lactose Substances 0.000 description 4
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
239000000594 mannitol Substances 0.000 description 4
235000010355 mannitol Nutrition 0.000 description 4
238000005259 measurement Methods 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
229910052760 oxygen Inorganic materials 0.000 description 4
229910000027 potassium carbonate Inorganic materials 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000008569 process Effects 0.000 description 4
230000000770 proinflammatory effect Effects 0.000 description 4
230000017854 proteolysis Effects 0.000 description 4
125000003226 pyrazolyl group Chemical group 0.000 description 4
230000009257 reactivity Effects 0.000 description 4
238000012552 review Methods 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 4
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 4
239000003381 stabilizer Substances 0.000 description 4
229910052717 sulfur Inorganic materials 0.000 description 4
125000000335 thiazolyl group Chemical group 0.000 description 4
230000000699 topical effect Effects 0.000 description 4
238000013518 transcription Methods 0.000 description 4
230000035897 transcription Effects 0.000 description 4
125000006168 tricyclic group Chemical group 0.000 description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 3
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
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 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
208000023275 Autoimmune disease Diseases 0.000 description 3
238000011725 BALB/c mouse Methods 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
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 3
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 3
108010010803 Gelatin Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
102000000589 Interleukin-1 Human genes 0.000 description 3
108010002352 Interleukin-1 Proteins 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
239000012980 RPMI-1640 medium Substances 0.000 description 3
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
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 3
229930006000 Sucrose Natural products 0.000 description 3
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
108091023040 Transcription factor Proteins 0.000 description 3
102000040945 Transcription factor Human genes 0.000 description 3
108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 3
150000001241 acetals Chemical class 0.000 description 3
229960001138 acetylsalicylic acid Drugs 0.000 description 3
235000010443 alginic acid Nutrition 0.000 description 3
229920000615 alginic acid Polymers 0.000 description 3
230000029936 alkylation Effects 0.000 description 3
238000005804 alkylation reaction Methods 0.000 description 3
125000004429 atom Chemical group 0.000 description 3
YUFRAQHYKKPYLH-UHFFFAOYSA-N benzo[f]quinoxaline Chemical compound C1=CN=C2C3=CC=CC=C3C=CC2=N1 YUFRAQHYKKPYLH-UHFFFAOYSA-N 0.000 description 3
PQIUGRLKNKSKTC-UHFFFAOYSA-N benzo[h]quinazoline Chemical class N1=CN=C2C3=CC=CC=C3C=CC2=C1 PQIUGRLKNKSKTC-UHFFFAOYSA-N 0.000 description 3
WZJYKHNJTSNBHV-UHFFFAOYSA-N benzoquinoline Natural products C1=CN=C2C3=CC=CC=C3C=CC2=C1 WZJYKHNJTSNBHV-UHFFFAOYSA-N 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
210000004369 blood Anatomy 0.000 description 3
239000008280 blood Substances 0.000 description 3
238000009835 boiling Methods 0.000 description 3
238000004113 cell culture Methods 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
125000001309 chloro group Chemical group Cl* 0.000 description 3
238000000576 coating method Methods 0.000 description 3
206010009887 colitis Diseases 0.000 description 3
230000037020 contractile activity Effects 0.000 description 3
238000006880 cross-coupling reaction Methods 0.000 description 3
230000007423 decrease Effects 0.000 description 3
239000003623 enhancer Substances 0.000 description 3
238000013265 extended release Methods 0.000 description 3
239000000499 gel Substances 0.000 description 3
239000008273 gelatin Substances 0.000 description 3
229920000159 gelatin Polymers 0.000 description 3
235000019322 gelatine Nutrition 0.000 description 3
235000011852 gelatine desserts Nutrition 0.000 description 3
239000003862 glucocorticoid Substances 0.000 description 3
150000004795 grignard reagents Chemical class 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
239000008241 heterogeneous mixture Substances 0.000 description 3
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 3
239000012729 immediate-release (IR) formulation Substances 0.000 description 3
239000003018 immunosuppressive agent Substances 0.000 description 3
230000001939 inductive effect Effects 0.000 description 3
230000028709 inflammatory response Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011630 iodine Substances 0.000 description 3
239000012948 isocyanate Substances 0.000 description 3
150000002513 isocyanates Chemical class 0.000 description 3
125000000468 ketone group Chemical group 0.000 description 3
239000000314 lubricant Substances 0.000 description 3
238000002844 melting Methods 0.000 description 3
230000008018 melting Effects 0.000 description 3
229910052751 metal Inorganic materials 0.000 description 3
239000002184 metal Substances 0.000 description 3
231100000252 nontoxic Toxicity 0.000 description 3
230000003000 nontoxic effect Effects 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
239000000825 pharmaceutical preparation Substances 0.000 description 3
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 3
239000002953 phosphate buffered saline Substances 0.000 description 3
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
238000011160 research Methods 0.000 description 3
150000003873 salicylate salts Chemical class 0.000 description 3
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
150000003431 steroids Chemical class 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
229940037128 systemic glucocorticoids Drugs 0.000 description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
KWMGFYVFHSAISD-UHFFFAOYSA-N 1-methyl-4-chlorobenzo(g)imidazo(4,5-c)quinoline Chemical compound C1=CC=CC2=CC3=C4N(C)C=NC4=C(Cl)N=C3C=C21 KWMGFYVFHSAISD-UHFFFAOYSA-N 0.000 description 2
OMPIJMOZKLHFCC-UHFFFAOYSA-N 11,14,17-triazatetracyclo[8.7.0.03,8.011,15]heptadeca-1,3,5,7,9,12,14,16-octaene Chemical compound c1cn2c(cnc3cc4ccccc4cc23)n1 OMPIJMOZKLHFCC-UHFFFAOYSA-N 0.000 description 2
MRPXDPJAIOQHFO-UHFFFAOYSA-N 12-methyl-14,15,17-triazatetracyclo[8.7.0.03,8.011,15]heptadeca-1,3,5,7,9,11,13-heptaen-16-one Chemical compound Cc1cnn2c1c1cc3ccccc3cc1[nH]c2=O MRPXDPJAIOQHFO-UHFFFAOYSA-N 0.000 description 2
HTBIZVQWEZWUCQ-UHFFFAOYSA-N 1h-benzimidazolo[4,5-h]quinoline Chemical class C1=CC2=CC=CN=C2C2=C1C(N=CN1)=C1C=C2 HTBIZVQWEZWUCQ-UHFFFAOYSA-N 0.000 description 2
IWQXKMLJNVDOMB-UHFFFAOYSA-N 1h-benzimidazolo[5,4-f]quinoxaline Chemical class C1=CC2=NC=CN=C2C2=C1C(N=CN1)=C1C=C2 IWQXKMLJNVDOMB-UHFFFAOYSA-N 0.000 description 2
GDWJSZKXUXMVTM-UHFFFAOYSA-N 1h-indazolo[4,5-h]quinazoline Chemical class N1=CN=C2C3=CC=C4NN=CC4=C3C=CC2=C1 GDWJSZKXUXMVTM-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
LYIIBVSRGJSHAV-UHFFFAOYSA-N 2-aminoacetaldehyde Chemical compound NCC=O LYIIBVSRGJSHAV-UHFFFAOYSA-N 0.000 description 2
WZMOWQCNPFDWPA-UHFFFAOYSA-N 2-fluoro-4-methyl-1-nitrobenzene Chemical compound CC1=CC=C([N+]([O-])=O)C(F)=C1 WZMOWQCNPFDWPA-UHFFFAOYSA-N 0.000 description 2
XFXOLBNQYFRSLQ-UHFFFAOYSA-N 3-amino-2-naphthoic acid Chemical class C1=CC=C2C=C(C(O)=O)C(N)=CC2=C1 XFXOLBNQYFRSLQ-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
HATLLUIOEIXWGD-UHFFFAOYSA-N 5-bromo-1-methylimidazole Chemical compound CN1C=NC=C1Br HATLLUIOEIXWGD-UHFFFAOYSA-N 0.000 description 2
USVZHTBPMMSRHY-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-chlorophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Cl USVZHTBPMMSRHY-UHFFFAOYSA-N 0.000 description 2
102000008102 Ankyrins Human genes 0.000 description 2
108010049777 Ankyrins Proteins 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
238000006418 Brown reaction Methods 0.000 description 2
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
206010063094 Cerebral malaria Diseases 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
102000008186 Collagen Human genes 0.000 description 2
108010035532 Collagen Proteins 0.000 description 2
229940126062 Compound A Drugs 0.000 description 2
208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 2
208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 2
208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 2
241000283086 Equidae Species 0.000 description 2
