UA80093C2 - Спосіб оптичного розділення (1-бензил-4-метилпіперидин-3-іл)метиламіну і його використання для одержання похідних піроло[2,3-d]піримідину як інгібіторів протеїнкінази - Google Patents
Спосіб оптичного розділення (1-бензил-4-метилпіперидин-3-іл)метиламіну і його використання для одержання похідних піроло[2,3-d]піримідину як інгібіторів протеїнкінази Download PDFInfo
- Publication number
- UA80093C2 UA80093C2 UA20031110841A UA20031110841A UA80093C2 UA 80093 C2 UA80093 C2 UA 80093C2 UA 20031110841 A UA20031110841 A UA 20031110841A UA 20031110841 A UA20031110841 A UA 20031110841A UA 80093 C2 UA80093 C2 UA 80093C2
- Authority
- UA
- Ukraine
- Prior art keywords
- alkyl
- amino
- alkylamino
- trifluoromethyl
- cyano
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title description 21
- 102000001253 Protein Kinase Human genes 0.000 title description 5
- 239000003112 inhibitor Substances 0.000 title description 5
- 108060006633 protein kinase Proteins 0.000 title description 5
- 230000003287 optical effect Effects 0.000 title description 4
- NVKDDQBZODSEIN-UHFFFAOYSA-N 1-benzyl-n,4-dimethylpiperidin-3-amine Chemical compound C1CC(C)C(NC)CN1CC1=CC=CC=C1 NVKDDQBZODSEIN-UHFFFAOYSA-N 0.000 title description 2
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 115
- 238000000034 method Methods 0.000 claims abstract description 59
- 239000000203 mixture Substances 0.000 claims abstract description 54
- 239000002904 solvent Substances 0.000 claims abstract description 35
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 23
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 23
- 239000002244 precipitate Substances 0.000 claims abstract description 13
- 238000002156 mixing Methods 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 354
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 90
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 66
- -1 hydroxy, amino Chemical group 0.000 claims description 64
- 125000003282 alkyl amino group Chemical group 0.000 claims description 59
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 55
- 125000004442 acylamino group Chemical group 0.000 claims description 49
- 150000003839 salts Chemical class 0.000 claims description 49
- 125000002252 acyl group Chemical group 0.000 claims description 47
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 44
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 42
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 40
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 229910052736 halogen Inorganic materials 0.000 claims description 29
- 150000002367 halogens Chemical class 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 29
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 27
- 125000003342 alkenyl group Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 27
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 229910052805 deuterium Inorganic materials 0.000 claims description 27
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 25
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 24
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 125000004423 acyloxy group Chemical group 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 19
- 230000000707 stereoselective effect Effects 0.000 claims description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 238000000926 separation method Methods 0.000 claims description 16
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 15
- 229910002514 Co–Co Inorganic materials 0.000 claims description 14
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 241000124008 Mammalia Species 0.000 claims description 12
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 10
- 125000004414 alkyl thio group Chemical group 0.000 claims description 10
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000006239 protecting group Chemical group 0.000 claims description 10
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 9
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 8
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 8
- 108010036949 Cyclosporine Proteins 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 230000003993 interaction Effects 0.000 claims description 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 6
- 229930105110 Cyclosporin A Natural products 0.000 claims description 6
- 108091000080 Phosphotransferase Proteins 0.000 claims description 6
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 6
- 208000006673 asthma Diseases 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group 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 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 102000020233 phosphotransferase Human genes 0.000 claims description 6
- 238000001556 precipitation Methods 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 229960001967 tacrolimus Drugs 0.000 claims description 6
- 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 claims description 6
- 239000011975 tartaric acid Substances 0.000 claims description 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- 208000011231 Crohn disease Diseases 0.000 claims description 5
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 5
