NO326554B1 - Fenylalaninenamid-derivater som har en cyklobutengruppe, for anvendelse som integrin-inhibitorer og farmasoytisk sammensetning - Google Patents
Fenylalaninenamid-derivater som har en cyklobutengruppe, for anvendelse som integrin-inhibitorer og farmasoytisk sammensetning Download PDFInfo
- Publication number
- NO326554B1 NO326554B1 NO20033710A NO20033710A NO326554B1 NO 326554 B1 NO326554 B1 NO 326554B1 NO 20033710 A NO20033710 A NO 20033710A NO 20033710 A NO20033710 A NO 20033710A NO 326554 B1 NO326554 B1 NO 326554B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- phenyl
- spiro
- oxo
- dichloroisonicotinoyl
- Prior art date
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- 239000008194 pharmaceutical composition Substances 0.000 title claims 3
- 108010044426 integrins Proteins 0.000 title description 20
- 102000006495 integrins Human genes 0.000 title description 20
- 239000003112 inhibitor Substances 0.000 title description 3
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 title description 2
- OBSIQMZKFXFYLV-QMMMGPOBSA-N L-phenylalanine amide Chemical class NC(=O)[C@@H](N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-QMMMGPOBSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 508
- -1 amino- Chemical class 0.000 claims description 443
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 356
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 230
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 160
- 235000019260 propionic acid Nutrition 0.000 claims description 118
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 74
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 47
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 39
- 125000005843 halogen group Chemical group 0.000 claims description 38
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 36
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- 238000002360 preparation method Methods 0.000 claims description 20
- 125000004429 atom Chemical group 0.000 claims description 18
- 150000001204 N-oxides Chemical class 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 125000003003 spiro group Chemical group 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 150000004677 hydrates Chemical class 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims description 11
- 125000001931 aliphatic group Chemical group 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000003396 thiol group Chemical class [H]S* 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 6
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- HXHLKOHATAXUCC-SFHVURJKSA-N (2s)-2-[(2-bromo-3-oxospiro[3.6]dec-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCCC2)C(=O)C=1Br)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl HXHLKOHATAXUCC-SFHVURJKSA-N 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- WSWRFQZIBPTZRG-INIZCTEOSA-N (2s)-2-[(2-bromo-3-oxospiro[3.4]oct-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCC2)C(=O)C=1Br)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl WSWRFQZIBPTZRG-INIZCTEOSA-N 0.000 claims description 4
- SYSVEGKCBIVWHJ-INIZCTEOSA-N (2s)-2-[(2-bromo-3-oxospiro[3.4]octa-1,6-dien-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CC=CC2)C(=O)C=1Br)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl SYSVEGKCBIVWHJ-INIZCTEOSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005549 heteroarylene group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 229910052711 selenium Inorganic materials 0.000 claims description 4
- OTFWZPKUZIUYSS-FQEVSTJZSA-N (2s)-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[[2-(1,3-dithian-2-yl)-3-oxospiro[3.5]non-1-en-1-yl]amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCC2)C(=O)C=1C1SCCCS1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl OTFWZPKUZIUYSS-FQEVSTJZSA-N 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- RYVZYACBVYKUHD-UHFFFAOYSA-N Alk5 Natural products CC#CC#CCCCCC=CC(=O)NCC(C)C RYVZYACBVYKUHD-UHFFFAOYSA-N 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims description 3
- 229910006069 SO3H Inorganic materials 0.000 claims description 3
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000005649 substituted arylene group Chemical group 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 claims description 3