241000282326 Felis catus Species 0.000 description 2
239000007818 Grignard reagent Substances 0.000 description 2
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
102000003814 Interleukin-10 Human genes 0.000 description 2
108090000174 Interleukin-10 Proteins 0.000 description 2
108090001005 Interleukin-6 Proteins 0.000 description 2
108090001007 Interleukin-8 Proteins 0.000 description 2
108010063738 Interleukins Proteins 0.000 description 2
102000015696 Interleukins Human genes 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
229930194542 Keto Natural products 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
238000000585 Mann–Whitney U test Methods 0.000 description 2
201000009906 Meningitis Diseases 0.000 description 2
229920000168 Microcrystalline cellulose Polymers 0.000 description 2
HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
239000002202 Polyethylene glycol Substances 0.000 description 2
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
102000001253 Protein Kinase Human genes 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
206010040070 Septic Shock Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
208000006011 Stroke Diseases 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
238000010306 acid treatment Methods 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000783 alginic acid Substances 0.000 description 2
229960001126 alginic acid Drugs 0.000 description 2
150000004781 alginic acids Chemical class 0.000 description 2
150000001447 alkali salts Chemical class 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
230000001668 ameliorated effect Effects 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000001028 anti-proliverative effect Effects 0.000 description 2
239000000427 antigen Substances 0.000 description 2
102000036639 antigens Human genes 0.000 description 2
108091007433 antigens Proteins 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
238000007080 aromatic substitution reaction Methods 0.000 description 2
AQLMHYSWFMLWBS-UHFFFAOYSA-N arsenite(1-) Chemical compound O[As](O)[O-] AQLMHYSWFMLWBS-UHFFFAOYSA-N 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
IPWKHHSGDUIRAH-UHFFFAOYSA-N bis(pinacolato)diboron Chemical compound O1C(C)(C)C(C)(C)OB1B1OC(C)(C)C(C)(C)O1 IPWKHHSGDUIRAH-UHFFFAOYSA-N 0.000 description 2
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 2
150000001642 boronic acid derivatives Chemical class 0.000 description 2
210000004556 brain Anatomy 0.000 description 2
150000001649 bromium compounds Chemical class 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000007975 buffered saline Substances 0.000 description 2
229930194791 calphostin Natural products 0.000 description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
235000010980 cellulose Nutrition 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
210000003169 central nervous system Anatomy 0.000 description 2
KWTSZCJMWHGPOS-UHFFFAOYSA-M chloro(trimethyl)stannane Chemical compound C[Sn](C)(C)Cl KWTSZCJMWHGPOS-UHFFFAOYSA-M 0.000 description 2
101150116749 chuk gene Proteins 0.000 description 2
150000001860 citric acid derivatives Chemical class 0.000 description 2
229920001436 collagen Polymers 0.000 description 2
238000001816 cooling Methods 0.000 description 2
229920001577 copolymer Polymers 0.000 description 2
150000001879 copper Chemical class 0.000 description 2
239000003246 corticosteroid Substances 0.000 description 2
229960001334 corticosteroids Drugs 0.000 description 2
238000011161 development Methods 0.000 description 2
230000018109 developmental process Effects 0.000 description 2
229960000633 dextran sulfate Drugs 0.000 description 2
125000003963 dichloro group Chemical group Cl* 0.000 description 2
235000014113 dietary fatty acids Nutrition 0.000 description 2
WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 2
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
206010014599 encephalitis Diseases 0.000 description 2
210000003979 eosinophil Anatomy 0.000 description 2
230000003628 erosive effect Effects 0.000 description 2
150000002170 ethers Chemical class 0.000 description 2
FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
239000000194 fatty acid Substances 0.000 description 2
229930195729 fatty acid Natural products 0.000 description 2
239000010685 fatty oil Substances 0.000 description 2
239000012091 fetal bovine serum Substances 0.000 description 2
239000000945 filler Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
125000001153 fluoro group Chemical group F* 0.000 description 2
239000012458 free base Substances 0.000 description 2
230000006870 function Effects 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229960002706 gusperimus Drugs 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
230000011132 hemopoiesis Effects 0.000 description 2
125000000592 heterocycloalkyl group Chemical group 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
239000001863 hydroxypropyl cellulose Substances 0.000 description 2
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
230000036737 immune function Effects 0.000 description 2
229940125721 immunosuppressive agent Drugs 0.000 description 2
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
150000007529 inorganic bases Chemical class 0.000 description 2
230000003993 interaction Effects 0.000 description 2
229940076144 interleukin-10 Drugs 0.000 description 2
238000007918 intramuscular administration Methods 0.000 description 2
150000004694 iodide salts Chemical class 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
238000011813 knockout mouse model Methods 0.000 description 2
150000003951 lactams Chemical class 0.000 description 2
239000010410 layer Substances 0.000 description 2
231100000518 lethal Toxicity 0.000 description 2
230000001665 lethal effect Effects 0.000 description 2
239000003446 ligand Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
206010025135 lupus erythematosus Diseases 0.000 description 2
210000004698 lymphocyte Anatomy 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
238000004949 mass spectrometry Methods 0.000 description 2
108020004999 messenger RNA Proteins 0.000 description 2
FCTVQOVDYDWVEP-UHFFFAOYSA-N methyl 3-iodonaphthalene-2-carboxylate Chemical compound C1=CC=C2C=C(I)C(C(=O)OC)=CC2=C1 FCTVQOVDYDWVEP-UHFFFAOYSA-N 0.000 description 2
229920000609 methyl cellulose Polymers 0.000 description 2
239000001923 methylcellulose Substances 0.000 description 2
235000010981 methylcellulose Nutrition 0.000 description 2
239000008108 microcrystalline cellulose Substances 0.000 description 2
229940016286 microcrystalline cellulose Drugs 0.000 description 2
235000019813 microcrystalline cellulose Nutrition 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
KFIGICHILYTCJF-UHFFFAOYSA-N n'-methylethane-1,2-diamine Chemical compound CNCCN KFIGICHILYTCJF-UHFFFAOYSA-N 0.000 description 2
IDINUJSAMVOPCM-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-INIZCTEOSA-N 0.000 description 2
XTBLDMQMUSHDEN-UHFFFAOYSA-N naphthalene-2,3-diamine Chemical class C1=CC=C2C=C(N)C(N)=CC2=C1 XTBLDMQMUSHDEN-UHFFFAOYSA-N 0.000 description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
230000005937 nuclear translocation Effects 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
201000008482 osteoarthritis Diseases 0.000 description 2
229940046781 other immunosuppressants in atc Drugs 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
230000001575 pathological effect Effects 0.000 description 2
229940049954 penicillin Drugs 0.000 description 2
125000003386 piperidinyl group Chemical group 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
159000000001 potassium salts Chemical class 0.000 description 2
238000012545 processing Methods 0.000 description 2
JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical class NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 2
150000003180 prostaglandins Chemical class 0.000 description 2
108060006633 protein kinase Proteins 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 2
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
239000002464 receptor antagonist Substances 0.000 description 2
229940044551 receptor antagonist Drugs 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 2
229950005741 rolipram Drugs 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
230000036303 septic shock Effects 0.000 description 2
230000019491 signal transduction Effects 0.000 description 2
230000011664 signaling Effects 0.000 description 2
229960002930 sirolimus Drugs 0.000 description 2
239000002002 slurry Substances 0.000 description 2
235000010413 sodium alginate Nutrition 0.000 description 2
239000000661 sodium alginate Substances 0.000 description 2