- 125000005110 aryl thio group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 201000008937 atopic dermatitis Diseases 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 201000011510 cancer Diseases 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 206010025135 lupus erythematosus Diseases 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 5
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 4
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 4
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 4
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 4
- 230000000996 additive effect Effects 0.000 claims description 4
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 4
- 229960002170 azathioprine Drugs 0.000 claims description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 4
- 239000006184 cosolvent Substances 0.000 claims description 4
- 229960002806 daclizumab Drugs 0.000 claims description 4
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 4
- 229960003957 dexamethasone Drugs 0.000 claims description 4
- 229960001680 ibuprofen Drugs 0.000 claims description 4
- 210000000987 immune system Anatomy 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims description 4
- 229940014456 mycophenolate Drugs 0.000 claims description 4
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims description 4
- 229960002009 naproxen Drugs 0.000 claims description 4
- 229960005489 paracetamol Drugs 0.000 claims description 4
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 4
- 229960002702 piroxicam Drugs 0.000 claims description 4
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 4
- 229960004618 prednisone Drugs 0.000 claims description 4
- 235000002906 tartaric acid Nutrition 0.000 claims description 4
- 150000003892 tartrate salts Chemical class 0.000 claims description 4
- 208000010928 autoimmune thyroid disease Diseases 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- OOKSMYZBWRKRGU-UHFFFAOYSA-N 2-benzoyl-2,3-dihydroxybutanedioic acid Chemical class OC(=O)C(O)C(O)(C(O)=O)C(=O)C1=CC=CC=C1 OOKSMYZBWRKRGU-UHFFFAOYSA-N 0.000 claims description 2
- 102000015617 Janus Kinases Human genes 0.000 claims description 2
- 108010024121 Janus Kinases Proteins 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 claims description 2
- QUUYRYYUKNNNNS-UHFFFAOYSA-N piperidine-1-carboximidamide Chemical compound NC(=N)N1CCCCC1 QUUYRYYUKNNNNS-UHFFFAOYSA-N 0.000 claims description 2
- 102000006395 Globulins Human genes 0.000 claims 3
- 108010044091 Globulins Proteins 0.000 claims 3
- 230000001494 anti-thymocyte effect Effects 0.000 claims 3
- 229960000681 leflunomide Drugs 0.000 claims 3
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 claims 3
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims 3
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims 3
- 229960002930 sirolimus Drugs 0.000 claims 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims 3
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims 2
- 125000001475 halogen functional group Chemical group 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 238000002689 xenotransplantation Methods 0.000 claims 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 claims 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims 1
- 125000004494 ethyl ester group Chemical group 0.000 claims 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 claims 1
- 125000005425 toluyl group Chemical group 0.000 claims 1
- 238000012876 topography Methods 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 description 33
- 239000000243 solution Substances 0.000 description 33
- 235000019441 ethanol Nutrition 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000000725 suspension Substances 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 239000011541 reaction mixture Substances 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 239000007787 solid Substances 0.000 description 8
- 239000000443 aerosol Substances 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 6
- 150000001447 alkali salts Chemical class 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 125000004404 heteroalkyl group Chemical group 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 230000035755 proliferation Effects 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 150000001768 cations Chemical class 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 239000012039 electrophile Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 150000003230 pyrimidines Chemical class 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229940095064 tartrate Drugs 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 229940077388 benzenesulfonate Drugs 0.000 description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 3
- 229910052791 calcium Inorganic materials 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 239000011630 iodine Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- 238000004859 neutralization-reionization mass spectrometry Methods 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 2
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 description 2
