CA3063963A1 - Glucuronide prodrugs of janus kinase inhibitors - Google Patents
Glucuronide prodrugs of janus kinase inhibitors Download PDFInfo
- Publication number
- CA3063963A1 CA3063963A1 CA3063963A CA3063963A CA3063963A1 CA 3063963 A1 CA3063963 A1 CA 3063963A1 CA 3063963 A CA3063963 A CA 3063963A CA 3063963 A CA3063963 A CA 3063963A CA 3063963 A1 CA3063963 A1 CA 3063963A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- methyl
- formula
- alkyl
- trifluoromethyl
- 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
- 150000008134 glucuronides Chemical class 0.000 title abstract description 23
- 239000000651 prodrug Substances 0.000 title abstract description 22
- 229940002612 prodrug Drugs 0.000 title abstract description 22
- 229930182480 glucuronide Natural products 0.000 title abstract description 17
- 229940122245 Janus kinase inhibitor Drugs 0.000 title description 31
- 150000001875 compounds Chemical class 0.000 claims abstract description 374
- 238000000034 method Methods 0.000 claims abstract description 68
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 33
- 208000017189 Gastrointestinal inflammatory disease Diseases 0.000 claims abstract description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 127
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 105
- 239000001257 hydrogen Substances 0.000 claims description 90
- 229910052739 hydrogen Inorganic materials 0.000 claims description 90
- 150000003839 salts Chemical class 0.000 claims description 82
- 125000001424 substituent group Chemical group 0.000 claims description 81
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 77
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 73
- 125000005843 halogen group Chemical group 0.000 claims description 68
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 64
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 56
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- -1 chloro, methyl Chemical group 0.000 claims description 49
- 125000003118 aryl group Chemical group 0.000 claims description 45
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 30
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 27
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 14
- 239000003937 drug carrier Substances 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 13
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims description 13
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims description 13
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 13
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 239000001301 oxygen Chemical group 0.000 claims description 13
- 229910052717 sulfur Chemical group 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 239000011593 sulfur Chemical group 0.000 claims description 12
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 9
- 241000124008 Mammalia Species 0.000 claims description 9
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 206010009887 colitis Diseases 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 7
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 6
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 238000013160 medical therapy Methods 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
- 239000003112 inhibitor Substances 0.000 abstract description 17
- 239000000543 intermediate Substances 0.000 abstract description 14
- 102000015617 Janus Kinases Human genes 0.000 abstract description 6
- 108010024121 Janus Kinases Proteins 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 190
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 164
- 238000002360 preparation method Methods 0.000 description 120
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 84
- 239000011541 reaction mixture Substances 0.000 description 76
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 238000006243 chemical reaction Methods 0.000 description 74
- 239000000203 mixture Substances 0.000 description 67
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- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 description 66
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
- 238000004440 column chromatography Methods 0.000 description 48
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- 239000007787 solid Substances 0.000 description 42
- 239000013543 active substance Substances 0.000 description 34
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 33
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 31
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 30
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 30
- 125000001309 chloro group Chemical group Cl* 0.000 description 29
- 229910052938 sodium sulfate Inorganic materials 0.000 description 29
- 235000011152 sodium sulphate Nutrition 0.000 description 29
- 238000004809 thin layer chromatography Methods 0.000 description 29
- 239000003795 chemical substances by application Substances 0.000 description 25
