JP2018513180A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2018513180A5 JP2018513180A5 JP2017555303A JP2017555303A JP2018513180A5 JP 2018513180 A5 JP2018513180 A5 JP 2018513180A5 JP 2017555303 A JP2017555303 A JP 2017555303A JP 2017555303 A JP2017555303 A JP 2017555303A JP 2018513180 A5 JP2018513180 A5 JP 2018513180A5
- Authority
- JP
- Japan
- Prior art keywords
- independently selected
- pharmaceutically acceptable
- acceptable salt
- compound according
- optionally substituted
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 6
- -1 = O Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 3
- 229940124597 therapeutic agent Drugs 0.000 claims description 3
- 238000011282 treatment Methods 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims 17
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 125000005843 halogen group Chemical group 0.000 claims 12
- 125000003545 alkoxy group Chemical group 0.000 claims 9
- 229910052760 oxygen Inorganic materials 0.000 claims 7
- 125000005842 heteroatom Chemical group 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 229910052717 sulfur Inorganic materials 0.000 claims 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 4
- 230000004968 inflammatory condition Effects 0.000 claims 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 4
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000002950 monocyclic group Chemical group 0.000 claims 3
- 208000023275 Autoimmune disease Diseases 0.000 claims 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims 2
- 208000035473 Communicable disease Diseases 0.000 claims 2
- 208000011231 Crohn disease Diseases 0.000 claims 2
- 206010048768 Dermatosis Diseases 0.000 claims 2
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims 2
- 206010030216 Oesophagitis Diseases 0.000 claims 2
- 201000004681 Psoriasis Diseases 0.000 claims 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 2
- 206010046851 Uveitis Diseases 0.000 claims 2
- 230000003915 cell function Effects 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000035475 disorder Diseases 0.000 claims 2
- 230000002124 endocrine Effects 0.000 claims 2
- 208000030172 endocrine system disease Diseases 0.000 claims 2
- 208000006881 esophagitis Diseases 0.000 claims 2
- 125000004366 heterocycloalkenyl group Chemical group 0.000 claims 2
- 210000002865 immune cell Anatomy 0.000 claims 2
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims 2
- 208000032839 leukemia Diseases 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 230000002956 necrotizing effect Effects 0.000 claims 2
- 230000000626 neurodegenerative effect Effects 0.000 claims 2
- 230000002314 neuroinflammatory effect Effects 0.000 claims 2
- 230000036407 pain Effects 0.000 claims 2
- 201000001245 periodontitis Diseases 0.000 claims 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims 2
- 208000017520 skin disease Diseases 0.000 claims 2
- 239000012453 solvate Substances 0.000 claims 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
- 125000002947 alkylene group Chemical group 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 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 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 125000004430 oxygen atom Chemical group O* 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 3