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 208000024799 Thyroid disease Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001350 alkyl halides Chemical class 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 238000012443 analytical study Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 150000001503 aryl iodides Chemical class 0.000 description 2
- 230000001363 autoimmune Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 229910001882 dioxygen Inorganic materials 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 2
- GHXZPUGJZVBLGC-UHFFFAOYSA-N iodoethene Chemical compound IC=C GHXZPUGJZVBLGC-UHFFFAOYSA-N 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000012669 liquid formulation Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium 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
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000010979 pH adjustment Methods 0.000 description 2
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 239000003880 polar aprotic solvent Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 125000003011 styrenyl group Chemical class [H]\C(*)=C(/[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229940104230 thymidine Drugs 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 239000011592 zinc chloride Substances 0.000 description 2
- 235000005074 zinc chloride Nutrition 0.000 description 2
- FKMJKEQHUVZBJG-UHFFFAOYSA-N (1-benzyl-4-methylpiperidin-3-yl)methanamine Chemical compound C1C(CN)C(C)CCN1CC1=CC=CC=C1 FKMJKEQHUVZBJG-UHFFFAOYSA-N 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000004529 1,2,3-triazinyl group Chemical group N1=NN=C(C=C1)* 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 1
- 125000004530 1,2,4-triazinyl group Chemical group N1=NC(=NC=C1)* 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
- 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 description 1
- CVQNXCBXFOIHLH-UHFFFAOYSA-N 1-benzyl-n,4-dimethylpiperidin-3-amine;dihydrochloride Chemical compound Cl.Cl.C1CC(C)C(NC)CN1CC1=CC=CC=C1 CVQNXCBXFOIHLH-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 244000291564 Allium cepa Species 0.000 description 1
- 235000002732 Allium cepa var. cepa Nutrition 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical class NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 102000006500 Janus Kinase 3 Human genes 0.000 description 1
- 108010019421 Janus Kinase 3 Proteins 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920002302 Nylon 6,6 Polymers 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 150000001543 aryl boronic acids Chemical class 0.000 description 1
- 238000000065 atmospheric pressure chemical ionisation Methods 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 229910052790 beryllium Inorganic materials 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000012455 biphasic mixture Substances 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 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 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- 229940042935 dichlorodifluoromethane Drugs 0.000 description 1
- 229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
- UZBQIPPOMKBLAS-UHFFFAOYSA-N diethylazanide Chemical compound CC[N-]CC UZBQIPPOMKBLAS-UHFFFAOYSA-N 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 150000002194 fatty esters Chemical class 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 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
- 229940050410 gluconate Drugs 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- OVEHNNQXLPJPPL-UHFFFAOYSA-N lithium;n-propan-2-ylpropan-2-amine Chemical compound [Li].CC(C)NC(C)C OVEHNNQXLPJPPL-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 210000005087 mononuclear cell Anatomy 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000005185 salting out Methods 0.000 description 1
- 229940063122 sandimmune Drugs 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 229940032147 starch Drugs 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
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 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
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base 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
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 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 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 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
- 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
- 125000001425 triazolyl group Chemical group 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- LSGOVYNHVSXFFJ-UHFFFAOYSA-N vanadate(3-) Chemical compound [O-][V]([O-])([O-])=O LSGOVYNHVSXFFJ-UHFFFAOYSA-N 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings 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
- C07D211/56—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Dermatology (AREA)
- Transplantation (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Oncology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US29477501P | 2001-05-31 | 2001-05-31 | |
| US34104801P | 2001-12-06 | 2001-12-06 | |
| PCT/IB2002/001905 WO2002096909A1 (fr) | 2001-05-31 | 2002-05-29 | Resolution optique de (1-benzyl-4-methylpiperidine-3-yle) methylamine et son utilisation pour la preparation de derives de pyrrolo 2,3-pyrimidine utilises comme inhibiteurs de proteines kinase |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| UA80093C2 true UA80093C2 (uk) | 2007-08-27 |