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 25
- 125000001153 fluoro group Chemical group F* 0.000 description 25
- 239000010410 layer Substances 0.000 description 24
- 239000003826 tablet Substances 0.000 description 24
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 22
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 21
- 239000002904 solvent Substances 0.000 description 21
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 20
- 238000012544 monitoring process Methods 0.000 description 19
- 229950000971 baricitinib Drugs 0.000 description 18
- XUZMWHLSFXCVMG-UHFFFAOYSA-N baricitinib Chemical compound C1N(S(=O)(=O)CC)CC1(CC#N)N1N=CC(C=2C=3C=CNC=3N=CN=2)=C1 XUZMWHLSFXCVMG-UHFFFAOYSA-N 0.000 description 18
- 210000001072 colon Anatomy 0.000 description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- HJWLJNBZVZDLAQ-HAQNSBGRSA-N chembl2103874 Chemical compound C1C[C@@H](CS(=O)(=O)NC)CC[C@@H]1N(C)C1=NC=NC2=C1C=CN2 HJWLJNBZVZDLAQ-HAQNSBGRSA-N 0.000 description 16
- 229960004955 oclacitinib Drugs 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- 239000005909 Kieselgur Substances 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000002775 capsule Substances 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 102000008096 B7-H1 Antigen Human genes 0.000 description 14
- 108010074708 B7-H1 Antigen Proteins 0.000 description 14
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- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 description 14
- 239000000706 filtrate Substances 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 229960000215 ruxolitinib Drugs 0.000 description 14
- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 description 14
- MQAYFGXOFCEZRW-UHFFFAOYSA-N oxane-2-carboxylic acid Chemical compound OC(=O)C1CCCCO1 MQAYFGXOFCEZRW-UHFFFAOYSA-N 0.000 description 13
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 230000002550 fecal effect Effects 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
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- 239000012267 brine Substances 0.000 description 10
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 9
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- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 description 1
- 229960003040 rifaximin Drugs 0.000 description 1
- 235000005713 safflower oil Nutrition 0.000 description 1
- 239000003813 safflower oil Substances 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910001958 silver carbonate Inorganic materials 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 201000008261 skin carcinoma Diseases 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QQWYQAQQADNEIC-RVDMUPIBSA-N tert-butyl [(z)-[cyano(phenyl)methylidene]amino] carbonate Chemical compound CC(C)(C)OC(=O)O\N=C(/C#N)C1=CC=CC=C1 QQWYQAQQADNEIC-RVDMUPIBSA-N 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- UBZYKBZMAMTNKW-UHFFFAOYSA-J titanium tetrabromide Chemical compound Br[Ti](Br)(Br)Br UBZYKBZMAMTNKW-UHFFFAOYSA-J 0.000 description 1
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 229960001350 tofacitinib Drugs 0.000 description 1
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 description 1
- 229950007217 tremelimumab Drugs 0.000 description 1
- 125000005591 trimellitate group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229960004914 vedolizumab Drugs 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229950000339 xinafoate Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
- C07H13/12—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by acids having the group -X-C(=X)-X-, or halides thereof, in which each X means nitrogen, oxygen, sulfur, selenium or tellurium, e.g. carbonic acid, carbamic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/26—Acyclic or carbocyclic radicals, substituted by hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/02—Heterocyclic radicals containing only nitrogen as ring hetero atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762509847P | 2017-05-23 | 2017-05-23 | |
| US62/509,847 | 2017-05-23 | ||
| PCT/US2018/033818 WO2018217700A1 (en) | 2017-05-23 | 2018-05-22 | Glucuronide prodrugs of janus kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3063963A1 true CA3063963A1 (en) | 2018-11-29 |
Family
ID=62621001
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3063963A Abandoned CA3063963A1 (en) | 2017-05-23 | 2018-05-22 | Glucuronide prodrugs of janus kinase inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US10745405B2 (https=) |
| EP (1) | EP3609899A1 (https=) |
| JP (1) | JP2020520955A (https=) |
| KR (1) | KR20200010440A (https=) |
| CN (1) | CN110662747A (https=) |
| AU (1) | AU2018273866B2 (https=) |
| BR (1) | BR112019024509A2 (https=) |
| CA (1) | CA3063963A1 (https=) |
| IL (1) | IL270693A (https=) |
| MX (1) | MX2019014054A (https=) |
| NZ (1) | NZ759764A (https=) |
| PH (1) | PH12019502605A1 (https=) |
| RU (1) | RU2019142472A (https=) |
