ZA200203533B - 4-pyrimidinyl-N-acyl-L-phenylalanines. - Google Patents
4-pyrimidinyl-N-acyl-L-phenylalanines. Download PDFInfo
- Publication number
- ZA200203533B ZA200203533B ZA200203533A ZA200203533A ZA200203533B ZA 200203533 B ZA200203533 B ZA 200203533B ZA 200203533 A ZA200203533 A ZA 200203533A ZA 200203533 A ZA200203533 A ZA 200203533A ZA 200203533 B ZA200203533 B ZA 200203533B
- Authority
- ZA
- South Africa
- Prior art keywords
- lower alkyl
- hydrogen
- carbonyl
- formula
- compound
- Prior art date
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 231
- 229910052739 hydrogen Inorganic materials 0.000 claims description 139
- 239000001257 hydrogen Substances 0.000 claims description 138
- 150000001875 compounds Chemical class 0.000 claims description 105
- 150000002431 hydrogen Chemical class 0.000 claims description 72
- -1 perfluoro Chemical group 0.000 claims description 71
- 125000003118 aryl group Chemical group 0.000 claims description 63
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 41
- 150000002367 halogens Chemical class 0.000 claims description 41
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 40
- 229960005190 phenylalanine Drugs 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 125000001589 carboacyl group Chemical group 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 229910052717 sulfur Inorganic materials 0.000 claims description 14
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 13
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 208000006673 asthma Diseases 0.000 claims description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 108010000134 Vascular Cell Adhesion Molecule-1 Proteins 0.000 claims description 12
- 102100023543 Vascular cell adhesion protein 1 Human genes 0.000 claims description 12
- 125000003435 aroyl group Chemical group 0.000 claims description 12
- 108010008212 Integrin alpha4beta1 Proteins 0.000 claims description 11
- 239000000203 mixture Substances 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 9
- 239000000126 substance Substances 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 6
- XWJUDXXALXRTIE-SFHVURJKSA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound CC1=CC=CC(Cl)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C(=O)N(C)C=2C)=O)C=C1 XWJUDXXALXRTIE-SFHVURJKSA-N 0.000 claims description 5
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- MEWSBKJAUCDJSK-KRWDZBQOSA-N (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound O=C1N(C)C(=O)N(C)C(C)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)C1=C(Cl)C=CC=C1Cl MEWSBKJAUCDJSK-KRWDZBQOSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 240000007594 Oryza sativa Species 0.000 claims description 3
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- KQFDKGNSBOLNCZ-IBGZPJMESA-N (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(1,3-diethyl-4-methyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound O=C1N(CC)C(=O)N(CC)C(C)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)C1=C(Cl)C=CC=C1Cl KQFDKGNSBOLNCZ-IBGZPJMESA-N 0.000 claims description 2
- XYXZMKHLXJARTF-SFHVURJKSA-N (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(1,3-dimethyl-2,4-dioxopyrimidin-5-yl)-3-methylphenyl]propanoic acid Chemical compound N([C@@H](CC=1C=C(C(=CC=1)C=1C(N(C)C(=O)N(C)C=1)=O)C)C(O)=O)C(=O)C1=C(Cl)C=CC=C1Cl XYXZMKHLXJARTF-SFHVURJKSA-N 0.000 claims description 2