Family
ID=26968730
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| UA20031110841A UA80093C2 (uk) | 2001-05-31 | 2002-05-29 | Спосіб оптичного розділення (1-бензил-4-метилпіперидин-3-іл)метиламіну і його використання для одержання похідних піроло[2,3-d]піримідину як інгібіторів протеїнкінази |
Country Status (52)
Families Citing this family (124)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| EP1382339B1 (fr) | 1999-12-10 | 2007-12-05 | Pfizer Products Inc. | Compositions contenant des dérivés de pyrrolo¬2,3-d pyrimidine |
| IL152771A0 (en) * | 2000-06-26 | 2003-06-24 | Pfizer Prod Inc | PYRROLO(2,3-d) PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS |
| PY0228255A (es) | 2001-12-06 | 2004-06-01 | Pfizer Prod Inc | Compuestos cristalinos novedosos |
| TWI329105B (en) | 2002-02-01 | 2010-08-21 | Rigel Pharmaceuticals Inc | 2,4-pyrimidinediamine compounds and their uses |
| ES2445208T3 (es) | 2002-07-29 | 2014-02-28 | Rigel Pharmaceuticals, Inc. | Compuestos de 2,4-pirimidindiamina para uso en métodos para tratar o prevenir enfermedades autoinmunitarias |
| DE60322544D1 (de) * | 2002-08-27 | 2008-09-11 | Merck Patent Gmbh | Glycinamid-derivate als raf-kinase-hemmer |
| NZ539901A (en) | 2002-11-26 | 2007-09-28 | Pfizer Prod Inc | Method of treatment of transplant rejection |
| BRPI0413018B8 (pt) | 2003-07-30 | 2021-05-25 | Rigel Pharmaceuticals Inc | composto, e, uso de um composto |
| AU2005237254B2 (en) * | 2004-05-03 | 2010-02-04 | Novartis Ag | Combinations comprising a S1P receptor agonist and a JAK3 kinase inhibitor |
| EP1768982A2 (fr) | 2004-06-29 | 2007-04-04 | Amgen Inc. | Pyrrolo[2, 3-d] pyrimidines qui modulent l'activite ack1 et lck |
| BRPI0514094A (pt) | 2004-08-02 | 2008-05-27 | Osi Pharm Inc | composto, composição, e, método de tratamento de distúrbio hiperproliferativo |
| RU2007123675A (ru) * | 2004-11-24 | 2008-12-27 | Новартис АГ (CH) | Комбинации ингибиторов jak |
| AR054416A1 (es) * | 2004-12-22 | 2007-06-27 | Incyte Corp | Pirrolo [2,3-b]piridin-4-il-aminas y pirrolo [2,3-b]pirimidin-4-il-aminas como inhibidores de las quinasas janus. composiciones farmaceuticas. |
| US20070203161A1 (en) | 2006-02-24 | 2007-08-30 | Rigel Pharmaceuticals, Inc. | Compositions and methods for inhibition of the jak pathway |
| WO2006133426A2 (fr) | 2005-06-08 | 2006-12-14 | Rigel Pharmaceuticals, Inc. | Compositions et procedes d'inhibition de la voie jak |
| WO2007007919A2 (fr) | 2005-07-14 | 2007-01-18 | Astellas Pharma Inc. | Nouveaux composes |
| EP2251341A1 (fr) | 2005-07-14 | 2010-11-17 | Astellas Pharma Inc. | Hétérocycles inhibiteurs de Janus kinase-3 |
| BRPI0613876A2 (pt) * | 2005-07-29 | 2011-02-15 | Pfizer Prod Inc | derivados de pirrolo [2,3-d] pirimidina; seus intermediários e sìntese |
| EP2270014A1 (fr) | 2005-09-22 | 2011-01-05 | Incyte Corporation | Inhibiteurs de l'azépine de janus kinases |
| EP2455382B1 (fr) | 2005-12-13 | 2016-10-26 | Incyte Holdings Corporation | Pyrrolo[2,3-b]pyridines et pyrrolo[2,3-b]pyrimidines à substitution hétéroaryle en tant qu'inhibiteurs de la janus kinase |
| CA2642229C (fr) | 2006-02-24 | 2015-05-12 | Rigel Pharmaceuticals, Inc. | Compositions et methodes destinees a l'inhibition de la voie jak |
| GB0605691D0 (en) * | 2006-03-21 | 2006-05-03 | Novartis Ag | Organic Compounds |
| EP2121692B1 (fr) | 2006-12-22 | 2013-04-10 | Incyte Corporation | Hétérocycles substitués servant d'inhibiteurs de janus kinases |
| EP3070090B1 (fr) | 2007-06-13 | 2018-12-12 | Incyte Holdings Corporation | Utilisation des sels de l'inhibiteur de janus kinase (r)-3-(4- (7h-pyrrolo [2,3-d] pyrimidin-4-yl)-1h-pyrazol-1-yl) -3-cyclopentylpropanenitrile |
| CL2008001709A1 (es) | 2007-06-13 | 2008-11-03 | Incyte Corp | Compuestos derivados de pirrolo [2,3-b]pirimidina, moduladores de quinasas jak; composicion farmaceutica; y uso en el tratamiento de enfermedades tales como cancer, psoriasis, artritis reumatoide, entre otras. |
| US8541426B2 (en) * | 2007-07-11 | 2013-09-24 | Pfizer Inc. | Pharmaceutical compositions and methods of treating dry eye disorders |
| US8309566B2 (en) | 2008-02-15 | 2012-11-13 | Rigel Pharmaceuticals, Inc. | Pyrimidine-2-amine compounds and their use as inhibitors of JAK kinases |
| US8158616B2 (en) | 2008-03-11 | 2012-04-17 | Incyte Corporation | Azetidine and cyclobutane derivatives as JAK inhibitors |
| US8138339B2 (en) | 2008-04-16 | 2012-03-20 | Portola Pharmaceuticals, Inc. | Inhibitors of protein kinases |
| MX2010011463A (es) | 2008-04-16 | 2011-06-03 | Portola Pharm Inc | 2,6-diamino-pirimidin-5-il-carboxamidas como inhibidores de syk o jak quinasas. |
| NZ588830A (en) | 2008-04-22 | 2012-11-30 | Portola Pharm Inc | Inhibitors of protein kinases |
| US20110165183A1 (en) * | 2008-08-01 | 2011-07-07 | Biocryst Pharmaceuticals, Inc. | Piperidine derivatives as jak3 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 |
| CA2752150A1 (fr) * | 2009-02-11 | 2010-08-19 | Reaction Biology Corp. | Inhibiteurs de kinase selectifs |
| EP2421867B1 (fr) * | 2009-04-20 | 2015-09-02 | Auspex Pharmaceuticals, Llc | Inhibiteurs pipéridiniques de la janus kinase 3 |