229940005550 sodium alginate Drugs 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
DAEPDZWVDSPTHF-UHFFFAOYSA-M sodium pyruvate Chemical compound [Na+].CC(=O)C([O-])=O DAEPDZWVDSPTHF-UHFFFAOYSA-M 0.000 description 2
239000012453 solvate Substances 0.000 description 2
239000008107 starch Substances 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
235000000346 sugar Nutrition 0.000 description 2
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical compound O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 2
MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 2
229960000894 sulindac Drugs 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
230000001629 suppression Effects 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
230000009897 systematic effect Effects 0.000 description 2
QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
239000000454 talc Substances 0.000 description 2
229910052623 talc Inorganic materials 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
238000004809 thin layer chromatography Methods 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
231100000331 toxic Toxicity 0.000 description 2
230000002588 toxic effect Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
230000002103 transcriptional effect Effects 0.000 description 2
BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
230000003827 upregulation Effects 0.000 description 2
230000002792 vascular Effects 0.000 description 2
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
229910052725 zinc Inorganic materials 0.000 description 2
239000011701 zinc Substances 0.000 description 2
239000011592 zinc chloride Substances 0.000 description 2
235000005074 zinc chloride Nutrition 0.000 description 2
DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical class CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 1
FRJJJAKBRKABFA-TYFAACHXSA-N (4r,6s)-6-[(e)-2-[6-chloro-4-(4-fluorophenyl)-2-propan-2-ylquinolin-3-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C(\[C@H]1OC(=O)C[C@H](O)C1)=C/C=1C(C(C)C)=NC2=CC=C(Cl)C=C2C=1C1=CC=C(F)C=C1 FRJJJAKBRKABFA-TYFAACHXSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
125000006059 1,1-dimethyl-2-butenyl group Chemical group 0.000 description 1
125000006033 1,1-dimethyl-2-propenyl group Chemical group 0.000 description 1
KLBLIQLOPBRDNC-UHFFFAOYSA-N 1,4-dihydrobenzo[g]quinoxaline-2,3-dione Chemical compound C1=CC=C2C=C(NC(C(=O)N3)=O)C3=CC2=C1 KLBLIQLOPBRDNC-UHFFFAOYSA-N 0.000 description 1
PGIODXBHGOGYHU-UHFFFAOYSA-N 1,8-dimethyl-3h-imidazo[4,5-f]quinoxalin-2-one Chemical compound C12=NC(C)=CN=C2C=CC2=C1N(C)C(=O)N2 PGIODXBHGOGYHU-UHFFFAOYSA-N 0.000 description 1
SOZFOLUZJUPGMQ-UHFFFAOYSA-N 1,8-dimethylimidazo[1,2-a]quinoxalin-2-amine Chemical compound C1=C(C)C=C2N3C(C)=C(N)N=C3C=NC2=C1 SOZFOLUZJUPGMQ-UHFFFAOYSA-N 0.000 description 1
125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical class CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
125000006025 1-methyl-1-butenyl group Chemical group 0.000 description 1
125000006019 1-methyl-1-propenyl group Chemical group 0.000 description 1
125000006028 1-methyl-2-butenyl group Chemical group 0.000 description 1
125000006021 1-methyl-2-propenyl group Chemical group 0.000 description 1
SOWFHRFETKCZMC-UHFFFAOYSA-N 1-methyl-4,5-dihydrobenzo(g)imidazo(4,5-c)quinolin-4-one Chemical compound C1=CC=C2C=C(NC(C=3N=CN(C=33)C)=O)C3=CC2=C1 SOWFHRFETKCZMC-UHFFFAOYSA-N 0.000 description 1
ODFIBXFJCDPCHA-UHFFFAOYSA-N 1-methyl-4-methylaminobenzo(g)imidazo(4,5-c)quinoline Chemical compound C1=CC=C2C=C(C3=C(C(NC)=N4)N=CN3C)C4=CC2=C1 ODFIBXFJCDPCHA-UHFFFAOYSA-N 0.000 description 1
125000006018 1-methyl-ethenyl group Chemical group 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
125000006017 1-propenyl group Chemical group 0.000 description 1
125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
NECFYTOWQYCZGB-UHFFFAOYSA-N 2,3-dichlorobenzo[g]quinoxaline Chemical compound C1=CC=C2C=C(N=C(C(Cl)=N3)Cl)C3=CC2=C1 NECFYTOWQYCZGB-UHFFFAOYSA-N 0.000 description 1
125000006068 2,3-dimethyl-1-butenyl group Chemical group 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 1
125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
KZMAWJRXKGLWGS-UHFFFAOYSA-N 2-chloro-n-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-n-(3-methoxypropyl)acetamide Chemical compound S1C(N(C(=O)CCl)CCCOC)=NC(C=2C=CC(OC)=CC=2)=C1 KZMAWJRXKGLWGS-UHFFFAOYSA-N 0.000 description 1
125000006026 2-methyl-1-butenyl group Chemical group 0.000 description 1
125000006029 2-methyl-2-butenyl group Chemical group 0.000 description 1
125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
125000004638 2-oxopiperazinyl group Chemical group O=C1N(CCNC1)* 0.000 description 1
125000004637 2-oxopiperidinyl group Chemical group O=C1N(CCCC1)* 0.000 description 1
125000006087 2-oxopyrrolodinyl group Chemical group 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
125000006071 3,3-dimethyl-1-butenyl group Chemical group 0.000 description 1
ABFYPGFZVLQWSD-UHFFFAOYSA-N 3-(3-methylimidazol-4-yl)naphthalen-2-amine Chemical compound CN1C=NC=C1C1=CC2=CC=CC=C2C=C1N ABFYPGFZVLQWSD-UHFFFAOYSA-N 0.000 description 1
SEWQJVRBABDFPJ-UHFFFAOYSA-N 3-(3-methylimidazol-4-yl)naphthalene-2-carboxylic acid Chemical compound CN1C=NC=C1C1=CC2=CC=CC=C2C=C1C(O)=O SEWQJVRBABDFPJ-UHFFFAOYSA-N 0.000 description 1
HGOMRLICFHELGF-UHFFFAOYSA-N 3-(4-methyl-1h-pyrazol-5-yl)naphthalene-2-carboxylic acid Chemical compound C1=NNC(C=2C(=CC3=CC=CC=C3C=2)C(O)=O)=C1C HGOMRLICFHELGF-UHFFFAOYSA-N 0.000 description 1
QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-N 0.000 description 1
125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
ZYRBKVBKUPYCFK-UHFFFAOYSA-N 3-chloro-n-prop-2-ynylbenzo[g]quinoxalin-2-amine Chemical compound C1=CC=C2C=C(N=C(C(Cl)=N3)NCC#C)C3=CC2=C1 ZYRBKVBKUPYCFK-UHFFFAOYSA-N 0.000 description 1
ZRPLANDPDWYOMZ-UHFFFAOYSA-N 3-cyclopentylpropionic acid Chemical class OC(=O)CCC1CCCC1 ZRPLANDPDWYOMZ-UHFFFAOYSA-N 0.000 description 1
125000006027 3-methyl-1-butenyl group Chemical group 0.000 description 1
IUQLFCKNGRPZIL-UHFFFAOYSA-N 4-chloro-1,8-dimethylimidazo[1,2-a]quinoxaline Chemical compound C1=C(C)C=C2N3C(C)=CN=C3C(Cl)=NC2=C1 IUQLFCKNGRPZIL-UHFFFAOYSA-N 0.000 description 1
RPHGKWDIBRGJGG-UHFFFAOYSA-N 4-chloro-1,8-dimethylimidazo[4,5-f]quinoxaline Chemical compound C12=NC(C)=CN=C2C=C(Cl)C2=C1N(C)C=N2 RPHGKWDIBRGJGG-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
125000005986 4-piperidonyl group Chemical group 0.000 description 1
DWUPYMSVAPQXMS-UHFFFAOYSA-N 5-bromo-1,3-thiazole Chemical compound BrC1=CN=CS1 DWUPYMSVAPQXMS-UHFFFAOYSA-N 0.000 description 1
125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
101150007969 ADORA1 gene Proteins 0.000 description 1
244000215068 Acacia senegal Species 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
208000026872 Addison Disease Diseases 0.000 description 1
206010001367 Adrenal insufficiency Diseases 0.000 description 1
229920001817 Agar Polymers 0.000 description 1
208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
201000004384 Alopecia Diseases 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
208000008822 Ankylosis Diseases 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
241000416162 Astragalus gummifer Species 0.000 description 1
206010003591 Ataxia Diseases 0.000 description 1
208000031212 Autoimmune polyendocrinopathy Diseases 0.000 description 1
208000006386 Bone Resorption Diseases 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
206010006187 Breast cancer Diseases 0.000 description 1
208000026310 Breast neoplasm Diseases 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
QUMCIHKVKQYNPA-RUZDIDTESA-N C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC Chemical compound C1(CCCCC1)CN1[C@@H](C=2N(C=3C=NC(=NC1=3)NC1=C(C=C(C(=O)NC3CCN(CC3)C)C=C1)OC)C(=NN=2)C)CC QUMCIHKVKQYNPA-RUZDIDTESA-N 0.000 description 1
WPZOOMBZZSELMO-UHFFFAOYSA-N C1=CC2=NC=CN=C2C2=C1C(N=C(N1)Cl)=C1C=C2 Chemical compound C1=CC2=NC=CN=C2C2=C1C(N=C(N1)Cl)=C1C=C2 WPZOOMBZZSELMO-UHFFFAOYSA-N 0.000 description 1
238000011740 C57BL/6 mouse Methods 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
208000005623 Carcinogenesis Diseases 0.000 description 1
108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
229930186147 Cephalosporin Natural products 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
229910052684 Cerium Inorganic materials 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
208000000668 Chronic Pancreatitis Diseases 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
102000000503 Collagen Type II Human genes 0.000 description 1
108010041390 Collagen Type II Proteins 0.000 description 1