- LYHCGYLAKNFJSM-KRWDZBQOSA-N (2s)-2-[(2,6-difluorobenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound O=C1N(C)C(=O)N(C)C(C)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)C1=C(F)C=CC=C1F LYHCGYLAKNFJSM-KRWDZBQOSA-N 0.000 claims description 2
- MWYWLZQVFNXNEI-IBGZPJMESA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-(1,3-dimethyl-2,4-dioxopyrimidin-5-yl)-3-methylphenyl]propanoic acid Chemical compound N([C@@H](CC=1C=C(C(=CC=1)C=1C(N(C)C(=O)N(C)C=1)=O)C)C(O)=O)C(=O)C1=C(C)C=CC=C1Cl MWYWLZQVFNXNEI-IBGZPJMESA-N 0.000 claims description 2
- PQEXVAMKRQHKJU-IBGZPJMESA-N (2s)-2-[[1-(2-methoxyethyl)cyclopentanecarbonyl]amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=CC(=CC=1)C=1C(N(C)C(=O)N(C)C=1C)=O)C(O)=O)C(=O)C1(CCOC)CCCC1 PQEXVAMKRQHKJU-IBGZPJMESA-N 0.000 claims description 2
- XUEMABPGUCMTNO-IBGZPJMESA-N ethyl (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OCC)NC(=O)C=1C(=CC=CC=1Cl)Cl)C(C=C1)=CC=C1C1=C(C)N(C)C(=O)N(C)C1=O XUEMABPGUCMTNO-IBGZPJMESA-N 0.000 claims description 2
- WUWFMJLSHFBJBN-IBGZPJMESA-N ethyl (2s)-2-[(2,6-difluorobenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OCC)NC(=O)C=1C(=CC=CC=1F)F)C(C=C1)=CC=C1C1=C(C)N(C)C(=O)N(C)C1=O WUWFMJLSHFBJBN-IBGZPJMESA-N 0.000 claims description 2
- DXBUTWPHLQEKCF-FQEVSTJZSA-N ethyl (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OCC)NC(=O)C=1C(=CC=CC=1C)Cl)C(C=C1)=CC=C1C1=C(C)N(C)C(=O)N(C)C1=O DXBUTWPHLQEKCF-FQEVSTJZSA-N 0.000 claims description 2
- 239000000543 intermediate Substances 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- IECKVUVUZIOYDW-FQEVSTJZSA-N (2s)-2-[(2-chloro-6-methylbenzoyl)amino]-3-[4-(1,3-diethyl-4-methyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound O=C1N(CC)C(=O)N(CC)C(C)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)C1=C(C)C=CC=C1Cl IECKVUVUZIOYDW-FQEVSTJZSA-N 0.000 claims 1
- JOABXWLBYGYELJ-NRFANRHFSA-N (2s)-3-[4-(1,3-diethyl-4-methyl-2,6-dioxopyrimidin-5-yl)phenyl]-2-[[1-(2-methoxyethyl)cyclopentanecarbonyl]amino]propanoic acid Chemical compound O=C1N(CC)C(=O)N(CC)C(C)=C1C(C=C1)=CC=C1C[C@@H](C(O)=O)NC(=O)C1(CCOC)CCCC1 JOABXWLBYGYELJ-NRFANRHFSA-N 0.000 claims 1
- XHXNVXQXRIGHCE-MRNPHLECSA-N 1-acetyloxyethyl (2s)-2-[(2,6-difluorobenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoate Chemical compound C([C@@H](C(=O)OC(OC(C)=O)C)NC(=O)C=1C(=CC=CC=1F)F)C(C=C1)=CC=C1C1=C(C)N(C)C(=O)N(C)C1=O XHXNVXQXRIGHCE-MRNPHLECSA-N 0.000 claims 1
- VMJNTFXCTXAXTC-UHFFFAOYSA-N 2,2-difluoro-1,3-benzodioxole-5-carbonitrile Chemical group C1=C(C#N)C=C2OC(F)(F)OC2=C1 VMJNTFXCTXAXTC-UHFFFAOYSA-N 0.000 claims 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 210000003979 eosinophil Anatomy 0.000 description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 210000004698 lymphocyte Anatomy 0.000 description 6
- 102000016359 Fibronectins Human genes 0.000 description 5
- 108010067306 Fibronectins Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 210000001616 monocyte Anatomy 0.000 description 5
- 229910052763 palladium Inorganic materials 0.000 description 5
- 206010035664 Pneumonia Diseases 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 210000003651 basophil Anatomy 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 210000003038 endothelium Anatomy 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 150000002993 phenylalanine derivatives Chemical class 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 102000016914 ras Proteins Human genes 0.000 description 3