- BSTNYQPSCASPQN-UHFFFAOYSA-N 1-ethyl-6-phenylmethoxy-3,4-dihydroisoquinoline Chemical compound C(C1=CC=CC=C1)OC=1C=C2CCN=C(C2=CC=1)CC BSTNYQPSCASPQN-UHFFFAOYSA-N 0.000 description 2
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- LFZAGIJXANFPFN-UHFFFAOYSA-N N-[3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]acetamide Chemical compound C(C)(C)C1=NN=C(N1C1CCN(CC1)CCC(C=1SC=CC=1)NC(C)=O)C LFZAGIJXANFPFN-UHFFFAOYSA-N 0.000 description 2
- HUCJFAOMUPXHDK-UHFFFAOYSA-N Xylometazoline Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC1=NCCN1 HUCJFAOMUPXHDK-UHFFFAOYSA-N 0.000 description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- WYWIFABBXFUGLM-UHFFFAOYSA-N oxymetazoline Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C)=C1CC1=NCCN1 WYWIFABBXFUGLM-UHFFFAOYSA-N 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 229960002052 salbutamol Drugs 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- SOYANKPFXHJUCE-RXMQYKEDSA-N (2S)-1,4-dioxane-2-carbaldehyde Chemical compound O1[C@@H](COCC1)C=O SOYANKPFXHJUCE-RXMQYKEDSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- NDAUXUAQIAJITI-LBPRGKRZSA-N (R)-salbutamol Chemical compound CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-LBPRGKRZSA-N 0.000 description 1
- RKOUFQLNMRAACI-UHFFFAOYSA-N 1,1,1-trifluoro-2-iodoethane Chemical compound FC(F)(F)CI RKOUFQLNMRAACI-UHFFFAOYSA-N 0.000 description 1
- DKJHLTHLTKAOJI-UHFFFAOYSA-N 1-methyl-4-(oxolan-2-ylmethylamino)-9-(oxolan-2-yloxy)-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound Cc1c2-c3ccc(OC4CCCO4)cc3CCn2c(NCC2CCCO2)cc1=O DKJHLTHLTKAOJI-UHFFFAOYSA-N 0.000 description 1
- CSIVQSHCWKFVDK-UHFFFAOYSA-N 1-methyl-9-phenylmethoxy-6,7-dihydrobenzo[a]quinolizine-2,4-dione Chemical compound C(C1=CC=CC=C1)OC1=CC2=C(C3=C(C(CC(N3CC2)=O)=O)C)C=C1 CSIVQSHCWKFVDK-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- NKSZCPBUWGZONP-UHFFFAOYSA-N 3,4-dihydroisoquinoline Chemical class C1=CC=C2C=NCCC2=C1 NKSZCPBUWGZONP-UHFFFAOYSA-N 0.000 description 1
- OFZYDDBHNSPUOS-UHFFFAOYSA-N 4-amino-1-methyl-6,7-dihydrobenzo[a]quinolizin-2-one Chemical compound NC=1N2CCC3=C(C2=C(C(C=1)=O)C)C=CC=C3 OFZYDDBHNSPUOS-UHFFFAOYSA-N 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
- PJFHZKIDENOSJB-UHFFFAOYSA-N Budesonide/formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1.C1CC2=CC(=O)C=CC2(C)C2C1C1CC3OC(CCC)OC3(C(=O)CO)C1(C)CC2O PJFHZKIDENOSJB-UHFFFAOYSA-N 0.000 description 1
- LHXSOGRLYOHBHA-UHFFFAOYSA-N CC(C(O)=C1)=C(c(c(CC2)c3)ccc3OCc3ccccc3)N2C1=O Chemical compound CC(C(O)=C1)=C(c(c(CC2)c3)ccc3OCc3ccccc3)N2C1=O LHXSOGRLYOHBHA-UHFFFAOYSA-N 0.000 description 1
- ISVGXBXADBBDME-UHFFFAOYSA-N CC[N](C)(C)CC Chemical compound CC[N](C)(C)CC ISVGXBXADBBDME-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- XJLXINKUBYWONI-NNYOXOHSSA-O NADP(+) Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-NNYOXOHSSA-O 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- YYAZJTUGSQOFHG-IAVNQIGZSA-N [(6s,8s,10s,11s,13s,14s,16r,17r)-6,9-difluoro-17-(fluoromethylsulfanylcarbonyl)-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl] propanoate;2-(hydroxymethyl)-4-[1-hydroxy-2-[6-(4-phenylbutoxy)hexylamino]eth Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)C1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O YYAZJTUGSQOFHG-IAVNQIGZSA-N 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 229960005370 atorvastatin Drugs 0.000 description 1
- 229960003060 bambuterol Drugs 0.000 description 1