- JJANVZGEUQXJGX-FQEVSTJZSA-N (2s)-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[(3-oxo-2-propyl-7-oxaspiro[3.5]non-1-en-1-yl)amino]propanoic acid Chemical compound C([C@H](NC1=C(C(C11CCOCC1)=O)CCC)C(O)=O)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl JJANVZGEUQXJGX-FQEVSTJZSA-N 0.000 claims description 2
- GUKHPVJGAOYUJF-SFHVURJKSA-N (2s)-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[(3-oxospiro[3.5]non-1-en-1-yl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCC2)C(=O)C=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl GUKHPVJGAOYUJF-SFHVURJKSA-N 0.000 claims description 2
- 101100448208 Human herpesvirus 6B (strain Z29) U69 gene Proteins 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 235000010290 biphenyl Nutrition 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 201000006417 multiple sclerosis Diseases 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 125000005650 substituted phenylene group Chemical group 0.000 claims description 2
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000565 sulfonamide group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- MWPREONFTFDTMG-KRWDZBQOSA-N (2s)-2-[(2-bromo-3-oxospiro[3.5]non-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCC2)C(=O)C=1Br)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl MWPREONFTFDTMG-KRWDZBQOSA-N 0.000 claims 1
- VWUCRCHOLPTURV-CLEJVJKTSA-N (2s)-2-[(2-bromo-7-methoxy-3-oxospiro[3.5]non-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C1CC(OC)CCC21C(N[C@@H](CC=1C=CC(NC(=O)C=3C(=CN=CC=3Cl)Cl)=CC=1)C(O)=O)=C(Br)C2=O VWUCRCHOLPTURV-CLEJVJKTSA-N 0.000 claims 1
- MJQMWWJGAYSXJX-INIZCTEOSA-N (2s)-2-[(2-chloro-3-oxospiro[3.4]oct-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCC2)C(=O)C=1Cl)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl MJQMWWJGAYSXJX-INIZCTEOSA-N 0.000 claims 1
- SQHJZCGOPOCHPA-KRWDZBQOSA-N (2s)-2-[(2-chloro-3-oxospiro[3.5]non-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCC2)C(=O)C=1Cl)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl SQHJZCGOPOCHPA-KRWDZBQOSA-N 0.000 claims 1
- PJZAIVXMZYUDRJ-QHCPKHFHSA-N (2s)-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]-2-[(3-oxo-2-propan-2-ylsulfanylspiro[3.5]non-1-en-1-yl)amino]propanoic acid Chemical compound O=C1C(SC(C)C)=C(N[C@@H](CC=2C=CC(NC=3C4=CN=CC=C4C=CN=3)=CC=2)C(O)=O)C21CCCCC2 PJZAIVXMZYUDRJ-QHCPKHFHSA-N 0.000 claims 1
- ZNLJKQYKZQJSKL-NRFANRHFSA-N (2s)-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[(3-oxo-2-propylspiro[3.5]non-1-en-1-yl)amino]propanoic acid Chemical compound C([C@H](NC1=C(C(C11CCCCC1)=O)CCC)C(O)=O)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl ZNLJKQYKZQJSKL-NRFANRHFSA-N 0.000 claims 1
- LKNPFXKUPAYTJD-IBGZPJMESA-N (2s)-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[(3-oxospiro[3.6]dec-1-en-1-yl)amino]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCCC2)C(=O)C=1)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl LKNPFXKUPAYTJD-IBGZPJMESA-N 0.000 claims 1
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 1
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims 1
- QCYAXXZCQKMTMO-QFIPXVFZSA-N ethyl (2s)-2-[(2-bromo-3-oxospiro[3.5]non-1-en-1-yl)amino]-3-[4-(2,7-naphthyridin-1-ylamino)phenyl]propanoate Chemical compound N([C@@H](CC=1C=CC(NC=2C3=CN=CC=C3C=CN=2)=CC=1)C(=O)OCC)C1=C(Br)C(=O)C11CCCCC1 QCYAXXZCQKMTMO-QFIPXVFZSA-N 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 345
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 219
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
- 238000000034 method Methods 0.000 description 122
- 239000000243 solution Substances 0.000 description 111
- 235000019439 ethyl acetate Nutrition 0.000 description 109
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 100
- 239000000543 intermediate Substances 0.000 description 95
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 94
- OLGHNEPFMCAVCT-SFHVURJKSA-N (2s)-2-[(2-chloro-3-oxospiro[3.6]dec-1-en-1-yl)amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid Chemical compound C([C@@H](C(=O)O)NC=1C2(CCCCCC2)C(=O)C=1Cl)C(C=C1)=CC=C1NC(=O)C1=C(Cl)C=NC=C1Cl OLGHNEPFMCAVCT-SFHVURJKSA-N 0.000 description 93
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 83
- 239000000843 powder Substances 0.000 description 73
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 61
- 239000007787 solid Substances 0.000 description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
