NO326014B1 - VLA-4 inhibitorer, medikamenter inneholdened slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom - Google Patents
VLA-4 inhibitorer, medikamenter inneholdened slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom Download PDFInfo
- Publication number
- NO326014B1 NO326014B1 NO20032994A NO20032994A NO326014B1 NO 326014 B1 NO326014 B1 NO 326014B1 NO 20032994 A NO20032994 A NO 20032994A NO 20032994 A NO20032994 A NO 20032994A NO 326014 B1 NO326014 B1 NO 326014B1
- Authority
- NO
- Norway
- Prior art keywords
- group
- mmol
- fluoro
- methyl
- reduced pressure
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 258
- 239000003814 drug Substances 0.000 title claims description 18
- 229940079593 drug Drugs 0.000 title claims description 16
- 238000004519 manufacturing process Methods 0.000 title claims description 15
- 201000010099 disease Diseases 0.000 title claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims description 10
- 108010008212 Integrin alpha4beta1 Proteins 0.000 title description 13
- 239000003112 inhibitor Substances 0.000 title 1
- -1 R11 Chemical compound 0.000 claims description 58
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 31
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 23
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000003277 amino group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 12
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- 125000001424 substituent group Chemical group 0.000 claims description 12
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004956 cyclohexylene group Chemical group 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 125000005551 pyridylene group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000004434 sulfur atom Chemical group 0.000 claims description 6
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 5
- 208000027866 inflammatory disease Diseases 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 230000021164 cell adhesion Effects 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 230000002757 inflammatory effect Effects 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 2
- 206010003246 arthritis Diseases 0.000 claims description 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000001041 indolyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 230000009401 metastasis Effects 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims 1
- 208000028774 intestinal disease Diseases 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- 238000002054 transplantation Methods 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 309
- 230000002829 reductive effect Effects 0.000 description 309
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 291
- 239000002904 solvent Substances 0.000 description 280
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 255
- 239000000203 mixture Substances 0.000 description 243
- 239000011541 reaction mixture Substances 0.000 description 243
- 230000015572 biosynthetic process Effects 0.000 description 199
- 238000005160 1H NMR spectroscopy Methods 0.000 description 198
- 238000003786 synthesis reaction Methods 0.000 description 198
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 186
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 184
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 163
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 150
- 239000000741 silica gel Substances 0.000 description 143
- 229910002027 silica gel Inorganic materials 0.000 description 143
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 141
- 238000004587 chromatography analysis Methods 0.000 description 120
- 239000000284 extract Substances 0.000 description 114
- 239000000243 solution Substances 0.000 description 114
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 109
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
- 238000003756 stirring Methods 0.000 description 104
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 103
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 103
- 235000019439 ethyl acetate Nutrition 0.000 description 103
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 99
- 150000001408 amides Chemical class 0.000 description 97
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 94
- 238000000605 extraction Methods 0.000 description 90
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 88
- NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 0.000 description 86
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 76
- 239000007787 solid Substances 0.000 description 73
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 68
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 64
- 239000000126 substance Substances 0.000 description 62
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 61
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 51
- 239000013078 crystal Substances 0.000 description 51
- 238000001914 filtration Methods 0.000 description 50
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 239000003921 oil Substances 0.000 description 46
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 44
- 238000001816 cooling Methods 0.000 description 44
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 description 35
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 33
- 238000009835 boiling Methods 0.000 description 33
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 33
- 239000000706 filtrate Substances 0.000 description 33
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 29
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 28
- 239000000843 powder Substances 0.000 description 27
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 26
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 26
- GKIRPKYJQBWNGO-OCEACIFDSA-N clomifene Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(\C=1C=CC=CC=1)=C(\Cl)C1=CC=CC=C1 GKIRPKYJQBWNGO-OCEACIFDSA-N 0.000 description 26
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
- 239000005711 Benzoic acid Substances 0.000 description 25
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 25
- 239000005457 ice water Substances 0.000 description 25
- 238000006243 chemical reaction Methods 0.000 description 24
- 235000010233 benzoic acid Nutrition 0.000 description 23
- 238000000034 method Methods 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 20
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 20
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 19
- 239000010410 layer Substances 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- QLHBVRZVXNLWKP-UHFFFAOYSA-N 2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=CC=C1NC1=NC2=CC=C(CC(O)=O)C=C2O1 QLHBVRZVXNLWKP-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 16
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- 150000002430 hydrocarbons Chemical group 0.000 description 15
- 210000000265 leukocyte Anatomy 0.000 description 15
- 239000012312 sodium hydride Substances 0.000 description 15
- 229910000104 sodium hydride Inorganic materials 0.000 description 15
- 239000012230 colorless oil Substances 0.000 description 14
- 150000008282 halocarbons Chemical class 0.000 description 14
- 239000002198 insoluble material Substances 0.000 description 14
- 239000002798 polar solvent Substances 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 13
- 239000004215 Carbon black (E152) Substances 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 235000011054 acetic acid Nutrition 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 229930195733 hydrocarbon Natural products 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 239000002994 raw material Substances 0.000 description 12
- 238000010992 reflux Methods 0.000 description 12
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 11
- 150000001298 alcohols Chemical class 0.000 description 11
- 125000000217 alkyl group Chemical group 0.000 description 11
- 239000003054 catalyst Substances 0.000 description 11
- 150000007529 inorganic bases Chemical class 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 description 10
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 description 10
- 150000002148 esters Chemical group 0.000 description 10
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 9
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 9
- FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical class ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 8
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 8
- 108010044426 integrins Proteins 0.000 description 8
- 102000006495 integrins Human genes 0.000 description 8
- ASKIHSLBPLCNKS-UHFFFAOYSA-N methyl 2-(4-amino-2-fluoro-3-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(N)C(O)=C1F ASKIHSLBPLCNKS-UHFFFAOYSA-N 0.000 description 8
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 8
- 239000008096 xylene Substances 0.000 description 8
- 102000016359 Fibronectins Human genes 0.000 description 7
- 108010067306 Fibronectins Proteins 0.000 description 7
- 125000006615 aromatic heterocyclic group Chemical group 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 125000000753 cycloalkyl group Chemical group 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 125000005905 mesyloxy group Chemical group 0.000 description 7
- GRWIABMEEKERFV-UHFFFAOYSA-N methanol;oxolane Chemical compound OC.C1CCOC1 GRWIABMEEKERFV-UHFFFAOYSA-N 0.000 description 7
- 239000011664 nicotinic acid Substances 0.000 description 7
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- 235000001968 nicotinic acid Nutrition 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 6
