SK9372000A3 - Substituted beta-alanines - Google Patents

Substituted beta-alanines Download PDF

Info

Publication number: SK9372000A3
Authority: SK; Slovakia
Prior art keywords: compound; group; alkyl; acetyl; amino
Prior art date: 1997-12-23

Application number

SK937-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Peter Charles Astles

Neil Victor Harris

Andrew David Morley

Original Assignee

Rhone Poulenc Rorer Ltd

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-12-23

Filing date

1998-12-23

Publication date

2002-03-05

1997-12-23 Priority claimed from GBGB9727532.5A external-priority patent/GB9727532D0/en

1998-12-23 Application filed by Rhone Poulenc Rorer Ltd filed Critical Rhone Poulenc Rorer Ltd

2002-03-05 Publication of SK9372000A3 publication Critical patent/SK9372000A3/sk

Links

UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical class NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 564
125000000217 alkyl group Chemical group 0.000 claims abstract description 94
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 60
150000003839 salts Chemical class 0.000 claims abstract description 58
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 53
239000000651 prodrug Substances 0.000 claims abstract description 35
229940002612 prodrug Drugs 0.000 claims abstract description 35
239000001257 hydrogen Substances 0.000 claims abstract description 21
239000012453 solvate Substances 0.000 claims abstract description 21
125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
229910052736 halogen Inorganic materials 0.000 claims abstract description 16
150000002367 halogens Chemical class 0.000 claims abstract description 16
150000002431 hydrogen Chemical class 0.000 claims abstract 7
-1 cyclic amine Chemical class 0.000 claims description 352
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 264
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 163
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 129
235000019260 propionic acid Nutrition 0.000 claims description 127
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 110
125000004432 carbon atom Chemical group C* 0.000 claims description 73
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 65
239000011347 resin Substances 0.000 claims description 64
229920005989 resin Polymers 0.000 claims description 64
125000003118 aryl group Chemical group 0.000 claims description 48
239000000203 mixture Substances 0.000 claims description 44
125000001072 heteroaryl group Chemical group 0.000 claims description 39
238000000034 method Methods 0.000 claims description 39
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 35
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
125000000753 cycloalkyl group Chemical group 0.000 claims description 25
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 23
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 21
230000002378 acidificating effect Effects 0.000 claims description 18
238000011282 treatment Methods 0.000 claims description 18
125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 14
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
125000002947 alkylene group Chemical group 0.000 claims description 13
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
229910052760 oxygen Inorganic materials 0.000 claims description 13
229910005965 SO 2 Inorganic materials 0.000 claims description 12
125000003342 alkenyl group Chemical group 0.000 claims description 12
239000003112 inhibitor Substances 0.000 claims description 12
230000021164 cell adhesion Effects 0.000 claims description 11
150000004677 hydrates Chemical class 0.000 claims description 11
229910052717 sulfur Inorganic materials 0.000 claims description 11
125000000524 functional group Chemical group 0.000 claims description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000000392 cycloalkenyl group Chemical group 0.000 claims description 8
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 7
125000004043 oxo group Chemical group O=* 0.000 claims description 7
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 6
230000001404 mediated effect Effects 0.000 claims description 6
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 6
229940126062 Compound A Drugs 0.000 claims description 5
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
230000001668 ameliorated effect Effects 0.000 claims description 5
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 5
125000004122 cyclic group Chemical group 0.000 claims description 5
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
239000001301 oxygen Substances 0.000 claims description 5
238000002560 therapeutic procedure Methods 0.000 claims description 5
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 4
125000002252 acyl group Chemical group 0.000 claims description 4
125000004450 alkenylene group Chemical group 0.000 claims description 4