208000014997 Crohn colitis Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
229940122204 Cyclooxygenase inhibitor Drugs 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
241000701022 Cytomegalovirus Species 0.000 description 1
102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
102000052510 DNA-Binding Proteins Human genes 0.000 description 1
108700020911 DNA-Binding Proteins Proteins 0.000 description 1
206010012438 Dermatitis atopic Diseases 0.000 description 1
206010012442 Dermatitis contact Diseases 0.000 description 1
229920002307 Dextran Polymers 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
241000551547 Dione <red algae> Species 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
102000015689 E-Selectin Human genes 0.000 description 1
108010024212 E-Selectin Proteins 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
238000002965 ELISA Methods 0.000 description 1
LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
241000196324 Embryophyta Species 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
239000004606 Fillers/Extenders Substances 0.000 description 1
238000000729 Fisher's exact test Methods 0.000 description 1
206010017533 Fungal infection Diseases 0.000 description 1
206010018364 Glomerulonephritis Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
102000018899 Glutamate Receptors Human genes 0.000 description 1
108010027915 Glutamate Receptors Proteins 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
229920000084 Gum arabic Polymers 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
208000017604 Hodgkin disease Diseases 0.000 description 1
208000021519 Hodgkin lymphoma Diseases 0.000 description 1
208000010747 Hodgkins lymphoma Diseases 0.000 description 1
101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 0.000 description 1
230000004950 I-kappaB phosphorylation Effects 0.000 description 1
229940122296 IKK2 inhibitor Drugs 0.000 description 1
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
108060003951 Immunoglobulin Proteins 0.000 description 1
108010064593 Intercellular Adhesion Molecule-1 Proteins 0.000 description 1
102000015271 Intercellular Adhesion Molecule-1 Human genes 0.000 description 1
241000087801 Ioba Species 0.000 description 1
QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 1
206010023198 Joint ankylosis Diseases 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-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
FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-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
239000002841 Lewis acid Substances 0.000 description 1
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
108060001084 Luciferase Proteins 0.000 description 1
239000005089 Luciferase Substances 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
241001529936 Murinae Species 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
208000031888 Mycoses Diseases 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
108091008648 NR7C Proteins 0.000 description 1
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
108010077850 Nuclear Localization Signals Proteins 0.000 description 1
102000007399 Nuclear hormone receptor Human genes 0.000 description 1
108020005497 Nuclear hormone receptor Proteins 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
240000007594 Oryza sativa Species 0.000 description 1
235000007164 Oryza sativa Nutrition 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
108010016731 PPAR gamma Proteins 0.000 description 1
206010033645 Pancreatitis Diseases 0.000 description 1
206010033647 Pancreatitis acute Diseases 0.000 description 1
206010033649 Pancreatitis chronic Diseases 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [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
229910002666 PdCl2 Inorganic materials 0.000 description 1
102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
208000020424 Polyglandular disease Diseases 0.000 description 1
208000006994 Precancerous Conditions Diseases 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
206010060862 Prostate cancer Diseases 0.000 description 1
208000000236 Prostatic Neoplasms Diseases 0.000 description 1
102000001708 Protein Isoforms Human genes 0.000 description 1
108010029485 Protein Isoforms Proteins 0.000 description 1
102000052575 Proto-Oncogene Human genes 0.000 description 1
108700020978 Proto-Oncogene Proteins 0.000 description 1
108010001859 Proto-Oncogene Proteins c-rel Proteins 0.000 description 1
102000000850 Proto-Oncogene Proteins c-rel Human genes 0.000 description 1
201000001263 Psoriatic Arthritis Diseases 0.000 description 1
208000036824 Psoriatic arthropathy Diseases 0.000 description 1
101800001554 RNA-directed RNA polymerase Proteins 0.000 description 1
241000700159 Rattus Species 0.000 description 1
108700008625 Reporter Genes Proteins 0.000 description 1
206010039085 Rhinitis allergic Diseases 0.000 description 1
108010073443 Ribi adjuvant Proteins 0.000 description 1
PQUGCKBLVKJMNT-UHFFFAOYSA-N SC560 Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(C(F)(F)F)=N1 PQUGCKBLVKJMNT-UHFFFAOYSA-N 0.000 description 1
101150055528 SPAM1 gene Proteins 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
229920002125 Sokalan® Polymers 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
241000282887 Suidae Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
206010043189 Telangiectasia Diseases 0.000 description 1
ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
229920001615 Tragacanth Polymers 0.000 description 1
235000021307 Triticum Nutrition 0.000 description 1
244000098338 Triticum aestivum Species 0.000 description 1
108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 1
102100040247 Tumor necrosis factor Human genes 0.000 description 1
102000006275 Ubiquitin-Protein Ligases Human genes 0.000 description 1
108010083111 Ubiquitin-Protein Ligases Proteins 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
208000024780 Urticaria Diseases 0.000 description 1
102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 1
208000036142 Viral infection Diseases 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
JVVXZOOGOGPDRZ-SLFFLAALSA-N [(1R,4aS,10aR)-1,4a-dimethyl-7-propan-2-yl-2,3,4,9,10,10a-hexahydrophenanthren-1-yl]methanamine Chemical compound NC[C@]1(C)CCC[C@]2(C)C3=CC=C(C(C)C)C=C3CC[C@H]21 JVVXZOOGOGPDRZ-SLFFLAALSA-N 0.000 description 1
SAFSECRCYPBHDL-UHFFFAOYSA-N [1,3]benzothiazolo[4,5-h]quinoline Chemical class C1=CC2=CC=CN=C2C2=C1C(N=CS1)=C1C=C2 SAFSECRCYPBHDL-UHFFFAOYSA-N 0.000 description 1
MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
229960004748 abacavir Drugs 0.000 description 1
229940124532 absorption promoter Drugs 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
GPWHDDKQSYOYBF-UHFFFAOYSA-N ac1l2u0q Chemical compound Br[Br-]Br GPWHDDKQSYOYBF-UHFFFAOYSA-N 0.000 description 1
235000010489 acacia gum Nutrition 0.000 description 1
239000000205 acacia gum Substances 0.000 description 1
SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
150000001242 acetic acid derivatives Chemical class 0.000 description 1
150000008043 acidic salts Chemical class 0.000 description 1
125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
201000003229 acute pancreatitis Diseases 0.000 description 1
238000007259 addition reaction Methods 0.000 description 1
229940121359 adenosine receptor antagonist Drugs 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical class OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 1
210000004100 adrenal gland Anatomy 0.000 description 1
208000017515 adrenocortical insufficiency Diseases 0.000 description 1
230000002411 adverse Effects 0.000 description 1
239000008272 agar Substances 0.000 description 1
235000010419 agar Nutrition 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
125000005234 alkyl aluminium group Chemical group 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
208000026935 allergic disease Diseases 0.000 description 1
201000010105 allergic rhinitis Diseases 0.000 description 1
230000007815 allergy Effects 0.000 description 1
231100000360 alopecia Toxicity 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
229940024546 aluminum hydroxide gel Drugs 0.000 description 1
SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000000540 analysis of variance Methods 0.000 description 1
210000003484 anatomy Anatomy 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000006368 anti-apoptosis response Effects 0.000 description 1
230000000947 anti-immunosuppressive effect Effects 0.000 description 1
229940124599 anti-inflammatory drug Drugs 0.000 description 1