- WKVZMKDXJFCMMD-UVWUDEKDSA-L (5ar,8ar,9r)-5-[[(2r,4ar,6r,7r,8r,8as)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one;azanide;n,3-bis(2-chloroethyl)-2-ox Chemical compound [NH2-].[NH2-].Cl[Pt+2]Cl.ClCCNP1(=O)OCCCN1CCCl.COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3C(O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 WKVZMKDXJFCMMD-UVWUDEKDSA-L 0.000 description 5
- LIQHPNDCQUCZKL-UHFFFAOYSA-N 3,5-difluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC(F)=C1[N+]([O-])=O LIQHPNDCQUCZKL-UHFFFAOYSA-N 0.000 description 5
- QVCYTKXGZLOVFA-UHFFFAOYSA-N 4-fluoro-2-isothiocyanato-1-methylbenzene Chemical compound CC1=CC=C(F)C=C1N=C=S QVCYTKXGZLOVFA-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 5
- 238000006751 Mitsunobu reaction Methods 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 5
- 125000003118 aryl group Chemical group 0.000 description 5
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 5
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 238000010511 deprotection reaction Methods 0.000 description 5
- 229910001873 dinitrogen Inorganic materials 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 238000006460 hydrolysis reaction Methods 0.000 description 5
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 5
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000007974 sodium acetate buffer Substances 0.000 description 5
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
- PPWSBYVFCTZAOM-UHFFFAOYSA-N 1-isocyanatosulfanyl-2-methylbenzene Chemical compound CC1=CC=CC=C1SN=C=O PPWSBYVFCTZAOM-UHFFFAOYSA-N 0.000 description 4
- CWZFEZBZSKMGRK-UHFFFAOYSA-N 2-[3-chloro-4-(1h-indole-3-carbonylamino)phenyl]acetic acid Chemical compound ClC1=CC(CC(=O)O)=CC=C1NC(=O)C1=CNC2=CC=CC=C12 CWZFEZBZSKMGRK-UHFFFAOYSA-N 0.000 description 4
- BBVQDWDBTWSGHQ-UHFFFAOYSA-N 2-chloro-1,3-benzoxazole Chemical compound C1=CC=C2OC(Cl)=NC2=C1 BBVQDWDBTWSGHQ-UHFFFAOYSA-N 0.000 description 4
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 4
- 239000012141 concentrate Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- CLPHAYNBNTVRDI-UHFFFAOYSA-N ditert-butyl propanedioate Chemical compound CC(C)(C)OC(=O)CC(=O)OC(C)(C)C CLPHAYNBNTVRDI-UHFFFAOYSA-N 0.000 description 4
- NHGYQADUGSHIGS-UHFFFAOYSA-N ethyl 2-(4-amino-3-chlorophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(N)C(Cl)=C1 NHGYQADUGSHIGS-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- LZGUTYHAHOXRTO-UHFFFAOYSA-N methyl 2-(4-amino-3-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(N)C(O)=C1 LZGUTYHAHOXRTO-UHFFFAOYSA-N 0.000 description 4
- MCIOQFIAMVXOIM-UHFFFAOYSA-N methyl 2-[7-fluoro-2-(4-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=CC=C(F)C=C1C MCIOQFIAMVXOIM-UHFFFAOYSA-N 0.000 description 4
- DBNZXILBYIYICU-UHFFFAOYSA-N methyl 2-[7-fluoro-2-(naphthalen-1-ylamino)-1,3-benzoxazol-6-yl]acetate Chemical compound C1=CC=C2C(NC3=NC4=CC=C(C(=C4O3)F)CC(=O)OC)=CC=CC2=C1 DBNZXILBYIYICU-UHFFFAOYSA-N 0.000 description 4
- 125000002950 monocyclic group Chemical group 0.000 description 4
- 238000006386 neutralization reaction Methods 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 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 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 150000003672 ureas Chemical class 0.000 description 4
- YOKPUTOXWQZWBO-UHFFFAOYSA-N 1,5-difluoro-2-nitro-3-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=C(F)C=C(F)C=C1OCC1=CC=CC=C1 YOKPUTOXWQZWBO-UHFFFAOYSA-N 0.000 description 3
- DXEGOHULGVHKCT-UHFFFAOYSA-N 1,5-difluoro-3-methoxy-2-nitrobenzene Chemical compound COC1=CC(F)=CC(F)=C1[N+]([O-])=O DXEGOHULGVHKCT-UHFFFAOYSA-N 0.000 description 3
- XRUCYUUUIYTUPY-UHFFFAOYSA-N 2-(2-anilino-1,3-benzoxazol-6-yl)acetic acid Chemical compound O1C2=CC(CC(=O)O)=CC=C2N=C1NC1=CC=CC=C1 XRUCYUUUIYTUPY-UHFFFAOYSA-N 0.000 description 3
- KOJTXYMBDJTUBR-UHFFFAOYSA-N 2-[2-(1-methylindol-3-yl)-1,3-benzoxazol-6-yl]acetic acid Chemical compound C12=CC=CC=C2N(C)C=C1C1=NC2=CC=C(CC(O)=O)C=C2O1 KOJTXYMBDJTUBR-UHFFFAOYSA-N 0.000 description 3
- ZDBPSPBQDUQEIG-UHFFFAOYSA-N 2-[2-(2-bromoanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound O1C2=CC(CC(=O)O)=CC=C2N=C1NC1=CC=CC=C1Br ZDBPSPBQDUQEIG-UHFFFAOYSA-N 0.000 description 3
- KLHULDCPLOHHLP-UHFFFAOYSA-N 2-[2-(2-chloro-6-methylanilino)-7-fluoro-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=CC(Cl)=C1NC1=NC2=CC=C(CC(O)=O)C(F)=C2O1 KLHULDCPLOHHLP-UHFFFAOYSA-N 0.000 description 3
- OTLFBWJXLRGRKL-UHFFFAOYSA-N 2-[2-(2-chloroanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound O1C2=CC(CC(=O)O)=CC=C2N=C1NC1=CC=CC=C1Cl OTLFBWJXLRGRKL-UHFFFAOYSA-N 0.000 description 3
- YAWXSMJXJKVOKR-UHFFFAOYSA-N 2-[2-(2-chloroanilino)-7-fluoro-1,3-benzoxazol-6-yl]acetic acid Chemical compound O1C2=C(F)C(CC(=O)O)=CC=C2N=C1NC1=CC=CC=C1Cl YAWXSMJXJKVOKR-UHFFFAOYSA-N 0.000 description 3
- SGRIGSRDUNZKAD-UHFFFAOYSA-N 2-[2-(2-methylanilino)-1,3-benzothiazol-6-yl]acetic acid Chemical compound CC1=CC=CC=C1NC1=NC2=CC=C(CC(O)=O)C=C2S1 SGRIGSRDUNZKAD-UHFFFAOYSA-N 0.000 description 3
- QDIKKYKMDQBYPK-UHFFFAOYSA-N 2-[2-(5-chloro-2-methylanilino)-7-fluoro-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=C(Cl)C=C1NC1=NC2=CC=C(CC(O)=O)C(F)=C2O1 QDIKKYKMDQBYPK-UHFFFAOYSA-N 0.000 description 3
- ZQMDKUYLVRZVPE-UHFFFAOYSA-N 2-[2-(5-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=C(F)C=C1NC1=NC2=CC=C(CC(O)=O)C=C2O1 ZQMDKUYLVRZVPE-UHFFFAOYSA-N 0.000 description 3
- LMIZIIDKYIJGDX-UHFFFAOYSA-N 2-[3-chloro-4-(2,3-dihydroindole-1-carbonylamino)phenyl]acetic acid Chemical compound ClC1=CC(CC(=O)O)=CC=C1NC(=O)N1C2=CC=CC=C2CC1 LMIZIIDKYIJGDX-UHFFFAOYSA-N 0.000 description 3
- NOTCARIGZIYOLE-UHFFFAOYSA-N 2-[3-chloro-4-[(1-methylindole-3-carbonyl)amino]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(C)C=C1C(=O)NC1=CC=C(CC(O)=O)C=C1Cl NOTCARIGZIYOLE-UHFFFAOYSA-N 0.000 description 3
- BPIOXOVENUQION-UHFFFAOYSA-N 2-[4-(1,3-benzoxazol-2-ylamino)-3-chlorophenyl]acetic acid Chemical compound ClC1=CC(CC(=O)O)=CC=C1NC1=NC2=CC=CC=C2O1 BPIOXOVENUQION-UHFFFAOYSA-N 0.000 description 3
- DCIMUIPWIQPCNR-UHFFFAOYSA-N 2-[4-(1,3-benzoxazol-2-ylamino)-3-methylphenyl]acetic acid Chemical compound CC1=CC(CC(O)=O)=CC=C1NC1=NC2=CC=CC=C2O1 DCIMUIPWIQPCNR-UHFFFAOYSA-N 0.000 description 3
- PVRYSLNDLYKLJA-UHFFFAOYSA-N 2-[4-(1,3-benzoxazol-2-ylamino)phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1NC1=NC2=CC=CC=C2O1 PVRYSLNDLYKLJA-UHFFFAOYSA-N 0.000 description 3
- DAXIIHPZZDDSKF-UHFFFAOYSA-N 2-[4-fluoro-2-(5-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=C(F)C=C1NC1=NC2=C(F)C=C(CC(O)=O)C=C2O1 DAXIIHPZZDDSKF-UHFFFAOYSA-N 0.000 description 3
- PWLJCUJMOIGXMJ-UHFFFAOYSA-N 2-[5-(1,3-benzoxazol-2-ylamino)-6-chloropyridin-2-yl]acetic acid Chemical compound ClC1=NC(CC(=O)O)=CC=C1NC1=NC2=CC=CC=C2O1 PWLJCUJMOIGXMJ-UHFFFAOYSA-N 0.000 description 3
- NWEUAJIWXGAOIG-UHFFFAOYSA-N 2-[7-fluoro-2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=CC=C1NC1=NC2=CC=C(CC(O)=O)C(F)=C2O1 NWEUAJIWXGAOIG-UHFFFAOYSA-N 0.000 description 3
- HWQSEAFPJJYTEB-UHFFFAOYSA-N 2-[7-fluoro-2-(3-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=C(F)C=CC=C1NC1=NC2=CC=C(CC(O)=O)C(F)=C2O1 HWQSEAFPJJYTEB-UHFFFAOYSA-N 0.000 description 3
- UXZCJBSMZDTAOS-UHFFFAOYSA-N 2-[7-fluoro-2-(5-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC=C(F)C=C1NC1=NC2=CC=C(CC(O)=O)C(F)=C2O1 UXZCJBSMZDTAOS-UHFFFAOYSA-N 0.000 description 3
- FEDLEBCVFZMHBP-UHFFFAOYSA-N 2-amino-3-methylphenol Chemical compound CC1=CC=CC(O)=C1N FEDLEBCVFZMHBP-UHFFFAOYSA-N 0.000 description 3
- DZPGXGGVNNQBGZ-UHFFFAOYSA-N 2h-isoindole;hydrochloride Chemical class Cl.C1=CC=CC2=CNC=C21 DZPGXGGVNNQBGZ-UHFFFAOYSA-N 0.000 description 3
- CKLRHQJRQRDDSO-UHFFFAOYSA-N 3-o-tert-butyl 1-o-ethyl 2-(3-fluoro-4-nitro-5-phenylmethoxyphenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OC(C)(C)C)C1=CC(F)=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=C1 CKLRHQJRQRDDSO-UHFFFAOYSA-N 0.000 description 3
- MCXBRPSQVCZTAY-ORFBVSJDSA-N 4-[[(2s)-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]cyclohexane-1-carboxylic acid Chemical compound CC1=CC=CC=C1NC(OC1=C2)=NC1=CC=C2CC(=O)N1[C@H](COC2CCC(CC2)C(O)=O)CCC1 MCXBRPSQVCZTAY-ORFBVSJDSA-N 0.000 description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 description 3
- 102000016289 Cell Adhesion Molecules Human genes 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 3
- 238000007126 N-alkylation reaction Methods 0.000 description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 3
- 150000000475 acetylene derivatives Chemical class 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 125000001931 aliphatic group Chemical group 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 125000000732 arylene group Chemical group 0.000 description 3
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 3
- 238000006664 bond formation reaction Methods 0.000 description 3
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- XHWGKWDWEIGNDM-UHFFFAOYSA-N ditert-butyl 2-(3-fluoro-4-nitrophenyl)propanedioate Chemical compound CC(C)(C)OC(=O)C(C(=O)OC(C)(C)C)C1=CC=C([N+]([O-])=O)C(F)=C1 XHWGKWDWEIGNDM-UHFFFAOYSA-N 0.000 description 3
- ZOOODBUHSVUZEM-UHFFFAOYSA-N ethoxymethanedithioic acid Chemical class CCOC(S)=S ZOOODBUHSVUZEM-UHFFFAOYSA-N 0.000 description 3
- FADMFPJVTVPKRD-UHFFFAOYSA-N ethyl 2-(3-fluoro-4-nitro-5-phenylmethoxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC(F)=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=C1 FADMFPJVTVPKRD-UHFFFAOYSA-N 0.000 description 3
- ZCKVAUOQFVWSKN-UHFFFAOYSA-N ethyl 2-(3-fluoro-4-nitrophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C([N+]([O-])=O)C(F)=C1 ZCKVAUOQFVWSKN-UHFFFAOYSA-N 0.000 description 3