| WO (1) | WO2018217700A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111094314B (zh) * | 2018-08-15 | 2022-08-12 | 江苏豪森药业集团有限公司 | 含有葡糖苷酸衍生物jak抑制剂的前药及其制备方法和应用 |
| BR112021026517A2 (pt) | 2019-06-28 | 2022-05-10 | Kymera Therapeutics Inc | Degradadores de irak e usos dos mesmos |
| WO2021011868A1 (en) | 2019-07-17 | 2021-01-21 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| US12551564B2 (en) | 2019-12-10 | 2026-02-17 | Kymera Therapeutics, Inc. | IRAK degraders and uses thereof |
| WO2021127190A1 (en) | 2019-12-17 | 2021-06-24 | Kymera Therapeutics, Inc. | Irak degraders and uses thereof |
| CN111196831B (zh) * | 2020-01-20 | 2023-05-09 | 山西医科大学 | 一种呋喃酚葡萄糖醛酸结合物的制备方法 |
| CN116867494A (zh) | 2021-02-15 | 2023-10-10 | 凯麦拉医疗公司 | Irak4降解剂和其用途 |
| EP4384173A1 (en) * | 2021-08-12 | 2024-06-19 | Sun Pharmaceutical Industries, Inc. | Treatment of jak-inhibition-responsive disorders with prodrugs of jak inhibitors |
| WO2023155905A1 (zh) * | 2022-02-21 | 2023-08-24 | 上海岸阔医药科技有限公司 | 化合物及其用途 |
| CN119923257A (zh) * | 2022-04-15 | 2025-05-02 | 密歇根大学董事会 | Jak抑制剂类似物、制剂及其用途 |
| CN115073543B (zh) * | 2022-07-20 | 2022-11-15 | 北京普祺医药科技股份有限公司 | 一种jak抑制剂的化合物前药及其制备与应用 |
| EP4637724A1 (en) | 2022-12-22 | 2025-10-29 | KRKA, d.d., Novo mesto | Veterinary composition comprising oclacitinib |
| WO2024148049A1 (en) * | 2023-01-04 | 2024-07-11 | Kymera Therapeutics, Inc. | Irak4 degraders and uses thereof |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993022334A1 (en) * | 1992-05-04 | 1993-11-11 | Sri International | Pharmaceutical compositions and methods for colonic delivery of corticosteroids |
| US5811388A (en) | 1995-06-07 | 1998-09-22 | Cibus Pharmaceutical, Inc. | Delivery of drugs to the lower GI tract |
| EP1382339B1 (en) | 1999-12-10 | 2007-12-05 | Pfizer Products Inc. | Compositions containing pyrrolo ¬2,3-d pyrimidine derivatives |
| US7798257B2 (en) | 2004-04-30 | 2010-09-21 | Smith International, Inc. | Shaped cutter surface |
| EP2455382B1 (en) | 2005-12-13 | 2016-10-26 | Incyte Holdings Corporation | Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors |
| US8158616B2 (en) | 2008-03-11 | 2012-04-17 | Incyte Corporation | Azetidine and cyclobutane derivatives as JAK inhibitors |
| JP4884570B2 (ja) | 2008-08-20 | 2012-02-29 | ファイザー・インク | ピロロ［２，３−ｄ］ピリミジン化合物 |
| KR101921850B1 (ko) * | 2009-10-09 | 2018-11-23 | 인사이트 홀딩스 코포레이션 | 3-（4-（7Ｈ-피롤로〔2,3-ｄ〕피리미딘-4-일）-1Ｈ-피라졸-1-일）-3-사이클로펜틸프로판니트릴의 하이드록실, 케토 및 글루쿠로나이드 유도체 |
| EP2695617B1 (en) | 2009-12-23 | 2019-01-09 | Glycomyr Inc. | Vitamin D glycosides and sulfates for treating intestinal diseases |
| CN102724967A (zh) | 2009-12-31 | 2012-10-10 | 安龙制药公司 | 包括可释放的脲连接体的含芳香胺化合物的聚合缀合物 |
| JP2013518882A (ja) | 2010-02-05 | 2013-05-23 | ファイザー・インク | ＪＡＫ阻害剤としてのピロロ［２，３−ｄ］ピリミジン尿素化合物 |
| JP2016528174A (ja) | 2013-05-31 | 2016-09-15 | セルリアン・ファーマ・インコーポレイテッド | 治療的送達用のシクロデキストリンベースのポリマー |
| ES2784523T3 (es) | 2015-11-24 | 2020-09-28 | Theravance Biopharma R&D Ip Llc | Profármacos de un compuesto inhibidor de JAK para el tratamiento de enfermedades inflamatorias gastrointestinales |
| CN106496233B (zh) * | 2016-09-26 | 2018-05-15 | 东南大学 | 吡咯并嘧啶类化合物、其制备方法及其用途 |
-
2018
- 2018-05-22 BR BR112019024509-0A patent/BR112019024509A2/pt not_active Application Discontinuation
- 2018-05-22 MX MX2019014054A patent/MX2019014054A/es unknown
- 2018-05-22 CN CN201880034623.7A patent/CN110662747A/zh active Pending
- 2018-05-22 CA CA3063963A patent/CA3063963A1/en not_active Abandoned
- 2018-05-22 RU RU2019142472A patent/RU2019142472A/ru not_active Application Discontinuation
- 2018-05-22 PH PH1/2019/502605A patent/PH12019502605A1/en unknown
- 2018-05-22 AU AU2018273866A patent/AU2018273866B2/en not_active Expired - Fee Related
- 2018-05-22 KR KR1020197037814A patent/KR20200010440A/ko not_active Withdrawn
- 2018-05-22 JP JP2019564506A patent/JP2020520955A/ja not_active Withdrawn
- 2018-05-22 WO PCT/US2018/033818 patent/WO2018217700A1/en not_active Ceased
- 2018-05-22 EP EP18731628.6A patent/EP3609899A1/en not_active Withdrawn
- 2018-05-22 US US15/986,028 patent/US10745405B2/en not_active Expired - Fee Related
- 2018-05-22 NZ NZ759764A patent/NZ759764A/en unknown
-
2019
- 2019-11-17 IL IL270693A patent/IL270693A/en unknown
-
2020
- 2020-07-13 US US16/926,992 patent/US20210032250A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| WO2018217700A1 (en) | 2018-11-29 |
| US10745405B2 (en) | 2020-08-18 |
| MX2019014054A (es) | 2020-02-05 |
| US20180339990A1 (en) | 2018-11-29 |
| RU2019142472A3 (https=) | 2021-09-23 |
| AU2018273866B2 (en) | 2021-09-30 |
| NZ759764A (en) | 2022-07-01 |
| EP3609899A1 (en) | 2020-02-19 |
| US20210032250A1 (en) | 2021-02-04 |
| JP2020520955A (ja) | 2020-07-16 |
| IL270693A (en) | 2020-01-30 |
| CN110662747A (zh) | 2020-01-07 |
| PH12019502605A1 (en) | 2020-10-26 |
| AU2018273866A1 (en) | 2019-12-19 |
| RU2019142472A (ru) | 2021-06-24 |
| KR20200010440A (ko) | 2020-01-30 |
| BR112019024509A2 (pt) | 2020-06-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20231124 |