CA2385412A1 - Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor - Google Patents
Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor Download PDFInfo
- Publication number
- CA2385412A1 CA2385412A1 CA002385412A CA2385412A CA2385412A1 CA 2385412 A1 CA2385412 A1 CA 2385412A1 CA 002385412 A CA002385412 A CA 002385412A CA 2385412 A CA2385412 A CA 2385412A CA 2385412 A1 CA2385412 A1 CA 2385412A1
- Authority
- CA
- Canada
- Prior art keywords
- phenylamino
- benzamide
- iodo
- methyl
- difluoro
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 238000000034 method Methods 0.000 title claims abstract description 53
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 title claims abstract description 47
- 229940124647 MEK inhibitor Drugs 0.000 title claims abstract description 46
- 230000002401 inhibitory effect Effects 0.000 title claims description 11
- 230000011242 neutrophil chemotaxis Effects 0.000 title abstract description 13
- 210000000440 neutrophil Anatomy 0.000 claims abstract description 65
- 230000005012 migration Effects 0.000 claims abstract description 28
- 238000013508 migration Methods 0.000 claims abstract description 28
- -1 (3-Hydroxy-pyrrolidin-1-yl)-[2-(4-iodo-2-methyl-phenylamino)-5-nitro-phenyl] Chemical class 0.000 claims description 108
- 150000001875 compounds Chemical class 0.000 claims description 84
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 239000001257 hydrogen Substances 0.000 claims description 46
- GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 claims description 42
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 claims description 40
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 claims description 40
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 150000002431 hydrogen Chemical group 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 22
- 230000005764 inhibitory process Effects 0.000 claims description 21
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 239000012828 PI3K inhibitor Substances 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 201000010099 disease Diseases 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 150000001408 amides Chemical class 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000004104 aryloxy group Chemical group 0.000 claims description 12
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 9
- 229940002612 prodrug Drugs 0.000 claims description 9
- 239000000651 prodrug Substances 0.000 claims description 9
- 229910052794 bromium Inorganic materials 0.000 claims description 8
- 229910052731 fluorine Chemical group 0.000 claims description 8
- 239000011737 fluorine Chemical group 0.000 claims description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 7
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical group 0.000 claims description 7
- CLOSFYSFDCNULT-UHFFFAOYSA-N 5-iodo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NOCC1=CC=CC=C1 CLOSFYSFDCNULT-UHFFFAOYSA-N 0.000 claims description 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 6
- SUDAHWBOROXANE-SECBINFHSA-N PD 0325901 Chemical compound OC[C@@H](O)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F SUDAHWBOROXANE-SECBINFHSA-N 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- DMXADGCWZHCXBU-UHFFFAOYSA-N 5-chloro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NCCO DMXADGCWZHCXBU-UHFFFAOYSA-N 0.000 claims description 5
- GQAZGSHVSAGDOJ-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)benzamide Chemical compound OCCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F GQAZGSHVSAGDOJ-UHFFFAOYSA-N 0.000 claims description 4