- ANZXOIAKUNOVQU-UHFFFAOYSA-N bambuterol Chemical compound CN(C)C(=O)OC1=CC(OC(=O)N(C)C)=CC(C(O)CNC(C)(C)C)=C1 ANZXOIAKUNOVQU-UHFFFAOYSA-N 0.000 description 1
- 102000014974 beta2-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006828 beta2-adrenergic receptor activity proteins Proteins 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229960004620 bitolterol Drugs 0.000 description 1
- FZGVEKPRDOIXJY-UHFFFAOYSA-N bitolterol Chemical compound C1=CC(C)=CC=C1C(=O)OC1=CC=C(C(O)CNC(C)(C)C)C=C1OC(=O)C1=CC=C(C)C=C1 FZGVEKPRDOIXJY-UHFFFAOYSA-N 0.000 description 1
- 229940080593 budesonide / formoterol Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- DERZBLKQOCDDDZ-JLHYYAGUSA-N cinnarizine Chemical compound C1CN(C(C=2C=CC=CC=2)C=2C=CC=CC=2)CCN1C\C=C\C1=CC=CC=C1 DERZBLKQOCDDDZ-JLHYYAGUSA-N 0.000 description 1
- 229960000876 cinnarizine Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940109248 cromoglycate Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 235000019439 ethyl acetate Nutrition 0.000 description 1
- 229960003592 fexofenadine Drugs 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229940114006 fluticasone / salmeterol Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 229960004958 ketotifen Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 229950008204 levosalbutamol Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 229940127212 long-acting beta 2 agonist Drugs 0.000 description 1
- 229940125386 long-acting bronchodilator Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000001589 microsome Anatomy 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 229960000470 omalizumab Drugs 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229960001528 oxymetazoline Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 238000012802 pre-warming Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229960002586 roflumilast Drugs 0.000 description 1
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229960001262 tramazoline Drugs 0.000 description 1
- QQJLHRRUATVHED-UHFFFAOYSA-N tramazoline Chemical compound N1CCN=C1NC1=CC=CC2=C1CCCC2 QQJLHRRUATVHED-UHFFFAOYSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 229960000833 xylometazoline Drugs 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1506894.3 | 2015-04-23 | ||
| GBGB1506894.3A GB201506894D0 (en) | 2015-04-23 | 2015-04-23 | Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
| PCT/EP2016/058607 WO2016169911A1 (en) | 2015-04-23 | 2016-04-19 | Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018513180A JP2018513180A (ja) | 2018-05-24 |
| JP2018513180A5 true JP2018513180A5 (https=) | 2019-05-23 |
| JP6777652B2 JP6777652B2 (ja) | 2020-10-28 |
Family
ID=53488521
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2017555303A Active JP6777652B2 (ja) | 2015-04-23 | 2016-04-19 | 炎症性障害の治療のための新規ジヒドロピリドイソキノリノン及びその医薬組成物 |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US10568879B2 (https=) |
| EP (1) | EP3286191B1 (https=) |
| JP (1) | JP6777652B2 (https=) |
| KR (1) | KR20170139142A (https=) |
| CN (1) | CN107531703B (https=) |
| AR (1) | AR104362A1 (https=) |
| AU (1) | AU2016251517A1 (https=) |
| BR (1) | BR112017022008A2 (https=) |
| CA (1) | CA2983342A1 (https=) |
| CO (1) | CO2017011093A2 (https=) |
| GB (1) | GB201506894D0 (https=) |
| IL (1) | IL255109A0 (https=) |
| MX (1) | MX2017013382A (https=) |
