CZ20004726A3 - Deriváty pyrrolo[2,3-d]pyrimidinu - Google Patents

Info

Publication number

CZ20004726A3

CZ20004726A3 CZ20004726A CZ20004726A CZ20004726A3 CZ 20004726 A3 CZ20004726 A3 CZ 20004726A3 CZ 20004726 A CZ20004726 A CZ 20004726A CZ 20004726 A CZ20004726 A CZ 20004726A CZ 20004726 A3 CZ20004726 A3 CZ 20004726A3

Authority

CZ

Czechia

Prior art keywords

carbon atoms

radical

groups

alkyl

alkyl radical

Prior art date

1998-06-19

Links

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• 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 103
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 14
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims abstract description 11
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims abstract description 11
• 208000006673 asthma Diseases 0.000 claims abstract description 11
• 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 10
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 10
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 10
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims abstract description 10
• 201000011510 cancer Diseases 0.000 claims abstract description 10
• 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 10
• 208000032839 leukemia Diseases 0.000 claims abstract description 10
• 210000000056 organ Anatomy 0.000 claims abstract description 10
• 208000011231 Crohn disease Diseases 0.000 claims abstract description 9
• 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
• 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 8
• 206010012438 Dermatitis atopic Diseases 0.000 claims abstract description 8
• 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 8
• 201000008937 atopic dermatitis Diseases 0.000 claims abstract description 8
• 208000024799 Thyroid disease Diseases 0.000 claims abstract description 6
• 230000001363 autoimmune Effects 0.000 claims abstract description 6
• -1 alkyl radical Chemical class 0.000 claims description 322
• 125000004432 carbon atom Chemical group C* 0.000 claims description 302
• 150000005840 aryl radicals Chemical class 0.000 claims description 62
• 238000000034 method Methods 0.000 claims description 56
• 125000000217 alkyl group Chemical group 0.000 claims description 39
• 150000003839 salts Chemical class 0.000 claims description 35
• 101000934996 Homo sapiens Tyrosine-protein kinase JAK3 Proteins 0.000 claims description 23
• 102100025387 Tyrosine-protein kinase JAK3 Human genes 0.000 claims description 23
• 241000124008 Mammalia Species 0.000 claims description 21
• 229910052739 hydrogen Inorganic materials 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 18
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 16
• 125000003118 aryl group Chemical group 0.000 claims description 16
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
• 125000001072 heteroaryl group Chemical group 0.000 claims description 15
• 125000003545 alkoxy group Chemical group 0.000 claims description 14
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000004429 atom Chemical group 0.000 claims description 12
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
• 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 11
• 208000025865 Ulcer Diseases 0.000 claims description 11
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 10
• 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 10
• 208000035475 disorder Diseases 0.000 claims description 10
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 10
• 125000005936 piperidyl group Chemical group 0.000 claims description 10
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 9
• 108010024121 Janus Kinases Proteins 0.000 claims description 9
• 102000015617 Janus Kinases Human genes 0.000 claims description 9
• 239000003518 caustics Substances 0.000 claims description 9
• 229910052717 sulfur Inorganic materials 0.000 claims description 9
• 231100000397 ulcer Toxicity 0.000 claims description 9
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
• 230000002401 inhibitory effect Effects 0.000 claims description 8
• 201000006417 multiple sclerosis Diseases 0.000 claims description 8
• 229910052760 oxygen Inorganic materials 0.000 claims description 8
• 229940121363 anti-inflammatory agent Drugs 0.000 claims description 7
• 239000002260 anti-inflammatory agent Substances 0.000 claims description 7
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 6
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 6
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 201000010099 disease Diseases 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• 229910052736 halogen Inorganic materials 0.000 claims description 5
• 125000005843 halogen group Chemical group 0.000 claims description 5
• 150000002367 halogens Chemical class 0.000 claims description 5
• 150000002431 hydrogen Chemical class 0.000 claims description 5
• 125000004845 (C1-C6) alkylsulfonylamino group Chemical group 0.000 claims description 4
• 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 4
• 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 4
• 206010052779 Transplant rejections Diseases 0.000 claims description 4
• 125000004442 acylamino group Chemical group 0.000 claims description 4
• 125000004945 acylaminoalkyl group Chemical group 0.000 claims description 4
• 125000005041 acyloxyalkyl group Chemical group 0.000 claims description 4
• 125000004687 alkyl sulfinyl alkyl group Chemical group 0.000 claims description 4
• 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims description 4
• 125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 4
• 125000006350 alkyl thio alkyl group Chemical group 0.000 claims description 4
• 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims description 4
• 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 4
• 125000005110 aryl thio group Chemical group 0.000 claims description 4
• 125000005164 aryl thioalkyl group Chemical group 0.000 claims description 4
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 4
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 4