230000000692 anti-sense effect Effects 0.000 description 1
229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
150000001502 aryl halides Chemical class 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
125000003289 ascorbyl group Chemical class [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-L aspartate group Chemical class N[C@@H](CC(=O)[O-])C(=O)[O-] CKLJMWTZIZZHCS-REOHCLBHSA-L 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
201000008937 atopic dermatitis Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000001363 autoimmune Effects 0.000 description 1
230000035578 autophosphorylation Effects 0.000 description 1
125000002785 azepinyl group Chemical group 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
238000010009 beating Methods 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000001185 bone marrow Anatomy 0.000 description 1
230000024279 bone resorption Effects 0.000 description 1
208000029028 brain injury Diseases 0.000 description 1
210000000133 brain stem Anatomy 0.000 description 1
FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical class BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 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
150000004648 butanoic acid derivatives Chemical class 0.000 description 1
210000004899 c-terminal region Anatomy 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical class C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
239000003560 cancer drug Substances 0.000 description 1
230000036952 cancer formation Effects 0.000 description 1
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
125000006243 carbonyl protecting group Chemical group 0.000 description 1
231100000504 carcinogenesis Toxicity 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
239000000969 carrier Substances 0.000 description 1
210000000845 cartilage Anatomy 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
229960000590 celecoxib Drugs 0.000 description 1
239000013592 cell lysate Substances 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
230000033077 cellular process Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
229940124587 cephalosporin Drugs 0.000 description 1
150000001780 cephalosporins Chemical class 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
KFIFSKNSIUVOCG-UHFFFAOYSA-N chembl230185 Chemical compound N=1C2=CC3=CC=CC=C3C=C2N2C(C)=CN=C2C=1NCCN1CCCCC1 KFIFSKNSIUVOCG-UHFFFAOYSA-N 0.000 description 1
UOQMKZIYNRHZEF-UHFFFAOYSA-N chembl231530 Chemical compound C1=CC=C2C=C(N3C(C(NC)=N4)=NC=C3C)C4=CC2=C1 UOQMKZIYNRHZEF-UHFFFAOYSA-N 0.000 description 1
239000013043 chemical agent Substances 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
210000000038 chest Anatomy 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
CZKMPDNXOGQMFW-UHFFFAOYSA-N chloro(triethyl)germane Chemical compound CC[Ge](Cl)(CC)CC CZKMPDNXOGQMFW-UHFFFAOYSA-N 0.000 description 1
125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
229940125797 compound 12 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
229940125833 compound 23 Drugs 0.000 description 1
229940125846 compound 25 Drugs 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
208000010247 contact dermatitis Diseases 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
210000004087 cornea Anatomy 0.000 description 1
125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
229940097362 cyclodextrins Drugs 0.000 description 1
ARUKYTASOALXFG-UHFFFAOYSA-N cycloheptylcycloheptane Chemical compound C1CCCCCC1C1CCCCCC1 ARUKYTASOALXFG-UHFFFAOYSA-N 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
231100000433 cytotoxic Toxicity 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
229960000975 daunorubicin Drugs 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000002950 deficient Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
230000005595 deprotonation Effects 0.000 description 1
238000010537 deprotonation reaction Methods 0.000 description 1
201000001981 dermatomyositis Diseases 0.000 description 1
239000002274 desiccant Substances 0.000 description 1
238000001514 detection method Methods 0.000 description 1
229960003957 dexamethasone Drugs 0.000 description 1
UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
229960002086 dextran Drugs 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
238000006193 diazotization reaction Methods 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
MQYQOVYIJOLTNX-UHFFFAOYSA-N dichloromethane;n,n-dimethylformamide Chemical group ClCCl.CN(C)C=O MQYQOVYIJOLTNX-UHFFFAOYSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
102000038379 digestive enzymes Human genes 0.000 description 1
108091007734 digestive enzymes Proteins 0.000 description 1
125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical class CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
239000003651 drinking water Substances 0.000 description 1
235000020188 drinking water Nutrition 0.000 description 1
239000000890 drug combination Substances 0.000 description 1
229940126534 drug product Drugs 0.000 description 1
210000000624 ear auricle Anatomy 0.000 description 1
238000001962 electrophoresis Methods 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
231100000317 environmental toxin Toxicity 0.000 description 1
238000001952 enzyme assay Methods 0.000 description 1
239000002532 enzyme inhibitor Substances 0.000 description 1
210000000981 epithelium Anatomy 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical class CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
ZYBWTEQKHIADDQ-UHFFFAOYSA-N ethanol;methanol Chemical compound OC.CCO ZYBWTEQKHIADDQ-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
VLDUBDZWWNLZCU-UHFFFAOYSA-N ethyl 5-methyl-1h-imidazole-4-carboxylate Chemical compound CCOC(=O)C=1NC=NC=1C VLDUBDZWWNLZCU-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
RIKMMFOAQPJVMX-UHFFFAOYSA-N fomepizole Chemical compound CC=1C=NNC=1 RIKMMFOAQPJVMX-UHFFFAOYSA-N 0.000 description 1
229960004285 fomepizole Drugs 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
230000037406 food intake Effects 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 description 1
125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
108020001507 fusion proteins Proteins 0.000 description 1
102000037865 fusion proteins Human genes 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000000762 glandular Effects 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
150000002315 glycerophosphates Chemical class 0.000 description 1
QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
238000000227 grinding Methods 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
230000036541 health Effects 0.000 description 1
210000005003 heart tissue Anatomy 0.000 description 1
MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical class CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
239000000833 heterodimer Substances 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical class CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
210000004124 hock Anatomy 0.000 description 1
238000009396 hybridization Methods 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
206010020718 hyperplasia Diseases 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
239000005457 ice water Substances 0.000 description 1
238000010191 image analysis Methods 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
102000018358 immunoglobulin Human genes 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
229940124589 immunosuppressive drug Drugs 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000000099 in vitro assay Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
238000011645 inflammation animal model Methods 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
108091006086 inhibitor proteins Proteins 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
239000007928 intraperitoneal injection Substances 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
239000006207 intravenous dosage form Substances 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 1
230000026045 iodination Effects 0.000 description 1
238000006192 iodination reaction Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
229910052742 iron Inorganic materials 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical class OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000003971 isoxazolinyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
229960000681 leflunomide Drugs 0.000 description 1
230000003902 lesion Effects 0.000 description 1
150000002617 leukotrienes Chemical class 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
239000002502 liposome Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