- YZVHIDUDGXLOLY-UHFFFAOYSA-N 5-bromo-2-(2-chloro-4-iodoanilino)-3,4-difluoro-n-(3-hydroxypropoxy)benzamide Chemical compound OCCCONC(=O)C1=CC(Br)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl YZVHIDUDGXLOLY-UHFFFAOYSA-N 0.000 claims description 4
- YNAWORHNPLOBBU-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-methyl-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC(Br)=CC=C1NC1=CC=C(I)C=C1C YNAWORHNPLOBBU-UHFFFAOYSA-N 0.000 claims description 4
- AANZSIPSXXHMRM-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-phenylmethoxybenzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NOCC1=CC=CC=C1 AANZSIPSXXHMRM-UHFFFAOYSA-N 0.000 claims description 4
- GUAFZVVAOQFCPJ-UHFFFAOYSA-N 5-bromo-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCCO GUAFZVVAOQFCPJ-UHFFFAOYSA-N 0.000 claims description 4
- ASLGKYRJGJLPAE-MRVPVSSYSA-N 5-chloro-2-(2-chloro-4-iodoanilino)-n-[(2r)-2,3-dihydroxypropoxy]-3,4-difluorobenzamide Chemical compound OC[C@@H](O)CONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl ASLGKYRJGJLPAE-MRVPVSSYSA-N 0.000 claims description 4
- ASLGKYRJGJLPAE-QMMMGPOBSA-N 5-chloro-2-(2-chloro-4-iodoanilino)-n-[(2s)-2,3-dihydroxypropoxy]-3,4-difluorobenzamide Chemical compound OC[C@H](O)CONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl ASLGKYRJGJLPAE-QMMMGPOBSA-N 0.000 claims description 4
- UVQPYTNHXUMIMH-UHFFFAOYSA-N 5-chloro-n-(2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide Chemical compound OCC(O)CONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1F UVQPYTNHXUMIMH-UHFFFAOYSA-N 0.000 claims description 4
- UVQPYTNHXUMIMH-MRVPVSSYSA-N 5-chloro-n-[(2r)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide Chemical compound OC[C@@H](O)CONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1F UVQPYTNHXUMIMH-MRVPVSSYSA-N 0.000 claims description 4
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
- SUDAHWBOROXANE-VIFPVBQESA-N PD 0325901-Cl Chemical compound OC[C@H](O)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F SUDAHWBOROXANE-VIFPVBQESA-N 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- HPFQWCKXOZLYJQ-UHFFFAOYSA-N n-but-2-enoxy-3,4-difluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC=CCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1C HPFQWCKXOZLYJQ-UHFFFAOYSA-N 0.000 claims description 4
- APDFSUINPPLQLM-UHFFFAOYSA-N n-cyclopropyl-5-fluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NC1CC1 APDFSUINPPLQLM-UHFFFAOYSA-N 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- WRIPZDWCGAIYEF-UHFFFAOYSA-N 2-(4-iodo-2-methylanilino)-5-nitro-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C([N+]([O-])=O)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 WRIPZDWCGAIYEF-UHFFFAOYSA-N 0.000 claims description 3
- SHKSNTSNKIULBG-UHFFFAOYSA-N 4,5-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxy-3-phenoxypropoxy)benzamide Chemical compound C=1C=CC=CC=1OCC(O)CONC(=O)C1=CC(F)=C(F)C=C1NC1=CC=C(I)C=C1F SHKSNTSNKIULBG-UHFFFAOYSA-N 0.000 claims description 3
- DSFQOJWTJQNGSU-UHFFFAOYSA-N 5-bromo-2-(4-iodo-2-methylanilino)-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 DSFQOJWTJQNGSU-UHFFFAOYSA-N 0.000 claims description 3
- VBFVICYZHVZQIF-UHFFFAOYSA-N 5-bromo-n-cyclopropyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Br)C=C1C(=O)NC1CC1 VBFVICYZHVZQIF-UHFFFAOYSA-N 0.000 claims description 3
- ASLGKYRJGJLPAE-UHFFFAOYSA-N 5-chloro-2-(2-chloro-4-iodoanilino)-n-(2,3-dihydroxypropoxy)-3,4-difluorobenzamide Chemical compound OCC(O)CONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl ASLGKYRJGJLPAE-UHFFFAOYSA-N 0.000 claims description 3
- DAVWVMNCZOSIBH-UHFFFAOYSA-N 5-chloro-n-(1,3-dihydroxypropan-2-yloxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide Chemical compound OCC(CO)ONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1F DAVWVMNCZOSIBH-UHFFFAOYSA-N 0.000 claims description 3