- 108010014186 ras Proteins Proteins 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 125000004434 sulfur atom Chemical group 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-Phenylalanine Natural products OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 210000001744 T-lymphocyte Anatomy 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 125000004185 ester group Chemical group 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000003993 interaction Effects 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
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical compound CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- 238000005897 peptide coupling reaction Methods 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- 229910052718 tin Inorganic materials 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 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 2
- HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 description 1
- NTFHSUUFBUDKFC-SFHVURJKSA-N (2s)-2-[(2,6-dichlorobenzoyl)amino]-3-[3-methyl-4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound N([C@@H](CC=1C=C(C(=CC=1)C=1C(N(C)C(=O)N(C)C=1C)=O)C)C(O)=O)C(=O)C1=C(Cl)C=CC=C1Cl NTFHSUUFBUDKFC-SFHVURJKSA-N 0.000 description 1
- YJBJPRUILPSVFT-IBGZPJMESA-N (2s)-2-[(2-chloro-6-ethylbenzoyl)amino]-3-[4-(1,3,4-trimethyl-2,6-dioxopyrimidin-5-yl)phenyl]propanoic acid Chemical compound CCC1=CC=CC(Cl)=C1C(=O)N[C@H](C(O)=O)CC1=CC=C(C=2C(N(C)C(=O)N(C)C=2C)=O)C=C1 YJBJPRUILPSVFT-IBGZPJMESA-N 0.000 description 1
- PEMUHKUIQHFMTH-QMMMGPOBSA-N (2s)-2-amino-3-(4-bromophenyl)propanoic acid Chemical class OC(=O)[C@@H](N)CC1=CC=C(Br)C=C1 PEMUHKUIQHFMTH-QMMMGPOBSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- 125000001216 2-naphthoyl group Chemical group C1=C(C=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 description 1
- PZNQZSRPDOEBMS-QMMMGPOBSA-N 4-iodo-L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(I)C=C1 PZNQZSRPDOEBMS-QMMMGPOBSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000030767 Autoimmune encephalitis Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical class [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- 102100039788 GTPase NRas Human genes 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 101000744505 Homo sapiens GTPase NRas Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010025102 Lung infiltration Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- LFMFPKKYRXFHHZ-UHFFFAOYSA-N R24 Chemical compound C1=C(Cl)C(C)=CC=C1NC1=NC(N)=C(C=CC=C2)C2=N1 LFMFPKKYRXFHHZ-UHFFFAOYSA-N 0.000 description 1
- 241000288960 Saguinus oedipus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical class [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000005210 alkyl ammonium group Chemical group 0.000 description 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl 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
- 125000000304 alkynyl group Chemical group 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 125000005015 aryl alkynyl group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229910052796 boron Chemical class 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Substances OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 210000004953 colonic tissue Anatomy 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-N dichloropalladium;triphenylphosphanium Chemical compound Cl[Pd]Cl.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-N formic acid Substances OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 150000005694 halopyrimidines Chemical class 0.000 description 1