- OLUJXZDAANGTBF-UHFFFAOYSA-N ethyl 2-(4-amino-3-fluoro-5-hydroxyphenyl)acetate Chemical compound CCOC(=O)CC1=CC(O)=C(N)C(F)=C1 OLUJXZDAANGTBF-UHFFFAOYSA-N 0.000 description 3
- QWQMIDDKCGVILM-UHFFFAOYSA-N ethyl 2-[2-(2-bromoanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=CC(CC(=O)OCC)=CC=C2N=C1NC1=CC=CC=C1Br QWQMIDDKCGVILM-UHFFFAOYSA-N 0.000 description 3
- VPMUICPFOLIXLI-UHFFFAOYSA-N ethyl 2-[2-(2-methylanilino)-1,3-benzothiazol-6-yl]acetate Chemical compound S1C2=CC(CC(=O)OCC)=CC=C2N=C1NC1=CC=CC=C1C VPMUICPFOLIXLI-UHFFFAOYSA-N 0.000 description 3
- SMVGGGNBBQPNFS-UHFFFAOYSA-N ethyl 2-[3-[(4-methoxyphenyl)methylsulfanyl]-4-[(2-methylphenyl)carbamothioylamino]phenyl]acetate Chemical compound C=1C=C(OC)C=CC=1CSC1=CC(CC(=O)OCC)=CC=C1NC(=S)NC1=CC=CC=C1C SMVGGGNBBQPNFS-UHFFFAOYSA-N 0.000 description 3
- LZOFIUNCKWPVLG-UHFFFAOYSA-N ethyl 2-[3-[(4-methoxyphenyl)methylsulfanyl]-4-nitrophenyl]acetate Chemical compound CCOC(=O)CC1=CC=C([N+]([O-])=O)C(SCC=2C=CC(OC)=CC=2)=C1 LZOFIUNCKWPVLG-UHFFFAOYSA-N 0.000 description 3
- PXGAMHPISZPEQY-UHFFFAOYSA-N ethyl 2-[3-chloro-4-(1h-indole-3-carbonylamino)phenyl]acetate Chemical compound ClC1=CC(CC(=O)OCC)=CC=C1NC(=O)C1=CNC2=CC=CC=C12 PXGAMHPISZPEQY-UHFFFAOYSA-N 0.000 description 3
- OPLXWMJSHPNJJC-UHFFFAOYSA-N ethyl 2-[3-chloro-4-(2,3-dihydroindole-1-carbonylamino)phenyl]acetate Chemical compound ClC1=CC(CC(=O)OCC)=CC=C1NC(=O)N1C2=CC=CC=C2CC1 OPLXWMJSHPNJJC-UHFFFAOYSA-N 0.000 description 3
- NSEHHPRCMVDQAX-UHFFFAOYSA-N ethyl 2-[3-chloro-4-[(1-methylindole-3-carbonyl)amino]phenyl]acetate Chemical compound ClC1=CC(CC(=O)OCC)=CC=C1NC(=O)C1=CN(C)C2=CC=CC=C12 NSEHHPRCMVDQAX-UHFFFAOYSA-N 0.000 description 3
- HRDWEQSODKEDOU-UHFFFAOYSA-N ethyl 2-[4-(1,3-benzoxazol-2-ylamino)-3-chlorophenyl]acetate Chemical compound ClC1=CC(CC(=O)OCC)=CC=C1NC1=NC2=CC=CC=C2O1 HRDWEQSODKEDOU-UHFFFAOYSA-N 0.000 description 3
- XKFNXTDEZQFQDW-UHFFFAOYSA-N ethyl 2-[4-(1,3-benzoxazol-2-ylamino)phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1NC1=NC2=CC=CC=C2O1 XKFNXTDEZQFQDW-UHFFFAOYSA-N 0.000 description 3
- ORRIWYZDLJSNHG-UHFFFAOYSA-N ethyl 2-[4-amino-3-[(4-methoxyphenyl)methylsulfanyl]phenyl]acetate Chemical compound CCOC(=O)CC1=CC=C(N)C(SCC=2C=CC(OC)=CC=2)=C1 ORRIWYZDLJSNHG-UHFFFAOYSA-N 0.000 description 3
- MEXIIYATLAMMAS-UHFFFAOYSA-N ethyl 2-[4-fluoro-2-(5-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=CC(CC(=O)OCC)=CC(F)=C2N=C1NC1=CC(F)=CC=C1C MEXIIYATLAMMAS-UHFFFAOYSA-N 0.000 description 3
- RHDZBPIGCUBSSR-UHFFFAOYSA-N ethyl 2-[5-(1,3-benzoxazol-2-ylamino)-6-chloropyridin-2-yl]acetate Chemical compound ClC1=NC(CC(=O)OCC)=CC=C1NC1=NC2=CC=CC=C2O1 RHDZBPIGCUBSSR-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 3
- 125000005549 heteroarylene group Chemical group 0.000 description 3
- 125000000623 heterocyclic group Chemical group 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 150000002513 isocyanates Chemical class 0.000 description 3
- NONOKGVFTBWRLD-UHFFFAOYSA-N isocyanatosulfanylimino(oxo)methane Chemical class O=C=NSN=C=O NONOKGVFTBWRLD-UHFFFAOYSA-N 0.000 description 3
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 3
- DPLBLJCNRIGICE-UHFFFAOYSA-N methyl 2-(2-anilino-1,3-benzoxazol-6-yl)acetate Chemical compound O1C2=CC(CC(=O)OC)=CC=C2N=C1NC1=CC=CC=C1 DPLBLJCNRIGICE-UHFFFAOYSA-N 0.000 description 3
- VVILHRMULRCJAU-UHFFFAOYSA-N methyl 2-(3-chloro-4-isothiocyanatophenyl)acetate Chemical compound COC(=O)CC1=CC=C(N=C=S)C(Cl)=C1 VVILHRMULRCJAU-UHFFFAOYSA-N 0.000 description 3
- GKMFAKNUHMDTJS-UHFFFAOYSA-N methyl 2-(3-hydroxy-4-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C([N+]([O-])=O)C(O)=C1 GKMFAKNUHMDTJS-UHFFFAOYSA-N 0.000 description 3
- OJBQKTGRJXLCDJ-UHFFFAOYSA-N methyl 2-[2-(1-methylindol-3-yl)-1,3-benzoxazol-6-yl]acetate Chemical compound C1=CC=C2C(C3=NC4=CC=C(C=C4O3)CC(=O)OC)=CN(C)C2=C1 OJBQKTGRJXLCDJ-UHFFFAOYSA-N 0.000 description 3
- ZEPGNYHZLXLZAX-UHFFFAOYSA-N methyl 2-[2-(2-chloro-6-methylanilino)-7-fluoro-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=C(C)C=CC=C1Cl ZEPGNYHZLXLZAX-UHFFFAOYSA-N 0.000 description 3
- LMECOBVPZYXSQS-UHFFFAOYSA-N methyl 2-[2-(2-chloroanilino)-7-fluoro-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=CC=CC=C1Cl LMECOBVPZYXSQS-UHFFFAOYSA-N 0.000 description 3
- MZMBHJYEQBUGBD-UHFFFAOYSA-N methyl 2-[2-(5-chloro-2-methylanilino)-7-fluoro-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=CC(Cl)=CC=C1C MZMBHJYEQBUGBD-UHFFFAOYSA-N 0.000 description 3
- JYYCJKRLRZMQOZ-UHFFFAOYSA-N methyl 2-[2-(5-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=CC(CC(=O)OC)=CC=C2N=C1NC1=CC(F)=CC=C1C JYYCJKRLRZMQOZ-UHFFFAOYSA-N 0.000 description 3
- HHTUJVIWLCISIG-UHFFFAOYSA-N methyl 2-[7-fluoro-2-(3-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=CC=CC(F)=C1C HHTUJVIWLCISIG-UHFFFAOYSA-N 0.000 description 3
- ABBWYZQVBXFEGF-UHFFFAOYSA-N methyl 2-[7-fluoro-2-(5-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=CC(F)=CC=C1C ABBWYZQVBXFEGF-UHFFFAOYSA-N 0.000 description 3
- KLCWSGHNASVHDD-UNMCSNQZSA-N methyl 4-[[(2s,4s)-1-[2-[4-(1,3-benzoxazol-2-ylamino)phenyl]acetyl]-4-fluoropyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=CC(NC=3OC4=CC=CC=C4N=3)=CC=2)C[C@@H](F)C1 KLCWSGHNASVHDD-UNMCSNQZSA-N 0.000 description 3
- XYLRYEZAHZNGOG-QWRGUYRKSA-N methyl 4-[[(2s,4s)-4-fluoropyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1NC[C@@H](F)C1 XYLRYEZAHZNGOG-QWRGUYRKSA-N 0.000 description 3
- QBMHMOKIFSCFCX-UHFFFAOYSA-N methyl 4-hydroxy-3-methylbenzoate Chemical compound COC(=O)C1=CC=C(O)C(C)=C1 QBMHMOKIFSCFCX-UHFFFAOYSA-N 0.000 description 3
- 229960003512 nicotinic acid Drugs 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 150000007530 organic bases Chemical class 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000012453 solvate Substances 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- ODBWAMHLBZXYGH-UHFFFAOYSA-N tert-butyl 2-[4-(1,3-benzoxazol-2-ylamino)-3-methylphenyl]acetate Chemical compound CC1=CC(CC(=O)OC(C)(C)C)=CC=C1NC1=NC2=CC=CC=C2O1 ODBWAMHLBZXYGH-UHFFFAOYSA-N 0.000 description 3
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 3
- 150000003585 thioureas Chemical class 0.000 description 3
- 238000005406 washing Methods 0.000 description 3
- MUZBVLZKNSSONR-IRXDYDNUSA-N (2s,4s)-1-[(2-methylpropan-2-yl)oxycarbonyl]-4-naphthalen-2-yloxypyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@H]1OC1=CC=C(C=CC=C2)C2=C1 MUZBVLZKNSSONR-IRXDYDNUSA-N 0.000 description 2
- IQFZJNCETIGXIO-STQMWFEESA-N (2s,4s)-1-[(2-methylpropan-2-yl)oxycarbonyl]-4-phenoxypyrrolidine-2-carboxylic acid Chemical compound C1[C@@H](C(O)=O)N(C(=O)OC(C)(C)C)C[C@H]1OC1=CC=CC=C1 IQFZJNCETIGXIO-STQMWFEESA-N 0.000 description 2
- UWYZHKAOTLEWKK-UHFFFAOYSA-N 1,2,3,4-tetrahydroisoquinoline Chemical compound C1=CC=C2CNCCC2=C1 UWYZHKAOTLEWKK-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- LWPPAGGWCDNCCV-UHFFFAOYSA-N 1,2-difluoro-4-nitro-3-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C(F)=C1OCC1=CC=CC=C1 LWPPAGGWCDNCCV-UHFFFAOYSA-N 0.000 description 2
- PWRFDGYYJWQIAB-UHFFFAOYSA-N 1,3,5-trifluoro-2-nitrobenzene Chemical compound [O-][N+](=O)C1=C(F)C=C(F)C=C1F PWRFDGYYJWQIAB-UHFFFAOYSA-N 0.000 description 2
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-bis(diphenylphosphino)propane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 2
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- JYKYYPPZLPVIBY-UHFFFAOYSA-N 1-isothiocyanato-2-methylbenzene Chemical compound CC1=CC=CC=C1N=C=S JYKYYPPZLPVIBY-UHFFFAOYSA-N 0.000 description 2
- HVRCLXXJIQTXHC-UHFFFAOYSA-N 1-methylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C)C=C(C(O)=O)C2=C1 HVRCLXXJIQTXHC-UHFFFAOYSA-N 0.000 description 2
- MZMNEDXVUJLQAF-YUMQZZPRSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-hydroxypyrrolidine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1C[C@H](O)CN1C(=O)OC(C)(C)C MZMNEDXVUJLQAF-YUMQZZPRSA-N 0.000 description 2
- CGEPPFRNMQDKGV-ROUUACIJSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-naphthalen-2-yloxypyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@@H]1OC1=CC=C(C=CC=C2)C2=C1 CGEPPFRNMQDKGV-ROUUACIJSA-N 0.000 description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 2
- FJGDXURFXISSJC-UHFFFAOYSA-N 2-(3-fluoro-5-methoxy-4-nitrophenyl)acetic acid Chemical compound COC1=CC(CC(O)=O)=CC(F)=C1[N+]([O-])=O FJGDXURFXISSJC-UHFFFAOYSA-N 0.000 description 2
- USYXXSPSICUYRL-UHFFFAOYSA-N 2-(3-hydroxy-4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C(O)=C1 USYXXSPSICUYRL-UHFFFAOYSA-N 0.000 description 2
- VKMINUCMEBUDIN-UHFFFAOYSA-N 2-[2-(2-methylanilino)-1,3-benzoxazol-5-yl]acetic acid Chemical compound CC1=CC=CC=C1NC1=NC2=CC(CC(O)=O)=CC=C2O1 VKMINUCMEBUDIN-UHFFFAOYSA-N 0.000 description 2
- IVGVFAQJXBBRFI-UHFFFAOYSA-N 2-[4-methoxy-2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound N=1C=2C(OC)=CC(CC(O)=O)=CC=2OC=1NC1=CC=CC=C1C IVGVFAQJXBBRFI-UHFFFAOYSA-N 0.000 description 2
- DCAIVJKVPWOODX-UHFFFAOYSA-N 2-[7-fluoro-2-(4-fluoro-2-methylanilino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound CC1=CC(F)=CC=C1NC1=NC2=CC=C(CC(O)=O)C(F)=C2O1 DCAIVJKVPWOODX-UHFFFAOYSA-N 0.000 description 2
- KQFAGHOSNQLFKG-UHFFFAOYSA-N 2-[7-fluoro-2-(naphthalen-1-ylamino)-1,3-benzoxazol-6-yl]acetic acid Chemical compound C1=CC=C2C(NC3=NC4=CC=C(C(=C4O3)F)CC(=O)O)=CC=CC2=C1 KQFAGHOSNQLFKG-UHFFFAOYSA-N 0.000 description 2
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
- BJBUEDPLEOHJGE-UHFFFAOYSA-N 3-hydroxyproline Chemical compound OC1CCNC1C(O)=O BJBUEDPLEOHJGE-UHFFFAOYSA-N 0.000 description 2
- HHKHMUILGRKZJI-UHFFFAOYSA-N 3-methoxy-4-nitro-5-phenylmethoxyphenol Chemical compound COC1=CC(O)=CC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O HHKHMUILGRKZJI-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