230000033001 locomotion Effects 0.000 description 1
239000008176 lyophilized powder Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229910001629 magnesium chloride Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
229940057948 magnesium stearate Drugs 0.000 description 1
150000002688 maleic acid derivatives Chemical class 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
229960004963 mesalazine Drugs 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
GWJVQQSRDYMGDC-UHFFFAOYSA-N methyl 3-(3-methylimidazol-4-yl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=CC2=CC=CC=C2C=C1C1=CN=CN1C GWJVQQSRDYMGDC-UHFFFAOYSA-N 0.000 description 1
PAUIXQJXAOSPHP-UHFFFAOYSA-N methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalene-2-carboxylate Chemical compound COC(=O)C1=CC2=CC=CC=C2C=C1B1OC(C)(C)C(C)(C)O1 PAUIXQJXAOSPHP-UHFFFAOYSA-N 0.000 description 1
HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000000329 molecular dynamics simulation Methods 0.000 description 1
238000012806 monitoring device Methods 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
229940035032 monophosphoryl lipid a Drugs 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
229960000951 mycophenolic acid Drugs 0.000 description 1
HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
201000005962 mycosis fungoides Diseases 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
239000007922 nasal spray Substances 0.000 description 1
210000005170 neoplastic cell Anatomy 0.000 description 1
230000004770 neurodegeneration Effects 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
210000000440 neutrophil Anatomy 0.000 description 1
150000002814 niacins Chemical class 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
239000012457 nonaqueous media Substances 0.000 description 1
231100000956 nontoxicity Toxicity 0.000 description 1
108020004017 nuclear receptors Proteins 0.000 description 1
238000010534 nucleophilic substitution reaction Methods 0.000 description 1
239000002773 nucleotide Substances 0.000 description 1
125000003729 nucleotide group Chemical group 0.000 description 1
239000002674 ointment Substances 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
230000000771 oncological effect Effects 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
150000002902 organometallic compounds Chemical class 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
150000003901 oxalic acid esters Chemical class 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000003566 oxetanyl group Chemical group 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
LVSJDHGRKAEGLX-UHFFFAOYSA-N oxolane;2,2,2-trifluoroacetic acid Chemical compound C1CCOC1.OC(=O)C(F)(F)F LVSJDHGRKAEGLX-UHFFFAOYSA-N 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
229940094443 oxytocics prostaglandins Drugs 0.000 description 1
MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
210000000496 pancreas 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
239000008188 pellet Substances 0.000 description 1
239000003961 penetration enhancing agent Substances 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
JRKICGRDRMAZLK-UHFFFAOYSA-L persulfate group Chemical group S(=O)(=O)([O-])OOS(=O)(=O)[O-] JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 description 1
229940031826 phenolate Drugs 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
150000004714 phosphonium salts Chemical class 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
230000000865 phosphorylative effect Effects 0.000 description 1
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 1
OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical class OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 1
239000000049 pigment Substances 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000005547 pivalate group Chemical group 0.000 description 1
230000036470 plasma concentration Effects 0.000 description 1
229920002401 polyacrylamide Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
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 description 1
229960004618 prednisone Drugs 0.000 description 1
125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012746 preparative thin layer chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
229940072288 prograf Drugs 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
230000004850 protein–protein interaction Effects 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
230000010349 pulsation Effects 0.000 description 1
238000000746 purification Methods 0.000 description 1
239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000002755 pyrazolinyl group Chemical group 0.000 description 1
ONCMJWSDNCJMLL-UHFFFAOYSA-N pyrazolo[1,5-c]quinazoline Chemical compound C12=CC=CC=C2N=CN2C1=CC=N2 ONCMJWSDNCJMLL-UHFFFAOYSA-N 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000006085 pyrrolopyridyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
SAEMKKTVBSCOFX-UHFFFAOYSA-N quinoxalin-1-ium;chloride Chemical compound Cl.N1=CC=NC2=CC=CC=C21 SAEMKKTVBSCOFX-UHFFFAOYSA-N 0.000 description 1
SEPKUNXLGWMPHL-UHFFFAOYSA-N quinoxaline-2,3-dione Chemical class C1=CC=CC2=NC(=O)C(=O)N=C21 SEPKUNXLGWMPHL-UHFFFAOYSA-N 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
230000005855 radiation Effects 0.000 description 1
229940099538 rapamune Drugs 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
201000004335 respiratory allergy Diseases 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
238000003757 reverse transcription PCR Methods 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
229960000371 rofecoxib Drugs 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
235000004400 serine Nutrition 0.000 description 1
150000003355 serines Chemical class 0.000 description 1
206010040400 serum sickness Diseases 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229940054269 sodium pyruvate Drugs 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000012439 solid excipient Substances 0.000 description 1
230000003381 solubilizing effect Effects 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000011272 standard treatment Methods 0.000 description 1
229940032147 starch Drugs 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
208000024891 symptom Diseases 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
230000002194 synthesizing effect Effects 0.000 description 1
239000012622 synthetic inhibitor Substances 0.000 description 1
238000007910 systemic administration Methods 0.000 description 1
230000001839 systemic circulation Effects 0.000 description 1
229960001967 tacrolimus Drugs 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
230000008685 targeting Effects 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
208000009056 telangiectasis Diseases 0.000 description 1
LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
229960003676 tenidap Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
HQOJMTATBXYHNR-UHFFFAOYSA-M thallium(I) acetate Chemical compound [Tl+].CC([O-])=O HQOJMTATBXYHNR-UHFFFAOYSA-M 0.000 description 1
231100001274 therapeutic index Toxicity 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000006090 thiamorpholinyl sulfone group Chemical group 0.000 description 1
125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003555 thioacetals Chemical class 0.000 description 1
150000003567 thiocyanates Chemical class 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
108091006106 transcriptional activators Proteins 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
150000003626 triacylglycerols Chemical class 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
JQKHNBQZGUKYPX-UHFFFAOYSA-N tris(2,4,6-trimethoxyphenyl)phosphane Chemical compound COC1=CC(OC)=CC(OC)=C1P(C=1C(=CC(OC)=CC=1OC)OC)C1=C(OC)C=C(OC)C=C1OC JQKHNBQZGUKYPX-UHFFFAOYSA-N 0.000 description 1
DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
102000003298 tumor necrosis factor receptor Human genes 0.000 description 1
238000009281 ultraviolet germicidal irradiation Methods 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical class CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
230000009385 viral infection Effects 0.000 description 1
239000003643 water by type Substances 0.000 description 1
230000003442 weekly effect Effects 0.000 description 1
238000005303 weighing Methods 0.000 description 1
238000001262 western blot Methods 0.000 description 1
238000009736 wetting Methods 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
238000001086 yeast two-hybrid system Methods 0.000 description 1
AIFRHYZBTHREPW-UHFFFAOYSA-N β-carboline Chemical class N1=CC=C2C3=CC=CC=C3NC2=C1 AIFRHYZBTHREPW-UHFFFAOYSA-N 0.000 description 1