- UVQPYTNHXUMIMH-QMMMGPOBSA-N 5-chloro-n-[(2s)-2,3-dihydroxypropoxy]-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide Chemical compound OC[C@H](O)CONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1F UVQPYTNHXUMIMH-QMMMGPOBSA-N 0.000 claims description 3
- NRQYGGWYEHEXEJ-UHFFFAOYSA-N 5-chloro-n-cyclopropyl-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(Cl)C=C1C(=O)NC1CC1 NRQYGGWYEHEXEJ-UHFFFAOYSA-N 0.000 claims description 3
- PJCPYFYKAWDPLX-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-[(4-sulfamoylphenyl)methyl]benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCC1=CC=C(S(N)(=O)=O)C=C1 PJCPYFYKAWDPLX-UHFFFAOYSA-N 0.000 claims description 3
- KCOUCDQMKMTOGV-UHFFFAOYSA-N 5-fluoro-2-(4-iodo-2-methylanilino)-n-methyl-n-phenylbenzamide Chemical compound C=1C=CC=CC=1N(C)C(=O)C1=CC(F)=CC=C1NC1=CC=C(I)C=C1C KCOUCDQMKMTOGV-UHFFFAOYSA-N 0.000 claims description 3
- YSXVOTVVUSIKNI-UHFFFAOYSA-N 5-fluoro-n-(2-hydroxyethyl)-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(F)C=C1C(=O)NCCO YSXVOTVVUSIKNI-UHFFFAOYSA-N 0.000 claims description 3
- 208000033116 Asbestos intoxication Diseases 0.000 claims description 3
- 206010014561 Emphysema Diseases 0.000 claims description 3
- 208000037487 Endotoxemia Diseases 0.000 claims description 3
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 3
- UHAXDAKQGVISBZ-UHFFFAOYSA-N N-(cyclopropylmethoxy)-3,4,5-trifluoro-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C(F)=C(F)C=C1C(=O)NOCC1CC1 UHAXDAKQGVISBZ-UHFFFAOYSA-N 0.000 claims description 3
- 206010063837 Reperfusion injury Diseases 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
- 206010003441 asbestosis Diseases 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000000460 chlorine Substances 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 3
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 3
- AEAMPCCYDKGXCC-UHFFFAOYSA-N n-(1,3-dihydroxypropan-2-yloxy)-3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzamide Chemical compound OCC(CO)ONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F AEAMPCCYDKGXCC-UHFFFAOYSA-N 0.000 claims description 3
- IGVMHOOQGPQIMZ-UHFFFAOYSA-N n-(2-anilinoethoxy)-2-(2-chloro-4-iodoanilino)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCCNC1=CC=CC=C1 IGVMHOOQGPQIMZ-UHFFFAOYSA-N 0.000 claims description 3
- JDQKKPHXLMZTFM-UHFFFAOYSA-N n-(2-hydroxyethyl)-5-iodo-2-(4-iodo-2-methylanilino)benzamide Chemical compound CC1=CC(I)=CC=C1NC1=CC=C(I)C=C1C(=O)NCCO JDQKKPHXLMZTFM-UHFFFAOYSA-N 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 claims description 2
- IWZZOJQMYWDXJN-UHFFFAOYSA-N 2,3,5-trifluoro-4-(4-iodo-2-methylanilino)benzoic acid Chemical compound CC1=CC(I)=CC=C1NC1=C(F)C=C(C(O)=O)C(F)=C1F IWZZOJQMYWDXJN-UHFFFAOYSA-N 0.000 claims description 2
- GLQYKBQRDMOSAE-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-(1-hydroxypropan-2-yloxy)benzamide Chemical compound OCC(C)ONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(F)C=C1F GLQYKBQRDMOSAE-UHFFFAOYSA-N 0.000 claims description 2
- BPORPGYWYCZFIQ-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-(2-hydroxy-2-methylpropoxy)benzamide Chemical compound CC(C)(O)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(F)C=C1F BPORPGYWYCZFIQ-UHFFFAOYSA-N 0.000 claims description 2
- BUCUZFYTODLSLK-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-(2-hydroxy-3-methoxypropoxy)benzamide Chemical compound COCC(O)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(F)C=C1F BUCUZFYTODLSLK-UHFFFAOYSA-N 0.000 claims description 2
- QEIPHLNZHZGILN-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-(2-hydroxyethoxy)benzamide Chemical compound OCCONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(F)C=C1F QEIPHLNZHZGILN-UHFFFAOYSA-N 0.000 claims description 2