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
125000000732 arylene group Chemical group 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 4
125000002993 cycloalkylene group Chemical group 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
239000008194 pharmaceutical composition Substances 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
PRZMGAZLBSVGFD-UHFFFAOYSA-N 3-[(3,4-dimethoxyphenyl)methyl-[2-[[2-[3-methoxy-4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]-methylamino]acetyl]amino]propanoic acid Chemical compound C1=C(OC)C(OC)=CC=C1CN(CCC(O)=O)C(=O)CN(C)C(=O)CC(C=C1OC)=CC=C1NC(=O)NC1=CC=CC=C1C PRZMGAZLBSVGFD-UHFFFAOYSA-N 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
125000005518 carboxamido group Chemical group 0.000 claims description 3
125000006588 heterocycloalkylene group Chemical group 0.000 claims description 3
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
208000027866 inflammatory disease Diseases 0.000 claims description 2
125000004434 sulfur atom Chemical group 0.000 claims description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 11
238000004519 manufacturing process Methods 0.000 claims 2
125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
125000004356 hydroxy functional group Chemical group O* 0.000 claims 1
108010067306 Fibronectins Proteins 0.000 abstract description 14
102000016359 Fibronectins Human genes 0.000 abstract description 14
108010008212 Integrin alpha4beta1 Proteins 0.000 abstract description 10
230000003993 interaction Effects 0.000 abstract description 8
108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 abstract 1
102100023543 Vascular cell adhesion protein 1 Human genes 0.000 abstract 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 235
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 96
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 87
230000000052 comparative effect Effects 0.000 description 51
239000002253 acid Substances 0.000 description 47
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 44
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 41
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 31
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
238000001819 mass spectrum Methods 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
239000007787 solid Substances 0.000 description 27
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 26
210000004027 cell Anatomy 0.000 description 22
238000004128 high performance liquid chromatography Methods 0.000 description 22
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 20
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 18
239000002585 base Substances 0.000 description 17
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
108010044426 integrins Proteins 0.000 description 16
102000006495 integrins Human genes 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
238000000921 elemental analysis Methods 0.000 description 15
239000011734 sodium Substances 0.000 description 15
125000003373 pyrazinyl group Chemical group 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
238000010828 elution Methods 0.000 description 9
150000002148 esters Chemical class 0.000 description 9
BEYOHIUUBRQWQF-UHFFFAOYSA-N ethyl 3-[(3,4-dimethoxyphenyl)methylamino]propanoate Chemical compound CCOC(=O)CCNCC1=CC=C(OC)C(OC)=C1 BEYOHIUUBRQWQF-UHFFFAOYSA-N 0.000 description 9
239000006260 foam Substances 0.000 description 9
239000012458 free base Substances 0.000 description 9
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 9
241000699670 Mus sp. Species 0.000 description 8
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
241000700159 Rattus Species 0.000 description 8
239000012442 inert solvent Substances 0.000 description 8
239000003446 ligand Substances 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
238000002360 preparation method Methods 0.000 description 8
HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
125000001931 aliphatic group Chemical group 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
125000002883 imidazolyl group Chemical group 0.000 description 7
238000003018 immunoassay Methods 0.000 description 7
125000004076 pyridyl group Chemical group 0.000 description 7
238000003756 stirring Methods 0.000 description 7
210000001519 tissue Anatomy 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
125000004442 acylamino group Chemical group 0.000 description 6
239000000427 antigen Substances 0.000 description 6
102000036639 antigens Human genes 0.000 description 6
108091007433 antigens Proteins 0.000 description 6
206010003246 arthritis Diseases 0.000 description 6
230000027455 binding Effects 0.000 description 6
239000012267 brine Substances 0.000 description 6
125000004494 ethyl ester group Chemical group 0.000 description 6
230000007062 hydrolysis Effects 0.000 description 6