Classifications

- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- 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
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Landscapes

Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Immunology (AREA)
Neurology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Epidemiology (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pain & Pain Management (AREA)
Psychology (AREA)
Surgery (AREA)
Transplantation (AREA)
Vascular Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA002436770A 2001-02-01 2002-02-01 Methods of treating inflammatory and immune diseases using inhibitors of ikb kinase (ikk) Abandoned CA2436770A1 (en)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US26585301P	2001-02-01	2001-02-01
US60/265,853		2001-02-01
US09/965,977 US6960585B2 (en)	2000-10-03	2001-09-27	Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same
US09/965,977		2001-09-27
PCT/US2002/003060 WO2002060386A2 (en)	2001-02-01	2002-02-01	METHODS OF TREATING INFLAMMATORY AND IMMUNE DISEASES USING INHIBITORS OF IλB KINASE (IKK)

Publications (1)

Publication Number	Publication Date
CA2436770A1 true CA2436770A1 (en)	2002-08-08

Family

ID=26951465

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002436770A Abandoned CA2436770A1 (en)	2001-02-01	2002-02-01	Methods of treating inflammatory and immune diseases using inhibitors of ikb kinase (ikk)

Country Status (10)

Country	Link
EP (1)	EP1363993A4 (cs)
JP (1)	JP2004529088A (cs)
AU (1)	AU2002247059B2 (cs)
CA (1)	CA2436770A1 (cs)
CZ (1)	CZ20032287A3 (cs)
HU (1)	HUP0304045A3 (cs)
MX (1)	MXPA03006817A (cs)
NO (1)	NO20033429L (cs)
PL (1)	PL364111A1 (cs)
WO (1)	WO2002060386A2 (cs)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2424303A1 (en) *	2000-10-03	2002-04-11	Bristol-Myers Squibb Company	Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same
ES2305125T3 (es)	2000-10-26	2008-11-01	Amgen Inc.	Agentes anti-inflamatorios.
AR037641A1 (es)	2001-12-05	2004-11-17	Tularik Inc	Moduladores de inflamacion
DE10237722A1 (de)	2002-08-17	2004-08-19	Aventis Pharma Deutschland Gmbh	Indol- oder Benzimidazolderivate zur Modulation der IKappaB-Kinase
WO2004041285A1 (en)	2002-10-31	2004-05-21	Amgen Inc.	Antiinflammation agents
AR050253A1 (es)	2004-06-24	2006-10-11	Smithkline Beecham Corp	Compuesto derivado de indazol carboxamida, composicion que lo comprende y su uso para la preparacion de un medicamento
PE20060748A1 (es)	2004-09-21	2006-10-01	Smithkline Beecham Corp	Derivados de indolcarboxamida como inhibidores de quinasa ikk2
AR055343A1 (es)	2005-06-30	2007-08-22	Smithkline Beecham Corp	Derivados de indolcarboxamida inhibidores de quinasas ikk2
US8063071B2 (en)	2007-10-31	2011-11-22	GlaxoSmithKline, LLC	Chemical compounds
AU2006287767B2 (en) *	2005-09-07	2010-05-13	Merck Serono Sa	IKK inhibitors for the treatment of endometriosis
US20090175852A1 (en)	2006-06-06	2009-07-09	Schering Corporation	Imidazopyrazines as protein kinase inhibitors
US8299080B2 (en) *	2006-12-13	2012-10-30	Aska Pharmaceutical Co., Ltd.	Substituted imidazo[1,5-A] quinoxalines as a PDE9 inhibitor
PE20081889A1 (es)	2007-03-23	2009-03-05	Smithkline Beecham Corp	Indol carboxamidas como inhibidores de ikk2
US11969501B2 (en)	2008-04-21	2024-04-30	Dompé Farmaceutici S.P.A.	Auris formulations for treating otic diseases and conditions
EP2278999B1 (en)	2008-04-21	2025-01-29	Dompé farmaceutici S.p.A.	Auris formulations for treating otic diseases and conditions
WO2010000903A2 (es) *	2008-06-30	2010-01-07	Centro De Investigaciones Energéticas, Medioambientales Y Tecnológicas (Ciemat)	Composición capaz de modular la actividad de ikkalpha para el tratamiento de enfermedades que cursan con acantolisis
EP2366699B1 (en)	2008-10-02	2013-08-07	Asahi Kasei Pharma Corporation	8-substituted isoquinoline derivative and use thereof
WO2010102968A1 (en)	2009-03-10	2010-09-16	Glaxo Group Limited	Indole derivatives as ikk2 inhibitors
AU2017290256A1 (en)	2016-06-29	2019-01-17	Otonomy, Inc.	Triglyceride otic formulations and uses thereof
EP3494994A1 (en) *	2017-12-07	2019-06-12	Universität zu Köln	Combinations of ripk1- and ikk-inhibitors for the prevention or treatment of immune diseases

