ES2393385T3 - 3-((3R,4R)-4-Metil-3-[metil-(7H-pirrolo[2,3-d]pirimidin-4-il)-amino]-piperidinil)-3-oxo-propionitrilo como inhibidor de proteína cinasa - Google Patents
3-((3R,4R)-4-Metil-3-[metil-(7H-pirrolo[2,3-d]pirimidin-4-il)-amino]-piperidinil)-3-oxo-propionitrilo como inhibidor de proteína cinasa Download PDFInfo
- Publication number
- ES2393385T3 ES2393385T3 ES05015454T ES05015454T ES2393385T3 ES 2393385 T3 ES2393385 T3 ES 2393385T3 ES 05015454 T ES05015454 T ES 05015454T ES 05015454 T ES05015454 T ES 05015454T ES 2393385 T3 ES2393385 T3 ES 2393385T3
- Authority
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- Prior art keywords
- alkyl
- amino
- compound
- alkoxy
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- 102000001253 Protein Kinase Human genes 0.000 title claims description 6
- 108060006633 protein kinase Proteins 0.000 title claims description 6
- 239000003112 inhibitor Substances 0.000 title description 3
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 229940126214 compound 3 Drugs 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 88
- 108010019421 Janus Kinase 3 Proteins 0.000 claims description 13
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- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 5
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- 230000001363 autoimmune Effects 0.000 claims description 5
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- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 72
- 125000000217 alkyl group Chemical group 0.000 description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 61
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 54
- -1 cyano, amino Chemical group 0.000 description 46
- 125000003118 aryl group Chemical group 0.000 description 45
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- 125000003545 alkoxy group Chemical group 0.000 description 25
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- 125000000753 cycloalkyl group Chemical group 0.000 description 24
- 235000019441 ethanol Nutrition 0.000 description 24
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 125000001072 heteroaryl group Chemical group 0.000 description 19
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 18
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- 238000002360 preparation method Methods 0.000 description 17
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 15
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
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- 229910052805 deuterium Inorganic materials 0.000 description 14
- 125000005843 halogen group Chemical group 0.000 description 14
- 239000002253 acid Substances 0.000 description 13
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
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- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 125000006239 protecting group Chemical group 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 9
- 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 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 125000000304 alkynyl group Chemical group 0.000 description 8
- 125000000266 alpha-aminoacyl group Chemical group 0.000 description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- 125000004093 cyano group Chemical group *C#N 0.000 description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 description 8
- 125000004971 nitroalkyl group Chemical group 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
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- 102200031660 rs730880032 Human genes 0.000 description 8
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 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 description 7
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- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- 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 4
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- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
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- 0 *[n]1c2ncnc(O)c2cc1 Chemical compound *[n]1c2ncnc(O)c2cc1 0.000 description 3
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- 125000005102 carbonylalkoxy group Chemical group 0.000 description 3
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- 125000000000 cycloalkoxy group Chemical group 0.000 description 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 3
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- 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 description 2
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- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- 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
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- 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
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- 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
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- 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
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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| ES05015454T Expired - Lifetime ES2393385T3 (es) | 2001-05-31 | 2002-05-29 | 3-((3R,4R)-4-Metil-3-[metil-(7H-pirrolo[2,3-d]pirimidin-4-il)-amino]-piperidinil)-3-oxo-propionitrilo como inhibidor de proteína cinasa |
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