| JP5775070B2 (ja) | 2009-05-22 | 2015-09-09 | インサイト・コーポレイションＩｎｃｙｔｅ Ｃｏｒｐｏｒａｔｉｏｎ | ヤヌスキナーゼ阻害剤としてのピラゾール−４−イル−ピロロ［２，３−ｄ］ピリミジンおよびピロール−３−イル−ピロロ［２，３−ｄ］ピリミジンのＮ−（ヘテロ）アリール−ピロリジン誘導体 |
| SG176111A1 (en) | 2009-05-22 | 2011-12-29 | Incyte Corp | 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors |
| AR078012A1 (es) | 2009-09-01 | 2011-10-05 | Incyte Corp | Derivados heterociclicos de las pirazol-4-il- pirrolo (2,3-d) pirimidinas como inhibidores de la quinasa janus |
| EP2475667A1 (fr) * | 2009-09-10 | 2012-07-18 | F. Hoffmann-La Roche AG | Inhibiteurs de jak |
| 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 |
| CA2776028C (fr) | 2009-10-15 | 2015-12-01 | Pfizer Inc. | Composes pyrrolo[2,3-d]pyrimidine |
| ES2461967T3 (es) | 2009-12-18 | 2014-05-21 | Pfizer Inc. | Compuestos de pirrolo[2,3-d]pirimidina |
| EP2523957A1 (fr) * | 2010-01-12 | 2012-11-21 | F. Hoffmann-La Roche AG | Composés hétérocycliques tricycliques, leurs compositions et procédés d'utilisation |
| 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 |
| PT3354652T (pt) | 2010-03-10 | 2020-07-20 | Incyte Holdings Corp | Derivados de piperidin-4-ilazetidina como inibidores de jak1 |
| RS54824B1 (sr) | 2010-05-21 | 2016-10-31 | Incyte Holdings Corp | Topikalna formulacija za inhibiciju jak-a |
| US9102625B2 (en) | 2010-11-01 | 2015-08-11 | Portola Pharmaceuticals, Inc. | Nicotinamides as JAK kinase modulators |
| WO2012068440A1 (fr) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Pyrrolopyridines et pyrrolopyrimidines à substitution hétérocyclique utilisées en tant qu'inhibiteurs des jak |
| CA2818542A1 (fr) | 2010-11-19 | 2012-05-24 | Incyte Corporation | Derives pyrrolopyridine et pyrrolopyrimidine a substitution cyclobutyle utilises comme inhibiteurs des jak |
| EP2481397A1 (fr) | 2011-01-27 | 2012-08-01 | Ratiopharm GmbH | Compositions pharmaceutiques comportant du tasocitinib |
| EP2481411A1 (fr) | 2011-01-27 | 2012-08-01 | Ratiopharm GmbH | Formes galéniques orales pour libération modifiée comportant l'inhibiteur de JAK3 tasocitinib |
| CA2827673C (fr) | 2011-02-18 | 2020-10-27 | Novartis Pharma Ag | Pluritherapie impliquant un inhibiteur de mtor et un inhibiteur de jak |
| EP2691395B1 (fr) | 2011-03-28 | 2017-08-30 | ratiopharm GmbH | Procédés pour la préparation de sels de tofacitinib |
| US9050342B2 (en) | 2011-03-29 | 2015-06-09 | Pfizer Inc. | Beneficial effects of combination therapy on cholesterol |
| RU2013144975A (ru) * | 2011-04-08 | 2015-05-20 | Пфайзер Инк. | Кристаллические и некристаллические формы тофацитиниба и фармацевтическая композиция, содержащая тофацитиниб, и усилитель проникновения |
| EP2524688B1 (fr) | 2011-05-11 | 2013-05-01 | ratiopharm GmbH | Composition de libération modifiée comportant de la ranolazine |
| MY165963A (en) | 2011-06-20 | 2018-05-18 | Incyte Holdings Corp | Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors |
| EP2741747A1 (fr) | 2011-08-10 | 2014-06-18 | Novartis Pharma AG | Polythérapie par jak p13k/mtor |
| TW201313721A (zh) | 2011-08-18 | 2013-04-01 | Incyte Corp | 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物 |
| UA111854C2 (uk) | 2011-09-07 | 2016-06-24 | Інсайт Холдінгс Корпорейшн | Способи і проміжні сполуки для отримання інгібіторів jak |
| CA3094793A1 (fr) | 2011-11-23 | 2013-05-30 | Portola Pharmaceuticals, Inc. | Inhibiteurs de de la pyrazine kinase |
| EP4556010A3 (fr) * | 2011-11-30 | 2025-07-23 | Emory University | Inhibiteurs jak destinées à la prévention ou au traitement d'une maladie causé par une coronaviridée |
| US10821111B2 (en) | 2011-11-30 | 2020-11-03 | Emory University | Antiviral JAK inhibitors useful in treating or preventing retroviral and other viral infections |
| WO2013090490A1 (fr) | 2011-12-15 | 2013-06-20 | Ratiopharm Gmbh | Sels de tofacitinib |
| TW201406761A (zh) | 2012-05-18 | 2014-02-16 | Incyte Corp | 做爲ｊａｋ抑制劑之哌啶基環丁基取代之吡咯并吡啶及吡咯并嘧啶衍生物 |
| WO2014016338A1 (fr) | 2012-07-25 | 2014-01-30 | Lek Pharmaceuticals D.D. | Nouvelle voie de synthèse pour la préparation de composés 3-amino-pipéridine |
| US9676756B2 (en) | 2012-10-08 | 2017-06-13 | Portola Pharmaceuticals, Inc. | Substituted pyrimidinyl kinase inhibitors |
| CN113384546A (zh) | 2012-11-15 | 2021-09-14 | 因赛特公司 | 鲁索利替尼的缓释剂型 |
| CN104955803B (zh) * | 2012-11-30 | 2017-11-28 | 斯洛文尼亚莱柯制药股份有限公司 | 通过硝基‑四氢吡啶前体制备3‑氨基‑哌啶化合物 |
| US9481679B2 (en) | 2012-12-17 | 2016-11-01 | Sun Pharmaceutical Industries Limited | Process for the preparation of tofacitinib and intermediates thereof |
| WO2014102826A1 (fr) | 2012-12-28 | 2014-07-03 | Glenmark Pharmaceuticals Limited; | Procédé de préparation de tofacitinib et d'intermédiaires |
| CU24275B1 (es) | 2013-02-22 | 2017-10-05 | Pfizer | Derivados de cicloalquilo pirrolo [2,3-d] pirimidina-4-il amino útiles como inhibidores de quinasas janus relacionadas y composiciones farmacéuticas que contienen tales compuestos |
| WO2014138168A1 (fr) | 2013-03-06 | 2014-09-12 | Incyte Corporation | Procédés et intermédiaires pour la génération d'un inhibiteur de jak |
| JP6041823B2 (ja) | 2013-03-16 | 2016-12-14 | ファイザー・インク | トファシチニブの経口持続放出剤形 |
| US20140343034A1 (en) | 2013-04-25 | 2014-11-20 | Japan Tobacco Inc. | Skin barrier function improving agent |
| WO2014174073A1 (fr) | 2013-04-26 | 2014-10-30 | Sandoz Ag | Formulations de tofacitinib à libération prolongée |
