CA2335186C - Pyrrolo[2,3-d]pyrimidine compounds - Google Patents
Pyrrolo[2,3-d]pyrimidine compounds Download PDFInfo
- Publication number
- CA2335186C CA2335186C CA002335186A CA2335186A CA2335186C CA 2335186 C CA2335186 C CA 2335186C CA 002335186 A CA002335186 A CA 002335186A CA 2335186 A CA2335186 A CA 2335186A CA 2335186 C CA2335186 C CA 2335186C
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- CA
- Canada
- Prior art keywords
- alkyl
- pharmaceutically acceptable
- compound
- aryl
- acceptable salt
- 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 - Fee Related
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- 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 125
- 108010019421 Janus Kinase 3 Proteins 0.000 claims abstract description 40
- 102000006500 Janus Kinase 3 Human genes 0.000 claims abstract description 40
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 21
- 208000006673 asthma Diseases 0.000 claims abstract description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 14
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 13
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 13
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 13
- 208000011231 Crohn disease Diseases 0.000 claims abstract description 13
- 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 13
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 13
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 13
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 13
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 13
- 208000024799 Thyroid disease Diseases 0.000 claims abstract description 13
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 13
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 13
- 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 13
- 230000001363 autoimmune Effects 0.000 claims abstract description 13
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 208000032839 leukemia Diseases 0.000 claims abstract description 13
- 206010025135 lupus erythematosus Diseases 0.000 claims abstract description 13
- 210000000056 organ Anatomy 0.000 claims abstract description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 111
- 150000003839 salts Chemical class 0.000 claims description 67
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 65
- -1 amino, hydroxy Chemical group 0.000 claims description 55
- 125000003118 aryl group Chemical group 0.000 claims description 55
- 125000001072 heteroaryl group Chemical group 0.000 claims description 45
- 241000124008 Mammalia Species 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 239000001257 hydrogen Substances 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 22
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 18
- 239000002552 dosage form Substances 0.000 claims description 18
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 17
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 17
- 239000003937 drug carrier Substances 0.000 claims description 16
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 16
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 150000002431 hydrogen Chemical group 0.000 claims description 14
- 210000000987 immune system Anatomy 0.000 claims description 14
- 206010052779 Transplant rejections Diseases 0.000 claims description 12
- 201000006417 multiple sclerosis Diseases 0.000 claims description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000005936 piperidyl group Chemical group 0.000 claims description 10
- 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 claims description 9
- 125000004442 acylamino group Chemical group 0.000 claims description 8
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 8
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 8
- 125000005110 aryl thio group Chemical group 0.000 claims description 8
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 8
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 229910052805 deuterium Inorganic materials 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 5
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 5
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 4
- 125000005256 alkoxyacyl group Chemical group 0.000 claims description 4
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 3
- 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 3
- ZYUZIQCTDGCTPB-UHFFFAOYSA-N 5-chloro-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=12C(Cl)=CNC2=NC=NC=1N1CCCCC1 ZYUZIQCTDGCTPB-UHFFFAOYSA-N 0.000 claims description 3
- 101100244083 Arabidopsis thaliana PKL gene Proteins 0.000 claims description 3
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 3
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000001769 aryl amino group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- LERUYXUJSAVVIZ-UHFFFAOYSA-N 2-[1-[5-(3-methylphenyl)-7h-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl]ethanol Chemical compound CC1=CC=CC(C=2C3=C(N4CCC(CCO)CC4)N=CN=C3NC=2)=C1 LERUYXUJSAVVIZ-UHFFFAOYSA-N 0.000 claims description 2
- BHEXESBBAOCUEW-UHFFFAOYSA-N 4-(3,3-dimethylpiperidin-1-yl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1C(C)(C)CCCN1C1=NC=NC2=C1C=CN2 BHEXESBBAOCUEW-UHFFFAOYSA-N 0.000 claims description 2
- WOJIDULOACFYJL-UHFFFAOYSA-N 4-piperidin-1-yl-5-(3-propan-2-ylphenyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CC(C)C1=CC=CC(C=2C3=C(N4CCCCC4)N=CN=C3NC=2)=C1 WOJIDULOACFYJL-UHFFFAOYSA-N 0.000 claims description 2
- GUWZKQIDHRZALH-UHFFFAOYSA-N 5-(1-methylimidazol-4-yl)-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CN1C=NC(C=2C3=C(N4CCCCC4)N=CN=C3NC=2)=C1 GUWZKQIDHRZALH-UHFFFAOYSA-N 0.000 claims description 2
- XMDULOSPOORHTJ-UHFFFAOYSA-N 5-(2-methylpyridin-4-yl)-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1=NC(C)=CC(C=2C3=C(N4CCCCC4)N=CN=C3NC=2)=C1 XMDULOSPOORHTJ-UHFFFAOYSA-N 0.000 claims description 2
- LWQNDUSDVLVELT-UHFFFAOYSA-N 5-(3-methylimidazol-4-yl)-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CN1C=NC=C1C1=CNC2=NC=NC(N3CCCCC3)=C12 LWQNDUSDVLVELT-UHFFFAOYSA-N 0.000 claims description 2
- CIPYWMYUPREAMJ-UHFFFAOYSA-N 5-ethynyl-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=12C(C#C)=CNC2=NC=NC=1N1CCCCC1 CIPYWMYUPREAMJ-UHFFFAOYSA-N 0.000 claims description 2