- NZSBCDAQWXGWKH-OALUTQOASA-N 4-[[(2s,4s)-1-[2-[2-(2-chloroanilino)-1,3-benzoxazol-6-yl]acetyl]-4-fluoropyrrolidin-2-yl]methoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)Cl)=NC3=CC=2)C[C@@H](F)C1 NZSBCDAQWXGWKH-OALUTQOASA-N 0.000 description 2
- FHLJNGQVYLJIQI-NYDCQLBNSA-N 4-[[(2s,4s)-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]-4-naphthalen-2-yloxypyrrolidin-2-yl]methoxy]benzoic acid Chemical compound CC1=CC=CC=C1NC(OC1=C2)=NC1=CC=C2CC(=O)N1[C@H](COC=2C=CC(=CC=2)C(O)=O)C[C@H](OC=2C=C3C=CC=CC3=CC=2)C1 FHLJNGQVYLJIQI-NYDCQLBNSA-N 0.000 description 2
- GAGYNYYHTXQVHF-LSYYVWMOSA-N 4-[[(2s,4s)-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]-4-phenoxypyrrolidin-2-yl]methoxy]benzoic acid Chemical compound CC1=CC=CC=C1NC(OC1=C2)=NC1=CC=C2CC(=O)N1[C@H](COC=2C=CC(=CC=2)C(O)=O)C[C@H](OC=2C=CC=CC=2)C1 GAGYNYYHTXQVHF-LSYYVWMOSA-N 0.000 description 2
- XOWXFBWUDVUYNS-FPOVZHCZSA-N 4-[[(2s,4s)-1-[2-[4-(1,3-benzoxazol-2-ylamino)phenyl]acetyl]-4-fluoropyrrolidin-2-yl]methoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OC[C@H]1N(C(=O)CC=2C=CC(NC=3OC4=CC=CC=C4N=3)=CC=2)C[C@@H](F)C1 XOWXFBWUDVUYNS-FPOVZHCZSA-N 0.000 description 2
- PDGDGHYIOYTRML-SFTDATJTSA-N 4-[[(2s,4s)-4-fluoro-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-5-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoic acid Chemical compound CC1=CC=CC=C1NC1=NC2=CC(CC(=O)N3[C@@H](C[C@H](F)C3)COC=3C=CC(=CC=3)C(O)=O)=CC=C2O1 PDGDGHYIOYTRML-SFTDATJTSA-N 0.000 description 2
- JRELJDYNGKHCTR-PMACEKPBSA-N 4-[[(2s,4s)-4-fluoro-1-[2-[7-fluoro-2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoic acid Chemical compound CC1=CC=CC=C1NC(OC1=C2F)=NC1=CC=C2CC(=O)N1[C@H](COC=2C=CC(=CC=2)C(O)=O)C[C@H](F)C1 JRELJDYNGKHCTR-PMACEKPBSA-N 0.000 description 2
- HCSCMFAAYORARA-SFTDATJTSA-N 4-[[(2s,4s)-4-hydroxy-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoic acid Chemical compound CC1=CC=CC=C1NC(OC1=C2)=NC1=CC=C2CC(=O)N1[C@H](COC=2C=CC(=CC=2)C(O)=O)C[C@H](O)C1 HCSCMFAAYORARA-SFTDATJTSA-N 0.000 description 2
- FOYQTDKPDAJMPF-UHFFFAOYSA-N 4-fluoro-1-nitro-2-phenylmethoxybenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1OCC1=CC=CC=C1 FOYQTDKPDAJMPF-UHFFFAOYSA-N 0.000 description 2
- GNRFCLMIDAFUQY-UHFFFAOYSA-N 5-fluoro-1-methoxy-2-nitro-3-phenylmethoxybenzene Chemical compound COC1=CC(F)=CC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O GNRFCLMIDAFUQY-UHFFFAOYSA-N 0.000 description 2
- QWNOVJWYWPXEAH-UHFFFAOYSA-N 5-fluoro-3-methoxy-2-nitrophenol Chemical compound COC1=CC(F)=CC(O)=C1[N+]([O-])=O QWNOVJWYWPXEAH-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 125000000815 N-oxide group Chemical group 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000001241 acetals Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 150000001448 anilines Chemical class 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
- 230000001363 autoimmune Effects 0.000 description 2
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- XJHCXCQVJFPJIK-UHFFFAOYSA-M caesium fluoride Chemical compound [F-].[Cs+] XJHCXCQVJFPJIK-UHFFFAOYSA-M 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 125000002993 cycloalkylene group Chemical group 0.000 description 2
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- TXCDCPKCNAJMEE-UHFFFAOYSA-N dibenzofuran Chemical compound C1=CC=C2C3=CC=CC=C3OC2=C1 TXCDCPKCNAJMEE-UHFFFAOYSA-N 0.000 description 2
- IYYZUPMFVPLQIF-UHFFFAOYSA-N dibenzothiophene Chemical compound C1=CC=C2C3=CC=CC=C3SC2=C1 IYYZUPMFVPLQIF-UHFFFAOYSA-N 0.000 description 2
- QUGPNQNFQMRLMO-UHFFFAOYSA-N diethyl 2-(4-nitro-3-phenylmethoxyphenyl)propanedioate Chemical compound CCOC(=O)C(C(=O)OCC)C1=CC=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=C1 QUGPNQNFQMRLMO-UHFFFAOYSA-N 0.000 description 2
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- JDDWHNKYVBMRCE-UHFFFAOYSA-N ditert-butyl 2-(2-fluoro-4-nitro-3-phenylmethoxyphenyl)propanedioate Chemical compound CC(C)(C)OC(=O)C(C(=O)OC(C)(C)C)C1=CC=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=C1F JDDWHNKYVBMRCE-UHFFFAOYSA-N 0.000 description 2
- FUAPKPMCOTVQJB-UHFFFAOYSA-N ditert-butyl 2-(3-fluoro-5-methoxy-4-nitrophenyl)propanedioate Chemical compound COC1=CC(C(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=CC(F)=C1[N+]([O-])=O FUAPKPMCOTVQJB-UHFFFAOYSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012156 elution solvent Substances 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 229940013688 formic acid Drugs 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- KMAKOBLIOCQGJP-UHFFFAOYSA-N indole-3-carboxylic acid Chemical compound C1=CC=C2C(C(=O)O)=CNC2=C1 KMAKOBLIOCQGJP-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- OXXHKZZUMZFYKD-UHFFFAOYSA-N methyl 2-(2-fluoro-3-hydroxy-4-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C([N+]([O-])=O)C(O)=C1F OXXHKZZUMZFYKD-UHFFFAOYSA-N 0.000 description 2
- CEPDWEWFQRUWPP-UHFFFAOYSA-N methyl 2-(3-amino-4-hydroxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C(N)=C1 CEPDWEWFQRUWPP-UHFFFAOYSA-N 0.000 description 2
- HRZJBKAYJFHZMV-UHFFFAOYSA-N methyl 2-(3-methoxy-4-nitro-5-phenylmethoxyphenoxy)acetate Chemical compound COC(=O)COC1=CC(OC)=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=C1 HRZJBKAYJFHZMV-UHFFFAOYSA-N 0.000 description 2
- QMYKNHKITJIHMS-UHFFFAOYSA-N methyl 2-(3-methoxy-4-nitro-5-phenylmethoxyphenyl)acetate Chemical compound COC(=O)CC1=CC(OC)=C([N+]([O-])=O)C(OCC=2C=CC=CC=2)=C1 QMYKNHKITJIHMS-UHFFFAOYSA-N 0.000 description 2
- SPCRIUSIYZYZKN-UHFFFAOYSA-N methyl 2-(4-hydroxy-3-nitrophenyl)acetate Chemical compound COC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 SPCRIUSIYZYZKN-UHFFFAOYSA-N 0.000 description 2
- GSLIFTZEPGERAL-UHFFFAOYSA-N methyl 2-[2-(2-chloroanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=CC(CC(=O)OC)=CC=C2N=C1NC1=CC=CC=C1Cl GSLIFTZEPGERAL-UHFFFAOYSA-N 0.000 description 2
- UASRKJQBGPCMQH-UHFFFAOYSA-N methyl 2-[2-(2-methylanilino)-1,3-benzoxazol-5-yl]acetate Chemical compound N=1C2=CC(CC(=O)OC)=CC=C2OC=1NC1=CC=CC=C1C UASRKJQBGPCMQH-UHFFFAOYSA-N 0.000 description 2
- HBTNNYJNCYAWJM-UHFFFAOYSA-N methyl 2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=CC(CC(=O)OC)=CC=C2N=C1NC1=CC=CC=C1C HBTNNYJNCYAWJM-UHFFFAOYSA-N 0.000 description 2
- MBJHYRQFBVNOLO-UHFFFAOYSA-N methyl 2-[7-fluoro-2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetate Chemical compound O1C2=C(F)C(CC(=O)OC)=CC=C2N=C1NC1=CC=CC=C1C MBJHYRQFBVNOLO-UHFFFAOYSA-N 0.000 description 2
- SAAZLTBXEQMNSP-KOENEWCDSA-N methyl 4-[[(2s)-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]cyclohexane-1-carboxylate Chemical compound C1CC(C(=O)OC)CCC1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)C)=NC3=CC=2)CCC1 SAAZLTBXEQMNSP-KOENEWCDSA-N 0.000 description 2
- YJWDGDNNDBQODN-NRFANRHFSA-N methyl 4-[[(2s)-4,4-difluoro-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)C)=NC3=CC=2)CC(F)(F)C1 YJWDGDNNDBQODN-NRFANRHFSA-N 0.000 description 2
- UKFOKRFBGWHHIO-PMACEKPBSA-N methyl 4-[[(2s,4s)-1-[2-[2-(2-chloroanilino)-1,3-benzoxazol-6-yl]acetyl]-4-fluoropyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)Cl)=NC3=CC=2)C[C@@H](F)C1 UKFOKRFBGWHHIO-PMACEKPBSA-N 0.000 description 2
- INFGGYYLVJHZHX-DITALETJSA-N methyl 4-[[(2s,4s)-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]-4-naphthalen-2-yloxypyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)C)=NC3=CC=2)C[C@@H](OC=2C=C3C=CC=CC3=CC=2)C1 INFGGYYLVJHZHX-DITALETJSA-N 0.000 description 2
- CBPNTDUYILICRD-WNJJXGMVSA-N methyl 4-[[(2s,4s)-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]-4-phenoxypyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)C)=NC3=CC=2)C[C@@H](OC=2C=CC=CC=2)C1 CBPNTDUYILICRD-WNJJXGMVSA-N 0.000 description 2
- UFZJSJLARIUFGA-ZCYQVOJMSA-N methyl 4-[[(2s,4s)-4-acetyloxy-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3OC(NC=4C(=CC=CC=4)C)=NC3=CC=2)C[C@@H](OC(C)=O)C1 UFZJSJLARIUFGA-ZCYQVOJMSA-N 0.000 description 2
- YUQLZCFTESYRKJ-VXKWHMMOSA-N methyl 4-[[(2s,4s)-4-fluoro-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-5-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C=C3N=C(NC=4C(=CC=CC=4)C)OC3=CC=2)C[C@@H](F)C1 YUQLZCFTESYRKJ-VXKWHMMOSA-N 0.000 description 2
- CGLPVDAMTCETOW-SFTDATJTSA-N methyl 4-[[(2s,4s)-4-fluoro-1-[2-[7-fluoro-2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)CC=2C(=C3OC(NC=4C(=CC=CC=4)C)=NC3=CC=2)F)C[C@@H](F)C1 CGLPVDAMTCETOW-SFTDATJTSA-N 0.000 description 2
- UHCNLSHFUNJJAR-UGKGYDQZSA-N methyl 4-[[(2s,4s)-4-naphthalen-2-yloxypyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1NC[C@@H](OC=2C=C3C=CC=CC3=CC=2)C1 UHCNLSHFUNJJAR-UGKGYDQZSA-N 0.000 description 2
- PMTCQIBXBTUHMQ-YJBOKZPZSA-N methyl 4-[[(2s,4s)-4-phenoxypyrrolidin-2-yl]methoxy]benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1NC[C@@H](OC=2C=CC=CC=2)C1 PMTCQIBXBTUHMQ-YJBOKZPZSA-N 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 238000013508 migration Methods 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- QKFJKGMPGYROCL-UHFFFAOYSA-N phenyl isothiocyanate Chemical compound S=C=NC1=CC=CC=C1 QKFJKGMPGYROCL-UHFFFAOYSA-N 0.000 description 2
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 150000003138 primary alcohols Chemical class 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 238000005096 rolling process Methods 0.000 description 2
- 229930195734 saturated hydrocarbon Natural products 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000012916 structural analysis Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 125000001174 sulfone group Chemical group 0.000 description 2