| SG10201801069QA (en) | 2013-08-07 | 2018-03-28 | Incyte Corp | Sustained release dosage forms for a jak1 inhibitor |
| CN104513248B (zh) * | 2013-09-30 | 2019-05-24 | 重庆医药工业研究院有限责任公司 | 一种托法替尼中间体的纯化方法 |
| MX368464B (es) | 2013-12-05 | 2019-10-02 | Pfizer | Acrilamidas de pirrolo[2,3-d]pirimidinilo, pirrolo[2,3-b]pirazinil o y pirrolo[2,3-d]piridinilo. |
| SI3539965T1 (sl) | 2013-12-09 | 2021-07-30 | Unichem Laboratories Limited | Izboljšan postopek za pripravo (3R,4R)-(1-benzil-4-metilpiperidin-3-il)-metilamina |
| US9260438B2 (en) | 2014-02-06 | 2016-02-16 | Apotex Inc. | Solid forms of tofacitinib salts |
| US9498467B2 (en) | 2014-05-30 | 2016-11-22 | Incyte Corporation | Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1 |
| EP3180344B1 (fr) | 2014-08-12 | 2019-09-18 | Pfizer Inc | Dérivés de pyrrolo[2,3-d]pyrimidine utiles pour inhiber la janus kinase |
| EP3248980B1 (fr) * | 2015-01-20 | 2023-09-06 | Wuxi Fortune Pharmaceutical Co., Ltd | Inhibiteur de jak |
| BR112017001516B1 (pt) | 2015-02-17 | 2023-10-31 | Amorepacific Corporation | Método de ressolubilização quiral, estereoisômero, método para preparar um composto, composto, composição, e kit de ressolubilização quiral |
| CN104761556B (zh) * | 2015-03-21 | 2017-06-23 | 河北国龙制药有限公司 | 托法替布中间体杂质、托法替布杂质及其合成方法，以及托法替布的质量监控方法 |
| EP3078665A1 (fr) | 2015-04-10 | 2016-10-12 | OLON S.p.A. | Procédé efficace pour la préparation de tofacitinib citrate |
| ES2734048T3 (es) | 2015-04-29 | 2019-12-04 | Wuxi Fortune Pharmaceutical Co Ltd | Inhibidores de Janus cinasas (JAK) |
| US10703756B2 (en) | 2015-05-01 | 2020-07-07 | Pfizer Inc. | Pyrrolo[2,3-D]pyrimidinyl, pyrrolo[2,3-B]pyrazinyl, pyrrolo[2,3-B]pyridinyl acrylamides and epoxides thereof |
| ES2822748T3 (es) | 2015-05-29 | 2021-05-04 | Wuxi Fortune Pharmaceutical Co Ltd | Inhibidor de cinasa Janus |
| US10034882B2 (en) * | 2015-07-27 | 2018-07-31 | Unichem Laboratories Limited | Tofacitinib orally disintegrating tablets |
| KR101771219B1 (ko) * | 2015-08-21 | 2017-09-05 | 양지화학 주식회사 | 야누스 키나제 1 선택적 억제제 및 그 의약 용도 |
| CN108472298B (zh) | 2015-11-24 | 2021-04-20 | 深圳阿拉丁医疗科技有限公司 | 选择性激酶抑制剂 |
| CN105348287A (zh) * | 2015-11-30 | 2016-02-24 | 宁波立华制药有限公司 | 一种枸橼酸托法替布的新型合成工艺 |
| KR102565407B1 (ko) * | 2016-01-04 | 2023-08-10 | (주)아모레퍼시픽 | 극성 비양자성 용매를 이용한 n-[4-(1-아미노에틸)-페닐]-술폰아미드 유도체의 카이랄 분할 방법 |
| WO2017125417A1 (fr) | 2016-01-18 | 2017-07-27 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Tofacitinib comme immunomodulateur de vaccination |
| RU2714206C1 (ru) | 2016-06-30 | 2020-02-13 | Даевунг Фармасьютикал Ко., Лтд. | Пиразолопиримидиновые производные в качестве ингибитора киназы |
| CN106831538B (zh) * | 2017-01-22 | 2019-06-25 | 苏州楚凯药业有限公司 | 托法替尼中间体的制备方法 |
| KR102398659B1 (ko) | 2017-03-17 | 2022-05-16 | 주식회사 대웅제약 | 카이네이즈 저해제로서의 피롤로트리아진 유도체 |
| CN107602569A (zh) * | 2017-10-23 | 2018-01-19 | 上海博悦生物科技有限公司 | 一种新型吡咯并[2,3‑d]嘧啶化合物及其合成方法和用途 |
| KR102078805B1 (ko) | 2017-11-30 | 2020-02-19 | 보령제약 주식회사 | 토파시티닙을 포함하는 약제학적 조성물 |
| AR113922A1 (es) | 2017-12-08 | 2020-07-01 | Incyte Corp | Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas |
| KR102577241B1 (ko) | 2017-12-28 | 2023-09-11 | 주식회사 대웅제약 | 카이네이즈 저해제로서의 아미노-플루오로피페리딘 유도체 |
| IL275207B (en) | 2017-12-28 | 2022-09-01 | Daewoong Pharmaceutical Co Ltd | An oxy-fluoropiperidine derivative as a kinase inhibitor |
| KR102577242B1 (ko) * | 2017-12-28 | 2023-09-11 | 주식회사 대웅제약 | 카이네이즈 저해제로서의 아미노-메틸피페리딘 유도체 |
| EA202091830A1 (ru) | 2018-01-30 | 2020-12-29 | Инсайт Корпорейшн | Способы и промежуточные соединения для получения ингибитора jak |
| US10960006B2 (en) * | 2018-01-31 | 2021-03-30 | Twi Pharmaceuticals, Inc. | Topical formulations comprising tofacitinib |
| US12161748B2 (en) | 2018-01-31 | 2024-12-10 | Twi Biotechnology, Inc. | Topical formulations comprising tofacitinib |
| MD3773593T2 (ro) | 2018-03-30 | 2024-10-31 | Incyte Corp | Tratament hidradenitei supurative utilizând inhibitori ai JAK |
| KR102131107B1 (ko) * | 2019-01-15 | 2020-07-07 | 주식회사 다산제약 | 3-아미노-피페리딘 화합물의 신규한 제조 방법 |
| NL2022471B1 (en) | 2019-01-29 | 2020-08-18 | Vationpharma B V | Solid state forms of oclacitinib |
| WO2020172714A1 (fr) | 2019-02-27 | 2020-09-03 | Samson Clinical Pty Ltd | Traitement de maladie auto-immune |
| US12269830B2 (en) | 2019-03-13 | 2025-04-08 | Intas Pharmaceuticals Ltd. | Process for preparation of tofacitinib and pharmaceutically acceptable salt thereof |
| WO2020198583A1 (fr) | 2019-03-27 | 2020-10-01 | Insilico Medicine Ip Limited | Inhibiteurs de jak bicycliques et leurs utilisations |
| WO2020204647A1 (fr) * | 2019-04-05 | 2020-10-08 | Yuhan Corporation | Procédés de préparation de (3r,4r)-1-benzyl-n,4-diméthylpipéridin-3-amine ou d'un sel de celui-ci et procédés de préparation de tofacitinib l'utilisant |
| CN115348858A (zh) | 2019-11-08 | 2022-11-15 | 凯奇生物公司 | 使用离子液体的托法替尼表面递送 |
| WO2021094953A1 (fr) | 2019-11-14 | 2021-05-20 | Pfizer Inc. | Combinaisons de 1-(((2s,3s,4s)-3-éthyl-4-fluoro-5-oxopyrrolidin-2-yl)méthoxy)-7-méthoxyisoquinoléine-6-carboxamide et formes pharmaceutiques orales |
| CN114728963B (zh) | 2019-11-25 | 2023-10-31 | 株式会社大熊制药 | 新型三唑吡啶衍生物和包括其的药物组合物 |
