CA3038106A1

CA3038106A1 - Compounds and methods for treating lupus

Compounds and methods for treating lupus Download PDF

Info

Publication number: CA3038106A1
Authority: CA; Canada
Prior art keywords: alkyl; compound; occurrence; cooh; groups
Prior art date: 2016-09-29
Legal status : Pending

Application number

CA3038106A

Other languages

English (en)

French (fr)

Inventor

Fiona Lorraine Scott

Kristen R. Taylor Meadows

Robert Peach

Current Assignee

Receptos LLC

Original Assignee

Celgene International II SARL

Priority date

2016-09-29

Filing date

2017-09-28

Publication date

2018-04-05

2017-09-28 Application filed by Celgene International II SARL filed Critical Celgene International II SARL

2018-04-05 Publication of CA3038106A1 publication Critical patent/CA3038106A1/en

Status Pending legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 50
150000001875 compounds Chemical class 0.000 title claims description 184
206010025135 lupus erythematosus Diseases 0.000 title abstract description 9
239000000203 mixture Substances 0.000 claims abstract description 21
201000000596 systemic lupus erythematosus Diseases 0.000 claims abstract description 13
-1 cyclobutinyl Chemical group 0.000 claims description 150
108090000623 proteins and genes Proteins 0.000 claims description 55
125000000217 alkyl group Chemical group 0.000 claims description 54
150000003839 salts Chemical class 0.000 claims description 52
230000014509 gene expression Effects 0.000 claims description 49
125000005842 heteroatom Chemical group 0.000 claims description 49
125000000623 heterocyclic group Chemical group 0.000 claims description 45
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 44
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 37
229910052799 carbon Inorganic materials 0.000 claims description 23
229940125898 compound 5 Drugs 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 21
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
125000005843 halogen group Chemical group 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
239000012453 solvate Substances 0.000 claims description 17
125000002883 imidazolyl group Chemical group 0.000 claims description 15
125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000002757 morpholinyl group Chemical group 0.000 claims description 14
125000003386 piperidinyl group Chemical group 0.000 claims description 14
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
125000001424 substituent group Chemical group 0.000 claims description 13
230000003247 decreasing effect Effects 0.000 claims description 12
230000003287 optical effect Effects 0.000 claims description 12
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 11
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
230000028993 immune response Effects 0.000 claims description 9
125000004193 piperazinyl group Chemical group 0.000 claims description 9
206010016654 Fibrosis Diseases 0.000 claims description 8
230000004761 fibrosis Effects 0.000 claims description 8
102100035405 Neutrophil gelatinase-associated lipocalin Human genes 0.000 claims description 7
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
125000003226 pyrazolyl group Chemical group 0.000 claims description 7
125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
125000002393 azetidinyl group Chemical group 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
102100032367 C-C motif chemokine 5 Human genes 0.000 claims description 4
102100025248 C-X-C motif chemokine 10 Human genes 0.000 claims description 4
102100036170 C-X-C motif chemokine 9 Human genes 0.000 claims description 4
102100036769 Girdin Human genes 0.000 claims description 4
101710199302 Girdin Proteins 0.000 claims description 4
101000797762 Homo sapiens C-C motif chemokine 5 Proteins 0.000 claims description 4
101000858088 Homo sapiens C-X-C motif chemokine 10 Proteins 0.000 claims description 4
101000947172 Homo sapiens C-X-C motif chemokine 9 Proteins 0.000 claims description 4
101001043321 Homo sapiens Lysyl oxidase homolog 1 Proteins 0.000 claims description 4
108010051335 Lipocalin-2 Proteins 0.000 claims description 4
102100021958 Lysyl oxidase homolog 1 Human genes 0.000 claims description 4
102100031013 Transgelin Human genes 0.000 claims description 4
108090000333 Transgelin Proteins 0.000 claims description 4
101001023833 Homo sapiens Neutrophil gelatinase-associated lipocalin Proteins 0.000 claims description 3
101000652736 Homo sapiens Transgelin Proteins 0.000 claims description 3
102000009618 Transforming Growth Factors Human genes 0.000 claims description 3
108010009583 Transforming Growth Factors Proteins 0.000 claims description 3
102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 claims description 3
101710181056 Tumor necrosis factor ligand superfamily member 13B Proteins 0.000 claims description 3
102000005353 Tissue Inhibitor of Metalloproteinase-1 Human genes 0.000 claims description 2
125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
108010002352 Interleukin-1 Proteins 0.000 claims 1
101150077804 TIMP1 gene Proteins 0.000 claims 1
238000011282 treatment Methods 0.000 abstract description 56
102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 abstract description 4
