MXPA04007637A

MXPA04007637A - Compuestos de pirimidina.

Compuestos de pirimidina.

Info

Publication number: MXPA04007637A
Authority: MX; Mexico
Prior art keywords: amino; phenyl; methyl; alkyl; hydrogen
Prior art date: 2002-02-08

Application number

MXPA04007637A

Other languages

English (en)

Spanish (es)

Inventor

Marvin Veal James

Original Assignee

Smithkline Beecham Corp

Priority date

2002-02-08

Filing date

2003-02-07

Publication date

2004-11-10

2003-02-07 Application filed by Smithkline Beecham Corp filed Critical Smithkline Beecham Corp

2004-11-10 Publication of MXPA04007637A publication Critical patent/MXPA04007637A/es

Links

150000003230 pyrimidines Chemical class 0.000 title abstract description 7
238000000034 method Methods 0.000 claims abstract description 55
101000753291 Homo sapiens Angiopoietin-1 receptor Proteins 0.000 claims abstract description 36
102100022014 Angiopoietin-1 receptor Human genes 0.000 claims abstract description 35
238000011282 treatment Methods 0.000 claims abstract description 29
229940091171 VEGFR-2 tyrosine kinase inhibitor Drugs 0.000 claims abstract description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 257
-1 C 1 -C 4 alkyl Chemical group 0.000 claims description 207
150000001875 compounds Chemical class 0.000 claims description 152
229910052739 hydrogen Inorganic materials 0.000 claims description 122
239000001257 hydrogen Substances 0.000 claims description 121
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 118
125000000217 alkyl group Chemical group 0.000 claims description 114
150000002431 hydrogen Chemical group 0.000 claims description 114
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 99
125000000753 cycloalkyl group Chemical group 0.000 claims description 88
125000000623 heterocyclic group Chemical group 0.000 claims description 80
125000003545 alkoxy group Chemical group 0.000 claims description 77
125000003118 aryl group Chemical group 0.000 claims description 74
150000003839 salts Chemical class 0.000 claims description 72
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 66
125000001072 heteroaryl group Chemical group 0.000 claims description 61
239000012453 solvate Substances 0.000 claims description 57
125000004104 aryloxy group Chemical group 0.000 claims description 49
125000001188 haloalkyl group Chemical group 0.000 claims description 49
239000004202 carbamide Substances 0.000 claims description 41
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 39
230000000694 effects Effects 0.000 claims description 38
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 37
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 claims description 36
229910052736 halogen Inorganic materials 0.000 claims description 36
150000002367 halogens Chemical group 0.000 claims description 35
206010028980 Neoplasm Diseases 0.000 claims description 33
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 32
125000004438 haloalkoxy group Chemical group 0.000 claims description 32
125000003710 aryl alkyl group Chemical group 0.000 claims description 30
201000011510 cancer Diseases 0.000 claims description 30
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 29
230000033115 angiogenesis Effects 0.000 claims description 28
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 28
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 27
239000008194 pharmaceutical composition Substances 0.000 claims description 27
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 26
241000124008 Mammalia Species 0.000 claims description 25
125000003282 alkyl amino group Chemical group 0.000 claims description 25
125000001769 aryl amino group Chemical group 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 23
239000003795 chemical substances by application Substances 0.000 claims description 21
239000003814 drug Substances 0.000 claims description 17
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 17
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
102000009465 Growth Factor Receptors Human genes 0.000 claims description 16
108010009202 Growth Factor Receptors Proteins 0.000 claims description 16
125000004093 cyano group Chemical group *C#N 0.000 claims description 16
125000001691 aryl alkyl amino group Chemical group 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 13
150000001412 amines Chemical class 0.000 claims description 10
239000000460 chlorine Substances 0.000 claims description 10
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims description 9
125000004966 cyanoalkyl group Chemical group 0.000 claims description 9
230000002401 inhibitory effect Effects 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
239000002246 antineoplastic agent Substances 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 7
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
239000000546 pharmaceutical excipient Substances 0.000 claims description 7
238000002560 therapeutic procedure Methods 0.000 claims description 7
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 6
102000001301 EGF receptor Human genes 0.000 claims description 6
108060006698 EGF receptor Proteins 0.000 claims description 6
101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 claims description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
229940034982 antineoplastic agent Drugs 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
239000003085 diluting agent Substances 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
108091008605 VEGF receptors Proteins 0.000 claims description 4
102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 claims description 4
102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 4
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 claims description 3
101000851030 Homo sapiens Vascular endothelial growth factor receptor 3 Proteins 0.000 claims description 3
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims description 3
108010090091 TIE-2 Receptor Proteins 0.000 claims description 3
102000012753 TIE-2 Receptor Human genes 0.000 claims description 3
102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 3
ALNINMRLVFPRDH-UHFFFAOYSA-N [4-(4-methylpiperazine-1-carbonyl)phenyl]urea Chemical compound C1CN(C)CCN1C(=O)C1=CC=C(NC(N)=O)C=C1 ALNINMRLVFPRDH-UHFFFAOYSA-N 0.000 claims description 3
125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
NKDDWNXOKDWJAK-UHFFFAOYSA-N dimethoxymethane Chemical compound COCOC NKDDWNXOKDWJAK-UHFFFAOYSA-N 0.000 claims description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
238000011275 oncology therapy Methods 0.000 claims description 3
YBLPVRFSDNONDP-UHFFFAOYSA-N 1-[4-[[2-(5-ethylsulfonyl-2-methoxyanilino)pyrimidin-4-yl]-methylamino]phenyl]-3-(3-fluorophenyl)urea Chemical compound CCS(=O)(=O)C1=CC=C(OC)C(NC=2N=C(C=CN=2)N(C)C=2C=CC(NC(=O)NC=3C=C(F)C=CC=3)=CC=2)=C1 YBLPVRFSDNONDP-UHFFFAOYSA-N 0.000 claims description 2