| MX2022012135A (es) | 2020-04-04 | 2023-01-18 | Pfizer | Métodos para tratar la enfermedad de coronavirus de 2019. |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| EP4308568A1 (fr) * | 2021-03-15 | 2024-01-24 | Chiesi Farmaceutici S.p.A. | Dérivés hétérocycliques utilisés en tant qu'inhibiteurs de janus kinase |
| CN113549075B (zh) * | 2021-06-23 | 2025-09-23 | 合肥华方医药科技有限公司 | 一种枸橼酸托法替布非对映异构体杂质的合成方法 |
| EP4180042A1 (fr) | 2021-11-15 | 2023-05-17 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Comprimé enrobé d'un film comprenant du tofacitinib micronisé |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8403224A (nl) * | 1984-10-24 | 1986-05-16 | Oce Andeno Bv | Dioxafosforinanen, de bereiding ervan en de toepassing voor het splitsen van optisch actieve verbindingen. |
| US6136595A (en) * | 1993-07-29 | 2000-10-24 | St. Jude Children's Research Hospital | Jak kinases and regulations of cytokine signal transduction |
| US5389509A (en) * | 1993-10-04 | 1995-02-14 | Eastman Kodak Company | Ultrathin high chloride tabular grain emulsions |
| IL112249A (en) | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| EP0682027B1 (fr) | 1994-05-03 | 1997-10-15 | Novartis AG | Dérivés de la pyrrolopyrimidine avec une activité anti-proliférative |
| JPH07330732A (ja) * | 1994-06-10 | 1995-12-19 | Kyorin Pharmaceut Co Ltd | 光学活性な３−アミノ−１−ベンジルピペリジン誘導体 |
| US6136596A (en) * | 1995-05-19 | 2000-10-24 | University Of Massachusetts | Cytokine-, stress-, and oncoprotein-activated human protein kinase kinases |
| ATE247469T1 (de) | 1995-06-07 | 2003-09-15 | Pfizer | Heterocyclische kondensierte pyrimidin-derivate |
| BR9609613A (pt) | 1995-07-05 | 1999-05-25 | Du Pont | Composto composição fungicida e método de controle de doenças de plantas |
| MX9800215A (es) | 1995-07-06 | 1998-03-31 | Novartis Ag | Pirrolopirimidas y procesos para su preparacion. |
| AR004010A1 (es) | 1995-10-11 | 1998-09-30 | Glaxo Group Ltd | Compuestos heterociclicos |
| ATE201873T1 (de) | 1995-11-14 | 2001-06-15 | Pharmacia & Upjohn Spa | Aryl- und heteroaryl- purin- und pyridopyrimidin- derivate |
| ATE217873T1 (de) | 1996-01-23 | 2002-06-15 | Novartis Erfind Verwalt Gmbh | Pyrrolopyrimidinen und verfahren zu deren herstellung |
| CH690773A5 (de) | 1996-02-01 | 2001-01-15 | Novartis Ag | Pyrrolo(2,3-d)pyrimide und ihre Verwendung. |
| GB9604361D0 (en) | 1996-02-29 | 1996-05-01 | Pharmacia Spa | 4-Substituted pyrrolopyrimidine compounds as tyrosine kinase inhibitors |
| AU1794697A (en) | 1996-03-06 | 1997-09-22 | Novartis Ag | 7-alkyl-pyrrolo{2,3-d}pyrimidines |
| AU3176297A (en) | 1996-06-25 | 1998-01-14 | Novartis Ag | Substituted 7-amino-pyrrolo{3,2-d}pyrimidines and the use thereof |
| ES2191187T3 (es) | 1996-07-13 | 2003-09-01 | Glaxo Group Ltd | Compuestos heteroaromaticos biciclicos como inhibidores de la proteina tirosin-quinasa. |
| HRP970371A2 (en) | 1996-07-13 | 1998-08-31 | Kathryn Jane Smith | Heterocyclic compounds |
| WO1998007726A1 (fr) | 1996-08-23 | 1998-02-26 | Novartis Ag | Pyrrolopyrimidines substituees et procede pour leur preparation |
| US6413971B1 (en) | 1996-11-27 | 2002-07-02 | Pfizer Inc | Fused bicyclic pyrimidine derivatives |
| ES2301194T3 (es) | 1997-02-05 | 2008-06-16 | Warner-Lambert Company Llc | Pirido 2,3-d pirimidinas y 4-aminopirimidinas como inhibidores de la proliferacion celular. |
| WO1998043087A1 (fr) * | 1997-03-24 | 1998-10-01 | Pharmacia & Upjohn Company | Procede d'identification d'inhibiteurs de la liaison proteine jak2/recepteur de cytokine |
| JP2002510687A (ja) | 1998-04-02 | 2002-04-09 | ニューロゲン コーポレイション | アミノアルキル置換ピロロ［２，３−ｂ］ピリジンおよびピロロ［２，３−ｄ］ピリミジン誘導体：ｃｒｆ１レセプタのモジュレータ |
| WO1999061428A1 (fr) | 1998-05-28 | 1999-12-02 | Parker Hughes Institute | Utilisation des quinazolines pour le traitement de tumeurs cerebrales |
| BR9911365A (pt) | 1998-06-19 | 2001-03-13 | Pfizer Prod Inc | Compostos pirrolo[2,3-d]pirimidina |
| PA8474101A1 (es) | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
| WO2000000202A1 (fr) | 1998-06-30 | 2000-01-06 | Parker Hughes Institute | Procede pour inhiber l'expression de c-jun en utilisant les inhibiteurs de jak-3 |
| US6313129B1 (en) | 1998-08-21 | 2001-11-06 | Hughes Institute | Therapeutic compounds |
| US6080747A (en) * | 1999-03-05 | 2000-06-27 | Hughes Institute | JAK-3 inhibitors for treating allergic disorders |
| EP1382339B1 (fr) * | 1999-12-10 | 2007-12-05 | Pfizer Products Inc. | Compositions contenant des dérivés de pyrrolo¬2,3-d pyrimidine |
| IL152771A0 (en) * | 2000-06-26 | 2003-06-24 | Pfizer Prod Inc | PYRROLO(2,3-d) PYRIMIDINE COMPOUNDS AS IMMUNOSUPPRESSIVE AGENTS |
| PY0228255A (es) * | 2001-12-06 | 2004-06-01 | Pfizer Prod Inc | Compuestos cristalinos novedosos |
| EP1768982A2 (fr) * | 2004-06-29 | 2007-04-04 | Amgen Inc. | Pyrrolo[2, 3-d] pyrimidines qui modulent l'activite ack1 et lck |
-
2002
- 2002-05-23 US US10/154,699 patent/US7301023B2/en not_active Expired - Lifetime
- 2002-05-29 PL PL02367945A patent/PL367945A1/xx unknown
- 2002-05-29 CZ CZ2003-3260A patent/CZ304366B6/cs not_active IP Right Cessation
- 2002-05-29 SK SK50033-2011A patent/SK288192B6/sk active Protection Beyond IP Right Term
- 2002-05-29 EA EA200600575A patent/EA012666B1/ru active Protection Beyond IP Right Term
- 2002-05-29 ES ES05015454T patent/ES2393385T3/es not_active Expired - Lifetime
- 2002-05-29 SI SI200231004T patent/SI1666481T1/sl unknown