108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 abstract description 4
241000699670 Mus sp. Species 0.000 description 66
230000009467 reduction Effects 0.000 description 61
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 51
229960004397 cyclophosphamide Drugs 0.000 description 51
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 46
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 45
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 33
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 29
210000001744 T-lymphocyte Anatomy 0.000 description 28
239000011541 reaction mixture Substances 0.000 description 27
102000005962 receptors Human genes 0.000 description 24
108020003175 receptors Proteins 0.000 description 24
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
210000003734 kidney Anatomy 0.000 description 22
210000002966 serum Anatomy 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
201000001474 proteinuria Diseases 0.000 description 21
125000003118 aryl group Chemical group 0.000 description 20
125000004432 carbon atom Chemical group C* 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
239000007787 solid Substances 0.000 description 19
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 18
238000005481 NMR spectroscopy Methods 0.000 description 17
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 17
101150041968 CDC13 gene Proteins 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
210000003719 b-lymphocyte Anatomy 0.000 description 16
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
125000001072 heteroaryl group Chemical group 0.000 description 15
239000000243 solution Substances 0.000 description 15
210000004988 splenocyte Anatomy 0.000 description 15
102000006992 Interferon-alpha Human genes 0.000 description 14
108010047761 Interferon-alpha Proteins 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
230000003902 lesion Effects 0.000 description 14
102000004169 proteins and genes Human genes 0.000 description 14
210000000952 spleen Anatomy 0.000 description 14
125000000753 cycloalkyl group Chemical group 0.000 description 13
230000000694 effects Effects 0.000 description 13
210000005134 plasmacytoid dendritic cell Anatomy 0.000 description 13
239000002253 acid Substances 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
238000012360 testing method Methods 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
241001465754 Metazoa Species 0.000 description 11
150000001412 amines Chemical class 0.000 description 11
238000003757 reverse transcription PCR Methods 0.000 description 11
125000003545 alkoxy group Chemical group 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
239000011734 sodium Substances 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
108020004999 messenger RNA Proteins 0.000 description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
229910019142 PO4 Inorganic materials 0.000 description 8
230000037396 body weight Effects 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
201000010099 disease Diseases 0.000 description 8
231100000853 glomerular lesion Toxicity 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
238000010172 mouse model Methods 0.000 description 8
239000010452 phosphate Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
239000002904 solvent Substances 0.000 description 8
229910052717 sulfur Inorganic materials 0.000 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
239000000556 agonist Substances 0.000 description 7
125000003342 alkenyl group Chemical group 0.000 description 7
125000004429 atom Chemical group 0.000 description 7
239000000460 chlorine Substances 0.000 description 7
231100000673 dose–response relationship Toxicity 0.000 description 7
125000001041 indolyl group Chemical group 0.000 description 7
230000002757 inflammatory effect Effects 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
238000001543 one-way ANOVA Methods 0.000 description 7
238000000746 purification Methods 0.000 description 7
229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
235000017557 sodium bicarbonate Nutrition 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
125000001544 thienyl group Chemical group 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 6
238000009007 Diagnostic Kit Methods 0.000 description 6
101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 6
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
238000003556 assay Methods 0.000 description 6
239000002585 base Substances 0.000 description 6
239000012267 brine Substances 0.000 description 6
238000004296 chiral HPLC Methods 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
125000000392 cycloalkenyl group Chemical group 0.000 description 6
208000035475 disorder Diseases 0.000 description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
239000003446 ligand Substances 0.000 description 6
238000005259 measurement Methods 0.000 description 6
239000000523 sample Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000000725 suspension Substances 0.000 description 6
210000001266 CD8-positive T-lymphocyte Anatomy 0.000 description 5
206010061218 Inflammation Diseases 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
125000000304 alkynyl group Chemical group 0.000 description 5