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4160097A (en) *	1977-01-07	1979-07-03	Westwind Pharmaceuticals, Inc.	1-(2-Phenylureylene)imidazoles
US5851812A (en) *	1997-07-01	1998-12-22	Tularik Inc.	IKK-β proteins, nucleic acids and methods
US6235740B1 (en) *	1997-08-25	2001-05-22	Bristol-Myers Squibb Co.	Imidazoquinoxaline protein tyrosine kinase inhibitors
US6030834A (en) *	1997-12-30	2000-02-29	Chiron Corporation	Human IKK-beta DNA constructs and cells
GB0003154D0 (en) *	2000-02-12	2000-04-05	Astrazeneca Uk Ltd	Novel compounds
HK1054039B (zh) *	2000-03-15	2010-04-16	萨诺费－阿文蒂斯德国有限公司	取代的β-咔啉
CA2424303A1 (en) *	2000-10-03	2002-04-11	Bristol-Myers Squibb Company	Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same

2002
- 2002-02-01 PL PL02364111A patent/PL364111A1/xx not_active Application Discontinuation
- 2002-02-01 HU HU0304045A patent/HUP0304045A3/hu unknown
- 2002-02-01 EP EP02714815A patent/EP1363993A4/en not_active Withdrawn
- 2002-02-01 CZ CZ20032287A patent/CZ20032287A3/cs unknown
- 2002-02-01 WO PCT/US2002/003060 patent/WO2002060386A2/en not_active Ceased
- 2002-02-01 JP JP2002560582A patent/JP2004529088A/ja active Pending
- 2002-02-01 AU AU2002247059A patent/AU2002247059B2/en not_active Ceased
- 2002-02-01 MX MXPA03006817A patent/MXPA03006817A/es active IP Right Grant
- 2002-02-01 CA CA002436770A patent/CA2436770A1/en not_active Abandoned
2003
- 2003-07-31 NO NO20033429A patent/NO20033429L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
HUP0304045A3 (en)	2005-05-30
EP1363993A2 (en)	2003-11-26
JP2004529088A (ja)	2004-09-24
MXPA03006817A (es)	2003-11-13
AU2002247059B2 (en)	2006-11-16
NO20033429L (no)	2003-09-24
HUP0304045A2 (hu)	2004-04-28
NO20033429D0 (no)	2003-07-31
WO2002060386A3 (en)	2002-10-10
CZ20032287A3 (cs)	2004-02-18
WO2002060386A2 (en)	2002-08-08
PL364111A1 (en)	2004-12-13
EP1363993A4 (en)	2008-11-12

Legal Events

Date	Code	Title	Description
2007-01-24	EEER	Examination request
2010-02-01	FZDE	Discontinued

Publication	Publication Date	Title
US6869956B2 (en)	2005-03-22	Methods of treating inflammatory and immune diseases using inhibitors of IκB kinase (IKK)
AU2002247059B2 (en)	2006-11-16	Method of treating inflammatory and immune diseases using inhibitors of IkappaB kinase (IKK)
AU2002247059A1 (en)	2003-02-20	Method of treating inflammatory and immune diseases using inhibitors of IkappaB kinase (IKK)
US9890153B2 (en)	2018-02-13	Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors
EP1325009B1 (en)	2006-03-08	Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same
CN106232583B (zh)	2020-04-24	用于抑制肌成束蛋白的化合物和方法
AU2002211827A1 (en)	2002-06-27	Amino-substituted tetracyclic compounds useful as anti-inflammatory agents and pharmaceutical compositions comprising same
CA2666360C (en)	2014-12-09	An alzheimer's disease progression inhibitor containing heterocyclic compound having specific structure
CN103582478A (zh)	2014-02-12	治疗神经退行性疾病的方法和组合物
KR20170103838A (ko)	2017-09-13	염증 및 암의 치료를 위한 헤테로시클릭 itk 저해제
CN101511837A (zh)	2009-08-19	用于药物组合物的吡咯并嘧啶
CN103596568A (zh)	2014-02-19	治疗帕金森病的方法以及组合物
JP2013509442A (ja)	2013-03-14	サーチュイン調節因子としての二環式ピリジンおよび類似体
TW200946521A (en)	2009-11-16	Compounds useful as inhibitors of ROCK kinases
CN104736202A (zh)	2015-06-24	用于抑制肌成束蛋白的方法
US10316038B2 (en)	2019-06-11	Pyrrolopyrimidine ITK inhibitors for treating inflammation and cancer
WO2018236971A1 (en)	2018-12-27	Single molecule compounds providing multi-target inhibition of parp and other proteins and methods of use thereof
TW200825083A (en)	2008-06-16	Novel fluorene derivatives, compositions containing them and use thereof
Asif et al.	2013	Anticonvulsant and Antitubercular Activities of 6-Phenyl/Biphenyl-4-yl-2-[2-(pyridin-2-ylamino)-ethyl]-and 6-(Biphenyl-4yl)-2-(2N-subtituted amin-1-yl)-ethyl derivatives of 4, 5-dihydropyridazin-3 (2H)-one
CN120092010A (zh)	2025-06-03	多环类聚（adp核糖）聚合酶选择性抑制剂
JP2008521855A (ja)	2008-06-26	新規ピリドチエノピリミジン誘導体
EP4229055B1 (en)	2026-03-04	Compounds and compositions for the treatment of cryptosporidiosis
AU2007200555A1 (en)	2007-03-01	Methods of treating inflammatory and immune diseases using inhibitors of IKappaB kinase (IKK)
WO2024223907A1 (en)	2024-10-31	1,2,4-triazole-3-thione inhibitors of trex2 for use in the treatment of psoriasis, atopic dermatitis or ichthyosis
JPS61118386A (ja)	1986-06-05	トリアゾロキノリン誘導体