- 2002-05-29 WO PCT/IB2002/001905 patent/WO2002096909A1/fr not_active Ceased
- 2002-05-29 GE GE5361A patent/GEP20063784B/en unknown
- 2002-05-29 NZ NZ530380A patent/NZ530380A/en not_active IP Right Cessation
- 2002-05-29 RS YU92303A patent/RS52144B/sr unknown
- 2002-05-29 ES ES05015461T patent/ES2369226T3/es not_active Expired - Lifetime
- 2002-05-29 EP EP05015454.1A patent/EP1666481B9/fr not_active Expired - Lifetime
- 2002-05-29 BR BR0209246-8A patent/BR0209246A/pt not_active Application Discontinuation
- 2002-05-29 TN TNPCT/IB2002/001905A patent/TNSN03128A1/fr unknown
- 2002-05-29 HR HR20030943A patent/HRP20030943B1/xx not_active IP Right Cessation
- 2002-05-29 JP JP2003500088A patent/JP4381137B2/ja not_active Expired - Lifetime
- 2002-05-29 PE PE2002000452A patent/PE20030561A1/es not_active Application Discontinuation
- 2002-05-29 EP EP02733058A patent/EP1392694A1/fr not_active Withdrawn
- 2002-05-29 UA UA20031110841A patent/UA80093C2/uk unknown
- 2002-05-29 EE EEP200300594A patent/EE05332B1/xx active Protection Beyond IP Right Term
- 2002-05-29 TW TW091111480A patent/TWI310384B/zh active
- 2002-05-29 AU AU2002304401A patent/AU2002304401C1/en not_active Expired
- 2002-05-29 CN CNA028108175A patent/CN1729192A/zh active Pending
- 2002-05-29 TW TW092133699A patent/TWI316061B/zh not_active IP Right Cessation
- 2002-05-29 IL IL15858802A patent/IL158588A0/xx active IP Right Grant
- 2002-05-29 HU HUP0400152A patent/HU230876B1/hu active Protection Beyond IP Right Term
- 2002-05-29 MX MXPA03011062A patent/MXPA03011062A/es active IP Right Grant
- 2002-05-29 KR KR1020087018519A patent/KR100926875B1/ko not_active Expired - Lifetime
- 2002-05-29 NZ NZ540332A patent/NZ540332A/en not_active IP Right Cessation
- 2002-05-29 PT PT50154541T patent/PT1666481E/pt unknown
- 2002-05-29 PL PL409305A patent/PL228155B1/pl unknown
- 2002-05-29 KR KR1020067025590A patent/KR20060133117A/ko not_active Ceased
- 2002-05-29 EA EA200301193A patent/EA007251B1/ru active Protection Beyond IP Right Term
- 2002-05-29 OA OA1200300308A patent/OA12612A/en unknown
- 2002-05-29 EP EP05015461A patent/EP1609781B1/fr not_active Expired - Lifetime
- 2002-05-29 CA CA002448281A patent/CA2448281C/fr not_active Expired - Lifetime
- 2002-05-29 DK DK05015454.1T patent/DK1666481T3/da active
- 2002-05-29 KR KR1020067001821A patent/KR100869409B1/ko not_active Expired - Lifetime
- 2002-05-29 KR KR10-2003-7015681A patent/KR20040003037A/ko not_active Ceased
- 2002-05-29 AT AT05015461T patent/ATE519741T1/de not_active IP Right Cessation
- 2002-05-29 SK SK1465-2003A patent/SK288199B6/sk unknown
- 2002-05-29 KR KR1020077025832A patent/KR100868814B1/ko not_active Expired - Lifetime
- 2002-05-30 GT GT200200100A patent/GT200200100A/es unknown
- 2002-05-30 UY UY27317A patent/UY27317A1/es not_active Application Discontinuation
- 2002-05-30 AR ARP020102017A patent/AR037321A1/es not_active Application Discontinuation
- 2002-05-30 MY MYPI20021988A patent/MY129649A/en unknown
- 2002-05-30 GT GT200200100AK patent/GT200200100AA/es unknown
- 2002-05-30 PA PA20028546301A patent/PA8546301A1/es unknown
- 2002-05-31 AP APAP/P/2002/002550A patent/AP1859A/en active
-
2003
- 2003-10-13 IS IS6993A patent/IS3023B/is unknown
- 2003-10-13 CU CU20030229A patent/CU23337B7/es not_active IP Right Cessation
- 2003-10-14 ZA ZA200307982A patent/ZA200307982B/en unknown
- 2003-11-21 MA MA27410A patent/MA27029A1/fr unknown
- 2003-11-24 NO NO20035201A patent/NO328578B1/no not_active IP Right Cessation
- 2003-11-26 EC EC2003004865A patent/ECSP034865A/es unknown
- 2003-11-27 BG BG108389A patent/BG66489B1/bg unknown
-
2004
- 2004-05-07 AR ARP040101561A patent/AR045680A2/es unknown
- 2004-06-16 US US10/869,101 patent/US7432370B2/en not_active Expired - Lifetime
-
2008
- 2008-03-14 CL CL200800762A patent/CL2008000762A1/es unknown
- 2008-07-16 AU AU2008203170A patent/AU2008203170B2/en active Active
- 2008-07-24 CR CR10177A patent/CR10177A/es unknown
-
2009
- 2009-10-13 NO NO20093135A patent/NO20093135L/no not_active Application Discontinuation
-
2012
- 2012-11-09 CY CY20121101069T patent/CY1113322T1/el unknown
-
2017
- 2017-08-02 NL NL300887C patent/NL300887I2/nl unknown
- 2017-08-08 LT LTPA2017025C patent/LTC1666481I2/lt unknown
- 2017-08-09 LU LU00031C patent/LUC00031I2/fr unknown
- 2017-08-17 BE BE2017C032C patent/BE2017C032I2/fr unknown
- 2017-09-01 CY CY2017028C patent/CY2017028I1/el unknown
- 2017-09-04 FR FR17C1031C patent/FR17C1031I2/fr active Active
- 2017-09-08 NO NO2017047C patent/NO2017047I1/no unknown
-
2019
- 2019-02-19 HU HUS1900008C patent/HUS1900008I1/hu unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| UA80093C2 (uk) | Спосіб оптичного розділення (1-бензил-4-метилпіперидин-3-іл)метиламіну і його використання для одержання похідних піроло[2,3-d]піримідину як інгібіторів протеїнкінази | |
| AU2002304401A1 (en) | Optical resolution of (1-benzyl-4-methylpiperidin-3-yl) -methylamine and the use thereof for the preparation of pyrrolo 2,3-pyrimidine derivatives as protein kinases inhibitors | |
| UA72290C2 (uk) | СПОЛУКИ ПІРОЛО[2.3-d]ПІРИМІДИНУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ (ВАРІАНТИ), СПОСІБ ІНГІБУВАННЯ ПРОТЕЇНКІНАЗ АБО JANUS КІНАЗИ 3 (ВАРІАНТИ) | |
| AU2003276591A1 (en) | Method of treatment of transplant rejection |