- AIECUIFSQFTVPD-WMZOPIPTSA-N tert-butyl (2s,4s)-2-(hydroxymethyl)-4-naphthalen-2-yloxypyrrolidine-1-carboxylate Chemical compound C1[C@@H](CO)N(C(=O)OC(C)(C)C)C[C@H]1OC1=CC=C(C=CC=C2)C2=C1 AIECUIFSQFTVPD-WMZOPIPTSA-N 0.000 description 2
- KQXJVGJKCCKERE-JSGCOSHPSA-N tert-butyl (2s,4s)-2-(hydroxymethyl)-4-phenoxypyrrolidine-1-carboxylate Chemical compound C1[C@@H](CO)N(C(=O)OC(C)(C)C)C[C@H]1OC1=CC=CC=C1 KQXJVGJKCCKERE-JSGCOSHPSA-N 0.000 description 2
- OLMDDEHUTVYMNH-DHLKQENFSA-N tert-butyl (2s,4s)-2-[(4-methoxycarbonylphenoxy)methyl]-4-naphthalen-2-yloxypyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)OC(C)(C)C)C[C@@H](OC=2C=C3C=CC=CC3=CC=2)C1 OLMDDEHUTVYMNH-DHLKQENFSA-N 0.000 description 2
- MYHZTLYGOZVUSE-RXVVDRJESA-N tert-butyl (2s,4s)-2-[(4-methoxycarbonylphenoxy)methyl]-4-phenoxypyrrolidine-1-carboxylate Chemical compound C1=CC(C(=O)OC)=CC=C1OC[C@H]1N(C(=O)OC(C)(C)C)C[C@@H](OC=2C=CC=CC=2)C1 MYHZTLYGOZVUSE-RXVVDRJESA-N 0.000 description 2
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical group CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 description 2
- JNELGWHKGNBSMD-UHFFFAOYSA-N xanthone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3OC2=C1 JNELGWHKGNBSMD-UHFFFAOYSA-N 0.000 description 2
- 229910052727 yttrium Inorganic materials 0.000 description 2
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- QBHBHOSRLDPIHG-UHFFFAOYSA-N (4-hydroxy-3-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(O)C([N+]([O-])=O)=C1 QBHBHOSRLDPIHG-UHFFFAOYSA-N 0.000 description 1
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 description 1
- PKORYTIUMAOPED-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinazoline Chemical compound C1=CC=C2NCNCC2=C1 PKORYTIUMAOPED-UHFFFAOYSA-N 0.000 description 1
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical compound C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 description 1
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 description 1
- MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
- PAFORXDSYWMYGP-UHFFFAOYSA-N 1-bromo-2-isothiocyanatobenzene Chemical compound BrC1=CC=CC=C1N=C=S PAFORXDSYWMYGP-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
- MLQPKPCDKLACIG-UHFFFAOYSA-N 1-chloro-2-isothiocyanato-3-methylbenzene Chemical compound CC1=CC=CC(Cl)=C1N=C=S MLQPKPCDKLACIG-UHFFFAOYSA-N 0.000 description 1
- DASSPOJBUMBXLU-UHFFFAOYSA-N 1-chloro-2-isothiocyanatobenzene Chemical compound ClC1=CC=CC=C1N=C=S DASSPOJBUMBXLU-UHFFFAOYSA-N 0.000 description 1
- JBDOSUUXMYMWQH-UHFFFAOYSA-N 1-naphthyl isothiocyanate Chemical compound C1=CC=C2C(N=C=S)=CC=CC2=C1 JBDOSUUXMYMWQH-UHFFFAOYSA-N 0.000 description 1
- OTDKILWMUJUUSV-KBPBESRZSA-N 1-o-tert-butyl 2-o-methyl (2s,4s)-4-phenoxypyrrolidine-1,2-dicarboxylate Chemical compound C1N(C(=O)OC(C)(C)C)[C@H](C(=O)OC)C[C@@H]1OC1=CC=CC=C1 OTDKILWMUJUUSV-KBPBESRZSA-N 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical group CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- 125000006023 1-pentenyl group Chemical group 0.000 description 1
- TZMSYXZUNZXBOL-UHFFFAOYSA-N 10H-phenoxazine Chemical compound C1=CC=C2NC3=CC=CC=C3OC2=C1 TZMSYXZUNZXBOL-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 1
- XLKDJOPOOHHZAN-UHFFFAOYSA-N 1h-pyrrolo[2,3-c]pyridine Chemical compound C1=NC=C2NC=CC2=C1 XLKDJOPOOHHZAN-UHFFFAOYSA-N 0.000 description 1
- ISZHENWZNICKIC-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2N[C]=CC2=N1 ISZHENWZNICKIC-UHFFFAOYSA-N 0.000 description 1
- WFZCVZZPXZKOPL-UHFFFAOYSA-N 1h-pyrrolo[3,2-c]pyridine Chemical compound N1=CC=C2N[C]=CC2=C1 WFZCVZZPXZKOPL-UHFFFAOYSA-N 0.000 description 1
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- ALUQMCBDQKDRAK-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzothiazole Chemical compound C1C=CC=C2SCNC21 ALUQMCBDQKDRAK-UHFFFAOYSA-N 0.000 description 1
- HNBXASAJXOOGQD-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1,3-benzoxazole Chemical compound C1C=CC=C2OCNC21 HNBXASAJXOOGQD-UHFFFAOYSA-N 0.000 description 1
- WGSMVIHKBMAWRN-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1-benzofuran Chemical compound C1C=CC=C2OCCC21 WGSMVIHKBMAWRN-UHFFFAOYSA-N 0.000 description 1
- KELIOZMTDOSCMM-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1-benzothiophene Chemical compound C1C=CC=C2SCCC21 KELIOZMTDOSCMM-UHFFFAOYSA-N 0.000 description 1
- OJHWPOJTJKJBLA-UHFFFAOYSA-N 2,3,3a,4-tetrahydro-1h-benzimidazole Chemical compound C1C=CC=C2NCNC21 OJHWPOJTJKJBLA-UHFFFAOYSA-N 0.000 description 1
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
- OXBLVCZKDOZZOJ-UHFFFAOYSA-N 2,3-Dihydrothiophene Chemical compound C1CC=CS1 OXBLVCZKDOZZOJ-UHFFFAOYSA-N 0.000 description 1
- KEGOHDCHURMFKX-UHFFFAOYSA-N 2,3-difluoro-6-nitrophenol Chemical compound OC1=C(F)C(F)=CC=C1[N+]([O-])=O KEGOHDCHURMFKX-UHFFFAOYSA-N 0.000 description 1
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- RJXOVESYJFXCGI-UHFFFAOYSA-N 2,4-difluoro-1-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1F RJXOVESYJFXCGI-UHFFFAOYSA-N 0.000 description 1
- YKZZBLCYYILKNM-UHFFFAOYSA-N 2-(2-fluoro-3-hydroxy-4-nitrophenyl)acetic acid Chemical compound OC(=O)CC1=CC=C([N+]([O-])=O)C(O)=C1F YKZZBLCYYILKNM-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- NXKMBRCOLUKRIQ-UHFFFAOYSA-N 2-(3-methoxy-4-nitro-5-phenylmethoxyphenoxy)acetic acid Chemical compound COC1=CC(OCC(O)=O)=CC(OCC=2C=CC=CC=2)=C1[N+]([O-])=O NXKMBRCOLUKRIQ-UHFFFAOYSA-N 0.000 description 1
- NETVMMWXQWMPBP-UHFFFAOYSA-N 2-(4-amino-2-fluoro-3-hydroxyphenyl)acetic acid Chemical compound NC1=CC=C(CC(O)=O)C(F)=C1O NETVMMWXQWMPBP-UHFFFAOYSA-N 0.000 description 1
- BEYOJGRZCGKLGN-UHFFFAOYSA-N 2-(6-fluoro-2-nitro-1-phenylmethoxycyclohexa-2,4-dien-1-yl)acetic acid Chemical compound C=1C=CC=CC=1COC1(CC(=O)O)C(F)C=CC=C1[N+]([O-])=O BEYOJGRZCGKLGN-UHFFFAOYSA-N 0.000 description 1
- QNYBOILAKBSWFG-UHFFFAOYSA-N 2-(phenylmethoxymethyl)oxirane Chemical compound C1OC1COCC1=CC=CC=C1 QNYBOILAKBSWFG-UHFFFAOYSA-N 0.000 description 1
- IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
- WATKZADSEKSSFD-UHFFFAOYSA-N 2-[[4-methoxy-2-(2-methylanilino)-1,3-benzoxazol-6-yl]oxy]acetic acid Chemical compound N=1C=2C(OC)=CC(OCC(O)=O)=CC=2OC=1NC1=CC=CC=C1C WATKZADSEKSSFD-UHFFFAOYSA-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
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- VAYMIYBJLRRIFR-UHFFFAOYSA-N 2-tolyl isocyanate Chemical compound CC1=CC=CC=C1N=C=O VAYMIYBJLRRIFR-UHFFFAOYSA-N 0.000 description 1
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- JZIBVTUXIVIFGC-UHFFFAOYSA-N 2H-pyrrole Chemical compound C1C=CC=N1 JZIBVTUXIVIFGC-UHFFFAOYSA-N 0.000 description 1
- SLDLVGFPFFLYBM-UHFFFAOYSA-N 3-fluoro-2-methyl-aniline Chemical compound CC1=C(N)C=CC=C1F SLDLVGFPFFLYBM-UHFFFAOYSA-N 0.000 description 1
- QIORDSKCCHRSSD-UHFFFAOYSA-N 3-methyl-2-nitrophenol Chemical compound CC1=CC=CC(O)=C1[N+]([O-])=O QIORDSKCCHRSSD-UHFFFAOYSA-N 0.000 description 1
- OCOBFMZGRJOSOU-UHFFFAOYSA-N 3-o-tert-butyl 1-o-ethyl propanedioate Chemical compound CCOC(=O)CC(=O)OC(C)(C)C OCOBFMZGRJOSOU-UHFFFAOYSA-N 0.000 description 1
- MQVPEPQLLRCIIJ-UHFFFAOYSA-N 3h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC=C2CC=NC2=N1 MQVPEPQLLRCIIJ-UHFFFAOYSA-N 0.000 description 1
- IOVSATJFPJHKHE-UHFFFAOYSA-N 3h-pyrrolo[2,3-c]pyridine Chemical compound N1=CC=C2CC=NC2=C1 IOVSATJFPJHKHE-UHFFFAOYSA-N 0.000 description 1
- MAZGUESXTVKPCZ-UHFFFAOYSA-N 3h-pyrrolo[3,2-b]pyridine Chemical compound C1=CN=C2CC=NC2=C1 MAZGUESXTVKPCZ-UHFFFAOYSA-N 0.000 description 1
- DXQVHYJTSXAFJL-UHFFFAOYSA-N 3h-pyrrolo[3,2-c]pyridine Chemical compound C1=NC=C2CC=NC2=C1 DXQVHYJTSXAFJL-UHFFFAOYSA-N 0.000 description 1
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 description 1
- FBKITRIRLKVKDU-SFTDATJTSA-N 4-[[(2s,4s)-4-fluoro-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]benzoic acid Chemical compound CC1=CC=CC=C1NC(OC1=C2)=NC1=CC=C2CC(=O)N1[C@H](COC=2C=CC(=CC=2)C(O)=O)C[C@H](F)C1 FBKITRIRLKVKDU-SFTDATJTSA-N 0.000 description 1
- VDBDGAPNWNWUSA-UHFFFAOYSA-N 4-chloro-2-isothiocyanato-1-methylbenzene Chemical compound CC1=CC=C(Cl)C=C1N=C=S VDBDGAPNWNWUSA-UHFFFAOYSA-N 0.000 description 1
- WFIPMZZOAIIOOG-UHFFFAOYSA-N 4-fluoro-1-isothiocyanato-2-methylbenzene Chemical compound CC1=CC(F)=CC=C1N=C=S WFIPMZZOAIIOOG-UHFFFAOYSA-N 0.000 description 1
- WSBDSSKIWDFOBQ-UHFFFAOYSA-N 4-iodo-2-methylphenol Chemical compound CC1=CC(I)=CC=C1O WSBDSSKIWDFOBQ-UHFFFAOYSA-N 0.000 description 1
- MRUWJENAYHTDQG-UHFFFAOYSA-N 4H-pyran Chemical compound C1C=COC=C1 MRUWJENAYHTDQG-UHFFFAOYSA-N 0.000 description 1
- VFMCUTPRJLZEEW-UHFFFAOYSA-N 4h-pyrido[1,2-a]pyrimidine Chemical compound C1=CC=CN2CC=CN=C21 VFMCUTPRJLZEEW-UHFFFAOYSA-N 0.000 description 1
- JLCDTNNLXUMYFQ-UHFFFAOYSA-N 5-fluoro-2-methylaniline Chemical compound CC1=CC=C(F)C=C1N JLCDTNNLXUMYFQ-UHFFFAOYSA-N 0.000 description 1
- QQURWFRNETXFTN-UHFFFAOYSA-N 5-fluoro-2-nitrophenol Chemical compound OC1=CC(F)=CC=C1[N+]([O-])=O QQURWFRNETXFTN-UHFFFAOYSA-N 0.000 description 1
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 1
- KYNSBQPICQTCGU-UHFFFAOYSA-N Benzopyrane Chemical compound C1=CC=C2C=CCOC2=C1 KYNSBQPICQTCGU-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZNZZEAWJSDXYKF-AAEUAGOBSA-N C1[C@H](OC(=O)C)CN[C@@H]1COC1=CC=C(C(O)=O)C=C1 Chemical compound C1[C@H](OC(=O)C)CN[C@@H]1COC1=CC=C(C(O)=O)C=C1 ZNZZEAWJSDXYKF-AAEUAGOBSA-N 0.000 description 1
- SSUFDOMYCBCHML-UHFFFAOYSA-N CCCCC[S](=O)=O Chemical group CCCCC[S](=O)=O SSUFDOMYCBCHML-UHFFFAOYSA-N 0.000 description 1
- 101100454807 Caenorhabditis elegans lgg-1 gene Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 108050001049 Extracellular proteins Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 206010019315 Heart transplant rejection Diseases 0.000 description 1
