CA2393027A1 - Inhibiteurs d'expression du gene de l'interleukine 5 - Google Patents
Inhibiteurs d'expression du gene de l'interleukine 5 Download PDFInfo
- Publication number
- CA2393027A1 CA2393027A1 CA002393027A CA2393027A CA2393027A1 CA 2393027 A1 CA2393027 A1 CA 2393027A1 CA 002393027 A CA002393027 A CA 002393027A CA 2393027 A CA2393027 A CA 2393027A CA 2393027 A1 CA2393027 A1 CA 2393027A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- phenyl
- fluoro
- phenoxy
- pyran
- 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
- 108010002616 Interleukin-5 Proteins 0.000 title claims abstract description 34
- 102000000743 Interleukin-5 Human genes 0.000 title claims abstract description 32
- 229940100602 interleukin-5 Drugs 0.000 title claims abstract description 31
- 230000014509 gene expression Effects 0.000 title claims abstract description 19
- 239000003112 inhibitor Substances 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 364
- 238000000034 method Methods 0.000 claims abstract description 60
- 241000124008 Mammalia Species 0.000 claims abstract description 24
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 171
- -1 azocanyl Chemical group 0.000 claims description 160
- 229910052739 hydrogen Inorganic materials 0.000 claims description 127
- 239000001257 hydrogen Substances 0.000 claims description 127
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 118
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 239000000203 mixture Substances 0.000 claims description 102
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 83
- 125000000623 heterocyclic group Chemical group 0.000 claims description 53
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 40
- 150000002367 halogens Chemical group 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 38
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 36
- 125000001188 haloalkyl group Chemical group 0.000 claims description 35
- 125000003118 aryl group Chemical group 0.000 claims description 34
- 125000000304 alkynyl group Chemical group 0.000 claims description 32
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 28
- 208000006673 asthma Diseases 0.000 claims description 28
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 27
- 150000002431 hydrogen Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 239000000460 chlorine Chemical group 0.000 claims description 24
- 229910052731 fluorine Chemical group 0.000 claims description 24
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 23
- 239000011737 fluorine Chemical group 0.000 claims description 23
- 229910052801 chlorine Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 20
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 20
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 18
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 18
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000004193 piperazinyl group Chemical group 0.000 claims description 13
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 12
- WOALWQDGURQZDO-UHFFFAOYSA-N n-[4-[(3-fluoro-5-morpholin-4-ylphenoxy)methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCOCC2)=C1 WOALWQDGURQZDO-UHFFFAOYSA-N 0.000 claims description 12
- 208000026935 allergic disease Diseases 0.000 claims description 11
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 11
- 125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- SCLDAHPMYQEOOV-UHFFFAOYSA-N n-[4-[[6-(4-hydroxyoxan-4-yl)pyridin-2-yl]oxymethyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC=CC(C2(O)CCOCC2)=N1 SCLDAHPMYQEOOV-UHFFFAOYSA-N 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000005942 tetrahydropyridyl group Chemical group 0.000 claims description 6
- 125000001984 thiazolidinyl group Chemical group 0.000 claims description 6
- JGRCOASJDIFSEF-UHFFFAOYSA-N 1-[3-chloro-4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1,3,3-trimethylurea Chemical compound C=1C(F)=CC(OCC=2C(=CC(=CC=2)N(C)C(=O)N(C)C)Cl)=CC=1C1(OC)CCOCC1 JGRCOASJDIFSEF-UHFFFAOYSA-N 0.000 claims description 5
- 125000003725 azepanyl group Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- YQNUSOJKYANHDX-HSZRJFAPSA-N (2r)-n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-2-(hydroxymethyl)-n-methylpyrrolidine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2[C@H](CCC2)CO)=CC=1C1(OC)CCOCC1 YQNUSOJKYANHDX-HSZRJFAPSA-N 0.000 claims description 4
- BHHQSOPAZUJKFB-UHFFFAOYSA-N 1,1-diethyl-3-[4-[(3-fluoro-5-morpholin-4-ylphenoxy)methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCOCC2)=C1 BHHQSOPAZUJKFB-UHFFFAOYSA-N 0.000 claims description 4
- SUXUXUJDGLJOEU-UHFFFAOYSA-N 1,1-diethyl-3-[4-[(3-fluoro-5-piperidin-1-ylphenoxy)methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCCCC2)=C1 SUXUXUJDGLJOEU-UHFFFAOYSA-N 0.000 claims description 4
- JZBKGGATNDSHEH-UHFFFAOYSA-N 1,1-diethyl-3-[4-[(3-fluoro-5-pyrrolidin-1-ylphenoxy)methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCCC2)=C1 JZBKGGATNDSHEH-UHFFFAOYSA-N 0.000 claims description 4
- CUFLJEUIRKGVLI-UHFFFAOYSA-N 1,1-diethyl-3-[4-[(3-fluoro-5-thiomorpholin-4-ylphenoxy)methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCSCC2)=C1 CUFLJEUIRKGVLI-UHFFFAOYSA-N 0.000 claims description 4
- QLSQMRLOIVHBPB-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-(4-ethyloxan-4-yl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC=CC(C2(CC)CCOCC2)=C1 QLSQMRLOIVHBPB-UHFFFAOYSA-N 0.000 claims description 4
- CBVIZXWBMDIBBE-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-[ethyl(2-methoxyethyl)amino]-5-fluorophenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N(CC)CCOC)=C1 CBVIZXWBMDIBBE-UHFFFAOYSA-N 0.000 claims description 4
- NQIVJAIGOWKHIN-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-fluoro-5-(4-hydroxypiperidin-1-yl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCC(O)CC2)=C1 NQIVJAIGOWKHIN-UHFFFAOYSA-N 0.000 claims description 4
- CBALREJPAJJFDB-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-fluoro-5-(oxan-4-yl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(C2CCOCC2)=C1 CBALREJPAJJFDB-UHFFFAOYSA-N 0.000 claims description 4
- NCGKNTSLYMHSNM-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-fluoro-5-[4-(2-hydroxyethyl)piperazin-1-yl]phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCN(CCO)CC2)=C1 NCGKNTSLYMHSNM-UHFFFAOYSA-N 0.000 claims description 4
- WLKIEWXNWMTEKE-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[6-(4-hydroxyoxan-4-yl)pyridin-2-yl]oxymethyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC=CC(C2(O)CCOCC2)=N1 WLKIEWXNWMTEKE-UHFFFAOYSA-N 0.000 claims description 4
- REPDCWOVUWSCBY-UHFFFAOYSA-N 1-(2-cyanoethyl)-1-cyclopropyl-3-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N(CCC#N)C2CC2)=CC=1C1(OC)CCOCC1 REPDCWOVUWSCBY-UHFFFAOYSA-N 0.000 claims description 4
- ZXACBCHCFHWLBC-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-methyl-1-propylurea Chemical compound C=1C=C(COC=2C=C(C=C(F)C=2)C2(CCOCC2)OC)C=CC=1N(C)C(=O)N(CCC)CC1CC1 ZXACBCHCFHWLBC-UHFFFAOYSA-N 0.000 claims description 4
- KCJLFJJARIZZIU-UHFFFAOYSA-N 1-[2-(1,3-dioxolan-2-yl)ethyl]-3-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1,3-dimethylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N(C)CCC2OCCO2)=CC=1C1(OC)CCOCC1 KCJLFJJARIZZIU-UHFFFAOYSA-N 0.000 claims description 4
- SWQTYOGXLCUDGL-UHFFFAOYSA-N 1-[4-[[3-(2,6-dimethylmorpholin-4-yl)-5-fluorophenoxy]methyl]phenyl]-3,3-diethyl-1-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CC(C)OC(C)C2)=C1 SWQTYOGXLCUDGL-UHFFFAOYSA-N 0.000 claims description 4
- QQHMOXQCXAJLAE-UHFFFAOYSA-N 1-[4-[[3-(cyclohexylamino)-5-fluorophenoxy]methyl]phenyl]-3,3-diethyl-1-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(NC2CCCCC2)=C1 QQHMOXQCXAJLAE-UHFFFAOYSA-N 0.000 claims description 4
- BFINTFMNWSIOQT-UHFFFAOYSA-N 1-[4-[[3-(cyclopentylamino)-5-fluorophenoxy]methyl]phenyl]-3,3-diethyl-1-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(NC2CCCC2)=C1 BFINTFMNWSIOQT-UHFFFAOYSA-N 0.000 claims description 4
- FIXNRPFTJOIBJD-UHFFFAOYSA-N 1-[4-[[3-[bis(2-methoxyethyl)amino]-5-fluorophenoxy]methyl]phenyl]-3,3-diethyl-1-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N(CCOC)CCOC)=C1 FIXNRPFTJOIBJD-UHFFFAOYSA-N 0.000 claims description 4
- WFZOVCYNRQXHHS-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1,3-dimethyl-3-prop-2-ynylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N(C)CC#C)=CC=1C1(OC)CCOCC1 WFZOVCYNRQXHHS-UHFFFAOYSA-N 0.000 claims description 4
- XBSARVMNKQGMPX-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methyl-3-(2-methylprop-2-enyl)urea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCC(C)=C)=CC=1C1(OC)CCOCC1 XBSARVMNKQGMPX-UHFFFAOYSA-N 0.000 claims description 4
- IJNWOXKIFAOUSW-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methyl-3-(oxolan-2-ylmethyl)urea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCC2OCCC2)=CC=1C1(OC)CCOCC1 IJNWOXKIFAOUSW-UHFFFAOYSA-N 0.000 claims description 4
- FXZIOMWRCFQNCE-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methyl-3-prop-2-ynylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCC#C)=CC=1C1(OC)CCOCC1 FXZIOMWRCFQNCE-UHFFFAOYSA-N 0.000 claims description 4
- AXJFXYNSTQJWQE-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-(1-methoxypropan-2-yl)-1-methylurea Chemical compound C1=CC(N(C)C(=O)NC(C)COC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 AXJFXYNSTQJWQE-UHFFFAOYSA-N 0.000 claims description 4
- HTRMNAYPGRWADH-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-(2-methoxyethyl)-1,3-dimethylurea Chemical compound C1=CC(N(C)C(=O)N(C)CCOC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 HTRMNAYPGRWADH-UHFFFAOYSA-N 0.000 claims description 4
- DUBFPACLXYCLKT-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-(2-methoxyethyl)-1-methylurea Chemical compound C1=CC(N(C)C(=O)NCCOC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 DUBFPACLXYCLKT-UHFFFAOYSA-N 0.000 claims description 4
- AZKRBFDAQYURTC-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-[1-(hydroxymethyl)cyclopentyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NC2(CO)CCCC2)=CC=1C1(OC)CCOCC1 AZKRBFDAQYURTC-UHFFFAOYSA-N 0.000 claims description 4
- JIHOZBPKECMZLH-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-[2-(2-hydroxyethoxy)ethyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCCOCCO)=CC=1C1(OC)CCOCC1 JIHOZBPKECMZLH-UHFFFAOYSA-N 0.000 claims description 4
- WDNVUZVPBPGKDZ-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-[2-(4-hydroxyphenyl)ethyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCCC=2C=CC(O)=CC=2)=CC=1C1(OC)CCOCC1 WDNVUZVPBPGKDZ-UHFFFAOYSA-N 0.000 claims description 4
- JFCKHWIHKIOOQO-UHFFFAOYSA-N 1-butyl-1-(cyanomethyl)-3-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC#N)CCCC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 JFCKHWIHKIOOQO-UHFFFAOYSA-N 0.000 claims description 4
- RDCIMFVQBYNQCL-UHFFFAOYSA-N 2-ethyl-n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylbutanamide Chemical compound C1=CC(N(C)C(=O)C(CC)CC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 RDCIMFVQBYNQCL-UHFFFAOYSA-N 0.000 claims description 4
- YSSKTSZKKYWTCE-UHFFFAOYSA-N 3-(2-cyanoethyl)-1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCCC#N)=CC=1C1(OC)CCOCC1 YSSKTSZKKYWTCE-UHFFFAOYSA-N 0.000 claims description 4
- ZCLDJYPLCRTVJZ-UHFFFAOYSA-N 3-(cyanomethyl)-1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCC#N)=CC=1C1(OC)CCOCC1 ZCLDJYPLCRTVJZ-UHFFFAOYSA-N 0.000 claims description 4
- KMLUQLGCPMMOGH-UHFFFAOYSA-N 3-(cyclopropylmethyl)-1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NCC2CC2)=CC=1C1(OC)CCOCC1 KMLUQLGCPMMOGH-UHFFFAOYSA-N 0.000 claims description 4
- CAHBSZXVDPWBHD-UHFFFAOYSA-N 3-cyclobutyl-1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NC2CCC2)=CC=1C1(OC)CCOCC1 CAHBSZXVDPWBHD-UHFFFAOYSA-N 0.000 claims description 4
- HKENFFVVRLKKJH-UHFFFAOYSA-N 3-cyclopropyl-1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NC2CC2)=CC=1C1(OC)CCOCC1 HKENFFVVRLKKJH-UHFFFAOYSA-N 0.000 claims description 4
- GGBMMJNAEVLNBA-UHFFFAOYSA-N 3-ethyl-n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n,2,4-trimethylpyrrolidine-1-carboxamide Chemical compound CC1C(CC)C(C)CN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 GGBMMJNAEVLNBA-UHFFFAOYSA-N 0.000 claims description 4
- HDYFLZHTVVRGRJ-UHFFFAOYSA-N 5-[[3-(1-benzyl-4-hydroxypiperidin-4-yl)-5-fluorophenoxy]methyl]-1,3-dimethylbenzimidazol-2-one Chemical compound C1=C2N(C)C(=O)N(C)C2=CC=C1COC(C=1)=CC(F)=CC=1C(CC1)(O)CCN1CC1=CC=CC=C1 HDYFLZHTVVRGRJ-UHFFFAOYSA-N 0.000 claims description 4
- GZVMKEOEWBJILU-UHFFFAOYSA-N 5-[[3-fluoro-5-(8-hydroxy-1,4-dioxaspiro[4.5]decan-8-yl)phenoxy]methyl]-1,3-dimethylbenzimidazol-2-one Chemical compound C1=C2N(C)C(=O)N(C)C2=CC=C1COC(C=1)=CC(F)=CC=1C(CC1)(O)CCC21OCCO2 GZVMKEOEWBJILU-UHFFFAOYSA-N 0.000 claims description 4
- QXLGQRUXSRSRFM-UHFFFAOYSA-N ethyl 4-[3-[[4-[diethylcarbamoyl(methyl)amino]phenyl]methoxy]-5-fluorophenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C1=CC(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N(CC)CC)=C1 QXLGQRUXSRSRFM-UHFFFAOYSA-N 0.000 claims description 4
- FCCRXHXSTRTPDN-UHFFFAOYSA-N ethyl 4-[3-fluoro-5-[[4-[methyl-(2-methylpyrrolidine-1-carbonyl)amino]phenyl]methoxy]phenyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCN1C1=CC(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C(CCC2)C)=C1 FCCRXHXSTRTPDN-UHFFFAOYSA-N 0.000 claims description 4
- WYLJTBWSTFBLGR-UHFFFAOYSA-N n-[4-[(3-fluoro-5-pyrrolidin-1-ylphenoxy)methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCCC2)=C1 WYLJTBWSTFBLGR-UHFFFAOYSA-N 0.000 claims description 4
- ZTYLZFYHMILUNO-UHFFFAOYSA-N n-[4-[2-[3-fluoro-5-(4-methoxyoxan-4-yl)phenyl]ethyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound C=1C(F)=CC(CCC=2C=CC(=CC=2)N(C)C(=O)N2C(CCC2)C)=CC=1C1(OC)CCOCC1 ZTYLZFYHMILUNO-UHFFFAOYSA-N 0.000 claims description 4
- SLPPIRXRBLDDQB-UHFFFAOYSA-N n-[4-[[3-(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)-5-fluorophenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCC3(CC2)OCCO3)=C1 SLPPIRXRBLDDQB-UHFFFAOYSA-N 0.000 claims description 4
- NIBIOKIBNJTDKK-UHFFFAOYSA-N n-[4-[[3-(2,6-dimethylmorpholin-4-yl)-5-fluorophenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CC(C)OC(C)C2)=C1 NIBIOKIBNJTDKK-UHFFFAOYSA-N 0.000 claims description 4
- DMUKWWFTNQDWLR-UHFFFAOYSA-N n-[4-[[3-(4-acetylpiperazin-1-yl)-5-fluorophenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCN(CC2)C(C)=O)=C1 DMUKWWFTNQDWLR-UHFFFAOYSA-N 0.000 claims description 4
- CFLMPUPBVWFNHI-UHFFFAOYSA-N n-[4-[[3-[ethyl(2-methoxyethyl)amino]-5-fluorophenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound COCCN(CC)C1=CC(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C(CCC2)C)=C1 CFLMPUPBVWFNHI-UHFFFAOYSA-N 0.000 claims description 4
- PZVWORFWEXXCRV-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(2-methyl-3-oxopiperazin-1-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2C(C(=O)NCC2)C)=C1 PZVWORFWEXXCRV-UHFFFAOYSA-N 0.000 claims description 4
- PKPWVSAIZDCOGC-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(3-hydroxypyrrolidin-1-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CC(O)CC2)=C1 PKPWVSAIZDCOGC-UHFFFAOYSA-N 0.000 claims description 4
- GROXVHMYFRIOAP-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-hydroxy-4-phenylpiperidin-1-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCC(O)(CC2)C=2C=CC=CC=2)=C1 GROXVHMYFRIOAP-UHFFFAOYSA-N 0.000 claims description 4
- YODSGIMLYDMOQD-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-hydroxypiperidin-1-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCC(O)CC2)=C1 YODSGIMLYDMOQD-UHFFFAOYSA-N 0.000 claims description 4
- QUKBGCXAMGPPBB-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n,2,2-trimethylpropanamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)C(C)(C)C)=CC=1C1(OC)CCOCC1 QUKBGCXAMGPPBB-UHFFFAOYSA-N 0.000 claims description 4
- OBTZQRXCLBOCCL-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n,2,5-trimethyl-2,5-dihydropyrrole-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C(C=CC2C)C)=CC=1C1(OC)CCOCC1 OBTZQRXCLBOCCL-UHFFFAOYSA-N 0.000 claims description 4
- GIJLMCMXTXECAD-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n,2-dimethylpropanamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)C(C)C)=CC=1C1(OC)CCOCC1 GIJLMCMXTXECAD-UHFFFAOYSA-N 0.000 claims description 4
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- DOVMDRGVHNFOHQ-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methyl-1,3-thiazolidine-3-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CSCC2)=CC=1C1(OC)CCOCC1 DOVMDRGVHNFOHQ-UHFFFAOYSA-N 0.000 claims description 4
- IWWSPZVQXNSMJS-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methyl-3,6-dihydro-2h-pyridine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CC=CCC2)=CC=1C1(OC)CCOCC1 IWWSPZVQXNSMJS-UHFFFAOYSA-N 0.000 claims description 4
- PPIRZEALPLMXNX-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylazepane-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CCCCCC2)=CC=1C1(OC)CCOCC1 PPIRZEALPLMXNX-UHFFFAOYSA-N 0.000 claims description 4
- CMAHHVLVORFPTG-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylazetidine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CCC2)=CC=1C1(OC)CCOCC1 CMAHHVLVORFPTG-UHFFFAOYSA-N 0.000 claims description 4
- MVDCBFRBYLUFRU-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylcyclopentanecarboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)C2CCCC2)=CC=1C1(OC)CCOCC1 MVDCBFRBYLUFRU-UHFFFAOYSA-N 0.000 claims description 4
- UOPUHMDUGQYKEE-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylcyclopropanecarboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)C2CC2)=CC=1C1(OC)CCOCC1 UOPUHMDUGQYKEE-UHFFFAOYSA-N 0.000 claims description 4
- ZZVMXGVMWBYYES-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylfuran-2-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)C=2OC=CC=2)=CC=1C1(OC)CCOCC1 ZZVMXGVMWBYYES-UHFFFAOYSA-N 0.000 claims description 4
- VSGPZHAPWPPFRB-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylpyrrole-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C=CC=C2)=CC=1C1(OC)CCOCC1 VSGPZHAPWPPFRB-UHFFFAOYSA-N 0.000 claims description 4
- ZVYQVECDZBSGTH-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methylpiperidin-1-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCC(C)CC2)=C1 ZVYQVECDZBSGTH-UHFFFAOYSA-N 0.000 claims description 4
- YCMATSYPJMOYOA-UHFFFAOYSA-N n-[4-[[3-fluoro-5-[4-(2-hydroxyethyl)piperazin-1-yl]phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCN(CCO)CC2)=C1 YCMATSYPJMOYOA-UHFFFAOYSA-N 0.000 claims description 4
- DETYQZIAARBCMG-UHFFFAOYSA-N n-[4-[[3-fluoro-5-[4-(2-methoxyethyl)piperazin-1-yl]phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound C1CN(CCOC)CCN1C1=CC(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C(CCC2)C)=C1 DETYQZIAARBCMG-UHFFFAOYSA-N 0.000 claims description 4
- FYBUGXFZMYQCCC-UHFFFAOYSA-N propyl n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylcarbamate Chemical compound C1=CC(N(C)C(=O)OCCC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 FYBUGXFZMYQCCC-UHFFFAOYSA-N 0.000 claims description 4
- 125000001422 pyrrolinyl group Chemical group 0.000 claims description 4
- GXJLSZJCKBDBLD-UHFFFAOYSA-N tert-butyl 4-[3-[[4-[diethylcarbamoyl(methyl)amino]phenyl]methoxy]-5-fluorophenyl]-4-hydroxypiperidine-1-carboxylate Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(C2(O)CCN(CC2)C(=O)OC(C)(C)C)=C1 GXJLSZJCKBDBLD-UHFFFAOYSA-N 0.000 claims description 4
- YQNUSOJKYANHDX-QHCPKHFHSA-N (2s)-n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-2-(hydroxymethyl)-n-methylpyrrolidine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2[C@@H](CCC2)CO)=CC=1C1(OC)CCOCC1 YQNUSOJKYANHDX-QHCPKHFHSA-N 0.000 claims description 3
- XQKSGUJSLGOUNY-JOCHJYFZSA-N (3r)-n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-hydroxy-n-methylpyrrolidine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C[C@H](O)CC2)=CC=1C1(OC)CCOCC1 XQKSGUJSLGOUNY-JOCHJYFZSA-N 0.000 claims description 3
- UTIULCXSJDWMAA-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-fluoro-5-(2-methyl-3-oxopiperazin-1-yl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2C(C(=O)NCC2)C)=C1 UTIULCXSJDWMAA-UHFFFAOYSA-N 0.000 claims description 3
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- STMZKUUEQKQGAZ-UHFFFAOYSA-N 1-[4-[[3-(4-acetylpiperazin-1-yl)-5-fluorophenoxy]methyl]phenyl]-3,3-diethyl-1-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(N2CCN(CC2)C(C)=O)=C1 STMZKUUEQKQGAZ-UHFFFAOYSA-N 0.000 claims description 3
- WFPUFLAUQIBECH-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-prop-2-ynoxyoxan-4-yl)phenoxy]methyl]phenyl]-1,3,3-trimethylurea Chemical compound C1=CC(N(C)C(=O)N(C)C)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OCC#C)=C1 WFPUFLAUQIBECH-UHFFFAOYSA-N 0.000 claims description 3
- HIBIACGOUUJLIU-UHFFFAOYSA-N 1-ethyl-3-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-(2-methoxyethyl)-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CCOC)CC)=CC=C1COC1=CC(F)=CC(C2(CCOCC2)OC)=C1 HIBIACGOUUJLIU-UHFFFAOYSA-N 0.000 claims description 3
- OPWOHVTTXCHXDD-UHFFFAOYSA-N 3-cyclopentyl-1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methylurea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NC2CCCC2)=CC=1C1(OC)CCOCC1 OPWOHVTTXCHXDD-UHFFFAOYSA-N 0.000 claims description 3
- IDPBUVZSNZBYNP-UHFFFAOYSA-N 5-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]-1,3-dimethylbenzimidazol-2-one Chemical compound C=1C(F)=CC(OCC=2C=C3N(C)C(=O)N(C)C3=CC=2)=CC=1C1(OC)CCOCC1 IDPBUVZSNZBYNP-UHFFFAOYSA-N 0.000 claims description 3
- NDRNOLBXZMNJDH-UHFFFAOYSA-N ethyl 4-[3-[[4-[diethylcarbamoyl(methyl)amino]phenyl]methoxy]phenyl]oxane-4-carboxylate Chemical compound C=1C=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N(CC)CC)=CC=1C1(C(=O)OCC)CCOCC1 NDRNOLBXZMNJDH-UHFFFAOYSA-N 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- FRNBZLMPNPFJNG-UHFFFAOYSA-N n-[4-[(3-fluoro-5-piperidin-1-ylphenoxy)methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(N2CCCCC2)=C1 FRNBZLMPNPFJNG-UHFFFAOYSA-N 0.000 claims description 3
- FYWHMULCLGFQRX-UHFFFAOYSA-N n-[4-[[3-[bis(2-methoxyethyl)amino]-5-fluorophenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound COCCN(CCOC)C1=CC(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2C(CCC2)C)=C1 FYWHMULCLGFQRX-UHFFFAOYSA-N 0.000 claims description 3
- MTBYBNAXWPTLBI-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-hydroxyoxan-4-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(C2(O)CCOCC2)=C1 MTBYBNAXWPTLBI-UHFFFAOYSA-N 0.000 claims description 3
- XQKSGUJSLGOUNY-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-3-hydroxy-n-methylpyrrolidine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CC(O)CC2)=CC=1C1(OC)CCOCC1 XQKSGUJSLGOUNY-UHFFFAOYSA-N 0.000 claims description 3
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- WDFHYGICKCMDBH-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methyl-2,5-dihydropyrrole-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CC=CC2)=CC=1C1(OC)CCOCC1 WDFHYGICKCMDBH-UHFFFAOYSA-N 0.000 claims description 3
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- VNIBGYQSJKNTAO-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylpyrrolidine-1-carboxamide Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)N2CCCC2)=CC=1C1(OC)CCOCC1 VNIBGYQSJKNTAO-UHFFFAOYSA-N 0.000 claims description 3
- CEAARIGIAJIKBE-UHFFFAOYSA-N n-[4-[[3-fluoro-5-(oxan-4-yl)phenoxy]methyl]phenyl]-n,2-dimethylpyrrolidine-1-carboxamide Chemical compound CC1CCCN1C(=O)N(C)C(C=C1)=CC=C1COC1=CC(F)=CC(C2CCOCC2)=C1 CEAARIGIAJIKBE-UHFFFAOYSA-N 0.000 claims description 3
- ADHWQKUYVPVISL-UHFFFAOYSA-N tert-butyl n-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-n-methylcarbamate Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)OC(C)(C)C)=CC=1C1(OC)CCOCC1 ADHWQKUYVPVISL-UHFFFAOYSA-N 0.000 claims description 3
- IRYWDQHPBKDXMF-UHFFFAOYSA-N 1,1-diethyl-3-[4-[[3-fluoro-5-(1-hydroxycyclohexyl)phenoxy]methyl]phenyl]-3-methylurea Chemical compound C1=CC(N(C)C(=O)N(CC)CC)=CC=C1COC1=CC(F)=CC(C2(O)CCCCC2)=C1 IRYWDQHPBKDXMF-UHFFFAOYSA-N 0.000 claims description 2
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- QVGYRHBEASOAOU-UHFFFAOYSA-N 1-[4-[[3-fluoro-5-(4-methoxyoxan-4-yl)phenoxy]methyl]phenyl]-1-methyl-3-(3-methylbutan-2-yl)urea Chemical compound C=1C(F)=CC(OCC=2C=CC(=CC=2)N(C)C(=O)NC(C)C(C)C)=CC=1C1(OC)CCOCC1 QVGYRHBEASOAOU-UHFFFAOYSA-N 0.000 claims description 2
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- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
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- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
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- 229940095064 tartrate Drugs 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- RUPAXCPQAAOIPB-UHFFFAOYSA-N tert-butyl formate Chemical compound CC(C)(C)OC=O RUPAXCPQAAOIPB-UHFFFAOYSA-N 0.000 description 1
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
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- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
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- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
- 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
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- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- JQORXVNSBSKOQE-UHFFFAOYSA-N thiomorpholine-4-carboxamide Chemical compound NC(=O)N1CCSCC1 JQORXVNSBSKOQE-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 125000003944 tolyl group Chemical group 0.000 description 1
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- 125000004306 triazinyl group Chemical group 0.000 description 1
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- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
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- 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
- C07C275/32—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 singly-bound oxygen atoms
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- 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
- C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
- C07D207/10—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 no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
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- C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
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- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/205—Radicals derived from carbonic acid
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- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
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- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/04—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrane Compounds (AREA)
Abstract
La présente invention concerne un procédé d'inhibition de l'expression du gène de l'interleukine 5 chez un mammifère. Ce procédé consiste à administrer à un mammifère nécessitant un tel traitement une quantité efficace d'un point de vue pharmaceutique d'un ou plusieurs composés choisi(s) à partir de la formule (I) et/ou de la formule (II).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46660899A | 1999-12-17 | 1999-12-17 | |
| US09/466,608 | 1999-12-17 | ||
| PCT/US2000/034229 WO2001044223A1 (fr) | 1999-12-17 | 2000-12-15 | Inhibiteurs d'expression du gene de l'interleukine 5 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2393027A1 true CA2393027A1 (fr) | 2001-06-21 |
Family
ID=23852424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002393027A Abandoned CA2393027A1 (fr) | 1999-12-17 | 2000-12-15 | Inhibiteurs d'expression du gene de l'interleukine 5 |
Country Status (8)
| Country | Link |
|---|---|
| EP (1) | EP1250332A1 (fr) |
| JP (1) | JP2003523956A (fr) |
| AU (1) | AU2271701A (fr) |
| BR (1) | BR0012502A (fr) |
| CA (1) | CA2393027A1 (fr) |
| HK (1) | HK1051033A1 (fr) |
| MX (1) | MXPA02005982A (fr) |
| WO (1) | WO2001044223A1 (fr) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ537301A (en) | 2002-06-07 | 2006-06-30 | Cortical Pty Ltd | Therapeutic molecules and methods-1 |
| BRPI0813990A2 (pt) * | 2007-07-06 | 2011-09-13 | Paratek Pharmaceuticals, Inc. | métodos para sintetizar compostos de minociclina substituìda |
| AU2009304596A1 (en) | 2008-10-17 | 2010-04-22 | Akaal Pharma Pty Ltd | S1P receptors modulators |
| JP2012505836A (ja) | 2008-10-17 | 2012-03-08 | アカール ファーマ ピーティーワイ リミテッド | S1p受容体モジュレーターおよびそれらの使用 |
| TW201341356A (zh) * | 2012-02-28 | 2013-10-16 | 皮拉馬爾企業有限公司 | 作為gpr促效劑之苯基烷酸衍生物 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5622977A (en) * | 1992-12-23 | 1997-04-22 | Celltech Therapeutics Limited | Tri-substituted (aryl or heteroaryl) derivatives and pharmaceutical compositions containing the same |
| GB9701453D0 (en) * | 1997-01-24 | 1997-03-12 | Leo Pharm Prod Ltd | Aminobenzophenones |
-
2000
- 2000-12-15 BR BR0012502-4A patent/BR0012502A/pt not_active IP Right Cessation
- 2000-12-15 MX MXPA02005982A patent/MXPA02005982A/es unknown
- 2000-12-15 EP EP00986489A patent/EP1250332A1/fr not_active Withdrawn
- 2000-12-15 WO PCT/US2000/034229 patent/WO2001044223A1/fr not_active Ceased
- 2000-12-15 AU AU22717/01A patent/AU2271701A/en not_active Abandoned
- 2000-12-15 JP JP2001544713A patent/JP2003523956A/ja not_active Withdrawn
- 2000-12-15 CA CA002393027A patent/CA2393027A1/fr not_active Abandoned
- 2000-12-15 HK HK03101827.4A patent/HK1051033A1/zh unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR0012502A (pt) | 2003-06-24 |
| EP1250332A1 (fr) | 2002-10-23 |
| HK1051033A1 (zh) | 2003-07-18 |
| JP2003523956A (ja) | 2003-08-12 |
| AU2271701A (en) | 2001-06-25 |
| MXPA02005982A (es) | 2003-01-28 |
| WO2001044223A1 (fr) | 2001-06-21 |
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