- SDNFEPSSQCCTDP-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-(3,3,3-trifluoro-2-hydroxypropoxy)benzamide Chemical compound FC(F)(F)C(O)CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(F)C=C1F SDNFEPSSQCCTDP-UHFFFAOYSA-N 0.000 claims description 2
- AJBLOQYWEWENKM-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-[[1-(hydroxymethyl)cyclopropyl]methoxy]benzamide Chemical compound C=1C=C(F)C(F)=C(NC=2C(=CC(F)=CC=2)F)C=1C(=O)NOCC1(CO)CC1 AJBLOQYWEWENKM-UHFFFAOYSA-N 0.000 claims description 2
- HTAQKRHMBXAWBW-UHFFFAOYSA-N 2-(2,4-difluoroanilino)-3,4-difluoro-n-[[2-(hydroxymethyl)cyclopropyl]methoxy]benzamide Chemical compound OCC1CC1CONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(F)C=C1F HTAQKRHMBXAWBW-UHFFFAOYSA-N 0.000 claims description 2
- ZHMSIFGQMCBYIY-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-3,4,5-trifluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(F)=C(F)C(F)=C1NC1=CC=C(I)C=C1Br ZHMSIFGQMCBYIY-UHFFFAOYSA-N 0.000 claims description 2
- BZJWSLFAFFNFIW-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1Br BZJWSLFAFFNFIW-UHFFFAOYSA-N 0.000 claims description 2
- XYYUOXLXTADKMW-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-4-fluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC=C(F)C=C1NC1=CC=C(I)C=C1Br XYYUOXLXTADKMW-UHFFFAOYSA-N 0.000 claims description 2
- AVIWCXSGNKPKKK-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-5-chloro-3,4-difluoro-n-hydroxybenzamide Chemical compound ONC(=O)C1=CC(Cl)=C(F)C(F)=C1NC1=CC=C(I)C=C1Br AVIWCXSGNKPKKK-UHFFFAOYSA-N 0.000 claims description 2
- QMALWSSCPZJMOO-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-5-nitrobenzoic acid Chemical compound OC(=O)C1=CC([N+]([O-])=O)=CC=C1NC1=CC=C(I)C=C1Br QMALWSSCPZJMOO-UHFFFAOYSA-N 0.000 claims description 2
- BWOZEHCSZGOGER-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-(cyclopropylmethoxy)-3,4,5-trifluorobenzamide Chemical compound C=1C=C(I)C=C(Br)C=1NC=1C(F)=C(F)C(F)=CC=1C(=O)NOCC1CC1 BWOZEHCSZGOGER-UHFFFAOYSA-N 0.000 claims description 2
- NMGPTKSLPIARAK-UHFFFAOYSA-N 2-(2-bromo-4-iodoanilino)-n-hydroxy-4-nitrobenzamide Chemical compound ONC(=O)C1=CC=C([N+]([O-])=O)C=C1NC1=CC=C(I)C=C1Br NMGPTKSLPIARAK-UHFFFAOYSA-N 0.000 claims description 2
- PYMZEKGOVJOENJ-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4,5-trifluoro-n-(1-hydroxypropan-2-yloxy)benzamide Chemical compound OCC(C)ONC(=O)C1=CC(F)=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl PYMZEKGOVJOENJ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/12—Mucolytics
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- 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]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28988101P | 2001-05-09 | 2001-05-09 | |
| US60/289,881 | 2001-05-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2385412A1 true CA2385412A1 (en) | 2002-11-09 |
Family
ID=23113527
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002385412A Abandoned CA2385412A1 (en) | 2001-05-09 | 2002-05-06 | Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US6972298B2 (OSRAM) |
| EP (1) | EP1262176A1 (OSRAM) |
| JP (1) | JP2002332247A (OSRAM) |
| KR (1) | KR20020085852A (OSRAM) |
| CN (1) | CN1383823A (OSRAM) |
| AU (1) | AU3821502A (OSRAM) |
| CA (1) | CA2385412A1 (OSRAM) |
| HU (1) | HUP0201542A3 (OSRAM) |
| IL (1) | IL149462A0 (OSRAM) |
| NZ (1) | NZ518726A (OSRAM) |
| PL (1) | PL353785A1 (OSRAM) |
| ZA (1) | ZA200203668B (OSRAM) |
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| EP2298768A1 (en) | 2004-06-11 | 2011-03-23 | Japan Tobacco, Inc. | 5-amino-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-d]pyrimidine derivatives and related compounds for the treatment of cancer |