- 101000994375 Homo sapiens Integrin alpha-4 Proteins 0.000 description 1
- 101000935043 Homo sapiens Integrin beta-1 Proteins 0.000 description 1
- 238000006546 Horner-Wadsworth-Emmons reaction Methods 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102100032818 Integrin alpha-4 Human genes 0.000 description 1
- 102100025304 Integrin beta-1 Human genes 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical group CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical class CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
- 229940083963 Peptide antagonist Drugs 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 101100247669 Quaranfil virus (isolate QrfV/Tick/Afghanistan/EG_T_377/1968) PB1 gene Proteins 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 102100030852 Run domain Beclin-1-interacting and cysteine-rich domain-containing protein Human genes 0.000 description 1
- 101150025928 Segment-1 gene Proteins 0.000 description 1
- 108090000184 Selectins Proteins 0.000 description 1
- 102000003800 Selectins Human genes 0.000 description 1
- 229940124639 Selective inhibitor Drugs 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- 238000006859 Swern oxidation reaction Methods 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical compound C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 101100242902 Thogoto virus (isolate SiAr 126) Segment 1 gene Proteins 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- ZATXVRSLQDRAHZ-UHFFFAOYSA-N [1,3]oxazolo[4,5-c]pyridine Chemical compound N1=CC=C2OC=NC2=C1 ZATXVRSLQDRAHZ-UHFFFAOYSA-N 0.000 description 1
- BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
- XRVDKIQEFCJTBZ-UHFFFAOYSA-N [1,3]oxazolo[5,4-c]pyridine Chemical compound C1=NC=C2OC=NC2=C1 XRVDKIQEFCJTBZ-UHFFFAOYSA-N 0.000 description 1
- BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
- FIPLAFRCDDWERW-UHFFFAOYSA-N [1,3]thiazolo[4,5-c]pyridine Chemical compound N1=CC=C2SC=NC2=C1 FIPLAFRCDDWERW-UHFFFAOYSA-N 0.000 description 1
- WFIHKLWVLPBMIQ-UHFFFAOYSA-N [1,3]thiazolo[5,4-b]pyridine Chemical compound C1=CN=C2SC=NC2=C1 WFIHKLWVLPBMIQ-UHFFFAOYSA-N 0.000 description 1
- FHIMYVFGWKCROK-UHFFFAOYSA-N [1,3]thiazolo[5,4-c]pyridine Chemical compound C1=NC=C2SC=NC2=C1 FHIMYVFGWKCROK-UHFFFAOYSA-N 0.000 description 1
- QQIRAVWVGBTHMJ-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;lithium Chemical compound [Li].C[Si](C)(C)N[Si](C)(C)C QQIRAVWVGBTHMJ-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- CDXSJGDDABYYJV-UHFFFAOYSA-N acetic acid;ethanol Chemical compound CCO.CC(O)=O CDXSJGDDABYYJV-UHFFFAOYSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001266 acyl halides Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 102000019997 adhesion receptor Human genes 0.000 description 1
- 108010013985 adhesion receptor Proteins 0.000 description 1
- 239000003470 adrenal cortex hormone Substances 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
- 125000005360 alkyl sulfoxide group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002682 anti-psoriatic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 229940124346 antiarthritic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 229940125708 antidiabetic agent Drugs 0.000 description 1
- 239000003435 antirheumatic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
- 239000012964 benzotriazole Substances 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229950011260 betanaphthol Drugs 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 229910000085 borane Inorganic materials 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 238000010531 catalytic reduction reaction Methods 0.000 description 1
- 230000020411 cell activation Effects 0.000 description 1
- 239000002975 chemoattractant Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000005144 cycloalkylsulfonyl group Chemical group 0.000 description 1
- 125000005366 cycloalkylthio 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
- 125000004976 cyclobutylene group Chemical group 0.000 description 1
- 150000001934 cyclohexanes Chemical class 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
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004980 cyclopropylene group Chemical group 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- CDHICTNQMQYRSM-UHFFFAOYSA-N di(propan-2-yl)alumane Chemical compound CC(C)[AlH]C(C)C CDHICTNQMQYRSM-UHFFFAOYSA-N 0.000 description 1
- YDVNLQGCLLPHAH-UHFFFAOYSA-N dichloromethane;hydrate Chemical compound O.ClCCl YDVNLQGCLLPHAH-UHFFFAOYSA-N 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- YWWZCHLUQSHMCL-UHFFFAOYSA-N diphenyl diselenide Chemical compound C=1C=CC=CC=1[Se][Se]C1=CC=CC=C1 YWWZCHLUQSHMCL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 230000002500 effect on skin Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 210000003989 endothelium vascular Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 230000002327 eosinophilic effect Effects 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- CFNDVXUTYPXOPG-UHFFFAOYSA-N ethyl 2-(4-aminophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(N)C=C1 CFNDVXUTYPXOPG-UHFFFAOYSA-N 0.000 description 1
- RNZJPZQLYBBZJG-UHFFFAOYSA-N ethyl 2-(5-amino-6-chloropyridin-2-yl)acetate Chemical compound CCOC(=O)CC1=CC=C(N)C(Cl)=N1 RNZJPZQLYBBZJG-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 239000002038 ethyl acetate fraction Substances 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000012025 fluorinating agent Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000005553 heteroaryloxy group Chemical group 0.000 description 1
- 125000006588 heterocycloalkylene group Chemical group 0.000 description 1
- 125000003707 hexyloxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 1
- 229960002591 hydroxyproline Drugs 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 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
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 230000023404 leukocyte cell-cell adhesion Effects 0.000 description 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 description 1
- 239000011981 lindlar catalyst Substances 0.000 description 1
- GUWHRJQTTVADPB-UHFFFAOYSA-N lithium azide Chemical compound [Li+].[N-]=[N+]=[N-] GUWHRJQTTVADPB-UHFFFAOYSA-N 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- DBYQHFPBWKKZAT-UHFFFAOYSA-N lithium;benzene Chemical compound [Li+].C1=CC=[C-]C=C1 DBYQHFPBWKKZAT-UHFFFAOYSA-N 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- FDEHBKRHLQPVSL-UHFFFAOYSA-N methyl 2-(4-amino-3-chlorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(N)C(Cl)=C1 FDEHBKRHLQPVSL-UHFFFAOYSA-N 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- RVVAGWAATWTKFD-LLVKDONJSA-N methyl 4-[(3r)-pyrrolidin-3-yl]oxybenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1O[C@H]1CNCC1 RVVAGWAATWTKFD-LLVKDONJSA-N 0.000 description 1
- LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004957 naphthylene group Chemical group 0.000 description 1
- 125000005146 naphthylsulfonyl group Chemical group C1(=CC=CC2=CC=CC=C12)S(=O)(=O)* 0.000 description 1
- 125000005029 naphthylthio group Chemical group C1(=CC=CC2=CC=CC=C12)S* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000002347 octyl 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])[H] 0.000 description 1
- 125000005447 octyloxy 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])O* 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 229940117953 phenylisothiocyanate Drugs 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- AAEVYOVXGOFMJO-UHFFFAOYSA-N prometryn Chemical compound CSC1=NC(NC(C)C)=NC(NC(C)C)=N1 AAEVYOVXGOFMJO-UHFFFAOYSA-N 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000005554 pyridyloxy group Chemical group 0.000 description 1
- JCZPOYAMKJFOLA-UHFFFAOYSA-N pyrrolidine-3,4-diol Chemical compound OC1CNCC1O JCZPOYAMKJFOLA-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- KWWPLMMECWKOFF-UHFFFAOYSA-M sodium;benzeneselenolate Chemical compound [Na+].[Se-]C1=CC=CC=C1 KWWPLMMECWKOFF-UHFFFAOYSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- RQHNYVPOQUCOBM-UHFFFAOYSA-N tert-butyl 2-(4-amino-3-methylphenyl)acetate Chemical compound CC1=CC(CC(=O)OC(C)(C)C)=CC=C1N RQHNYVPOQUCOBM-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 125000000101 thioether group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 230000036964 tight binding Effects 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
- 150000003852 triazoles Chemical class 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical class OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
- C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
-
- 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
- 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
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C275/00—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C275/28—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C275/42—Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton being further substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
- C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Emergency Medicine (AREA)
- Hematology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Oncology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000402890 | 2000-12-28 | ||
JP2001149923 | 2001-05-18 | ||
PCT/JP2001/011641 WO2002053534A1 (fr) | 2000-12-28 | 2001-12-28 | Inhibiteurs de vla-4 |
Publications (3)
Publication Number | Publication Date |
---|---|
NO20032994D0 NO20032994D0 (no) | 2003-06-27 |
NO20032994L NO20032994L (no) | 2003-08-27 |
NO326014B1 true NO326014B1 (no) | 2008-09-01 |