- 125000005113 hydroxyalkoxy group Chemical group 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 238000000338 in vitro Methods 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
- 239000012442 inert solvent Substances 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 108010044426 integrins Proteins 0.000 description 1
- 102000006495 integrins Human genes 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 210000002433 mononuclear leukocyte Anatomy 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 150000003605 tin Chemical class 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- REDSKZBUUUQMSK-UHFFFAOYSA-N tributyltin Chemical compound CCCC[Sn](CCCC)CCCC.CCCC[Sn](CCCC)CCCC REDSKZBUUUQMSK-UHFFFAOYSA-N 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
-
- 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
-
- 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
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/553—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06165—Dipeptides with the first amino acid being heterocyclic and Pro-amino acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Physical Education & Sports Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US16908999P | 1999-12-06 | 1999-12-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200203533B true ZA200203533B (en) | 2003-08-04 |
Family
ID=22614222
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200203533A ZA200203533B (en) | 1999-12-06 | 2002-05-03 | 4-pyrimidinyl-N-acyl-L-phenylalanines. |
Country Status (35)
Country | Link |
---|---|
EP (1) | EP1237878B1 (fr) |
JP (1) | JP3824935B2 (fr) |
KR (1) | KR100522344B1 (fr) |
CN (1) | CN1218943C (fr) |
AR (1) | AR034401A1 (fr) |
AT (1) | ATE357433T1 (fr) |
AU (1) | AU783348B2 (fr) |
BR (1) | BR0016195A (fr) |
CA (1) | CA2392570C (fr) |
CO (1) | CO5080772A1 (fr) |
CY (1) | CY1106626T1 (fr) |
CZ (1) | CZ303435B6 (fr) |
DE (1) | DE60034061T2 (fr) |
DK (1) | DK1237878T3 (fr) |
EG (1) | EG24361A (fr) |
ES (1) | ES2282162T3 (fr) |
HK (1) | HK1054384B (fr) |
HR (1) | HRP20020468B1 (fr) |
HU (1) | HU229105B1 (fr) |
IL (2) | IL149617A0 (fr) |
JO (1) | JO2283B1 (fr) |
MA (1) | MA26850A1 (fr) |
MX (1) | MXPA02005564A (fr) |
MY (1) | MY126972A (fr) |
NO (1) | NO322866B1 (fr) |
NZ (1) | NZ518828A (fr) |
PE (1) | PE20010961A1 (fr) |
PL (1) | PL207160B1 (fr) |
PT (1) | PT1237878E (fr) |
RS (1) | RS50371B (fr) |
RU (1) | RU2266901C2 (fr) |
SI (1) | SI1237878T1 (fr) |
TW (1) | TWI256387B (fr) |
WO (1) | WO2001042225A2 (fr) |
ZA (1) | ZA200203533B (fr) |
Families Citing this family (32)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6960597B2 (en) | 2000-06-30 | 2005-11-01 | Orth-Mcneil Pharmaceutical, Inc. | Aza-bridged-bicyclic amino acid derivatives as α4 integrin antagonists |
CN1325480C (zh) | 2000-08-18 | 2007-07-11 | 味之素株式会社 | 苯基丙氨酸衍生物 |
AR033765A1 (es) * | 2001-05-22 | 2004-01-07 | Syngenta Participations Ag | Procedimiento para la preparacion de derivados 3-alquil-3h-isobenzofuran-1-ona 7-sustituidos. |
AU2002354224A1 (en) | 2001-12-13 | 2003-07-09 | Ajinomoto Co., Inc. | Novel phenylalanine derivative |
RU2390520C2 (ru) | 2003-12-22 | 2010-05-27 | Адзиномото Ко., Инк. | Новые производные фенилаланина |
US7618981B2 (en) * | 2004-05-06 | 2009-11-17 | Cytokinetics, Inc. | Imidazopyridinyl-benzamide anti-cancer agents |
BRPI0514415A (pt) * | 2004-08-16 | 2008-06-10 | Merck & Co Inc | composto, composição farmacêutica, e, uso de um composto |