238000006460 hydrolysis reaction Methods 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium;hydroxide;hydrate Chemical compound [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
238000005897 peptide coupling reaction Methods 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000000725 suspension Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
125000002102 aryl alkyloxo group Chemical group 0.000 description 5
239000000872 buffer Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
239000000460 chlorine Substances 0.000 description 5
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 5
239000000284 extract Substances 0.000 description 5
125000002541 furyl group Chemical group 0.000 description 5
125000001041 indolyl group Chemical group 0.000 description 5
210000004072 lung Anatomy 0.000 description 5
230000014759 maintenance of location Effects 0.000 description 5
239000003921 oil Substances 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
230000008569 process Effects 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
239000000377 silicon dioxide Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
102000010834 Extracellular Matrix Proteins Human genes 0.000 description 4
108010037362 Extracellular Matrix Proteins Proteins 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 4
210000001744 T-lymphocyte Anatomy 0.000 description 4
239000002671 adjuvant Substances 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
125000003435 aroyl group Chemical group 0.000 description 4
210000003719 b-lymphocyte Anatomy 0.000 description 4
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
125000005843 halogen group Chemical group 0.000 description 4
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
125000002950 monocyclic group Chemical group 0.000 description 4
230000003647 oxidation Effects 0.000 description 4
238000007254 oxidation reaction Methods 0.000 description 4
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
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229910052708 sodium Inorganic materials 0.000 description 4
239000000126 substance Substances 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
HJORCZCMNWLHMB-UHFFFAOYSA-N 1-(3-aminopropyl)pyrrolidin-2-one Chemical compound NCCCN1CCCC1=O HJORCZCMNWLHMB-UHFFFAOYSA-N 0.000 description 3
LQAWZBVFPYYFGB-UHFFFAOYSA-N 2-[3-methoxy-4-[(2-methylphenyl)carbamoylamino]phenyl]acetic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1NC(=O)NC1=CC=CC=C1C LQAWZBVFPYYFGB-UHFFFAOYSA-N 0.000 description 3
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 3
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
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KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
239000012980 RPMI-1640 medium Substances 0.000 description 3
239000003875 Wang resin Substances 0.000 description 3
NERFNHBZJXXFGY-UHFFFAOYSA-N [4-[(4-methylphenyl)methoxy]phenyl]methanol Chemical compound C1=CC(C)=CC=C1COC1=CC=C(CO)C=C1 NERFNHBZJXXFGY-UHFFFAOYSA-N 0.000 description 3
239000013543 active substance Substances 0.000 description 3
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125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
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125000004419 alkynylene group Chemical group 0.000 description 3
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
125000004659 aryl alkyl thio group Chemical group 0.000 description 3
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125000005110 aryl thio group Chemical group 0.000 description 3
125000004104 aryloxy group Chemical group 0.000 description 3
238000003556 assay Methods 0.000 description 3
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
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239000012230 colorless oil Substances 0.000 description 3
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239000011737 fluorine Substances 0.000 description 3
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125000005114 heteroarylalkoxy group Chemical group 0.000 description 3
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238000000338 in vitro Methods 0.000 description 3
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KBMBVTRWEAAZEY-UHFFFAOYSA-N trisulfane Chemical class SSS KBMBVTRWEAAZEY-UHFFFAOYSA-N 0.000 description 1
210000004881 tumor cell Anatomy 0.000 description 1
210000005167 vascular cell Anatomy 0.000 description 1
210000005166 vasculature Anatomy 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
230000029663 wound healing Effects 0.000 description 1
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
229910021511 zinc hydroxide Inorganic materials 0.000 description 1
229940007718 zinc hydroxide Drugs 0.000 description 1
GSQBIOQCECCMOQ-UHFFFAOYSA-N β-alanine ethyl ester Chemical compound CCOC(=O)CCN GSQBIOQCECCMOQ-UHFFFAOYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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

Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
General Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pulmonology (AREA)
Dermatology (AREA)
Cardiology (AREA)
Oncology (AREA)
Vascular Medicine (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Hydrogenated Pyridines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Polyamides (AREA)
Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Peptides Or Proteins (AREA)
Furan Compounds (AREA)
Pyridine Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Heterocyclic Compounds Containing Sulfur Atoms (AREA)
Pyrrole Compounds (AREA)

SK937-2000A 1997-12-23 1998-12-23 Substituted beta-alanines SK9372000A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9727532.5A GB9727532D0 (en)	1997-12-23	1997-12-23	Chemical compounds
US9260298P	1998-07-13	1998-07-13
PCT/GB1998/003859 WO1999033789A1 (en)	1997-12-23	1998-12-23	SUBSTITUTED β-ALANINES

Publications (1)

Publication Number	Publication Date
SK9372000A3 true SK9372000A3 (en)	2002-03-05

Family

ID=26312873

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK937-2000A SK9372000A3 (en)	1997-12-23	1998-12-23	Substituted beta-alanines

Country Status (18)

Country	Link
EP (1)	EP1042279B1 (de)
JP (1)	JP4555469B2 (de)
KR (1)	KR20010033520A (de)
CN (1)	CN1163477C (de)
AT (1)	ATE289991T1 (de)
AU (1)	AU747907B2 (de)
BR (1)	BR9814376A (de)
CA (1)	CA2316235A1 (de)
CZ (1)	CZ20002342A3 (de)
DE (1)	DE69829215T2 (de)
ES (1)	ES2235383T3 (de)
HU (1)	HUP0101701A3 (de)
IL (1)	IL136584A (de)
NO (1)	NO20003273D0 (de)
NZ (1)	NZ505363A (de)
SK (1)	SK9372000A3 (de)
TR (1)	TR200001947T2 (de)
WO (1)	WO1999033789A1 (de)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR20010034317A (ko) *	1998-01-23	2001-04-25	한스 루돌프 하우스	Ｖｌａ-4 길항제
ES2297943T3 (es)	1998-12-23	2008-05-01	Aventis Pharma Limited	Dihidro-benzo(1,4)oxacinas y tetrahidroquinoxalinas.
KR100649819B1 (ko) *	1999-02-18	2007-02-28	에프. 호프만-라 로슈 아게	티오아미드 유도체
YU41202A (sh) *	1999-12-28	2005-03-15	Pfizer Products Inc.	Ne-peptidni inhibitori vezivanja za ćeliju zavisnog od vla-4 korisni pri tretiranju inflamatornih, autoimunih i respiratornih bolesti
DE10019755A1 (de) *	2000-04-20	2001-11-08	Bayer Ag	Neue Aminoaryl/cycloalkylcarbonsäuren als Integrinantagonisten
FR2812633A1 (fr) *	2000-08-04	2002-02-08	Aventis Cropscience Sa	Derives de phenyl(thio)urees et phenyl(thio)carbamates fongicides
GB2369357A (en) *	2000-10-09	2002-05-29	Bayer Ag	Aliphatic, cyclic amino carboxylic acids as integrin antagonists
GB2367816A (en) *	2000-10-09	2002-04-17	Bayer Ag	Urea- and thiourea-containing derivatives of beta-amino acids
JP3786203B2 (ja)	2000-11-04	2006-06-14	アベンティス・フアーマ・リミテッド	置換アルカン酸
JP4212358B2 (ja)	2000-12-28	2009-01-21	第一三共株式会社	Ｖｌａ−４阻害薬
GB2377933A (en)	2001-07-06	2003-01-29	Bayer Ag	Succinic acid derivatives useful as integrin antagonists
CA2528586A1 (en)	2003-07-24	2005-02-03	Daiichi Pharmaceutical Co., Ltd.	Cyclohexanecarboxylic acid compound
JP2008539246A (ja) *	2005-04-28	2008-11-13	フェリングベスローテンフェンノートシャップ	Ｉｂｄ治療のための新規化合物の使用
EP1961750B1 (de)	2005-12-13	2013-09-18	Daiichi Sankyo Company, Limited	Vla-4-hemmendes arzneimittel
WO2008103378A2 (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

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6306840B1 (en) *	1995-01-23	2001-10-23	Biogen, Inc.	Cell adhesion inhibitors
IL123164A (en) *	1995-08-30	2001-03-19	Searle & Co	Meta-guanidine urea thiourea or azacyclic amino benzoic acid derivatives and pharmaceutical compositions containing them
DE69710319T2 (de) *	1996-03-29	2002-08-14	G.D. SEARLE & CO., CHICAGO	Para-substituierte phenylpropansäure derivate als integrin-antagonisten
DE69706407T2 (de) *	1996-03-29	2002-05-29	G.D. Searle & Co., Chicago	META-SUBSTITUIERTE PHENYLENDERIVATE UND IHRE VERWENDUNG ALS ALPHAvBETA3 INTERGRIN-ANTAGONISTEN ODER INHIBITOREN
PT1027328E (pt) *	1997-10-31	2006-11-30	Aventis Pharma Ltd	Anilidas substituídas