- LCTMPEQAHUTSGO-UHFFFAOYSA-N 5-fluoro-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=12C(F)=CNC2=NC=NC=1N1CCCCC1 LCTMPEQAHUTSGO-UHFFFAOYSA-N 0.000 claims description 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 2
- SDCGYRLQORKUBU-UHFFFAOYSA-N n',n'-dimethyl-n-[[3-(4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidin-5-yl)phenyl]methyl]ethane-1,2-diamine Chemical compound CN(C)CCNCC1=CC=CC(C=2C3=C(N4CCCCC4)N=CN=C3NC=2)=C1 SDCGYRLQORKUBU-UHFFFAOYSA-N 0.000 claims description 2
- 230000000069 prophylactic effect Effects 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 claims description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims 12
- 239000003814 drug Substances 0.000 claims 6
- 238000004519 manufacturing process Methods 0.000 claims 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 4
- 125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims 3
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- YAJAWZHVCVQZIW-UHFFFAOYSA-N 4-piperidin-1-yl-5-(trifluoromethyl)-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C=12C(C(F)(F)F)=CNC2=NC=NC=1N1CCCCC1 YAJAWZHVCVQZIW-UHFFFAOYSA-N 0.000 claims 1
- 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 claims 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 1
- 230000001506 immunosuppresive effect Effects 0.000 abstract description 4
- 239000003112 inhibitor Substances 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 238000000034 method Methods 0.000 description 60
- 238000002844 melting Methods 0.000 description 46
- 230000008018 melting Effects 0.000 description 46
- 239000000203 mixture Substances 0.000 description 38
- 229910052792 caesium Inorganic materials 0.000 description 35
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 32
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 238000006243 chemical reaction Methods 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 23
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
- 125000003282 alkyl amino group Chemical group 0.000 description 10
- 229940093499 ethyl acetate Drugs 0.000 description 10
- 235000019439 ethyl acetate Nutrition 0.000 description 10
- 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 9
- 108010036949 Cyclosporine Proteins 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 210000001744 T-lymphocyte Anatomy 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 230000003197 catalytic effect Effects 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 6
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 102000004388 Interleukin-4 Human genes 0.000 description 5
- 108090000978 Interleukin-4 Proteins 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 239000012267 brine Substances 0.000 description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 239000001301 oxygen Substances 0.000 description 5
- 229910052760 oxygen Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 229930105110 Cyclosporin A Natural products 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
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 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 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 4
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 4
- 229940077388 benzenesulfonate Drugs 0.000 description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 229960001265 ciclosporin Drugs 0.000 description 4
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 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 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 125000004193 piperazinyl group Chemical group 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 125000003342 alkenyl group Chemical group 0.000 description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 239000011777 magnesium Substances 0.000 description 3
- 229910052749 magnesium Inorganic materials 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 229940063121 neoral Drugs 0.000 description 3
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Classifications
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- 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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- 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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- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P37/02—Immunomodulators
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- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Endocrinology (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Psychiatry (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Transplantation (AREA)
- Pain & Pain Management (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Dermatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US8988698P | 1998-06-19 | 1998-06-19 | |
| US60/089,886 | 1998-06-19 | ||
| PCT/IB1999/001110 WO1999065909A1 (en) | 1998-06-19 | 1999-06-14 | PYRROLO[2,3-d]PYRIMIDINE COMPOUNDS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2335186A1 CA2335186A1 (en) | 1999-12-23 |
| CA2335186C true CA2335186C (en) | 2005-03-29 |
Family
ID=22220084
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002335186A Expired - Fee Related CA2335186C (en) | 1998-06-19 | 1999-06-14 | Pyrrolo[2,3-d]pyrimidine compounds |
Country Status (46)
Families Citing this family (168)
| 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 |
| EP1065207A1 (en) * | 1999-07-02 | 2001-01-03 | Aventis Pharma Deutschland GmbH | Naphthyridine derivatives, processes for their preparation, their use, and pharmaceutical compositions comprising them |
| ATE396978T1 (de) * | 1999-10-07 | 2008-06-15 | Amgen Inc | Triazin-kinase-hemmer |
| DE19948417A1 (de) * | 1999-10-07 | 2001-04-19 | Morphochem Ag | Imidazol-Derivate und ihre Verwendung als Arzneimittel |
| SK287188B6 (sk) | 1999-12-10 | 2010-02-08 | Pfizer Products Inc. | Pyrolo [2,3-d]pyrimidínová zlúčenina, jej použitie a farmaceutická kompozícia alebo kombinácia s jej obsahom |
| EP1875900A3 (en) * | 2000-01-24 | 2010-07-21 | Genzyme Corporation | JAK/STAT pathway inhibitors and the use thereof for the treatment of osteoarthritis |
| JP5512909B2 (ja) * | 2000-01-24 | 2014-06-04 | ジェンザイム・コーポレーション | Ｊａｋ／ｓｔａｔ経路阻害剤およびその使用 |
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