150000001768 cations Chemical class 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
125000001475 halogen functional group Chemical group 0.000 description 5
230000004054 inflammatory process Effects 0.000 description 5
210000004698 lymphocyte Anatomy 0.000 description 5
239000000463 material Substances 0.000 description 5
230000001404 mediated effect Effects 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
239000011593 sulfur Substances 0.000 description 5
230000003442 weekly effect Effects 0.000 description 5
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
206010061818 Disease progression Diseases 0.000 description 4
238000002965 ELISA Methods 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 4
150000001408 amides Chemical class 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
230000005750 disease progression Effects 0.000 description 4
239000003814 drug Substances 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
230000003325 follicular Effects 0.000 description 4
125000002541 furyl group Chemical group 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 4
230000028709 inflammatory response Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
210000003563 lymphoid tissue Anatomy 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
YPHURAORAWVSCR-GOSISDBHSA-N n-(4-cyano-2,3-dihydroinden-1-ylidene)-2-methylpropane-2-sulfinamide Chemical compound C1=CC=C(C#N)C2=C1C(=N[S@](=O)C(C)(C)C)CC2 YPHURAORAWVSCR-GOSISDBHSA-N 0.000 description 4
239000003921 oil Substances 0.000 description 4
150000007524 organic acids Chemical class 0.000 description 4
210000004180 plasmocyte Anatomy 0.000 description 4
238000007363 ring formation reaction Methods 0.000 description 4
125000003107 substituted aryl group Chemical group 0.000 description 4
150000003457 sulfones Chemical class 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
125000000335 thiazolyl group Chemical group 0.000 description 4
210000002700 urine Anatomy 0.000 description 4
YPJMOVVQKBFRNH-UHFFFAOYSA-N 1-(9-ethylcarbazol-3-yl)-n-(pyridin-2-ylmethyl)methanamine Chemical compound C=1C=C2N(CC)C3=CC=CC=C3C2=CC=1CNCC1=CC=CC=N1 YPJMOVVQKBFRNH-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
101000810330 Arabidopsis thaliana Eukaryotic translation initiation factor 3 subunit E Proteins 0.000 description 3
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 3
208000023275 Autoimmune disease Diseases 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
102000008016 Eukaryotic Initiation Factor-3 Human genes 0.000 description 3
241000982822 Ficus obtusifolia Species 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
OUBORTRIKPEZMG-UHFFFAOYSA-N INT-2 Chemical compound Nc1c(ncn1-c1ccc(F)cc1)C(=N)C#N OUBORTRIKPEZMG-UHFFFAOYSA-N 0.000 description 3
102000014150 Interferons Human genes 0.000 description 3
108010050904 Interferons Proteins 0.000 description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
101100317378 Mus musculus Wnt3 gene Proteins 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
101000767160 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) Intracellular protein transport protein USO1 Proteins 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 3
102000003932 Transgelin Human genes 0.000 description 3
101001060278 Xenopus laevis Fibroblast growth factor 3 Proteins 0.000 description 3
239000012190 activator Substances 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
PQNFLJBBNBOBRQ-UHFFFAOYSA-N benzocyclopentane Natural products C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 3
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
238000005251 capillar electrophoresis Methods 0.000 description 3
125000002837 carbocyclic group Chemical group 0.000 description 3
150000001721 carbon Chemical class 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000003745 diagnosis Methods 0.000 description 3
229940113088 dimethylacetamide Drugs 0.000 description 3
229940079593 drug Drugs 0.000 description 3
238000000921 elemental analysis Methods 0.000 description 3
210000003743 erythrocyte Anatomy 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
238000000684 flow cytometry Methods 0.000 description 3
239000012458 free base Substances 0.000 description 3
230000001434 glomerular Effects 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
125000004415 heterocyclylalkyl group Chemical group 0.000 description 3
125000000842 isoxazolyl group Chemical group 0.000 description 3
150000007522 mineralic acids Chemical class 0.000 description 3
210000001616 monocyte Anatomy 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
125000002971 oxazolyl group Chemical group 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 3
239000002245 particle Substances 0.000 description 3
238000002360 preparation method Methods 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
125000000168 pyrrolyl group Chemical group 0.000 description 3
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
210000003289 regulatory T cell Anatomy 0.000 description 3
125000006413 ring segment Chemical group 0.000 description 3
230000019491 signal transduction Effects 0.000 description 3
230000011664 signaling Effects 0.000 description 3
238000003756 stirring Methods 0.000 description 3