JP4784224B2 (ja) | 2004-09-24 | 2011-10-05 | 味の素株式会社 | 糖鎖転移方法および糖鎖転移酵素 |
JP2009516729A (ja) * | 2005-11-23 | 2009-04-23 | アストラゼネカ アクチボラグ | L−フェニルアラニン誘導体 |
AR059224A1 (es) * | 2006-01-31 | 2008-03-19 | Jerini Ag | Compuestos para la inhibicion de integrinas y uso de estas |
WO2007091046A1 (fr) * | 2006-02-09 | 2007-08-16 | Astrazeneca Ab | Composes chimiques |
EP2039687B1 (fr) | 2006-06-19 | 2012-05-02 | Toray Industries, Inc. | Agent thérapeutique ou prophylactique pour la sclérose en plaques |
SI2368882T1 (sl) | 2007-09-17 | 2015-02-27 | Abbvie Bahamas Ltd. | Antiinfekcijski pirimidini in njihove uporabe |
RU2542099C2 (ru) | 2007-09-17 | 2015-02-20 | Эббви Бахамаз Лтд. | N-фенил-диоксо-гидропиримидины, используемые в качестве ингибитора вируса гепатита с (hcv) |
RU2543620C2 (ru) | 2007-09-17 | 2015-03-10 | Эббви Бахамаз Лтд. | Производные урацила или тимина для лечения гепатита с |
TWI448470B (zh) * | 2008-12-22 | 2014-08-11 | Icl Ip America Inc | 基於水互溶性溶劑的方法 |
US9216952B2 (en) | 2010-03-23 | 2015-12-22 | Abbvie Inc. | Process for preparing antiviral compound |
AU2011278926B2 (en) | 2010-07-16 | 2014-09-25 | Abbvie Ireland Unlimited Company | Phosphine ligands for catalytic reactions |
US8975443B2 (en) | 2010-07-16 | 2015-03-10 | Abbvie Inc. | Phosphine ligands for catalytic reactions |
US9255074B2 (en) | 2010-07-16 | 2016-02-09 | Abbvie Inc. | Process for preparing antiviral compounds |
UA115025C2 (uk) | 2010-07-16 | 2017-09-11 | Еббві Айрленд Анлімітед Компані | Спосіб одержання противірусних сполук |
US8877815B2 (en) | 2010-11-16 | 2014-11-04 | Novartis Ag | Substituted carbamoylcycloalkyl acetic acid derivatives as NEP |
US9447035B2 (en) * | 2012-01-27 | 2016-09-20 | Hoffmann-La Roche Inc. | Integrin antagonist conjugates for targeted delivery to cells expressing VLA-4 |
RU2624731C2 (ru) * | 2012-01-27 | 2017-07-06 | Ф. Хоффманн-Ля Рош Аг | Конъюгаты антагонистов интегрина для нацеленной доставки к клеткам, экспрессирующим vla-4 |
EP3052515A4 (fr) | 2013-09-30 | 2017-03-15 | The Regents of the University of California | Composés d'intégrine anti-aphavbêta1 et méthodes correspondantes |
CN106414413A (zh) * | 2013-10-29 | 2017-02-15 | Ea制药株式会社 | 磺酰胺衍生物及其药物用途 |
EP3268369A4 (fr) | 2015-03-10 | 2018-08-08 | The Regents of The University of California | Inhibiteurs anti-intégrine alphavbeta1 et méthodes d'utilisation associées |
US11224600B2 (en) | 2018-10-30 | 2022-01-18 | Gilead Sciences, Inc. | Compounds for inhibition of alpha 4 beta 7 integrin |
WO2020092401A1 (fr) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | COMPOSÉS POUR INHIBITION DE L'INTÉGRINE ALPHA 4β7 |
CA3114240C (fr) | 2018-10-30 | 2023-09-05 | Gilead Sciences, Inc. | Derives d'imidazopyridine utilises en tant qu'inhibiteurs de l'integrine alpha4beta7 |
EP3873884A1 (fr) | 2018-10-30 | 2021-09-08 | Gilead Sciences, Inc. | Dérivés de quinoléine utilisés en tant qu'inhibiteurs de l'intégrine alpha4bêta7 |
JP7491996B2 (ja) | 2019-08-14 | 2024-05-28 | ギリアード サイエンシーズ, インコーポレイテッド | α4β7インテグリンの阻害のための化合物 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2291778A1 (fr) * | 1997-05-29 | 1998-12-03 | Merck & Co., Inc. | Composes d'amide heterocycliques utilises en tant qu'inhibiteurs de l'adhesion cellulaire |
DE69833654T2 (de) * | 1997-05-29 | 2006-12-14 | Merck & Co., Inc. (A New Jersey Corp.) | Biarylalkansäuren in der verwendung als zelladhäsionsinhibitoren |
HU229362B1 (en) * | 1997-08-22 | 2013-11-28 | Hoffmann La Roche | N-alkanoylphenylalanine derivatives |