1998
- 1998-12-23 IL IL13658498A patent/IL136584A/xx not_active IP Right Cessation
- 1998-12-23 DE DE69829215T patent/DE69829215T2/de not_active Expired - Lifetime
- 1998-12-23 CA CA002316235A patent/CA2316235A1/en not_active Abandoned
- 1998-12-23 ES ES98962586T patent/ES2235383T3/es not_active Expired - Lifetime
- 1998-12-23 BR BR9814376-0A patent/BR9814376A/pt not_active Application Discontinuation
- 1998-12-23 CZ CZ20002342A patent/CZ20002342A3/cs unknown
- 1998-12-23 WO PCT/GB1998/003859 patent/WO1999033789A1/en not_active Ceased
- 1998-12-23 TR TR2000/01947T patent/TR200001947T2/xx unknown
- 1998-12-23 EP EP98962586A patent/EP1042279B1/de not_active Expired - Lifetime
- 1998-12-23 AT AT98962586T patent/ATE289991T1/de not_active IP Right Cessation
- 1998-12-23 AU AU17719/99A patent/AU747907B2/en not_active Ceased
- 1998-12-23 KR KR1020007007022A patent/KR20010033520A/ko not_active Ceased
- 1998-12-23 CN CNB988125005A patent/CN1163477C/zh not_active Expired - Fee Related
- 1998-12-23 SK SK937-2000A patent/SK9372000A3/sk unknown
- 1998-12-23 JP JP2000526473A patent/JP4555469B2/ja not_active Expired - Lifetime
- 1998-12-23 HU HU0101701A patent/HUP0101701A3/hu unknown
- 1998-12-23 NZ NZ505363A patent/NZ505363A/en unknown
2000
- 2000-06-22 NO NO20003273A patent/NO20003273D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
HK1034508A1 (en)	2001-10-26
ATE289991T1 (de)	2005-03-15
IL136584A (en)	2005-03-20
NO20003273L (no)	2000-06-22
TR200001947T2 (tr)	2001-01-22
DE69829215T2 (de)	2005-07-21
EP1042279B1 (de)	2005-03-02
NZ505363A (en)	2005-02-25
CZ20002342A3 (cs)	2001-11-14
HUP0101701A3 (en)	2003-02-28
NO20003273D0 (no)	2000-06-22
BR9814376A (pt)	2000-10-10
KR20010033520A (ko)	2001-04-25
CA2316235A1 (en)	1999-07-08
CN1163477C (zh)	2004-08-25
AU1771999A (en)	1999-07-19
HUP0101701A2 (hu)	2001-11-28
IL136584A0 (en)	2001-06-14
JP4555469B2 (ja)	2010-09-29
AU747907B2 (en)	2002-05-30
WO1999033789A1 (en)	1999-07-08
EP1042279A1 (de)	2000-10-11
DE69829215D1 (de)	2005-04-07
JP2001527061A (ja)	2001-12-25
ES2235383T3 (es)	2005-07-01
CN1283181A (zh)	2001-02-07

Publication	Publication Date	Title
SK9372000A3 (en)	2002-03-05	Substituted beta-alanines
EP1114028B1 (de)	2006-11-29	Azabicyclo-verbindungen welche die inhibition der zell adhesion modulieren
EP1027328B1 (de)	2006-08-23	Substituierte anilide
CZ20013661A3 (cs)	2002-01-16	Substituované bicyklické heteroarylové sloučeniny jako antagonisté integrinu a farmaceutický prostředek, který je obsahuje
EP1153017B1 (de)	2006-05-03	Bicyclische verbindungen und ihre verwendung als integrinrezeptorliganden
EP1392306B1 (de)	2008-01-16	Substituierte tetrhydroisochinolin-derivate zur behandlung von entzündlichen erkrankungen
JP2001523711A (ja)	2001-11-27	細胞接着阻害薬としての環状アミノ酸誘導体
EP1177181B1 (de)	2009-01-28	Substituierte bizyclische verbindungen
WO1999054321A1 (en)	1999-10-28	Substituted diamines and their use as cell adhesion inhibitors
US6352977B1 (en)	2002-03-05	Substituted β-alanines
US6762199B2 (en)	2004-07-13	Indane derivatives
US6548533B2 (en)	2003-04-15	Ureido substituted pyrrolidines
US20040006056A1 (en)	2004-01-08	Substituted alkanoic acids
ES2297943T3 (es)	2008-05-01	Dihidro-benzo(1,4)oxacinas y tetrahidroquinoxalinas.
MXPA00006218A (en)	2002-02-26	SUBSTITUTED&bgr;-ALANINES
JP4856314B2 (ja)	2012-01-18	置換ピロリジン