LBHMMDUJKBJVQI-CYBMUJFWSA-N tert-butyl n-[(1r)-4-cyano-2,3-dihydro-1h-inden-1-yl]carbamate Chemical compound C1=CC=C(C#N)C2=C1[C@H](NC(=O)OC(C)(C)C)CC2 LBHMMDUJKBJVQI-CYBMUJFWSA-N 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 3
125000001425 triazolyl group Chemical group 0.000 description 3
108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
SCTBWJINDJVNDM-UHFFFAOYSA-N 1-oxo-2,3-dihydroindene-4-carbonitrile Chemical compound C1=CC=C(C#N)C2=C1C(=O)CC2 SCTBWJINDJVNDM-UHFFFAOYSA-N 0.000 description 2
WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 2
BTDQXGUEVVTAMD-UHFFFAOYSA-N 2-hydroxyethyl carbamate Chemical compound NC(=O)OCCO BTDQXGUEVVTAMD-UHFFFAOYSA-N 0.000 description 2
FQGLEMDXDTZJMJ-UHFFFAOYSA-N 3-cyano-4-propan-2-yloxybenzoic acid Chemical compound CC(C)OC1=CC=C(C(O)=O)C=C1C#N FQGLEMDXDTZJMJ-UHFFFAOYSA-N 0.000 description 2
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
108010017384 Blood Proteins Proteins 0.000 description 2
102000004506 Blood Proteins Human genes 0.000 description 2
238000000018 DNA microarray Methods 0.000 description 2
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
238000008157 ELISA kit Methods 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
206010018364 Glomerulonephritis Diseases 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 2
WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
101001046686 Homo sapiens Integrin alpha-M Proteins 0.000 description 2
101000852870 Homo sapiens Interferon alpha/beta receptor 1 Proteins 0.000 description 2
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
208000015580 Increased body weight Diseases 0.000 description 2
102100022338 Integrin alpha-M Human genes 0.000 description 2
108010086140 Interferon alpha-beta Receptor Proteins 0.000 description 2
102000007438 Interferon alpha-beta Receptor Human genes 0.000 description 2
102100036714 Interferon alpha/beta receptor 1 Human genes 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
101100348848 Mus musculus Notch4 gene Proteins 0.000 description 2
OKIZCWYLBDKLSU-UHFFFAOYSA-M N,N,N-Trimethylmethanaminium chloride Chemical compound [Cl-].C[N+](C)(C)C OKIZCWYLBDKLSU-UHFFFAOYSA-M 0.000 description 2
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
239000007832 Na2SO4 Substances 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
210000004286 T(FH) Anatomy 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000009471 action Effects 0.000 description 2
230000004913 activation Effects 0.000 description 2
125000005426 adeninyl group Chemical group N1=C(N=C2N=CNC2=C1N)* 0.000 description 2
230000001476 alcoholic effect Effects 0.000 description 2
125000003368 amide group Chemical group 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 2
230000000890 antigenic effect Effects 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
125000005602 azabenzimidazolyl group Chemical group 0.000 description 2
125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 2
125000005874 benzothiadiazolyl group Chemical group 0.000 description 2
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 2
239000000090 biomarker Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 2
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 2
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 2
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
230000008021 deposition Effects 0.000 description 2
229910052805 deuterium Inorganic materials 0.000 description 2
238000011161 development Methods 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
125000005879 dioxolanyl group Chemical group 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 2
229960000556 fingolimod Drugs 0.000 description 2
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 2
PTCGDEVVHUXTMP-UHFFFAOYSA-N flutolanil Chemical compound CC(C)OC1=CC=CC(NC(=O)C=2C(=CC=CC=2)C(F)(F)F)=C1 PTCGDEVVHUXTMP-UHFFFAOYSA-N 0.000 description 2
235000019253 formic acid Nutrition 0.000 description 2
DSLZVSRJTYRBFB-DUHBMQHGSA-N galactaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O DSLZVSRJTYRBFB-DUHBMQHGSA-N 0.000 description 2
210000001280 germinal center Anatomy 0.000 description 2
210000001102 germinal center b cell Anatomy 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
150000002367 halogens Chemical class 0.000 description 2
125000004446 heteroarylalkyl group Chemical group 0.000 description 2
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 2
230000006872 improvement Effects 0.000 description 2
YIAPLDFPUUJILH-UHFFFAOYSA-N indan-1-ol Chemical class C1=CC=C2C(O)CCC2=C1 YIAPLDFPUUJILH-UHFFFAOYSA-N 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
229940079322 interferon Drugs 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
125000005956 isoquinolyl group Chemical group 0.000 description 2
230000003907 kidney function Effects 0.000 description 2
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
210000004072 lung Anatomy 0.000 description 2
210000003826 marginal zone b cell Anatomy 0.000 description 2
239000013642 negative control Substances 0.000 description 2
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
150000002825 nitriles Chemical group 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