| PH (1) | PH12017501911A1 (https=) |
| RU (1) | RU2017134551A (https=) |
| SG (1) | SG11201708671RA (https=) |
| TW (1) | TW201702243A (https=) |
| WO (1) | WO2016169911A1 (https=) |
| ZA (1) | ZA201706674B (https=) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3403649A1 (en) * | 2017-05-16 | 2018-11-21 | Bayer Pharma Aktiengesellschaft | Inhibitors and antagonists of gpr84 for the treatment of endometriosis |
| CN106977483A (zh) * | 2017-06-02 | 2017-07-25 | 遵义医学院 | 一种二氟烷基取代的黄酮醇、异黄酮醇和香豆素类化合物的合成方法 |
| CN118239937A (zh) | 2017-08-09 | 2024-06-25 | 戴纳立制药公司 | 化合物、组合物及方法 |
| DK3676297T3 (da) | 2017-09-01 | 2023-08-14 | Denali Therapeutics Inc | Forbindelser, sammensætninger og fremgangsmåder |
| RU2020119415A (ru) * | 2017-11-15 | 2021-12-16 | Галапагос Нв | Соединения и их фармацевтические композиции для применения при лечении фиброзных заболеваний |
| WO2020007342A1 (zh) * | 2018-07-06 | 2020-01-09 | 中国科学院上海药物研究所 | 联苯磷酸酯类化合物作为gpr84拮抗剂的应用 |
| MA54953A (fr) * | 2019-02-13 | 2021-12-22 | Denali Therapeutics Inc | Composés, compositions et procédés |
| US12091392B2 (en) | 2019-02-13 | 2024-09-17 | Denali Therapeutics Inc. | Compounds, compositions and methods |
| BR112022011237A2 (pt) | 2019-12-19 | 2022-08-30 | Bayer Ag | Derivados de furoindazol |
| WO2021123394A1 (en) | 2019-12-20 | 2021-06-24 | University Of Copenhagen | G protein-coupled receptor modulators and a pharmaceutical composition |
| US12378229B2 (en) | 2021-02-02 | 2025-08-05 | Liminal Biosciences Limited | GPR84 antagonists and uses thereof |
| WO2022179940A1 (en) | 2021-02-23 | 2022-09-01 | Bayer Aktiengesellschaft | Furoindazole derivatives as gpr84 antagonists |
| WO2022218372A1 (zh) * | 2021-04-14 | 2022-10-20 | 武汉人福创新药物研发中心有限公司 | 一种二氢嘧啶并异喹啉酮类衍生物及用途 |
| EP4330260A1 (en) | 2021-04-29 | 2024-03-06 | Bayer Aktiengesellschaft | Furoindazole derivatives as antagonists or inhibitors of gpr84 |
| EP4355743A1 (en) | 2021-06-18 | 2024-04-24 | University of Copenhagen | Polysubstituted 4-hydroxypyridine and 4-hydroxyquinoline derivatives as gpr84 antagonists |
| CN115611944A (zh) | 2021-07-15 | 2023-01-17 | 中国科学院上海药物研究所 | 不对称gpr84拮抗剂及其用途 |
| WO2024083705A1 (en) | 2022-10-18 | 2024-04-25 | Bayer Aktiengesellschaft | Furoindazole derivatives for the treatment of pain |
| USD1117011S1 (en) * | 2024-07-10 | 2026-03-10 | Delta Electronics, Inc. | Charging connector |
| USD1119767S1 (en) * | 2024-07-10 | 2026-03-24 | Delta Electronics, Inc. | Charging connector |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0926148A1 (en) * | 1997-12-23 | 1999-06-30 | Applied Research Systems Ars Holding N.V. | Benzo (C)quinolizine derivatives, their preparation and use as 5-alphareductases inhibitors |
| WO2005050225A2 (en) * | 2003-10-31 | 2005-06-02 | Bayer Healthcare Ag | Diagnostics and therapeutics for diseases associated with g protein-coupled receptor 84 (gpr84) |
| EP1929310A2 (en) | 2005-09-02 | 2008-06-11 | Arena Pharmaceuticals, Inc. | Human g protein-coupled receptor and modulators thereof for the treatment of atherosclerosis and atherosclerotic disease and for the treatment of conditions related to mcp-1 expression |
| WO2012037782A1 (en) | 2010-09-20 | 2012-03-29 | Glaxo Group Limited | Tricyclic compounds, preparation methods, and their uses |
| AR089284A1 (es) * | 2011-12-22 | 2014-08-13 | Galapagos Nv | Dihidropirimidinoisoquinolinonas y composiciones farmaceuticas de las mismas para el tratamiento de trastornos inflamatorios |