ES2214728T3 (es) * | 1997-08-22 | 2004-09-16 | F. Hoffmann-La Roche Ag | Derivados de n-aroilfenilalanina. |
CN1231212C (zh) * | 1999-01-22 | 2005-12-14 | 依兰制药公司 | 抑制vla-4介导的白细胞粘着的多环化合物 |
-
2000
- 2000-11-28 DK DK00989906T patent/DK1237878T3/da active
- 2000-11-28 PL PL357601A patent/PL207160B1/pl unknown
- 2000-11-28 AU AU26696/01A patent/AU783348B2/en not_active Ceased
- 2000-11-28 KR KR10-2002-7007175A patent/KR100522344B1/ko not_active IP Right Cessation
- 2000-11-28 WO PCT/EP2000/011884 patent/WO2001042225A2/fr active IP Right Grant
- 2000-11-28 CN CNB008167958A patent/CN1218943C/zh not_active Expired - Fee Related
- 2000-11-28 ES ES00989906T patent/ES2282162T3/es not_active Expired - Lifetime
- 2000-11-28 HU HU0204081A patent/HU229105B1/hu not_active IP Right Cessation
- 2000-11-28 RS YUP-404/02A patent/RS50371B/sr unknown
- 2000-11-28 JP JP2001543526A patent/JP3824935B2/ja not_active Expired - Fee Related
- 2000-11-28 IL IL14961700A patent/IL149617A0/xx active IP Right Grant
- 2000-11-28 RU RU2002117422/04A patent/RU2266901C2/ru not_active IP Right Cessation
- 2000-11-28 SI SI200030948T patent/SI1237878T1/sl unknown
- 2000-11-28 NZ NZ518828A patent/NZ518828A/en not_active IP Right Cessation
- 2000-11-28 CA CA2392570A patent/CA2392570C/fr not_active Expired - Fee Related
- 2000-11-28 PT PT00989906T patent/PT1237878E/pt unknown
- 2000-11-28 EP EP00989906A patent/EP1237878B1/fr not_active Expired - Lifetime
- 2000-11-28 AT AT00989906T patent/ATE357433T1/de active
- 2000-11-28 MX MXPA02005564A patent/MXPA02005564A/es active IP Right Grant
- 2000-11-28 BR BR0016195-0A patent/BR0016195A/pt active Search and Examination
- 2000-11-28 DE DE60034061T patent/DE60034061T2/de not_active Expired - Lifetime
- 2000-11-28 CZ CZ20022351A patent/CZ303435B6/cs not_active IP Right Cessation
- 2000-11-29 JO JO2000190A patent/JO2283B1/en active
- 2000-12-03 EG EG20001502A patent/EG24361A/xx active
- 2000-12-04 AR ARP000106415A patent/AR034401A1/es not_active Application Discontinuation
- 2000-12-04 MY MYPI20005690A patent/MY126972A/en unknown
- 2000-12-05 TW TW089125890A patent/TWI256387B/zh not_active IP Right Cessation
- 2000-12-05 PE PE2000001293A patent/PE20010961A1/es not_active Application Discontinuation
- 2000-12-05 CO CO00092691A patent/CO5080772A1/es unknown
-
2002
- 2002-05-03 ZA ZA200203533A patent/ZA200203533B/en unknown
- 2002-05-13 IL IL149617A patent/IL149617A/en not_active IP Right Cessation
- 2002-05-28 HR HR20020468A patent/HRP20020468B1/xx not_active IP Right Cessation
- 2002-06-04 NO NO20022633A patent/NO322866B1/no not_active IP Right Cessation
- 2002-06-05 MA MA26673A patent/MA26850A1/fr unknown
-
2003
- 2003-09-16 HK HK03106628.4A patent/HK1054384B/zh not_active IP Right Cessation
-
2007
- 2007-05-29 CY CY20071100715T patent/CY1106626T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ZA200203533B (en) | 4-pyrimidinyl-N-acyl-L-phenylalanines. | |
US6380387B1 (en) | 4-Pyrimidinyl-n-acyl-l phenylalanines | |
US6388084B1 (en) | 4-pyridinyl-n-acyl-l-phenylalanines | |
US6423728B1 (en) | Heterocyclic thioamide derivatives | |
AU779063B2 (en) | 4-pyridinyl-N-acyl-L-phenylalanines | |
NZ525573A (en) | LFA-1 antagonist compounds | |
IL135488A (en) | Reliable Cyclic History | |
WO2001070670A1 (fr) | Nouveau derive de phenylalanine | |
EP2925746A1 (fr) | Composés de triazole et d'imidazole substitués | |
WO1997032863A1 (fr) | Derives de thiazolidine-2,4-dione | |
CA2362833C (fr) | Derives de phenylalaninol |