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- 239000000203 mixture Substances 0.000 description 53
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- 239000013067 intermediate product Substances 0.000 description 50
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 47
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- 239000011541 reaction mixture Substances 0.000 description 37
- 238000005481 NMR spectroscopy Methods 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 238000006243 chemical reaction Methods 0.000 description 34
- 238000004587 chromatography analysis Methods 0.000 description 34
- 239000002904 solvent Substances 0.000 description 33
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 31
- 239000012267 brine Substances 0.000 description 30
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 30
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- 239000011734 sodium Substances 0.000 description 23
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- 150000001412 amines Chemical class 0.000 description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 20
- 230000007062 hydrolysis Effects 0.000 description 18
- 238000006460 hydrolysis reaction Methods 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 16
- 229910052794 bromium Inorganic materials 0.000 description 16
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- 239000000284 extract Substances 0.000 description 16
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- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 14
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 11
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- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 9
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- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 235000019263 trisodium citrate Nutrition 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000004552 water soluble powder Substances 0.000 description 1
Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
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- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
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- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/10—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings
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- C07C233/00—Carboxylic acid amides
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- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
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- C07C233/00—Carboxylic acid amides
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- C07C233/81—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups
- C07C233/82—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by carboxyl groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
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- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/30—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 to ring carbon atoms
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- C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
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- C07D311/96—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings spiro-condensed with carbocyclic rings or ring systems
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- 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
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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- 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
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GB0104418A GB0104418D0 (en) | 2001-02-22 | 2001-02-22 | Chemical compounds |
GB0114000A GB0114000D0 (en) | 2001-06-08 | 2001-06-08 | Chemical compounds |
GB0127562A GB0127562D0 (en) | 2001-11-16 | 2001-11-16 | Chemical compounds |
PCT/GB2002/000206 WO2002068393A1 (en) | 2001-02-22 | 2002-01-18 | Phenylalanine enamide derivatives possessing a cyclobutene group, for use as integrin inhibitors |
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NO20033710D0 NO20033710D0 (no) | 2003-08-20 |
NO20033710L NO20033710L (no) | 2003-10-22 |
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NO20033710A NO326554B1 (no) | 2001-02-22 | 2003-08-20 | Fenylalaninenamid-derivater som har en cyklobutengruppe, for anvendelse som integrin-inhibitorer og farmasoytisk sammensetning |