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
241001024304 Mino Species 0.000 claims description 2
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 2
BSCCSDNZEIHXOK-UHFFFAOYSA-N phenyl carbamate Chemical compound NC(=O)OC1=CC=CC=C1 BSCCSDNZEIHXOK-UHFFFAOYSA-N 0.000 claims description 2
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims 3
238000011374 additional therapy Methods 0.000 claims 3
HMNKTRSOROOSPP-UHFFFAOYSA-N 3-Ethylphenol Chemical compound CCC1=CC=CC(O)=C1 HMNKTRSOROOSPP-UHFFFAOYSA-N 0.000 claims 2
HORNXRXVQWOLPJ-UHFFFAOYSA-N 3-chlorophenol Chemical compound OC1=CC=CC(Cl)=C1 HORNXRXVQWOLPJ-UHFFFAOYSA-N 0.000 claims 1
QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 claims 1
102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 claims 1
101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 claims 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 1
201000010099 disease Diseases 0.000 abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 abstract description 5
230000003463 hyperproliferative effect Effects 0.000 abstract 1
235000002639 sodium chloride Nutrition 0.000 description 60
238000001819 mass spectrum Methods 0.000 description 55
239000000203 mixture Substances 0.000 description 43
238000005481 NMR spectroscopy Methods 0.000 description 36
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 26
239000000543 intermediate Substances 0.000 description 26
239000000243 solution Substances 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 22
238000006243 chemical reaction Methods 0.000 description 22
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 20
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 20
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 20
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
239000000843 powder Substances 0.000 description 15
239000007787 solid Substances 0.000 description 14
BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 13
238000005160 1H NMR spectroscopy Methods 0.000 description 13
238000009472 formulation Methods 0.000 description 13
239000000725 suspension Substances 0.000 description 12
125000004432 carbon atom Chemical group C* 0.000 description 11
210000004027 cell Anatomy 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
239000004480 active ingredient Substances 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
230000006870 function Effects 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
230000002491 angiogenic effect Effects 0.000 description 9
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 9
235000019439 ethyl acetate Nutrition 0.000 description 9
239000002904 solvent Substances 0.000 description 9
238000006467 substitution reaction Methods 0.000 description 9
239000003826 tablet Substances 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
230000002159 abnormal effect Effects 0.000 description 8
150000001448 anilines Chemical class 0.000 description 8
239000003112 inhibitor Substances 0.000 description 8
239000003981 vehicle Substances 0.000 description 8
ZKHQWZAMYRWXGA-KQYNXXCUSA-J ATP(4-) Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-J 0.000 description 7
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 7
229910017711 NHRa Inorganic materials 0.000 description 7
230000004913 activation Effects 0.000 description 7
125000004390 alkyl sulfonyl group Chemical group 0.000 description 7
125000004414 alkyl thio group Chemical group 0.000 description 7
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 7
125000001424 substituent group Chemical group 0.000 description 7
BTTNYQZNBZNDOR-UHFFFAOYSA-N 2,4-dichloropyrimidine Chemical compound ClC1=CC=NC(Cl)=N1 BTTNYQZNBZNDOR-UHFFFAOYSA-N 0.000 description 6
125000004647 alkyl sulfenyl group Chemical group 0.000 description 6
230000022131 cell cycle Effects 0.000 description 6
210000002889 endothelial cell Anatomy 0.000 description 6
239000007788 liquid Substances 0.000 description 6
239000002609 medium Substances 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000003921 oil Substances 0.000 description 6
230000008569 process Effects 0.000 description 6
108090000765 processed proteins & peptides Proteins 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
239000011734 sodium Substances 0.000 description 6
238000012360 testing method Methods 0.000 description 6
108091003079 Bovine Serum Albumin Proteins 0.000 description 5
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 5
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
229940098773 bovine serum albumin Drugs 0.000 description 5
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 5
229940079593 drug Drugs 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
239000000463 material Substances 0.000 description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
235000019198 oils Nutrition 0.000 description 5
102000005962 receptors Human genes 0.000 description 5
108020003175 receptors Proteins 0.000 description 5
229920006395 saturated elastomer Polymers 0.000 description 5
229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
235000017557 sodium bicarbonate Nutrition 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
102000004190 Enzymes Human genes 0.000 description 4
108090000790 Enzymes Proteins 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
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
108091000080 Phosphotransferase Proteins 0.000 description 4
102100037787 Protein-tyrosine kinase 2-beta Human genes 0.000 description 4
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
125000004656 alkyl sulfonylamino group Chemical group 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
239000002775 capsule Substances 0.000 description 4
238000000576 coating method Methods 0.000 description 4
239000002552 dosage form Substances 0.000 description 4
229940088598 enzyme Drugs 0.000 description 4
239000008187 granular material Substances 0.000 description 4
239000003102 growth factor Substances 0.000 description 4
125000005647 linker group Chemical group 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
125000004043 oxo group Chemical group O=* 0.000 description 4
102000020233 phosphotransferase Human genes 0.000 description 4
238000000746 purification Methods 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
235000015424 sodium Nutrition 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
239000000126 substance Substances 0.000 description 4
229940124530 sulfonamide Drugs 0.000 description 4
150000003456 sulfonamides Chemical class 0.000 description 4
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
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