125000003367 polycyclic group Chemical group 0.000 description 2
239000013641 positive control Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
230000002206 pro-fibrotic effect Effects 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
125000005493 quinolyl group Chemical group 0.000 description 2
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 2
230000002285 radioactive effect Effects 0.000 description 2
238000011160 research Methods 0.000 description 2
238000010839 reverse transcription Methods 0.000 description 2
206010039073 rheumatoid arthritis Diseases 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
235000011152 sodium sulphate Nutrition 0.000 description 2
238000010186 staining Methods 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
125000000547 substituted alkyl group Chemical group 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
150000003462 sulfoxides Chemical class 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 2
125000003831 tetrazolyl group Chemical group 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
125000004927 thianaphthalenyl group Chemical group S1C(C=CC2=CC=CC=C12)* 0.000 description 2
239000010936 titanium Substances 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000004580 weight loss Effects 0.000 description 2
239000011701 zinc Substances 0.000 description 2
DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical group C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
125000003837 (C1-C20) alkyl group Chemical group 0.000 description 1
VMKAFJQFKBASMU-QGZVFWFLSA-N (r)-2-methyl-cbs-oxazaborolidine Chemical compound C([C@@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-QGZVFWFLSA-N 0.000 description 1
125000001359 1,2,3-triazol-4-yl group Chemical group [H]N1N=NC([*])=C1[H] 0.000 description 1
125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
QXQAPNSHUJORMC-UHFFFAOYSA-N 1-chloro-4-propylbenzene Chemical compound CCCC1=CC=C(Cl)C=C1 QXQAPNSHUJORMC-UHFFFAOYSA-N 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
FRPZMMHWLSIFAZ-UHFFFAOYSA-N 10-undecenoic acid Chemical compound OC(=O)CCCCCCCCC=C FRPZMMHWLSIFAZ-UHFFFAOYSA-N 0.000 description 1
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
125000004174 2-benzimidazolyl group Chemical group [H]N1C(*)=NC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 1
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
CESUXLKAADQNTB-SSDOTTSWSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@](N)=O CESUXLKAADQNTB-SSDOTTSWSA-N 0.000 description 1
CESUXLKAADQNTB-ZETCQYMHSA-N 2-methylpropane-2-sulfinamide Chemical compound CC(C)(C)[S@@](N)=O CESUXLKAADQNTB-ZETCQYMHSA-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
KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical compound OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
WDBQJSCPCGTAFG-QHCPKHFHSA-N 4,4-difluoro-N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-pyridin-3-ylpropyl]cyclohexane-1-carboxamide Chemical compound FC1(CCC(CC1)C(=O)N[C@@H](CCN1CCC(CC1)N1C(=NN=C1C)C(C)C)C=1C=NC=CC=1)F WDBQJSCPCGTAFG-QHCPKHFHSA-N 0.000 description 1
QCXJEYYXVJIFCE-UHFFFAOYSA-M 4-acetamidobenzoate Chemical compound CC(=O)NC1=CC=C(C([O-])=O)C=C1 QCXJEYYXVJIFCE-UHFFFAOYSA-M 0.000 description 1
WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
UVVYFYLSZIMKMC-UHFFFAOYSA-N 4-bromo-2,3-dihydroinden-1-one Chemical compound BrC1=CC=CC2=C1CCC2=O UVVYFYLSZIMKMC-UHFFFAOYSA-N 0.000 description 1
125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
KDDQRKBRJSGMQE-UHFFFAOYSA-N 4-thiazolyl Chemical group [C]1=CSC=N1 KDDQRKBRJSGMQE-UHFFFAOYSA-N 0.000 description 1
125000004539 5-benzimidazolyl group Chemical group N1=CNC2=C1C=CC(=C2)* 0.000 description 1
ODHCTXKNWHHXJC-VKHMYHEASA-N 5-oxo-L-proline Chemical compound OC(=O)[C@@H]1CCC(=O)N1 ODHCTXKNWHHXJC-VKHMYHEASA-N 0.000 description 1
CWDWFSXUQODZGW-UHFFFAOYSA-N 5-thiazolyl Chemical group [C]1=CN=CS1 CWDWFSXUQODZGW-UHFFFAOYSA-N 0.000 description 1
LCGTWRLJTMHIQZ-UHFFFAOYSA-N 5H-dibenzo[b,f]azepine Chemical compound C1=CC2=CC=CC=C2NC2=CC=CC=C21 LCGTWRLJTMHIQZ-UHFFFAOYSA-N 0.000 description 1
ZSMRRZONCYIFNB-UHFFFAOYSA-N 6,11-dihydro-5h-benzo[b][1]benzazepine Chemical compound C1CC2=CC=CC=C2NC2=CC=CC=C12 ZSMRRZONCYIFNB-UHFFFAOYSA-N 0.000 description 1
FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
208000006820 Arthralgia Diseases 0.000 description 1
206010003694 Atrophy Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
102100032912 CD44 antigen Human genes 0.000 description 1
PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
101100037762 Caenorhabditis elegans rnh-2 gene Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000283707 Capra Species 0.000 description 1
OKTJSMMVPCPJKN-OUBTZVSYSA-N Carbon-13 Chemical compound [13C] OKTJSMMVPCPJKN-OUBTZVSYSA-N 0.000 description 1
OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
241000282693 Cercopithecidae Species 0.000 description 1
206010008479 Chest Pain Diseases 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
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 1
AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
102100039621 Epithelial-stromal interaction protein 1 Human genes 0.000 description 1
JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