• 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 claims description 4
• 150000003254 radicals Chemical class 0.000 claims description 4
• 125000005505 thiomorpholino group Chemical group 0.000 claims description 4
• 210000001685 thyroid gland Anatomy 0.000 claims description 4
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
• 229910052721 tungsten Inorganic materials 0.000 claims description 4
• 229910052727 yttrium Inorganic materials 0.000 claims description 4
• 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
• SASXLRNIYRKHAE-UHFFFAOYSA-N 4-(2,3,3a,4,5,6,7,7a-octahydroindol-1-yl)-5-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound C1CC2CCCCC2N1C1=C2C(Cl)=CNC2=NC=N1 SASXLRNIYRKHAE-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 3
• 125000005256 alkoxyacyl group Chemical group 0.000 claims description 3
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 229910052805 deuterium Inorganic materials 0.000 claims description 3
• 210000000987 immune system Anatomy 0.000 claims description 3
• 125000002757 morpholinyl group Chemical group 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• 125000004193 piperazinyl group Chemical group 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
• 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 2
• 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 2
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
• 125000006763 (C3-C9) cycloalkyl group Chemical group 0.000 claims description 2
• KPPVNWGJXFMGAM-UUILKARUSA-N (e)-2-methyl-1-(6-methyl-3,4-dihydro-2h-quinolin-1-yl)but-2-en-1-one Chemical compound CC1=CC=C2N(C(=O)C(/C)=C/C)CCCC2=C1 KPPVNWGJXFMGAM-UUILKARUSA-N 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
• VIXNVCQFOFBIJM-UHFFFAOYSA-N 2-[3-ethyl-4-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclopentyl]propan-2-ol Chemical compound CCC1CC(C(C)(C)O)CC1N(C)C1=NC=NC2=C1C=CN2 VIXNVCQFOFBIJM-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
• 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 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
• WZFLNSVJMWZIGG-UHFFFAOYSA-N 5-(3-methylphenyl)-4-piperidin-1-yl-7h-pyrrolo[2,3-d]pyrimidine Chemical compound CC1=CC=CC(C=2C3=C(N4CCCCC4)N=CN=C3NC=2)=C1 WZFLNSVJMWZIGG-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
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
• 125000004423 acyloxy group Chemical group 0.000 claims description 2
• 125000005085 alkoxycarbonylalkoxy group Chemical group 0.000 claims description 2
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 2
• 125000003277 amino group Chemical group 0.000 claims description 2
• 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 2
• 125000005111 carboxyalkoxy group Chemical group 0.000 claims description 2
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
• LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 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
• 125000004434 sulfur atom Chemical group 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• YWTBBNIUCJYYNU-UHFFFAOYSA-N 2-[3-ethyl-4-[2-hydroxyethyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclopentyl]propan-2-ol Chemical compound CCC1CC(C(C)(C)O)CC1N(CCO)C1=NC=NC2=C1C=CN2 YWTBBNIUCJYYNU-UHFFFAOYSA-N 0.000 claims 1
• 230000001506 immunosuppresive effect Effects 0.000 abstract description 4
• 108010019421 Janus Kinase 3 Proteins 0.000 abstract description 2
• 239000003112 inhibitor Substances 0.000 abstract description 2
• 102000006500 Janus Kinase 3 Human genes 0.000 abstract 1
• 206010025135 lupus erythematosus Diseases 0.000 abstract 1
• 206010039073 rheumatoid arthritis Diseases 0.000 abstract 1
• 238000002560 therapeutic procedure Methods 0.000 abstract 1
• 238000006243 chemical reaction Methods 0.000 description 48
• 238000002844 melting Methods 0.000 description 46
• 230000008018 melting Effects 0.000 description 46
• 239000000203 mixture Substances 0.000 description 40
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 38
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
• 239000000243 solution Substances 0.000 description 35
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 25
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
• 239000011541 reaction mixture Substances 0.000 description 17
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 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
• 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 10
• 108010036949 Cyclosporine Proteins 0.000 description 10
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 239000002253 acid Substances 0.000 description 9
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
• 235000019441 ethanol Nutrition 0.000 description 8
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• 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 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
• 229910052763 palladium Inorganic materials 0.000 description 6
• 239000002244 precipitate Substances 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
• BPTCCCTWWAUJRK-UHFFFAOYSA-N 4-chloro-7h-pyrrolo[2,3-d]pyrimidine Chemical compound ClC1=NC=NC2=C1C=CN2 BPTCCCTWWAUJRK-UHFFFAOYSA-N 0.000 description 5
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
• 102000004388 Interleukin-4 Human genes 0.000 description 5
• 108090000978 Interleukin-4 Proteins 0.000 description 5
• 210000001744 T-lymphocyte Anatomy 0.000 description 5
• 229910052794 bromium Inorganic materials 0.000 description 5
• 238000001816 cooling Methods 0.000 description 5
• 239000012043 crude product Substances 0.000 description 5
• 239000002552 dosage form Substances 0.000 description 5
• 229910052740 iodine Inorganic materials 0.000 description 5
• 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 5
• 238000002360 preparation method Methods 0.000 description 5
• 229910052708 sodium Inorganic materials 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
• 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
• XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-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
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