| US9724413B2 (en) | 2011-08-01 | 2017-08-08 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors |
| US10946093B2 (en) | 2014-07-15 | 2021-03-16 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors |
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| WO2005028426A1 (ja) | 2003-09-19 | 2005-03-31 | Chugai Seiyaku Kabushiki Kaisha | 新規4−フェニルアミノ−ベンズアルドオキシム誘導体並びにそのmek阻害剤としての使用 |
| RU2352558C2 (ru) * | 2003-10-21 | 2009-04-20 | Уорнер-Ламберт Компани Ллс | Полиморфная форма n-[(r)-2,3-дигидроксипропокси]-3,4-дифтор-2-(2-фтор-4 йодфениламино)бензамида |
| MY144232A (en) | 2004-07-26 | 2011-08-15 | Chugai Pharmaceutical Co Ltd | 5-substituted-2-phenylamino benzamides as mek inhibitors |
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| EP2101759B1 (en) | 2006-12-14 | 2018-10-10 | Exelixis, Inc. | Methods of using mek inhibitors |
| CL2008001373A1 (es) * | 2007-05-11 | 2008-11-21 | Bayer Schering Pharma Ag | Compuestos derivados de fenilamino-benceno sustituidos; metodo de preparacion; composicion farmaceutica; kit farmceuticos; y uso de dichos compuestos en el tratamiento del cancer. |
| CN101868443A (zh) * | 2007-09-20 | 2010-10-20 | 特拉维夫大学拉莫特有限公司 | N-苯基邻氨基苯甲酸衍生物及其用途 |
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| KR20130113430A (ko) | 2010-08-05 | 2013-10-15 | 케이스 웨스턴 리저브 유니버시티 | 신경 연결의 발달 장애에 대한 erk 억제제 |
| US20120095060A1 (en) * | 2010-10-14 | 2012-04-19 | Hardie William D | Methods and compositions of mitogen-activated protein kinase (mapk) pathway inhibitors for treating pulmonary fibrosis |
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| SG10201600179RA (en) | 2011-01-10 | 2016-02-26 | Infinity Pharmaceuticals Inc | Processes for preparing isoquinolinones and solid forms of isoquinolinones |
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| BR112013025353A8 (pt) | 2011-04-01 | 2018-01-02 | Genentech Inc | combinação de a) um composto de fórmula ia, composto de fórmula ia ou um sal farmaceuticamente aceitável do mesmo, método para tratamento de um distúrbio hiperproliferativo em um mamífero, uso de um composto de fórmula ia ou um sal farmaceuticamente aceitável do mesmo, kit e produto |
| HRP20220319T1 (hr) | 2011-05-19 | 2022-05-13 | Fundación Del Sector Público Estatal Centro Nacional De Investigaciones Oncológicas Carlos III (F.S.P. CNIO) | Makrociklički spojevi kao inhibitori protein kinaze |
| EP2524918A1 (en) | 2011-05-19 | 2012-11-21 | Centro Nacional de Investigaciones Oncológicas (CNIO) | Imidazopyrazines derivates as kinase inhibitors |
| WO2013005041A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Tricyclic heterocyclic compounds as kinase inhibitors |
| WO2013004984A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Tricyclic compounds for use as kinase inhibitors |
| WO2013005057A1 (en) | 2011-07-07 | 2013-01-10 | Centro Nacional De Investigaciones Oncológicas (Cnio) | New compounds |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| GEP201706690B (en) | 2012-10-12 | 2017-06-26 | Exelixis Inc | Novel process for making compounds for use in treatment of cancer |
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| UA125216C2 (uk) | 2016-06-24 | 2022-02-02 | Інфініті Фармасьютікалз, Інк. | Комбінована терапія |
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| KR20200063227A (ko) | 2017-10-09 | 2020-06-04 | 라모트 앳 텔-아비브 유니버시티 리미티드 | 칼륨 이온 및 trpv1 채널의 조절제 및 이의 용도 |
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| TW202342018A (zh) | 2022-03-04 | 2023-11-01 | 美商奇奈特生物製藥公司 | Mek激酶抑制劑 |
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| US5525625A (en) * | 1995-01-24 | 1996-06-11 | Warner-Lambert Company | 2-(2-Amino-3-methoxyphenyl)-4-oxo-4H-[1]benzopyran for treating proliferative disorders |
| AU5610398A (en) * | 1997-02-28 | 1998-09-18 | Warner-Lambert Company | Method of treating or preventing septic shock by administering a mek inhibitor |
| CA2290509A1 (en) * | 1997-07-01 | 1999-01-14 | Warner-Lambert Company | 2-(4-bromo or 4-iodo phenylamino) benzoic acid derivatives and their use as mek inhibitors |
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| TR200200082T2 (tr) | 1999-07-16 | 2002-04-22 | Warner-Lambert Company | MEK inhibitörleri kullanılarak kronik ağrının tedavi edilmesi. |
| DE10017480A1 (de) * | 2000-04-07 | 2001-10-11 | Transmit Technologietransfer | Verwendung von Substanzen, die als MEK Inhibitor wirken, zur Herstellung eines Arneimittels gegen DNA- und RNA-Viren |
| HRP20020838A2 (en) * | 2000-04-25 | 2004-12-31 | Icos Corp | Inhibitors of human phosphatidyl-inositol 3-kinase delta |
| CN1219753C (zh) * | 2000-07-19 | 2005-09-21 | 沃尼尔·朗伯公司 | 4-碘苯氨基苯氧肟酸的氧合酯 |
| WO2002069960A2 (en) | 2001-03-06 | 2002-09-12 | Axxima Pharmaceuticals Ag | Use of mek inhibitors for treating inflammation and virus induced hemorrhagic shock |
| WO2002076496A1 (en) | 2001-03-22 | 2002-10-03 | Van Andel Institute | Anthrax lethal factor inhibits tumor growth and angiogenesis |
-
2002
- 2002-05-02 IL IL14946202A patent/IL149462A0/xx unknown
- 2002-05-02 NZ NZ518726A patent/NZ518726A/en unknown
- 2002-05-03 EP EP02009344A patent/EP1262176A1/en not_active Withdrawn
- 2002-05-06 CA CA002385412A patent/CA2385412A1/en not_active Abandoned
- 2002-05-07 AU AU38215/02A patent/AU3821502A/en not_active Abandoned
- 2002-05-08 JP JP2002132822A patent/JP2002332247A/ja active Pending
- 2002-05-08 HU HU0201542A patent/HUP0201542A3/hu unknown
- 2002-05-08 KR KR1020020025328A patent/KR20020085852A/ko not_active Ceased
- 2002-05-08 ZA ZA200203668A patent/ZA200203668B/xx unknown
- 2002-05-09 PL PL02353785A patent/PL353785A1/xx not_active Application Discontinuation
- 2002-05-09 CN CN02118988A patent/CN1383823A/zh active Pending
- 2002-05-09 US US10/144,315 patent/US6972298B2/en not_active Expired - Fee Related
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7378423B2 (en) | 2004-06-11 | 2008-05-27 | Japan Tobacco Inc. | Pyrimidine compound and medical use thereof |
| EP2298768A1 (en) | 2004-06-11 | 2011-03-23 | Japan Tobacco, Inc. | 5-amino-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-d]pyrimidine derivatives and related compounds for the treatment of cancer |
| US8835443B2 (en) | 2004-06-11 | 2014-09-16 | Japan Tobacco Inc. | Pyrimidine compound and medical use thereof |
| US9724413B2 (en) | 2011-08-01 | 2017-08-08 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors |
| US10646567B2 (en) | 2011-08-01 | 2020-05-12 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors |
| US10946093B2 (en) | 2014-07-15 | 2021-03-16 | Genentech, Inc. | Methods of treating cancer using PD-1 axis binding antagonists and MEK inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| US20030055095A1 (en) | 2003-03-20 |
| IL149462A0 (en) | 2002-11-10 |
| HU0201542D0 (OSRAM) | 2002-07-29 |
| ZA200203668B (en) | 2002-12-20 |
| EP1262176A1 (en) | 2002-12-04 |
| KR20020085852A (ko) | 2002-11-16 |
| US6972298B2 (en) | 2005-12-06 |
| HUP0201542A3 (en) | 2003-10-28 |
| JP2002332247A (ja) | 2002-11-22 |
| PL353785A1 (en) | 2002-11-18 |
| AU3821502A (en) | 2002-11-14 |
| NZ518726A (en) | 2004-06-25 |
| HUP0201542A2 (hu) | 2003-01-28 |
| CN1383823A (zh) | 2002-12-11 |
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Legal Events
| Date | Code | Title | Description |
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| EEER | Examination request | ||
| FZDE | Discontinued |