208000010201 Exanthema Diseases 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical group NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
108091006027 G proteins Proteins 0.000 description 1
102000030782 GTP binding Human genes 0.000 description 1
108091000058 GTP-Binding Proteins 0.000 description 1
DSLZVSRJTYRBFB-UHFFFAOYSA-N Galactaric acid Natural products OC(=O)C(O)C(O)C(O)C(O)C(O)=O DSLZVSRJTYRBFB-UHFFFAOYSA-N 0.000 description 1
IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 1
239000004471 Glycine Substances 0.000 description 1
229920002527 Glycogen Polymers 0.000 description 1
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical class OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 1
108090000288 Glycoproteins Proteins 0.000 description 1
102000003886 Glycoproteins Human genes 0.000 description 1
241001272567 Hominoidea Species 0.000 description 1
101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 1
101000814134 Homo sapiens Epithelial-stromal interaction protein 1 Proteins 0.000 description 1
101000926535 Homo sapiens Interferon-induced, double-stranded RNA-activated protein kinase Proteins 0.000 description 1
101001018097 Homo sapiens L-selectin Proteins 0.000 description 1
101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 description 1
101000657037 Homo sapiens Radical S-adenosyl methionine domain-containing protein 2 Proteins 0.000 description 1
101000828739 Homo sapiens SPATS2-like protein Proteins 0.000 description 1
101000577874 Homo sapiens Stromelysin-2 Proteins 0.000 description 1
101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
102100034170 Interferon-induced, double-stranded RNA-activated protein kinase Human genes 0.000 description 1
108010002350 Interleukin-2 Proteins 0.000 description 1
108090001005 Interleukin-6 Proteins 0.000 description 1
ZCYVEMRRCGMTRW-AHCXROLUSA-N Iodine-123 Chemical compound [123I] ZCYVEMRRCGMTRW-AHCXROLUSA-N 0.000 description 1
206010023232 Joint swelling Diseases 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
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
102100033467 L-selectin Human genes 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
208000008771 Lymphadenopathy Diseases 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 description 1
241000699666 Mus <mouse, genus> Species 0.000 description 1
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 1
QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 1
150000001204 N-oxides Chemical group 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
238000000636 Northern blotting Methods 0.000 description 1
102000019040 Nuclear Antigens Human genes 0.000 description 1
108010051791 Nuclear Antigens Proteins 0.000 description 1
208000007117 Oral Ulcer Diseases 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
241001494479 Pecora Species 0.000 description 1
241000288906 Primates Species 0.000 description 1
206010037660 Pyrexia Diseases 0.000 description 1
238000002123 RNA extraction Methods 0.000 description 1
102100033749 Radical S-adenosyl methionine domain-containing protein 2 Human genes 0.000 description 1
102100023521 SPATS2-like protein Human genes 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-N Salicylic acid Natural products OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
102100028848 Stromelysin-2 Human genes 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 description 1
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
PNDPGZBMCMUPRI-XXSWNUTMSA-N [125I][125I] Chemical compound [125I][125I] PNDPGZBMCMUPRI-XXSWNUTMSA-N 0.000 description 1
230000001594 aberrant effect Effects 0.000 description 1
125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
230000008484 agonism Effects 0.000 description 1
229940072056 alginate Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
125000005210 alkyl ammonium group Chemical group 0.000 description 1
230000004075 alteration Effects 0.000 description 1
150000001409 amidines Chemical class 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
230000003321 amplification Effects 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
150000001450 anions Chemical class 0.000 description 1
230000003460 anti-nuclear Effects 0.000 description 1
150000003974 aralkylamines Chemical class 0.000 description 1
150000004982 aromatic amines Chemical class 0.000 description 1
125000002102 aryl alkyloxo group Chemical group 0.000 description 1
125000004104 aryloxy group Chemical group 0.000 description 1
229940072107 ascorbate Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229940009098 aspartate Drugs 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
230000037444 atrophy Effects 0.000 description 1
230000006472 autoimmune response Effects 0.000 description 1
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
229960002170 azathioprine Drugs 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
125000003828 azulenyl group Chemical group 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000031018 biological processes and functions Effects 0.000 description 1
125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
125000005518 carboxamido group Chemical group 0.000 description 1