Family
ID=26607210
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20032994A NO326014B1 (no) | 2000-12-28 | 2003-06-27 | VLA-4 inhibitorer, medikamenter inneholdened slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom |
Country Status (17)
Country | Link |
---|---|
US (1) | US7157487B2 (zh) |
EP (1) | EP1346982B1 (zh) |
JP (1) | JP4212358B2 (zh) |
KR (1) | KR100884877B1 (zh) |
CN (1) | CN100471838C (zh) |
AR (1) | AR035218A1 (zh) |
AT (1) | ATE524441T1 (zh) |
AU (1) | AU2002219555B2 (zh) |
BR (1) | BR0116608A (zh) |
CA (1) | CA2430978C (zh) |
HK (2) | HK1060726A1 (zh) |
IL (1) | IL156064A0 (zh) |
MX (1) | MXPA03005838A (zh) |
NO (1) | NO326014B1 (zh) |
RU (1) | RU2290403C2 (zh) |
TW (1) | TWI312779B (zh) |
WO (1) | WO2002053534A1 (zh) |
Families Citing this family (75)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB0031315D0 (en) * | 2000-12-21 | 2001-02-07 | Glaxo Group Ltd | Indole derivatives |
DE60329910D1 (de) * | 2002-03-29 | 2009-12-17 | Novartis Vaccines & Diagnostic | Substituierte benzazole und ihre verwendung als raf-kinase-hemmer |
MXPA05003391A (es) * | 2002-10-03 | 2005-06-22 | Hoffmann La Roche | Indol-3-carboxamidas como activadores de glucocinasa. |
US20070066577A1 (en) * | 2003-04-03 | 2007-03-22 | Hea Young Park Choo | Benzoxazole derivative or analogue thereof for inhibiting 5-lipoxygenase and pharmaceutical composition containing same |
WO2004099136A1 (ja) * | 2003-05-09 | 2004-11-18 | Daiichi Pharmaceutical Co., Ltd. | ピロリジン誘導体の製造方法 |
EP1479675A1 (en) * | 2003-05-19 | 2004-11-24 | Aventis Pharma Deutschland GmbH | Indazole-derivatives as factor Xa inhibitors |
ES2382806T3 (es) | 2003-07-24 | 2012-06-13 | Daiichi Sankyo Company, Limited | Compuesto ácido ciclohexanocarboxílico |
US6984652B2 (en) | 2003-09-05 | 2006-01-10 | Warner-Lambert Company Llc | Gyrase inhibitors |
WO2005066124A1 (ja) * | 2003-12-26 | 2005-07-21 | Daiichi Pharmaceutical Co., Ltd. | ピロリジン誘導体の製造法 |
US20070149606A1 (en) * | 2003-12-26 | 2007-06-28 | Daiichi Pharmaceutical Co.,Ltd. | Process for producing phenylacetic acid derivative |
BRPI0509150B8 (pt) * | 2004-03-24 | 2021-05-25 | Jerini Ag | compostos para a inibição de angiogênese e uso destes |
JP2005350417A (ja) * | 2004-06-11 | 2005-12-22 | Dai Ichi Seiyaku Co Ltd | 還元的エーテル化法を用いたピロリジン誘導体の製造法 |
TW200610754A (en) * | 2004-06-14 | 2006-04-01 | Daiichi Seiyaku Co | Vla-4 inhibitor |
US7781478B2 (en) | 2004-07-14 | 2010-08-24 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US8013006B2 (en) | 2004-07-14 | 2011-09-06 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7772271B2 (en) | 2004-07-14 | 2010-08-10 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
US7868037B2 (en) | 2004-07-14 | 2011-01-11 | Ptc Therapeutics, Inc. | Methods for treating hepatitis C |
EP1781289A1 (en) | 2004-07-22 | 2007-05-09 | PTC Therapeutics, Inc. | Thienopyridines for treating hepatitis c |
JP2006056830A (ja) * | 2004-08-20 | 2006-03-02 | Dai Ichi Seiyaku Co Ltd | 2−アリールアミノベンゾオキサゾール誘導体 |
JP2008520744A (ja) * | 2004-11-19 | 2008-06-19 | ザ・レジェンツ・オブ・ザ・ユニバーシティ・オブ・カリフォルニア | 抗炎症性ピラゾロピリミジン |
AU2006282403B2 (en) * | 2005-08-26 | 2011-07-07 | Institute Of Medicinal Molecular Design, Inc. | Derivative having PPAR agonistic activity |
US8129366B2 (en) | 2005-12-13 | 2012-03-06 | Daiichi Sankyo Company, Limited | VLA-4 inhibitory drug |
MX2008012929A (es) | 2006-04-04 | 2008-12-17 | Univ California | Antagonistas de cinasa. |
DE102006021878A1 (de) * | 2006-05-11 | 2007-11-15 | Sanofi-Aventis | Phenylamino-benzoxazol substituierte Carbonsäuren, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
US7858645B2 (en) * | 2006-11-01 | 2010-12-28 | Hoffmann-La Roche Inc. | Indazole derivatives |
US20110160232A1 (en) * | 2007-10-04 | 2011-06-30 | Pingda Ren | Certain chemical entities and therapeutic uses thereof |
US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
SG187425A1 (en) | 2008-01-04 | 2013-02-28 | Intellikine Llc | Certain chemical entities, compositions and methods |
WO2009114874A2 (en) | 2008-03-14 | 2009-09-17 | Intellikine, Inc. | Benzothiazole kinase inhibitors and methods of use |
JP5547099B2 (ja) * | 2008-03-14 | 2014-07-09 | インテリカイン, エルエルシー | キナーゼ阻害剤および使用方法 |
WO2010006072A2 (en) * | 2008-07-08 | 2010-01-14 | The Regents Of The University Of California | Mtor modulators and uses thereof |
JP5788316B2 (ja) | 2008-07-08 | 2015-09-30 | インテリカイン, エルエルシー | キナーゼインヒビターおよび使用方法 |
US8703778B2 (en) | 2008-09-26 | 2014-04-22 | Intellikine Llc | Heterocyclic kinase inhibitors |
CA2740885C (en) | 2008-10-16 | 2018-04-03 | The Regents Of The University Of California | Fused ring heteroaryl kinase inhibitors |
US8476431B2 (en) | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
EP4059932A1 (en) | 2008-12-19 | 2022-09-21 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
WO2010098866A1 (en) | 2009-02-27 | 2010-09-02 | Supergen, Inc. | Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors |
WO2010129816A2 (en) | 2009-05-07 | 2010-11-11 | Intellikine, Inc. | Heterocyclic compounds and uses thereof |
CA2765053C (en) | 2009-06-09 | 2015-08-18 | California Capital Equity, Llc | Isoquinoline, quinoline, and quinazoline derivatives as inhibitors of hedgehog signaling |
CN102573484B (zh) | 2009-06-09 | 2015-07-01 | 加利福尼亚资本权益有限责任公司 | 苄基取代的三嗪衍生物及其治疗应用 |
JP5785940B2 (ja) | 2009-06-09 | 2015-09-30 | アブラクシス バイオサイエンス, エルエルシー | トリアジン誘導体類及びそれらの治療応用 |
WO2011020874A1 (en) | 2009-08-20 | 2011-02-24 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Vla-4 as a biomarker for prognosis and target for therapy in duchenne muscular dystrophy |
WO2011047384A2 (en) | 2009-10-16 | 2011-04-21 | The Regents Of The University Of California | Methods of inhibiting ire1 |
CA2778115C (en) | 2009-10-28 | 2016-04-05 | Newlink Genetics Corporation | Imidazole derivatives as ido inhibitors |
CA2799579A1 (en) | 2010-05-21 | 2011-11-24 | Intellikine, Inc. | Chemical compounds, compositions and methods for kinase modulation |
CN103298474B (zh) | 2010-11-10 | 2016-06-29 | 无限药品股份有限公司 | 杂环化合物及其用途 |
ES2637113T3 (es) | 2011-01-10 | 2017-10-10 | Infinity Pharmaceuticals, Inc. | Procedimientos para preparar isoquinolinonas y formas sólidas de isoquinolinonas |
JP6130305B2 (ja) | 2011-02-23 | 2017-05-17 | インテリカイン, エルエルシー | キナーゼ阻害剤の組み合わせおよびそれらの使用 |
CA2842190A1 (en) | 2011-07-19 | 2013-01-24 | Infinity Pharmaceuticals Inc. | Heterocyclic compounds and uses thereof |
US8969363B2 (en) | 2011-07-19 | 2015-03-03 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
RU2014111823A (ru) | 2011-08-29 | 2015-10-10 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения и их применения |
JP6342805B2 (ja) | 2011-09-02 | 2018-06-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 置換ピラゾロ[3,4−d]ピリミジンおよびその用途 |
US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
CN104995192A (zh) | 2012-09-26 | 2015-10-21 | 加利福尼亚大学董事会 | Ire1的调节 |
US9481667B2 (en) | 2013-03-15 | 2016-11-01 | Infinity Pharmaceuticals, Inc. | Salts and solid forms of isoquinolinones and composition comprising and methods of using the same |
MX2021012208A (es) | 2013-10-04 | 2023-01-19 | Infinity Pharmaceuticals Inc | Compuestos heterocíclicos y usos de los mismos. |
US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
MX2016012021A (es) | 2014-03-19 | 2017-04-13 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos para utilizarlos en el tratamiento de trastornos mediados por pi3k-gamma. |
US20150320755A1 (en) | 2014-04-16 | 2015-11-12 | Infinity Pharmaceuticals, Inc. | Combination therapies |
WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
WO2016071499A1 (en) * | 2014-11-06 | 2016-05-12 | Basf Se | 3-pyridyl heterobicyclic compound for controlling invertebrate pests |
SG10201911849SA (en) | 2015-06-09 | 2020-01-30 | Abbvie Inc | Nuclear receptor modulators |
EP3350183A1 (en) | 2015-09-14 | 2018-07-25 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same |
WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
AU2017281797A1 (en) | 2016-06-24 | 2019-01-24 | Infinity Pharmaceuticals, Inc. | Combination therapies |
CN112969687A (zh) | 2018-10-30 | 2021-06-15 | 吉利德科学公司 | 作为α4β7整合素抑制剂的喹啉衍生物 |
WO2020092401A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | COMPOUNDS FOR INHIBITION OF ALPHA 4β7 INTEGRIN |
AU2019373242B2 (en) | 2018-10-30 | 2023-07-13 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4 beta 7 integrin |
US11174256B2 (en) | 2018-10-30 | 2021-11-16 | Gilead Sciences, Inc. | Imidazopyridine derivatives |
CA3148613A1 (en) | 2019-08-14 | 2021-02-18 | Gilead Sciences, Inc. | Phenylalanine derived compounds and their use as inhinitors of alpha 4 beta 7 integrin |
AU2021289665A1 (en) | 2020-06-10 | 2022-12-15 | Aligos Therapeutics, Inc. | Anti-viral compounds for treating coronavirus, picornavirus, and norovirus infections |
EP4284947A1 (en) | 2021-01-29 | 2023-12-06 | Institut National de la Santé et de la Recherche Médicale (INSERM) | Methods of assessing the risk of developing progressive multifocal leukoencephalopathy in patients treated with vla-4 antagonists |
CA3224494A1 (en) | 2021-07-09 | 2023-01-12 | Koen Vandyck | Anti-viral compounds |
Family Cites Families (49)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6204261B1 (en) * | 1995-12-20 | 2001-03-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β Converting enzyme inhibitors |
DE2500157C2 (de) * | 1975-01-03 | 1983-09-15 | Hoechst Ag, 6230 Frankfurt | N-Acyl-4-(2-aminoäthyl)-benzoesäuren, deren Salze und Ester, Verfahren zu deren Herstellung und deren Verwendung |
DE2706977A1 (de) * | 1977-02-18 | 1978-08-24 | Hoechst Ag | Benzoesaeuren und deren derivate sowie verfahren zu ihrer herstellung |