NO20082587A NO20082587L (no) | 2001-02-22 | 2008-06-10 | Fenylalaninenamid-derivater som har en cyklobutengruppe, for anvendelse som integrininhibitorer |
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NO20082587A NO20082587L (no) | 2001-02-22 | 2008-06-10 | Fenylalaninenamid-derivater som har en cyklobutengruppe, for anvendelse som integrininhibitorer |
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EP (2) | EP1370531B1 (ko) |
JP (2) | JP4340064B2 (ko) |
KR (3) | KR100885780B1 (ko) |
CN (1) | CN100400513C (ko) |
AT (1) | ATE355276T1 (ko) |
AU (1) | AU2002225163B2 (ko) |
BG (1) | BG107991A (ko) |
BR (1) | BR0207166A (ko) |
CA (1) | CA2434666A1 (ko) |
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SI (1) | SI1370531T1 (ko) |
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BR0207166A (pt) * | 2001-02-22 | 2004-02-10 | Celltech R&D Ltd | Composto, e, composição farmacêutica |
WO2003011815A1 (en) * | 2001-07-26 | 2003-02-13 | Celltech R & D Limited | Bicyclic heteroaromatic alanines |
GB0216568D0 (en) | 2002-07-17 | 2002-08-28 | Celltech R&D Ltd | Chemical compounds |
GB0216574D0 (en) * | 2002-07-17 | 2002-08-28 | Celltech R&D Ltd | Chemical compounds |
GB0216571D0 (en) | 2002-07-17 | 2002-08-28 | Celltech R&D Ltd | Chemical compounds |
AU2008219007A1 (en) | 2007-02-20 | 2008-08-28 | Merrimack Pharmaceuticals, Inc. | Methods of treating multiple sclerosis by administration of alpha-fetoprotein in combination with an integrin antagonist |
PL2288715T3 (pl) | 2008-04-11 | 2015-03-31 | Merrimack Pharmaceuticals Inc | Łączniki będące albuminą surowicy ludzkiej i ich koniugaty |
KR20110112301A (ko) | 2008-11-18 | 2011-10-12 | 메리맥 파마슈티컬즈, 인크. | 인간 혈청 알부민 링커 및 그 콘쥬게이트 |
EP2632898A4 (en) | 2010-10-29 | 2014-04-02 | Biogen Idec Inc | HETEROCYCLIC TYROSINE KINASE HEMMER |
MX2014004025A (es) | 2011-10-17 | 2014-08-01 | Univ Muenster Wilhelms | Metodos de valoracion de riesgo de lmp y aparatos relacionados. |
CA2854658A1 (en) * | 2011-11-09 | 2013-05-16 | Aestus Therapeutics, Inc. | Methods of treating schizophrenia with phenylalanine enamide derivative inhibitors of .alpha.4 integrin possessing a cyclobutene group |
WO2014036520A1 (en) | 2012-08-30 | 2014-03-06 | Merrimack Pharmaceuticals, Inc. | Combination therapies comprising anti-erbb3 agents |
CA2969295A1 (en) | 2016-06-06 | 2017-12-06 | Pfizer Inc. | Substituted carbonucleoside derivatives, and use thereof as a prmt5 inhibitor |
US11560384B2 (en) | 2017-05-04 | 2023-01-24 | University Of Utah Research Foundation | Benzonorbornadiene derivatives and reactions thereof |
WO2020092394A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | Imidazopyridine derivatives as alpha4beta7 integrin inhibitors |
KR20240015737A (ko) | 2018-10-30 | 2024-02-05 | 길리애드 사이언시즈, 인코포레이티드 | 알파4베타7 인테그린 억제제로서의 퀴놀린 유도체 |
AU2019373245C1 (en) | 2018-10-30 | 2022-10-27 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4β7 integrin |
CA3115820A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | Compounds for inhibition of .alpha.4.beta.7 integrin |
US11578069B2 (en) | 2019-08-14 | 2023-02-14 | Gilead Sciences, Inc. | Compounds for inhibition of α4 β7 integrin |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3938367A (en) | 1975-03-28 | 1976-02-17 | Nasa | Sampler of gas borne particles |
FI982268A (fi) | 1998-10-20 | 2000-04-21 | Tomi Jaervinen | Ei-steroidaalisten anti-inflammatoristen karboksyylihappojen uudet pro drugit, niiden valmistus ja käyttö |
GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
US6518283B1 (en) * | 1999-05-28 | 2003-02-11 | Celltech R&D Limited | Squaric acid derivatives |
WO2001079173A2 (en) | 2000-04-17 | 2001-10-25 | Celltech R & D Limited | Enamine derivatives as cell adhesion molecules |
BR0207166A (pt) * | 2001-02-22 | 2004-02-10 | Celltech R&D Ltd | Composto, e, composição farmacêutica |
GB0216571D0 (en) * | 2002-07-17 | 2002-08-28 | Celltech R&D Ltd | Chemical compounds |
GB0216568D0 (en) * | 2002-07-17 | 2002-08-28 | Celltech R&D Ltd | Chemical compounds |
WO2010073260A1 (en) * | 2008-12-26 | 2010-07-01 | Jawaharlal Nehru Centre For Advanced Scientific Research | Sers active paper substrate, a process and a method thereof |
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