| WO2014095798A1 (en) | 2012-12-20 | 2014-06-26 | Galapagos Nv | Novel dihydropyrimidinoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders (gpr84 antagonists) |
| GB201411241D0 (en) * | 2014-06-25 | 2014-08-06 | Galapagos Nv | Novel dihydropyridoisoquinolinones and pharmaceutical compositions thereof for the treatment of inflammatory disorders |
-
2015
- 2015-04-23 GB GBGB1506894.3A patent/GB201506894D0/en not_active Ceased
-
2016
- 2016-04-19 JP JP2017555303A patent/JP6777652B2/ja active Active
- 2016-04-19 KR KR1020177033832A patent/KR20170139142A/ko not_active Withdrawn
- 2016-04-19 AU AU2016251517A patent/AU2016251517A1/en not_active Abandoned
- 2016-04-19 US US15/568,275 patent/US10568879B2/en active Active
- 2016-04-19 RU RU2017134551A patent/RU2017134551A/ru not_active Application Discontinuation
- 2016-04-19 BR BR112017022008-3A patent/BR112017022008A2/pt not_active Application Discontinuation
- 2016-04-19 EP EP16720370.2A patent/EP3286191B1/en active Active
- 2016-04-19 CA CA2983342A patent/CA2983342A1/en not_active Abandoned
- 2016-04-19 WO PCT/EP2016/058607 patent/WO2016169911A1/en not_active Ceased
- 2016-04-19 SG SG11201708671RA patent/SG11201708671RA/en unknown
- 2016-04-19 MX MX2017013382A patent/MX2017013382A/es unknown
- 2016-04-19 CN CN201680023369.1A patent/CN107531703B/zh active Active
- 2016-04-21 TW TW105112490A patent/TW201702243A/zh unknown
- 2016-04-22 AR ARP160101128A patent/AR104362A1/es unknown
-
2017
- 2017-10-04 ZA ZA2017/06674A patent/ZA201706674B/en unknown
- 2017-10-18 IL IL255109A patent/IL255109A0/en unknown
- 2017-10-19 PH PH12017501911A patent/PH12017501911A1/en unknown
- 2017-10-30 CO CONC2017/0011093A patent/CO2017011093A2/es unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2018513180A5 (https=) | ||
| JP6559324B2 (ja) | Ｂ型肝炎ウイルス感染の治療及び予防用の新規６，７−ジヒドロピリド［２，１−ａ］フタラジン−２−オン類 | |
| JP6568106B2 (ja) | Ｂ型肝炎ウイルス感染症の治療及び予防のための新規ジヒドロキノリジノン類 | |
| ES2292988T3 (es) | Derivados de nicotinamida utiles como inhibidores de pde4. | |
| JP5252404B2 (ja) | ピラジン化合物、その使用及び調製方法 | |
| JP6511083B2 (ja) | ピロール誘導体の結晶 | |
| JP6777652B2 (ja) | 炎症性障害の治療のための新規ジヒドロピリドイソキノリノン及びその医薬組成物 | |
| JP5373634B2 (ja) | ムスカリンｍ３アンタゴニストのナパジシル酸塩 | |
| JP2020503288A (ja) | 選択的ヤヌスキナーゼ阻害剤としてのアミノピラゾール類 | |
| JP7798362B2 (ja) | Ｂｃｌ－２阻害剤としての化合物 | |
| JP2004509855A (ja) | ＴＮＦαインヒビターとして有用なクマリン誘導体 | |
| SA05260265A (ar) | مركبات جديدة | |
| JP2009526037A (ja) | トリアゾロピリジン化合物 | |
| JP2022526364A5 (https=) | ||
| US9284320B2 (en) | Ticagrelor adducts with divalent metal salts | |
| JP2024032976A (ja) | アデノシン受容体アンタゴニストおよびその使用 | |
| US20170145019A1 (en) | 2-(2-aminocyclohexyl)amino-pyrimidine-5-carboxamides as spleen tyrosine kinase(syk) inhibitors | |
| JP2010526806A (ja) | 純粋なパリペリドン、およびその製造方法 | |
| JP7013446B2 (ja) | Ｇａｂａ（ａ）受容体モジュレーター、及び、喘息における気道過敏及び炎症を抑制するための方法 | |
| US10766883B2 (en) | Aminopyrazoles as janus kinase inhibitors | |
| TW202000650A (zh) | ４-甲基二氫嘧啶酮化合物及其醫藥用途 | |
| UA72017C2 (en) | Tetrahydropyridines, a method for the preparation thereof and a pharmaceutical composition containing them | |
| WO1998058930A1 (en) | Triazolo-1,4-diazepine compounds and medicinal composition containing the same | |
| JP5960138B2 (ja) | リン酸エステル誘導体 | |
| CZ20021382A3 (cs) | Deriváty fenyl- a pyridyl-tetrahydropyridinu, způsob jejich přípravy a farmaceutická kompozice, která je obsahuje |