150000007942 carboxylates Chemical class 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
230000005754 cellular signaling Effects 0.000 description 1
230000008859 change Effects 0.000 description 1
150000003841 chloride salts Chemical class 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
125000002676 chrysenyl group Chemical group C1(=CC=CC=2C3=CC=C4C=CC=CC4=C3C=CC12)* 0.000 description 1
229940114081 cinnamate Drugs 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
239000002299 complementary DNA Substances 0.000 description 1
229940125782 compound 2 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000003246 corticosteroid Substances 0.000 description 1
229960001334 corticosteroids Drugs 0.000 description 1
150000001913 cyanates Chemical class 0.000 description 1
229940109275 cyclamate Drugs 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
125000006165 cyclic alkyl group Chemical group 0.000 description 1
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
125000004367 cycloalkylaryl group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
210000000805 cytoplasm Anatomy 0.000 description 1
210000004544 dc2 Anatomy 0.000 description 1
125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 description 1
GHVNFZFCNZKVNT-UHFFFAOYSA-M decanoate Chemical compound CCCCCCCCCC([O-])=O GHVNFZFCNZKVNT-UHFFFAOYSA-M 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
OKKJLVBELUTLKV-MICDWDOJSA-N deuteriomethanol Chemical compound [2H]CO OKKJLVBELUTLKV-MICDWDOJSA-N 0.000 description 1
125000005265 dialkylamine group Chemical group 0.000 description 1
150000004985 diamines Chemical class 0.000 description 1
239000010432 diamond Substances 0.000 description 1
125000005266 diarylamine group Chemical group 0.000 description 1
229940120124 dichloroacetate Drugs 0.000 description 1
JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
150000004683 dihydrates Chemical class 0.000 description 1
125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
150000002081 enamines Chemical class 0.000 description 1
210000002889 endothelial cell Anatomy 0.000 description 1
230000008753 endothelial function Effects 0.000 description 1
YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
210000001339 epidermal cell Anatomy 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
201000005884 exanthem Diseases 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
206010016256 fatigue Diseases 0.000 description 1
230000003176 fibrotic effect Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
230000006870 function Effects 0.000 description 1
239000007789 gas Substances 0.000 description 1
238000001502 gel electrophoresis Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
229940114119 gentisate Drugs 0.000 description 1
210000000585 glomerular basement membrane Anatomy 0.000 description 1
229960001731 gluceptate Drugs 0.000 description 1
KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
229940097042 glucuronate Drugs 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 1
229940096919 glycogen Drugs 0.000 description 1
150000002357 guanidines Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
210000002216 heart Anatomy 0.000 description 1
208000007475 hemolytic anemia Diseases 0.000 description 1
125000002192 heptalenyl group Chemical group 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
238000004128 high performance liquid chromatography Methods 0.000 description 1
229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 1
150000007857 hydrazones Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
150000002443 hydroxylamines Chemical group 0.000 description 1
239000005457 ice water Substances 0.000 description 1
150000003949 imides Chemical class 0.000 description 1
150000002466 imines Chemical class 0.000 description 1
210000002865 immune cell Anatomy 0.000 description 1
238000003018 immunoassay Methods 0.000 description 1
239000002955 immunomodulating agent Substances 0.000 description 1
229940121354 immunomodulator Drugs 0.000 description 1
238000013394 immunophenotyping Methods 0.000 description 1
229960003444 immunosuppressant agent Drugs 0.000 description 1
239000003018 immunosuppressive agent Substances 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
125000003427 indacenyl group Chemical group 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000003999 initiator Substances 0.000 description 1
230000010354 integration Effects 0.000 description 1
230000010468 interferon response Effects 0.000 description 1
229940047124 interferons Drugs 0.000 description 1
238000011835 investigation Methods 0.000 description 1
239000011630 iodine Substances 0.000 description 1
229940044173 iodine-125 Drugs 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
125000000654 isopropylidene group Chemical group C(C)(C)=* 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
229940099584 lactobionate Drugs 0.000 description 1
JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
231100000518 lethal Toxicity 0.000 description 1
230000001665 lethal effect Effects 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
230000007774 longterm Effects 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
229940049920 malate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