US4184658A (en) | 1978-02-13 | 1980-01-22 | General Electric Company | Cushion mount for prime mover |
DE3063878D1 (en) | 1979-07-13 | 1983-07-28 | Thomae Gmbh Dr K | Derivatives of carboxylic acids, their preparation and medicaments containing them |
JPS60181081A (ja) | 1984-02-29 | 1985-09-14 | Kaken Pharmaceut Co Ltd | 新規ビスベンゾフラニルケトン誘導体 |
JPH04112868A (ja) | 1990-09-03 | 1992-04-14 | Otsuka Pharmaceut Co Ltd | 置換ヘテロ環を有するフェニルカルボン酸誘導体 |
JPH0543574A (ja) | 1991-08-13 | 1993-02-23 | Wakamoto Pharmaceut Co Ltd | ヘテロ環置換テトラゾール−1−酢酸誘導体 |
FR2694295B1 (fr) | 1992-07-28 | 1994-09-02 | Adir | Nouveaux peptides dérivés de trifluoromethylcetones, leur procéde de préparation et les compositions pharmaceutiques qui les contiennent. |
US5821231A (en) | 1993-12-06 | 1998-10-13 | Cytel Corporation | CS-1 peptidomimetics, compositions and methods of using same |
ES2103181B1 (es) * | 1994-08-01 | 1998-04-01 | Menarini Lab | Amidas naftalenicas con accion antagonista de los leucotrienos. |
GB9408936D0 (en) | 1994-05-05 | 1994-06-22 | Cancer Res Inst | Anti-cancer compounds |
US6306840B1 (en) | 1995-01-23 | 2001-10-23 | Biogen, Inc. | Cell adhesion inhibitors |
AU6405596A (en) * | 1995-06-30 | 1997-02-05 | Smithkline Beecham Corporation | Use of stat 5 sh2 domain specific compounds to enhance erythropoiesis |
US6248713B1 (en) | 1995-07-11 | 2001-06-19 | Biogen, Inc. | Cell adhesion inhibitors |
PL190866B1 (pl) | 1996-07-25 | 2006-02-28 | Biogen | Inhibitor adhezji komórek, sposób jego wytwarzania i jego zastosowanie oraz kompozycja farmaceutyczna i sposób jej wytwarzania |
CA2264020A1 (en) | 1996-08-26 | 1998-03-05 | Jean Bemis | Inhibitors of phospholipase enzymes |
DE19647381A1 (de) | 1996-11-15 | 1998-05-20 | Hoechst Ag | Neue Heterocyclen als Inhibitoren der Leukozytenadhäsion und VLA-4-Antagonisten |
CN1237960A (zh) | 1996-11-22 | 1999-12-08 | 伊兰药品公司 | N(-芳基/杂芳基乙酰基)氨基酸酯、包括这些酯的药用组合物以及用这些化合物抑制β淀粉样肽释放和/或合成的方法 |
US6117901A (en) * | 1996-11-22 | 2000-09-12 | Athena Neurosciences, Inc. | N-(aryl/heteroarylacetyl) amino acid esters, pharmaceutical compositions comprising same, and methods for use |
CZ20002342A3 (cs) | 1997-12-23 | 2001-11-14 | Aventis Pharma Limited | Substituované ß-alaniny |
CA2322163A1 (en) | 1998-02-25 | 1999-09-02 | John Mckew | Inhibitors of phospholipase a2 |
NZ509199A (en) | 1998-05-28 | 2003-10-31 | Biogen Inc | A VLA-4 inhibitor: oMePUPA-V |
WO1999064392A1 (fr) * | 1998-06-08 | 1999-12-16 | Ajinomoto Co., Inc. | Derive de benzamidine |
WO2000000477A1 (en) | 1998-06-30 | 2000-01-06 | Pfizer Products Inc. | Non-peptidyl inhibitors of vla-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases |
EP1133484A2 (en) * | 1998-07-23 | 2001-09-19 | AstraZeneca AB | Heterocyclic derivatives and their use as integrin inhibitors |
GB9916374D0 (en) | 1998-07-23 | 1999-09-15 | Zeneca Ltd | Chemical compounds |
DK1114028T3 (da) | 1998-08-26 | 2007-04-30 | Aventis Pharma Ltd | Azabicykliske forbindelser, der modulerer inhibering af celleadhæsion |
GB9821199D0 (en) * | 1998-09-30 | 1998-11-25 | Glaxo Group Ltd | Chemical compounds |
US6207700B1 (en) * | 1999-01-07 | 2001-03-27 | Vanderbilt University | Amide derivatives for antiangiogenic and/or antitumorigenic use |
ATE325105T1 (de) | 1999-02-16 | 2006-06-15 | Aventis Pharma Ltd | Bicyclische verbindungen und ihre verwendung als integrinrezeptorliganden |
JP2000344666A (ja) | 1999-04-01 | 2000-12-12 | Sankyo Co Ltd | 糖及び脂質代謝改善剤 |
EP1183254B1 (en) | 1999-04-12 | 2005-01-12 | Aventis Pharma Limited | Substituted bicyclic heteroaryl compounds as integrin antagonists |
AU769652B2 (en) | 1999-05-05 | 2004-01-29 | Cubist Pharmaceuticals, Inc. | Novel prolines as antimicrobial agents |
AU4591600A (en) | 1999-05-05 | 2000-11-21 | Aventis Pharma Limited | Substituted bicyclic compounds |
ATE263162T1 (de) | 1999-05-05 | 2004-04-15 | Aventis Pharma Ltd | Harnstoffderivate und ihr gebrauch als zell adhesion modulatoren |
CA2372836C (en) | 1999-05-05 | 2009-01-20 | Aventis Pharma Limited | Substituted pyrrolidines as cell adhesion inhibitors |
US6756378B2 (en) * | 1999-06-30 | 2004-06-29 | Pharmacopeia Drug Discovery, Inc. | VLA-4 inhibitor compounds |
JP2003503350A (ja) | 1999-06-30 | 2003-01-28 | 第一製薬株式会社 | Vla−4インヒビター化合物 |
CZ2002518A3 (cs) | 1999-08-13 | 2002-05-15 | Biogen, Inc. | Inhibitory buněčné adheze a farmaceutické prostředky, které je obsahují |
IL149544A0 (en) | 1999-11-10 | 2002-11-10 | Aventis Pharma Gmbh | N-ACYLPYRROLIDIN-2-YLALKYLBENZAMIDINE DERIVATIVES AS INHIBITORS OF FACTOR Xa |
NZ518886A (en) * | 1999-12-28 | 2004-02-27 | Pfizer Prod Inc | Non-peptidyl inhibitors of VLA-4 dependent cell binding useful in treating inflammatory, autoimmune, and respiratory diseases |
GB0001346D0 (en) | 2000-01-21 | 2000-03-08 | Astrazeneca Uk Ltd | Chemical compounds |
DE10006453A1 (de) | 2000-02-14 | 2001-08-16 | Bayer Ag | Piperidylcarbonsäuren als Integrinantagonisten |
GB0004686D0 (en) | 2000-02-28 | 2000-04-19 | Aventis Pharma Ltd | Chemical compounds |
AU2001235806A1 (en) | 2000-03-01 | 2001-09-12 | Aventis Pharma Limited | 2,3-dihydro-1h-indolinyl-alkanoic acids as cell adhesion inhibitors |
US6448281B1 (en) | 2000-07-06 | 2002-09-10 | Boehringer Ingelheim (Canada) Ltd. | Viral polymerase inhibitors |
BR0112580A (pt) | 2000-07-19 | 2003-06-17 | Hoffmann La Roche | Compostos, composições farmacêuticas que contêm os mesmos, utilização desses compostos, processo para tratamento terapêutico e/ou profilático e processo para a preparação desses compostos |
GB2377933A (en) | 2001-07-06 | 2003-01-29 | Bayer Ag | Succinic acid derivatives useful as integrin antagonists |
-
2001
- 2001-12-28 WO PCT/JP2001/011641 patent/WO2002053534A1/ja active Application Filing
- 2001-12-28 TW TW090133464A patent/TWI312779B/zh not_active IP Right Cessation
- 2001-12-28 EP EP01272548A patent/EP1346982B1/en not_active Expired - Lifetime
- 2001-12-28 AT AT01272548T patent/ATE524441T1/de not_active IP Right Cessation
- 2001-12-28 BR BR0116608-5A patent/BR0116608A/pt not_active IP Right Cessation
- 2001-12-28 CA CA2430978A patent/CA2430978C/en not_active Expired - Fee Related
- 2001-12-28 CN CNB018214843A patent/CN100471838C/zh not_active Expired - Fee Related
- 2001-12-28 US US10/451,159 patent/US7157487B2/en not_active Expired - Fee Related
- 2001-12-28 IL IL15606401A patent/IL156064A0/xx unknown
- 2001-12-28 KR KR1020037008702A patent/KR100884877B1/ko not_active IP Right Cessation
- 2001-12-28 JP JP2002554653A patent/JP4212358B2/ja not_active Expired - Fee Related
- 2001-12-28 AU AU2002219555A patent/AU2002219555B2/en not_active Ceased
- 2001-12-28 RU RU2003123115/04A patent/RU2290403C2/ru active
- 2001-12-28 MX MXPA03005838A patent/MXPA03005838A/es active IP Right Grant
- 2001-12-28 AR ARP010106105A patent/AR035218A1/es unknown
-
2003
- 2003-06-27 NO NO20032994A patent/NO326014B1/no not_active IP Right Cessation
-
2004
- 2004-05-07 HK HK04103218.6A patent/HK1060726A1/xx not_active IP Right Cessation
-
2006
- 2006-02-08 HK HK06101636.2A patent/HK1081545A1/xx not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
HK1060726A1 (en) | 2004-08-20 |
US20040110945A1 (en) | 2004-06-10 |
AR035218A1 (es) | 2004-05-05 |
HK1081545A1 (en) | 2006-05-19 |
CN100471838C (zh) | 2009-03-25 |
ATE524441T1 (de) | 2011-09-15 |
EP1346982A4 (en) | 2005-08-10 |
CN1483024A (zh) | 2004-03-17 |
NO20032994L (no) | 2003-08-27 |
IL156064A0 (en) | 2003-12-23 |
MXPA03005838A (es) | 2003-09-10 |
EP1346982B1 (en) | 2011-09-14 |
AU2002219555B2 (en) | 2006-11-30 |
KR100884877B1 (ko) | 2009-02-23 |
JPWO2002053534A1 (ja) | 2004-04-30 |
CA2430978C (en) | 2012-05-15 |
WO2002053534A8 (fr) | 2002-09-19 |
RU2290403C2 (ru) | 2006-12-27 |
KR20030067730A (ko) | 2003-08-14 |
RU2003123115A (ru) | 2005-03-27 |
NO20032994D0 (no) | 2003-06-27 |
EP1346982A1 (en) | 2003-09-24 |
TWI312779B (zh) | 2009-08-01 |
US7157487B2 (en) | 2007-01-02 |
CA2430978A1 (en) | 2002-07-11 |
BR0116608A (pt) | 2004-06-29 |
WO2002053534A1 (fr) | 2002-07-11 |
JP4212358B2 (ja) | 2009-01-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO326014B1 (no) | VLA-4 inhibitorer, medikamenter inneholdened slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom | |
TWI444378B (zh) | 具有β-分泌酶抑制作用之含硫雜環衍生物及其用途 | |
JP2022518860A (ja) | 免疫調節剤、組成物およびその使用方法 | |
RU2636050C2 (ru) | Замещенные пирролидины в качестве ингибиторов фактора xia для лечения тромбоэмболических заболеваний | |
JP2019537557A (ja) | Fxrアゴニストとしてのイソキサゾール類似体およびその使用方法 | |
TW201823208A (zh) | N-醯基胺基酸化合物及其使用方法 | |
KR20220102156A (ko) | Bcl6 표적화 모이어티에 연결된 e3 유비퀴틴 리가아제 결합 모이어티를 함유하는 이기능성 분자 | |
JP2008510006A (ja) | 化合物 | |
JP2012524760A (ja) | オレキシンアンタゴニストとして使用される3−アザビシクロ[4.1.0]ヘプタン | |
WO1998018794A1 (fr) | Nouveaux composes d'amide heterocycliques et leur utilisation a des fins medicinales | |
KR20060132966A (ko) | 콜레스테릴 에스테르 운반 단백질 저해제로서의테트라히드로나프티리딘 유도체 | |
EA039808B1 (ru) | Аминотриазолопиридины в качестве ингибиторов киназ | |
KR20080063288A (ko) | 신규 융합 피롤 유도체 | |
JP2017001991A (ja) | 新規ベンズオキサゾロン化合物 | |
RU2669701C2 (ru) | Производные пиперидина в качестве антагонистов рецептора орексина | |
CA2960791A1 (en) | Substituted 2-azabicycles and their use as orexin receptor modulators | |
JPWO2005121135A1 (ja) | Vla−4阻害薬 | |
JP2001294572A (ja) | 新規スルホニル誘導体 | |
CA3074059A1 (en) | Substituted 2-azabicyclo[3.1.1]heptane and 2-azabicyclo[3.2.1]octane derivatives as orexin receptor antagonists | |
KR20110025970A (ko) | 트롬빈 억제제로서 사용하기 위한 신규 복소환 카복스아미드 | |
TWI820266B (zh) | 巨環化合物及其用途 | |
KR20180050408A (ko) | 국부 약물 전달용의 비스테로이드성 글루코코르티코이드 수용체 조절제 | |
CN114641466A (zh) | 磺酰脲衍生物及其用途 | |
JP2000119253A (ja) | 新規なスルホニル誘導体 | |
CN100396680C (zh) | 极迟抗原-4抑制剂 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |