ES2393186T3 - Derivados de azol y composiciones farmacéuticas que los contienen - Google Patents
Derivados de azol y composiciones farmacéuticas que los contienen Download PDFInfo
- Publication number
- ES2393186T3 ES2393186T3 ES02793814T ES02793814T ES2393186T3 ES 2393186 T3 ES2393186 T3 ES 2393186T3 ES 02793814 T ES02793814 T ES 02793814T ES 02793814 T ES02793814 T ES 02793814T ES 2393186 T3 ES2393186 T3 ES 2393186T3
- Authority
- ES
- Spain
- Prior art keywords
- optionally substituted
- alkyl
- imidazol
- ylmethyl
- iodo
- 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.)
- Expired - Lifetime
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 20
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 310
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 142
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 113
- 150000002367 halogens Chemical class 0.000 claims abstract description 113
- -1 heteroalicyclic Chemical group 0.000 claims abstract description 112
- 125000003118 aryl group Chemical group 0.000 claims abstract description 84
- 238000011282 treatment Methods 0.000 claims abstract description 79
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 68
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 68
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 65
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 59
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 55
- 201000011510 cancer Diseases 0.000 claims abstract description 46
- 208000002193 Pain Diseases 0.000 claims abstract description 44
- 208000000509 infertility Diseases 0.000 claims abstract description 44
- 230000036512 infertility Effects 0.000 claims abstract description 44
- 231100000535 infertility Toxicity 0.000 claims abstract description 44
- 230000036407 pain Effects 0.000 claims abstract description 42
- 206010061218 Inflammation Diseases 0.000 claims abstract description 41
- 230000004054 inflammatory process Effects 0.000 claims abstract description 41
- 208000028867 ischemia Diseases 0.000 claims abstract description 41
- 206010040070 Septic Shock Diseases 0.000 claims abstract description 40
- 230000036303 septic shock Effects 0.000 claims abstract description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 39
- 208000006399 Premature Obstetric Labor Diseases 0.000 claims abstract description 34
- 206010036600 Premature labour Diseases 0.000 claims abstract description 34
- 208000026440 premature labor Diseases 0.000 claims abstract description 34
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 22
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 18
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 17
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 17
- 125000005017 substituted alkenyl group Chemical group 0.000 claims abstract description 15
- 125000004426 substituted alkynyl group Chemical group 0.000 claims abstract description 14
- 125000002723 alicyclic group Chemical group 0.000 claims abstract description 11
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims abstract description 11
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims abstract description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 11
- 125000005843 halogen group Chemical group 0.000 claims abstract description 11
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 11
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 11
- 125000006413 ring segment Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 10
- 125000002252 acyl group Chemical group 0.000 claims abstract description 9
- 239000000126 substance Substances 0.000 claims abstract description 8
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 8
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 7
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 6
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 6
- 125000004429 atom Chemical group 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims abstract description 3
- 125000001589 carboacyl group Chemical group 0.000 claims abstract 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 207
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 53
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 38
- ZEYHEAKUIGZSGI-UHFFFAOYSA-N para-methoxy benzoic acid Natural products COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 claims description 38
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 16
- GHICCUXQJBDNRN-UHFFFAOYSA-N 4-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(I)C=C1 GHICCUXQJBDNRN-UHFFFAOYSA-N 0.000 claims description 15
- 230000007717 exclusion Effects 0.000 claims description 14
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 239000005711 Benzoic acid Substances 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- JTWITXSRBQCTHA-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-nitrophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 JTWITXSRBQCTHA-UHFFFAOYSA-N 0.000 claims description 7
- 235000010233 benzoic acid Nutrition 0.000 claims description 7
- CTQRYNQVNOXJOQ-UHFFFAOYSA-N (1-imidazol-1-yl-3-pyridin-3-yloxypropan-2-yl) 4-iodobenzoate Chemical compound C1=CC(I)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CN=C1 CTQRYNQVNOXJOQ-UHFFFAOYSA-N 0.000 claims description 6
- JAVZWSOFJKYSDY-UHFFFAOYSA-N 4-bromo-2-chlorobenzoic acid Chemical compound OC(=O)C1=CC=C(Br)C=C1Cl JAVZWSOFJKYSDY-UHFFFAOYSA-N 0.000 claims description 6
- IQBUWEXLNJURKA-UHFFFAOYSA-N n-[1-(2-chloroimidazol-1-yl)-3-(4-cyanophenoxy)propan-2-yl]-4-iodobenzamide Chemical compound ClC1=NC=CN1CC(NC(=O)C=1C=CC(I)=CC=1)COC1=CC=C(C#N)C=C1 IQBUWEXLNJURKA-UHFFFAOYSA-N 0.000 claims description 6
- ZBIMAVFHIWZMKT-UHFFFAOYSA-N n-[1-(2-chloroimidazol-1-yl)-3-(4-fluorophenoxy)propan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1C(Cl)=NC=C1 ZBIMAVFHIWZMKT-UHFFFAOYSA-N 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 6
- CVSDGUSPTSMQBJ-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 3-methoxybenzoate Chemical compound COC1=CC=CC(C(=O)OC(COC=2C=CC=CC=2)CN2C=NC=C2)=C1 CVSDGUSPTSMQBJ-UHFFFAOYSA-N 0.000 claims description 5
- AQABPIBXKWPEIJ-UHFFFAOYSA-N [1-(2-methylimidazol-1-yl)-3-(oxan-2-yloxy)propan-2-yl] 4-iodobenzoate Chemical compound CC1=NC=CN1CC(OC(=O)C=1C=CC(I)=CC=1)COC1OCCCC1 AQABPIBXKWPEIJ-UHFFFAOYSA-N 0.000 claims description 5
- GVKYQAMIWRBSJC-UHFFFAOYSA-N [1-(4-cyanophenoxy)-3-imidazol-1-ylpropan-2-yl] 4-iodobenzoate Chemical compound C1=CC(I)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=C(C#N)C=C1 GVKYQAMIWRBSJC-UHFFFAOYSA-N 0.000 claims description 5
- MYYLIMLHXIIIMZ-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl] 2,4-dichlorobenzoate Chemical compound C1=CC(F)=CC=C1OCC(OC(=O)C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 MYYLIMLHXIIIMZ-UHFFFAOYSA-N 0.000 claims description 5
- ZQSZSWQNEFVKGG-UHFFFAOYSA-N [1-(cyclopropylmethoxy)-3-(2-methylimidazol-1-yl)propan-2-yl] 2-chloro-4-iodobenzoate Chemical compound CC1=NC=CN1CC(OC(=O)C=1C(=CC(I)=CC=1)Cl)COCC1CC1 ZQSZSWQNEFVKGG-UHFFFAOYSA-N 0.000 claims description 5
- GUUSBVNDBCVAIS-UHFFFAOYSA-N [1-imidazol-1-yl-3-(2-nitrophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 GUUSBVNDBCVAIS-UHFFFAOYSA-N 0.000 claims description 5
- YOPNHJJETCAFCE-UHFFFAOYSA-N [1-imidazol-1-yl-3-(3-nitrophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound [O-][N+](=O)C1=CC=CC(OCC(CN2C=NC=C2)OC(=O)C=2C=CC(I)=CC=2)=C1 YOPNHJJETCAFCE-UHFFFAOYSA-N 0.000 claims description 5
- DPTLLKCIWYDYRY-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-methoxyphenoxy)propan-2-yl] 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1OCC(OC(=O)C=1C=CC(OC)=CC=1)CN1C=NC=C1 DPTLLKCIWYDYRY-UHFFFAOYSA-N 0.000 claims description 5
- DRHNPUWRASFLHB-UHFFFAOYSA-N [3-imidazol-1-yl-2-(4-iodobenzoyl)oxy-2-methylpropyl] 4-nitrobenzoate Chemical compound C1=CN=CN1CC(OC(=O)C=1C=CC(I)=CC=1)(C)COC(=O)C1=CC=C([N+]([O-])=O)C=C1 DRHNPUWRASFLHB-UHFFFAOYSA-N 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 5
- DLSUFMMWXXPUHP-UHFFFAOYSA-N n-(1-imidazol-1-yl-3-phenoxypropan-2-yl)-4-methoxybenzamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=CC=C1 DLSUFMMWXXPUHP-UHFFFAOYSA-N 0.000 claims description 5
- NCRBSVCFQVEWOV-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-(1,2,4-triazol-1-yl)propan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1N=CN=C1 NCRBSVCFQVEWOV-UHFFFAOYSA-N 0.000 claims description 5
- WYFIBODGEGUMJK-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-(2-methylimidazol-1-yl)propan-2-yl]-4-iodobenzamide Chemical compound CC1=NC=CN1CC(NC(=O)C=1C=CC(I)=CC=1)COC1=CC=C(F)C=C1 WYFIBODGEGUMJK-UHFFFAOYSA-N 0.000 claims description 5
- YKSRQAMHHKDSQI-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 YKSRQAMHHKDSQI-UHFFFAOYSA-N 0.000 claims description 5
- HWDXDASZYYWECJ-UHFFFAOYSA-N n-[1-(4-tert-butylphenoxy)-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(C(C)(C)C)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 HWDXDASZYYWECJ-UHFFFAOYSA-N 0.000 claims description 5
- VDXFXTGIYZVGPA-UHFFFAOYSA-N n-[1-imidazol-1-yl-3-(4-nitrophenoxy)propan-2-yl]-4-iodobenzamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 VDXFXTGIYZVGPA-UHFFFAOYSA-N 0.000 claims description 5
- UHZIEFLWILBLGZ-UHFFFAOYSA-N (1-imidazol-1-yl-3-methoxypropan-2-yl) 4-iodobenzoate Chemical compound C=1C=C(I)C=CC=1C(=O)OC(COC)CN1C=CN=C1 UHZIEFLWILBLGZ-UHFFFAOYSA-N 0.000 claims description 4
- WXGSSMRODDWZFH-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-(trifluoromethyl)benzoate Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 WXGSSMRODDWZFH-UHFFFAOYSA-N 0.000 claims description 4
- FCNIAPWYVGTYIT-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-bromobenzoate Chemical compound C1=CC(Br)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 FCNIAPWYVGTYIT-UHFFFAOYSA-N 0.000 claims description 4
- DKDCTJRPQBGCFM-UHFFFAOYSA-N 2-chloro-n-[1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C(=CC(I)=CC=1)Cl)CN1C=NC=C1 DKDCTJRPQBGCFM-UHFFFAOYSA-N 0.000 claims description 4
- DKQCXNIDGIPIBX-UHFFFAOYSA-N [1-(4-cyanophenoxy)-3-(2-methylimidazol-1-yl)propan-2-yl] 4-iodobenzoate Chemical compound CC1=NC=CN1CC(OC(=O)C=1C=CC(I)=CC=1)COC1=CC=C(C#N)C=C1 DKQCXNIDGIPIBX-UHFFFAOYSA-N 0.000 claims description 4
- SGWCLRZNWVPFJX-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl] 4-iodobenzoate Chemical compound C1=CC(F)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 SGWCLRZNWVPFJX-UHFFFAOYSA-N 0.000 claims description 4
- VUIUMNPJDNTIKP-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl] 4-methoxybenzoate Chemical compound C1=CC(OC)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=C(F)C=C1 VUIUMNPJDNTIKP-UHFFFAOYSA-N 0.000 claims description 4
- CCKLUXJAXAWORF-UHFFFAOYSA-N [1-imidazol-1-yl-3-(4-iodophenoxy)propan-2-yl] 4-iodobenzoate Chemical compound C1=CC(I)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1C=NC=C1 CCKLUXJAXAWORF-UHFFFAOYSA-N 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- QAWIWTFXLCFEOO-UHFFFAOYSA-N n-(1-imidazol-1-yl-3-pyridin-3-yloxypropan-2-yl)-4-iodobenzamide Chemical compound C1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=CN=C1 QAWIWTFXLCFEOO-UHFFFAOYSA-N 0.000 claims description 4
- QFSOXHYEFJFLIL-UHFFFAOYSA-N n-[1-(3-cyanopyridin-2-yl)oxy-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=NC=CC=C1C#N QFSOXHYEFJFLIL-UHFFFAOYSA-N 0.000 claims description 4
- AQPCOTGUGIETJG-UHFFFAOYSA-N n-[1-(4-cyanophenoxy)-3-(2-methylimidazol-1-yl)propan-2-yl]-4-iodobenzamide Chemical compound CC1=NC=CN1CC(NC(=O)C=1C=CC(I)=CC=1)COC1=CC=C(C#N)C=C1 AQPCOTGUGIETJG-UHFFFAOYSA-N 0.000 claims description 4
- VNJZUFANCKZCQJ-UHFFFAOYSA-N n-[1-(4-cyanophenoxy)-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=C(C#N)C=C1 VNJZUFANCKZCQJ-UHFFFAOYSA-N 0.000 claims description 4
- QLLXRCLKWKJALI-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-(2-phenylimidazol-1-yl)propan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1C(C=2C=CC=CC=2)=NC=C1 QLLXRCLKWKJALI-UHFFFAOYSA-N 0.000 claims description 4
- FDVQXBWOPAKJQL-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-(tetrazol-1-yl)propan-2-yl]-4-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=CC(I)=CC=1)CN1N=NN=C1 FDVQXBWOPAKJQL-UHFFFAOYSA-N 0.000 claims description 4
- KQZATCYBCYMUDZ-UHFFFAOYSA-N n-[1-(4-fluorophenoxy)-3-imidazol-1-ylpropan-2-yl]-3-iodobenzamide Chemical compound C1=CC(F)=CC=C1OCC(NC(=O)C=1C=C(I)C=CC=1)CN1C=NC=C1 KQZATCYBCYMUDZ-UHFFFAOYSA-N 0.000 claims description 4
- ASKHKPOODHCNAG-UHFFFAOYSA-N n-[1-(5-cyanopyridin-2-yl)oxy-3-imidazol-1-ylpropan-2-yl]-4-iodobenzamide Chemical compound C1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=C(C#N)C=N1 ASKHKPOODHCNAG-UHFFFAOYSA-N 0.000 claims description 4
- ZRFIFBBEQSGQFS-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-fluorobenzoate Chemical compound C1=CC(F)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 ZRFIFBBEQSGQFS-UHFFFAOYSA-N 0.000 claims description 3
- HJMOACBJSLAGME-UHFFFAOYSA-N 2-chloro-n-(1-imidazol-1-yl-3-pyridin-3-yloxypropan-2-yl)-4-iodobenzamide Chemical compound ClC1=CC(I)=CC=C1C(=O)NC(CN1C=NC=C1)COC1=CC=CN=C1 HJMOACBJSLAGME-UHFFFAOYSA-N 0.000 claims description 3
- JTNXYKMQMWRALS-UHFFFAOYSA-N [1-(4-fluorophenoxy)-3-(1,2,4-triazol-1-yl)propan-2-yl] 4-iodobenzoate Chemical compound C1=CC(F)=CC=C1OCC(OC(=O)C=1C=CC(I)=CC=1)CN1N=CN=C1 JTNXYKMQMWRALS-UHFFFAOYSA-N 0.000 claims description 3
- 150000003857 carboxamides Chemical class 0.000 claims description 3
- 125000000468 ketone group Chemical group 0.000 claims description 3
- SVOVZDKVCARNGV-UHFFFAOYSA-N n-(3-imidazol-1-yl-2-phenoxypropyl)-4-iodo-n-methylbenzamide Chemical compound C=1C=C(I)C=CC=1C(=O)N(C)CC(OC=1C=CC=CC=1)CN1C=CN=C1 SVOVZDKVCARNGV-UHFFFAOYSA-N 0.000 claims description 3
- GCMCUFFVCDXDEZ-UHFFFAOYSA-N n-[1-[2-(difluoromethyl)imidazol-1-yl]-3-(4-fluorophenoxy)propan-2-yl]-4-iodobenzamide Chemical compound FC(F)C1=NC=CN1CC(NC(=O)C=1C=CC(I)=CC=1)COC1=CC=C(F)C=C1 GCMCUFFVCDXDEZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000003917 carbamoyl group Chemical class [H]N([H])C(*)=O 0.000 abstract 1
- 241000124008 Mammalia Species 0.000 description 63
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 58
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical class C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 57
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 50
- 210000004027 cell Anatomy 0.000 description 39
- 208000035475 disorder Diseases 0.000 description 31
- 102100031480 Dual specificity mitogen-activated protein kinase kinase 1 Human genes 0.000 description 29
- 101710146526 Dual specificity mitogen-activated protein kinase kinase 1 Proteins 0.000 description 29
- 102100024193 Mitogen-activated protein kinase 1 Human genes 0.000 description 24
- 125000003107 substituted aryl group Chemical group 0.000 description 23
- 108700015928 Mitogen-activated protein kinase 13 Proteins 0.000 description 20
- 239000000243 solution Substances 0.000 description 20
- 238000012360 testing method Methods 0.000 description 20
- 201000010099 disease Diseases 0.000 description 19
- 239000000203 mixture Substances 0.000 description 19
- 208000023275 Autoimmune disease Diseases 0.000 description 18
- 150000003852 triazoles Chemical class 0.000 description 18
- WIPYCGSITSDPLB-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) 4-chlorobenzoate Chemical compound C1=CC(Cl)=CC=C1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 WIPYCGSITSDPLB-UHFFFAOYSA-N 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 206010021143 Hypoxia Diseases 0.000 description 15
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 230000007954 hypoxia Effects 0.000 description 15
- 238000000034 method Methods 0.000 description 15
- 206010039073 rheumatoid arthritis Diseases 0.000 description 15
- SJCCMELPLHYEQU-UHFFFAOYSA-N (1-imidazol-1-yl-3-phenoxypropan-2-yl) benzoate Chemical compound C=1C=CC=CC=1C(=O)OC(CN1C=NC=C1)COC1=CC=CC=C1 SJCCMELPLHYEQU-UHFFFAOYSA-N 0.000 description 14
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 14
- 208000004429 Bacillary Dysentery Diseases 0.000 description 14
- 208000035143 Bacterial infection Diseases 0.000 description 14
- 206010007572 Cardiac hypertrophy Diseases 0.000 description 14
- 208000006029 Cardiomegaly Diseases 0.000 description 14
- 206010009900 Colitis ulcerative Diseases 0.000 description 14
- 208000011231 Crohn disease Diseases 0.000 description 14
- 208000007882 Gastritis Diseases 0.000 description 14
- 206010018364 Glomerulonephritis Diseases 0.000 description 14
- 208000009329 Graft vs Host Disease Diseases 0.000 description 14
- 206010020751 Hypersensitivity Diseases 0.000 description 14
- 206010029113 Neovascularisation Diseases 0.000 description 14
- 206010030113 Oedema Diseases 0.000 description 14
- 206010033645 Pancreatitis Diseases 0.000 description 14
- 201000004681 Psoriasis Diseases 0.000 description 14
- 206010037660 Pyrexia Diseases 0.000 description 14
- 206010039710 Scleroderma Diseases 0.000 description 14
- 206010040550 Shigella infections Diseases 0.000 description 14
- 108090000190 Thrombin Proteins 0.000 description 14
- 201000006704 Ulcerative Colitis Diseases 0.000 description 14
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 14
- 230000007815 allergy Effects 0.000 description 14
- 230000002491 angiogenic effect Effects 0.000 description 14
- 238000003556 assay Methods 0.000 description 14
- 208000006673 asthma Diseases 0.000 description 14
- 208000022362 bacterial infectious disease Diseases 0.000 description 14
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- C07D233/61—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms with hydrocarbon radicals, substituted by nitrogen atoms not forming part of a nitro radical, attached to ring nitrogen atoms
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- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
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- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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| US33604001P | 2001-10-23 | 2001-10-23 | |
| US336040P | 2001-10-23 | ||
| PCT/US2002/033963 WO2003035626A2 (en) | 2001-10-23 | 2002-10-23 | Azole derivatives and pharmaceutical compositions containing them |
Publications (1)
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| ES2393186T3 true ES2393186T3 (es) | 2012-12-19 |
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| WO (1) | WO2003035626A2 (enExample) |
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| US7253199B2 (en) * | 2001-10-23 | 2007-08-07 | Applied Research Systems Ars Holding N.V. | Azole derivatives and pharmaceutical compositions containing them |
| AR051248A1 (es) | 2004-10-20 | 2007-01-03 | Applied Research Systems | Derivados de 3-arilamino piridina |
| US8546404B2 (en) | 2005-12-13 | 2013-10-01 | Merck Sharp & Dohme | Compounds that are ERK inhibitors |
| ES2353437T3 (es) | 2006-02-16 | 2011-03-02 | Schering Corporation | Derivados de pirrolidina como inhibidores de erk. |
| SG188179A1 (en) | 2008-02-21 | 2013-03-28 | Merck Sharp & Dohme | Compounds that are erk inhibitors |
| US8951979B2 (en) * | 2008-06-13 | 2015-02-10 | Cornell University | Pain treatment using ERK2 inhibitors |
| WO2010051933A2 (en) | 2008-11-10 | 2010-05-14 | Bayer Schering Pharma Aktiengesellschaft | Substituted sulphonamido phenoxybenzamides |
| WO2010068738A1 (en) | 2008-12-10 | 2010-06-17 | Dana-Farber Cancer Institute, Inc. | Mek mutations conferring resistance to mek inhibitors |
| US8962606B2 (en) | 2009-10-21 | 2015-02-24 | Bayer Intellectual Property Gmbh | Substituted benzosulphonamides |
| CA2777071A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Substituted halophenoxybenzamide derivatives |
| CA2777430A1 (en) | 2009-10-21 | 2011-04-28 | Bayer Pharma Aktiengesellschaft | Substituted benzosulphonamides |
| WO2011106298A1 (en) | 2010-02-25 | 2011-09-01 | Dana-Farber Cancer Institute, Inc. | Braf mutations conferring resistance to braf inhibitors |
| AU2011224410B2 (en) | 2010-03-09 | 2015-05-28 | Dana-Farber Cancer Institute, Inc. | Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy |
| US9045429B2 (en) | 2010-10-29 | 2015-06-02 | Bayer Intellectual Property Gmbh | Substituted phenoxypyridines |
| WO2013109142A1 (en) | 2012-01-16 | 2013-07-25 | Stichting Het Nederlands Kanker Instituut | Combined pdk and mapk/erk pathway inhibition in neoplasia |
| US20150141470A1 (en) | 2012-05-08 | 2015-05-21 | The Broad Institute, Inc. | Diagnostic and treatment methods in patients having or at risk of developing resistance to cancer therapy |
| EP3046557A1 (en) | 2013-09-20 | 2016-07-27 | Stichting Het Nederlands Kanker Instituut | Rock in combination with mapk-pathway |
| WO2015041534A1 (en) | 2013-09-20 | 2015-03-26 | Stichting Het Nederlands Kanker Instituut | P90rsk in combination with raf/erk/mek |
| US20170027940A1 (en) | 2014-04-10 | 2017-02-02 | Stichting Het Nederlands Kanker Instituut | Method for treating cancer |
| WO2015178770A1 (en) | 2014-05-19 | 2015-11-26 | Stichting Het Nederlands Kanker Instituut | Compositions for cancer treatment |
| EP3355923B1 (en) | 2015-10-01 | 2022-02-23 | Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis | Histone deacetylase inhibitors for use in the treatment of drug resistant melanoma |
| WO2017099591A1 (en) | 2015-12-07 | 2017-06-15 | Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis | Treatment of inhibitor resistant braf-mutant cancers |
| WO2017204626A1 (en) | 2016-05-24 | 2017-11-30 | Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis | Combination therapy - combined map2k4/map3k1 and mek/erk inhibition |
| WO2021018866A1 (en) * | 2019-07-30 | 2021-02-04 | Edvince Ab | Mek inhibitor for treatment of stroke |
| CN110845703A (zh) * | 2019-10-28 | 2020-02-28 | 上海瀚岱化学有限公司 | 一种水性环氧树脂及其制备方法 |
| CN110903735A (zh) * | 2019-11-11 | 2020-03-24 | 上海瀚岱化学有限公司 | 一种水性环氧涂料及其制备方法与应用 |
| EP4142878B1 (en) | 2020-04-28 | 2024-06-26 | The Regents of The University of Michigan | Pyridine inhibitors of glucosylceramide synthase and therapeutic methods using the same |
| CN112759742A (zh) * | 2020-12-18 | 2021-05-07 | 江西瀚泰新材料科技有限公司 | 一种增韧型水性环氧树脂及其制备方法 |
| CN112794989A (zh) * | 2020-12-18 | 2021-05-14 | 江西瀚泰新材料科技有限公司 | 一种增韧阻燃水性环氧树脂及其制备方法 |
| CN112646123A (zh) * | 2020-12-18 | 2021-04-13 | 江西瀚泰新材料科技有限公司 | 一种低粘度水性环氧树脂及其制备方法 |
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| CA1271477A (en) * | 1983-11-18 | 1990-07-10 | John F. Gerster | 1h-imidazo[4,5-c]quinolin-4-amines |
| PL195600B1 (pl) * | 1998-05-15 | 2007-10-31 | Astrazeneca Ab | Pochodne benzamidowe, sposób ich wytwarzania, zawierające je kompozycje farmaceutyczne oraz ich zastosowanie do wytwarzania leku do leczenia stanów medycznych powstających za pośrednictwem cytokin |
| US6599910B1 (en) * | 1998-08-20 | 2003-07-29 | Smithkline Beecham Corporation | Substituted triazole compounds |
| AP2001002225A0 (en) * | 1999-01-13 | 2001-09-30 | Warner Lambert Co | 1-heterocycle substituted diarylamines. |
| US7253199B2 (en) * | 2001-10-23 | 2007-08-07 | Applied Research Systems Ars Holding N.V. | Azole derivatives and pharmaceutical compositions containing them |
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| JP4602667B2 (ja) | 2010-12-22 |
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| AU2002359291B2 (en) | 2008-04-03 |
| US20050054706A1 (en) | 2005-03-10 |
| AU2008202731A1 (en) | 2008-07-17 |
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| IL161580A0 (en) | 2004-09-27 |
| US7253199B2 (en) | 2007-08-07 |
| AU2002359291B8 (en) | 2008-04-17 |
| CA2463101A1 (en) | 2003-05-01 |
| WO2003035626A2 (en) | 2003-05-01 |
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