150000002689 maleic acids Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
229960003194 meglumine Drugs 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
229960000485 methotrexate Drugs 0.000 description 1
150000004682 monohydrates Chemical class 0.000 description 1
238000007837 multiplex assay Methods 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
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 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
210000000440 neutrophil Anatomy 0.000 description 1
238000007481 next generation sequencing Methods 0.000 description 1
101150009274 nhr-1 gene Proteins 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
238000003199 nucleic acid amplification method Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
150000004866 oxadiazoles Chemical class 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
229940039748 oxalate Drugs 0.000 description 1
150000002916 oxazoles Chemical class 0.000 description 1
150000002923 oximes Chemical class 0.000 description 1
125000004043 oxo group Chemical group O=* 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
230000001717 pathogenic effect Effects 0.000 description 1
230000007170 pathology Effects 0.000 description 1
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
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 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
150000003904 phospholipids Chemical class 0.000 description 1
235000011007 phosphoric acid Nutrition 0.000 description 1
150000003016 phosphoric acids Chemical class 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
238000006366 phosphorylation reaction Methods 0.000 description 1
LJCNRYVRMXRIQR-OLXYHTOASA-L potassium sodium L-tartrate Chemical class [Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O LJCNRYVRMXRIQR-OLXYHTOASA-L 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000000039 preparative column chromatography Methods 0.000 description 1
230000002265 prevention Effects 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
230000007112 pro inflammatory response Effects 0.000 description 1
210000001948 pro-b lymphocyte Anatomy 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
230000008569 process Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
230000035755 proliferation Effects 0.000 description 1
230000002035 prolonged 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
125000006239 protecting group Chemical group 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000001725 pyrenyl group Chemical group 0.000 description 1
125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
229940043131 pyroglutamate Drugs 0.000 description 1
206010037844 rash Diseases 0.000 description 1
238000010992 reflux Methods 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
230000037390 scarring Effects 0.000 description 1
229940116351 sebacate Drugs 0.000 description 1
CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
125000004469 siloxy group Chemical group [SiH3]O* 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
231100000046 skin rash Toxicity 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
241000894007 species Species 0.000 description 1
230000003393 splenic effect Effects 0.000 description 1
229940114926 stearate Drugs 0.000 description 1
239000000126 substance Substances 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229940086735 succinate Drugs 0.000 description 1
125000000565 sulfonamide group Chemical group 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
125000003375 sulfoxide group Chemical group 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
LBHMMDUJKBJVQI-ZDUSSCGKSA-N tert-butyl n-[(1s)-4-cyano-2,3-dihydro-1h-inden-1-yl]carbamate Chemical compound C1=CC=C(C#N)C2=C1[C@@H](NC(=O)OC(C)(C)C)CC2 LBHMMDUJKBJVQI-ZDUSSCGKSA-N 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
125000001935 tetracenyl group Chemical group C1(=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C12)* 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000000101 thioether group Chemical group 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
230000026683 transduction Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
238000011277 treatment modality Methods 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000005259 triarylamine group Chemical group 0.000 description 1
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
SZYJELPVAFJOGJ-UHFFFAOYSA-N trimethylamine hydrochloride Chemical compound Cl.CN(C)C SZYJELPVAFJOGJ-UHFFFAOYSA-N 0.000 description 1
NRZWQKGABZFFKE-UHFFFAOYSA-N trimethylsulfonium Chemical compound C[S+](C)C NRZWQKGABZFFKE-UHFFFAOYSA-N 0.000 description 1
125000003960 triphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C3=CC=CC=C3C12)* 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229940075466 undecylenate Drugs 0.000 description 1
XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
108700026220 vif Genes Proteins 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
238000001262 western blot Methods 0.000 description 1
125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
229950000339 xinafoate Drugs 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1
GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1